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Artery

An artery is a blood vessel in humans and most other animals that takes oxygenated blood away from the heart in the systemic circulation to one or more parts of the body. Exceptions that carry deoxygenated blood are the pulmonary arteries in the pulmonary circulation that carry blood to the lungs for oxygenation, and the umbilical arteries in the fetal circulation that carry deoxygenated blood to the placenta. It consists of a multi-layered artery wall wrapped into a tube-shaped channel.

Arteries contrast with veins, which carry deoxygenated blood back towards the heart; or in the pulmonary and fetal circulations carry oxygenated blood to the lungs and fetus respectively.

Structure

The anatomy of arteries can be separated into gross anatomy, at the macroscopic level, and microanatomy, which must be studied with a microscope. The arterial system of the human body is divided into systemic arteries, carrying blood from the heart to the whole body, and pulmonary arteries, carrying deoxygenated blood from the heart to the lungs.

Large arteries (such as the aorta) are composed of many different types of cells, namely endothelial, smooth muscle, fibroblast, and immune cells. As with veins, the arterial wall consists of three layers called tunics, namely the tunica intima, tunica media, and tunica externa, from innermost to outermost. The externa, alternatively known as the tunica adventitia, is composed of collagen fibers and elastic tissue—with the largest arteries containing vasa vasorum, small blood vessels that supply the walls of large blood vessels. Most of the layers have a clear boundary between them, however the tunica externa has a boundary that is ill-defined. Normally its boundary is considered when it meets or touches the connective tissue. Inside this layer is the tunica media, which is made up of smooth muscle cells, elastic tissue (also called connective tissue proper) and collagen fibres. The innermost layer, which is in direct contact with the flow of blood, is the tunica intima. The elastic tissue allows the artery to bend and fit through places in the body. This layer is mainly made up of endothelial cells (and a supporting layer of elastin rich collagen in elastic arteries). The hollow internal cavity in which the blood flows is called the lumen.

Development
Arterial formation begins and ends when endothelial cells begin to express arterial specific genes, such as ephrin B2.

Function

Arteries form part of the circulatory system. They carry blood that is oxygenated after it has been pumped from the heart. Coronary arteries also aid the heart in pumping blood by sending oxygenated blood to the heart, allowing the muscles to function. Arteries carry oxygenated blood away from the heart to the tissues, except for pulmonary arteries, which carry blood to the lungs for oxygenation (usually veins carry deoxygenated blood to the heart but the pulmonary veins carry oxygenated blood as well). There are two types of unique arteries. The pulmonary artery carries blood from the heart to the lungs, where it receives oxygen. It is unique because the blood in it is not "oxygenated", as it has not yet passed through the lungs. The other unique artery is the umbilical artery, which carries deoxygenated blood from a fetus to its mother.

Arteries have a blood pressure higher than other parts of the circulatory system. The pressure in arteries varies during the cardiac cycle. It is highest when the heart contracts and lowest when heart relaxes. The variation in pressure produces a pulse, which can be felt in different areas of the body, such as the radial pulse. Arterioles have the greatest collective influence on both local blood flow and on overall blood pressure. They are the primary "adjustable nozzles" in the blood system, across which the greatest pressure drop occurs. The combination of heart output (cardiac output) and systemic vascular resistance, which refers to the collective resistance of all of the body's arterioles, are the principal determinants of arterial blood pressure at any given moment.

Arteries have the highest pressure and have narrow lumen diameter.

Systemic arteries are the arteries (including the peripheral arteries), of the systemic circulation, which is the part of the cardiovascular system that carries oxygenated blood away from the heart, to the body, and returns deoxygenated blood back to the heart. Systemic arteries can be subdivided into two types—muscular and elastic—according to the relative compositions of elastic and muscle tissue in their tunica media as well as their size and the makeup of the internal and external elastic lamina. The larger arteries (>10 mm diameter) are generally elastic and the smaller ones (0.1–10 mm) tend to be muscular. Systemic arteries deliver blood to the arterioles, and then to the capillaries, where nutrients and gasses are exchanged.

After traveling from the aorta, blood travels through peripheral arteries into smaller arteries called arterioles, and eventually to capillaries. Arterioles help in regulating blood pressure by the variable contraction of the smooth muscle of their walls, and deliver blood to the capillaries. This smooth muscle contraction is primarily influenced by activity of the sympathetic vasomotor nerves innervating the arterioles. Enhanced sympathetic activation prompts vasoconstriction, reducing the lumen diameter. A reduced lumen diameter consequently elevates the blood pressure within the arterioles. Conversely, decreased sympathetic activity within the vasomotor nerves causes vasodilation of the vessels thereby decreasing blood pressure.

Aorta
The aorta is the root systemic artery (i.e., main artery). In humans, it receives blood directly from the left ventricle of the heart via the aortic valve. As the aorta branches and these arteries branch, in turn, they become successively smaller in diameter, down to the arterioles. The arterioles supply capillaries, which in turn empty into venules. The first branches off of the aorta are the coronary arteries, which supply blood to the heart muscle itself. These are followed by the branches of the aortic arch, namely the brachiocephalic artery, the left common carotid, and the left subclavian arteries.

Capillaries
The capillaries are the smallest of the blood vessels and are part of the microcirculation. The microvessels have a width of a single cell in diameter to aid in the fast and easy diffusion of gasses, sugars and nutrients to surrounding tissues. Capillaries have no smooth muscle surrounding them and have a diameter less than that of red blood cells; a red blood cell is typically 7 micrometers outside diameter, capillaries typically 5 micrometers inside diameter. The red blood cells must distort in order to pass through the capillaries.

These small diameters of the capillaries provide a relatively large surface area for the exchange of gasses and nutrients.

Clinical significance

Systemic arterial pressures are generated by the forceful contractions of the heart's left ventricle. High blood pressure is a factor in causing arterial damage. Healthy resting arterial pressures are relatively low, mean systemic pressures typically being under 100 mmHg above surrounding atmospheric pressure (about 760 mmHg at sea level). To withstand and adapt to the pressures within, arteries are surrounded by varying thicknesses of smooth muscle which have extensive elastic and inelastic connective tissues. The pulse pressure, being the difference between systolic and diastolic pressure, is determined primarily by the amount of blood ejected by each heart beat, stroke volume, versus the volume and elasticity of the major arteries.

A blood squirt, also known as an arterial gush, is the effect when an artery is cut due to the higher arterial pressures. Blood is spurted out at a rapid, intermittent rate, that coincides with the heartbeat. The amount of blood loss can be copious, can occur very rapidly, and be life-threatening.

Over time, factors such as elevated arterial blood sugar (particularly as seen in diabetes mellitus), lipoprotein, cholesterol, high blood pressure, stress and smoking, are all implicated in damaging both the endothelium and walls of the arteries, resulting in atherosclerosis. Atherosclerosis is a disease marked by the hardening of arteries. This is caused by an atheroma or plaque in the artery wall and is a build-up of cell debris, that contain lipids, (cholesterol and fatty acids), calcium and a variable amount of fibrous connective tissue.

Accidental intra-arterial injection either iatrogenically or through recreational drug use can cause symptoms such as intense pain, paresthesia and necrosis. It usually causes permanent damage to the limb; often amputation is necessary.

History
Among the Ancient Greeks before Hippocrates, all blood vessels were called Φλέβες, phlebes. The word arteria then referred to the windpipe. Herophilos was the first to describe anatomical differences between the two types of blood vessel. While Empedocles believed that the blood moved to and fro through the blood vessels, there was no concept of the capillary vessels that join arteries and veins, and there was no notion of circulation. Diogenes of Apollonia developed the theory of pneuma, originally meaning just air but soon identified with the soul itself, and thought to co-exist with the blood in the blood vessels. The arteries were thought to be responsible for the transport of air to the tissues and to be connected to the trachea. This was as a result of finding the arteries of cadavers devoid of blood.

In medieval times, it was supposed that arteries carried a fluid, called "spiritual blood" or "vital spirits", considered to be different from the contents of the veins. This theory went back to Galen. In the late medieval period, the trachea, and ligaments were also called "arteries".

William Harvey described and popularized the modern concept of the circulatory system and the roles of arteries and veins in the 17th century.

Alexis Carrel at the beginning of the 20th century first described the technique for vascular suturing and anastomosis and successfully performed many organ transplantations in animals; he thus actually opened the way to modern vascular surgery that was previously limited to vessels' permanent ligation.

title: Artery


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Todd Rundgren

Todd Harry Rundgren (born June 22, 1948) is an American musician, singer, songwriter, and record producer who has performed a diverse range of styles as a solo artist and as a member of the bands Nazz and Utopia. He is known for his sophisticated and often unorthodox music, his occasionally lavish stage shows, and his later experiments with interactive art. He also produced music videos and was an early adopter and promoter of various computer technologies, such as using the Internet as a means of music distribution in the late 1990s.

A native of Philadelphia, Rundgren began his professional career in the mid-1960s, forming the psychedelic band Nazz in 1967. After two years, he left Nazz to pursue a solo career and immediately scored his first US top 40 hit with "We Gotta Get You a Woman" (1970). His best-known songs include "Hello It's Me" and "I Saw the Light" from Something/Anything? (1972), which get frequent air time on classic rock radio stations, the 1978 "Can We Still Be Friends", and the 1983 single "Bang the Drum All Day", which is featured in many sports arenas, commercials, and movie trailers. Although lesser known, "Couldn't I Just Tell You" (1972) was influential to many artists in the power pop genre. His 1973 album A Wizard, a True Star remains an influence on later generations of bedroom musicians.

Rundgren is considered a pioneer in the fields of electronic music, progressive rock, music videos, computer software, and Internet music delivery. He organized the first interactive television concert in 1978, designed the first color graphics tablet in 1980, and created the first interactive album, No World Order, in 1994. Additionally, he was one of the first acts to be prominent as both an artist and producer. His notable production credits include Badfinger's Straight Up (1971), Grand Funk Railroad's We're an American Band (1973), the New York Dolls' New York Dolls (1973), Meat Loaf's Bat Out of Hell (1977), and XTC's Skylarking (1986). He was inducted into the Rock and Roll Hall of Fame in 2021.

Early influences and Nazz
Todd Harry Rundgren was born in Philadelphia on June 22, 1948, the son of Ruth (née Fleck; April 29, 1922 – April 6, 2016) and Harry W. Rundgren (1917–1996). His father was of Swedish descent and his mother was of Austrian and German descent. He grew up in the bordering town of Upper Darby Township, Pennsylvania and taught himself how to play guitar with little help. As a child, Rundgren was fascinated by his parents' small record collection, which consisted of show tunes and symphonic pieces, and especially by the operettas of Gilbert and Sullivan. Later, he grew infatuated with the music of the Beatles, the Rolling Stones, the Ventures, and the Yardbirds, as well as the Philadelphia soul of Gamble & Huff, the Delfonics, and the O'Jays. At the age of 17, he formed his first band, Money, with then-best friend and roommate Randy Reed and Reed's younger brother.

After graduating from Upper Darby High School in 1966, Rundgren moved to Philadelphia and began his career in Woody's Truck Stop, a blues rock group in the style of Paul Butterfield Blues Band. Rundgren stayed with the band for eight months, and in the process, they became the most popular group in Philadelphia. He and bassist Carson Van Osten left before they released the eponymous first album to form the rock band Nazz in 1967. By then, Rundgren had lost interest in the blues and wanted to pursue a recording career with original songs in the style of newer records by the Beatles and the Who. As a member of the Nazz, he learned his craft as a songwriter and vocal arranger, and was determined to equal the artistry of the Beatles.

In 1968, after recording four demo discs, the Nazz were signed by Atlantic Records subsidiary Screen Gems Columbia (SGC). They were flown to Los Angeles to produce their first album at ID Sound studio. Rundgren had no prior production experience and remembered that the producer, Bill Traut, "just whipped through the mixes in a day or two ... So I got it into my head, 'Well, he's gone now, so why don't we just mix it again, more like the way we want it?' Our engineer didn't mind if we went and just started diddling around on the board ... It was pretty much trial and error." He took an experimental approach to the recordings, employing techniques such as varispeed and flanging, and despite having no formal training, scored music charts for string and horn arrangements. Engineer James Lowe, who Rundgren recruited for his involvement with arranger Van Dyke Parks, believed that Rundgren had become the de facto leader of Nazz, and that a producer's credit was wrongfully withheld from him.

Nazz gained minor recognition with their debut single, July 1968's "Open My Eyes" backed with "Hello It's Me", both songs penned by Rundgren. They subsequently released three albums: Nazz (October 1968), Nazz Nazz (April 1969), and Nazz III (1971). In March 1968, New York singer-songwriter Laura Nyro released her second album, Eli and the Thirteenth Confession. When Rundgren heard the record, he was struck by "all the major seventh chords and variations on augmented and suspended chords", and it had an immediate impact on his songwriting, especially as he began to compose more on piano. He elaborated:

"I know for a fact that her influences were the more sophisticated side of R&B, like Jerry Ragovoy and Mann & Weil and Carole King. ... and she also had her own very original and very jazz-influenced way of seeing things. It was that extra layer that made her influential. A lot of those chords she got from other people. But beyond the elements of her composition, I always thought it was the way she played her own material that really sold it. ... I met her right after Eli and the Thirteenth Confession. I actually had arranged a meeting, just because I was so infatuated with her and I wanted to meet the person who had produced all this music. ... after I met her the first time, she asked me if I wanted to be her band leader. But the Nazz had just signed a record contract and I couldn't skip out on the band, even though it was incredibly tempting."

The rest of the band struggled to accommodate his changing tastes, and tensions between all the band members had begun to build up in the interval between recording their first and second albums as a result of their shared living quarters. Tensions further increased during the recording of Nazz's second album, as the other members bridled at the formerly unassuming Rundgren asserting complete control of the sessions as the producer. By the time Nazz Nazz was released, Rundgren and Van Osten had both left the Nazz, so the track selection was done without any input from them. Nazz III, which included leftover tracks from the Nazz Nazz sessions, was likewise released without Rundgren's involvement.

Production beginnings
After departing Nazz, the 21-year-old Rundgren briefly considered working as a computer programmer, and then decided that his calling was as a producer. He moved to New York in the summer of 1969 and involved himself with the clubs of Greenwich Village, particularly Steve Paul's Scene, and met a number of Manhattan musicians and fashion designers. Michael Friedman, formerly the assistant of Nazz manager John Kurland, offered Rundgren a job as staff engineer and producer under Albert Grossman, which Rundgren accepted. Grossman, known for his management of folk rock acts, had just founded Ampex Records, a joint business venture with the tape company of the same name, and built Bearsville Studios, near Woodstock. Bearsville soon became its own record imprint. Grossman promised to Rundgren that he would become the "highest-paid producer in the world", which later came true.

Rundgren said he was initially relegated to "various old folk artists that they had who needed an upgrade: people like Ian & Sylvia, James Cotton, and other artists in Albert's stable." Shortly after producing the eponymous 1969 album by Great Speckled Bird, he was promoted as Bearsville's house engineer. Accompanied by Robbie Robertson and Levon Helm of the Band, he traveled to Canada to record Jesse Winchester's eponymous 1970 debut album. Immediately afterward, he said, "the Band asked me to engineer their Stage Fright sessions. I think Jesse Winchester was a kind of run-through for that, because I was pretty quick to get the sounds and they liked that." Released in August 1970, Stage Fright reached number 5 on the Billboard 200, the highest chart showing the Band had to that point. Rundgren was dubbed Bearsville's "boy wonder".

His work for the Band was followed by a second album for Winchester (which was then shelved for two years) and the album Taking Care of Business by the James Cotton Blues Band (1970). This project resulted in Rundgren meeting Cotton's keyboard player Mark "Moogy" Klingman, who in turn introduced Rundgren to keyboard player Ralph Schuckett, both of whom worked extensively with Rundgren over the next few years. Rundgren was to produce Janis Joplin's third and ultimately final album, Pearl (1971), but plans fell through, as the two artists could not get along with each other.

Runt and Ballad of Todd Rundgren
Following a period where he thought he would never return to being a performing artist, Rundgren approached Grossman with the idea of what would become his debut solo record, Runt. Although his general attitude for any project was to "make the record [I] wanted to make and then hope the label can find a way to promote it", Rundgren ensured that any loss to Grossman would be minimal: "I didn't get an actual advance for Runt. I just asked for a recording budget to pay the studio costs. ... I had no idea how much money I even had in the bank. If I needed cash, I would show up at the accountants and they would just give me hundreds or thousands of dollars."

Released in mid-1970, Runt was not originally credited to Rundgren due to his anxieties about starting a full-fledged solo career, and instead bore the moniker "Runt". The album featured a bright sound and songs inspired by Laura Nyro. It was recorded with the 17-year-old bassist Tony Fox Sales and his 14-year-old brother Hunt Sales on drums. Nazz engineer James Lowe returned for the sessions and recalled that Rundgren seemed "more able to really lead a group. If you go back and listen to it, it's very sophisticated material, especially for a guy so young." Lead single "We Gotta Get You a Woman" reached number 20 on the Billboard charts. As he prepared a follow-up LP, he produced Halfnelson, the debut album by the band that would later become Sparks. Members Ron and Russell Mael later credited Rundgren with launching Sparks' career.

Rundgren's industry reputation grew substantially as a result of his success with Runt, and for the first time in his life, he began using recreational drugs. Initially this was limited to marijuana. He said that the drug gave him "a whole different sensibility about time and space and order" that influenced the writing for his second album, Runt. The Ballad of Todd Rundgren. The material was mostly piano ballads and still largely based on Nyro's template, but a more conscious effort by Rundgren was made to refine his music and choice of subject matter, and to distinguish himself from his influences. Released June 1971, The Ballad of Todd Rundgren bore two singles, "Be Nice to Me" and "A Long Time, a Long Way To Go", neither of which repeated the success of "We Gotta Get You a Woman". While initial reviews of Ballad were mixed, it came to be regarded as one of the greatest singer-songwriter albums of the era.

Something/Anything?
In late 1971, Rundgren was recruited to finish Badfinger's third album Straight Up, a project George Harrison had abandoned to organize the Concert for Bangladesh, in London. The album was a hit and its two singles were similarly successful, although Rundgren was not credited for the first ("Day After Day") and thus did not receive production royalties for that single. Rundgren said that the song "didn't sound much like what [Harrison had] done" and speculated that the credit to Harrison "may or may not have been something purposeful, just some by-product of a general Beatle hubris". The Straight Up sessions lasted two weeks in September, after which Rundgren returned to Los Angeles to work on his third solo album, originally planned as a single LP.

As with Ballad, much of the newer material was written or conceived under the influence of marijuana. However, by this time, he had also begun experimenting with Ritalin. He recalled, "my songwriting process had become almost too second-nature. I was writing songs formulaically, almost without thinking, knocking [them out], reflexively, in about 20 minutes." The use of Ritalin also helped him focus on the process as he worked up to 12 hours a day to beat the three-week deadline. To keep up the pace, he installed an eight-track recorder, mixer, and synthesizers into his living room so that he could continue recording after leaving the studio. For the first time in his career, Rundgren recorded every part by himself, including bass, drums, and vocals. About "an album and a half" was completed this way. He then decided to stretch the project into a double LP and quickly recorded the last few tracks with musicians, live in the studio.

Something/Anything?, the first album officially issued under the name "Todd Rundgren", was released in February 1972, shortly after Bearsville had signed a long-term distribution deal with Warner Bros. Records. The album included many songs that would become his best-known. Included among straightforward pop songs are extended jams and studio banter, such as the spoken-word track "Intro", in which he teaches the listener about recording flaws for an egg hunt-type game he calls "Sounds of the Studio". Magazine ads depicted a smiling Rundgren daring the reader to "ignore me". The album peaked at number 29 on the Billboard 200 and was certified gold in three years. Lead single "I Saw the Light" peaked at number 16 on the Billboard Hot 100. "Hello It's Me", which followed late in 1973, reached number 5.

According to music critic Colin Larkin, Something/Anything? has since been "rightly regarded as one of the landmark releases of the early 70s". "Couldn't I Just Tell You" was influential to artists in the power pop genre. Music journalist Paul Lester called the recording a "masterclass in compression" and said that Rundgren "staked his claim to powerpop immortality [and] set the whole ball rolling". Musician Scott Miller's 2010 book Music: What Happened? calls the song "likely the greatest power pop recording ever made," with lyrics "somehow both desperate and lighthearted at the same time," and a guitar solo having "truly amazing dexterity and inflection". In 2003, Something/Anything? was ranked number 173 on Rolling Stone magazine's list of the "500 Greatest Albums of All Time".

A Wizard, a True Star, Todd, and Utopia
Subsequent albums, beginning with A Wizard, a True Star and the spin-off group Utopia, saw a dramatic shift away from straightforward three-minute pop. After the success of Something/Anything?, Rundgren felt uncomfortable that he was being increasingly tagged as "the male Carole King". "With all due respect to Carole King," he said, "It wasn't what I was hoping to create as a musical legacy for myself." Now relocated back to New York and experimenting with a host of psychedelic drugs, he began to think that the writing on Something/Anything? was largely formulaic and borne from laziness, and sought to create a "more eclectic and more experimental" follow-up album. His music tastes also started to lean toward the progressive rock of Frank Zappa, Yes, and the Mahavishnu Orchestra. In 2017, while giving a commencement speech at the Berklee College of Music, he described the record as:

"... my act of tyranny after having achieved commercial success. ... I threw out all the rules of record making and decided I would try to imprint the chaos in my head onto a record without trying to clean it up for everyone else's benefit. The result was a complete loss of about half of my audience at that point ... This became the model for my life after that."

The sound and structure of Wizard was heavily informed by Rundgren's hallucinogenic experiences. It was envisioned as a hallucinogenic-inspired "flight plan" with all the tracks seguing seamlessly into each other, starting with a "chaotic" mood and ending with a medley of his favorite soul songs. He said: "With drugs I could suddenly abstract my thought processes in a certain way, and I wanted to see if I could put them on a record. A lot of people recognized it as the dynamics of a psychedelic trip—it was almost like painting with your head." Rundgren and Moogy Klingman established a professional recording studio, Secret Sound, to accommodate the Wizard sessions. The studio was designed to Rundgren's specifications and was created so that he could freely indulge in sound experimentation without having to worry about hourly studio costs, although he maintained that the album still felt "kind of rushed through because the studio wasn't finished". Some of the other influences on the album included musical theater, jazz, and funk.

A Wizard, a True Star was released in March 1973. At Rundgren's behest, no singles were issued from the album, as he wanted the tracks to be heard in the context of the LP. Its release coincided with the success of the "Hello It's Me" single, which gave Rundgren a reputation as a ballad singer, in marked contrast to the content on Wizard. Although critical reception to the album was mixed, Wizard became highly influential to musicians in the ensuing decades. In 2003, music journalist Barney Hoskyns called the record "the greatest album of all time ... a dizzying, intoxicating rollercoaster ride of emotions and genre mutations [that] still sounds more bravely futuristic than any ostensibly cutting-edge electro-pop being made in the 21st Century." In 2018, Pitchfork's Sam Sodomsky wrote that the "fingerprints" of Wizard remained "evident on bedroom auteurs to this day".

In the weeks following the album's release, Rundgren produced Grand Funk Railroad's We're an American Band and the New York Dolls' self-titled debut album, which were among the most significant LPs of the year. The former album reached number two on the US charts, while the latter became a seminal forerunner of punk rock, although Rundgren never became known as a "punk producer". Rundgren also prepared a technologically ambitious stage show with a band later to be known as Utopia Mark I, consisting of Tony Sales, Hunt Sales, keyboardist Dave Mason, and synthesizer specialist Jean-Yves "M Frog" Labat. The tour began in April and was cancelled after only a couple weeks on the road.

Once Rundgren was finished with his production duties, he began formulating plans for an improved configuration of Utopia, but first returned to Secret Sound to record the more synthesizer-heavy double album Todd, which was more material drawing on his hallucinogenic experiences. This time, he had also formed a fascination with religion and spirituality, reading books by authors such as Madame Blavatsky, Rudolf Steiner, and Jiddu Krishnamurti. Originally scheduled for release in December 1973, Todd was delayed to the next February due to a vinyl shortage caused by the 1973 oil crisis.

During the making of Todd, Rundgren took note of the "fusion jazz sensibility" between session musicians Kevin Ellman (drums) and John Siegler (bass). Rundgren chose them, along with Klingman and keyboardist Ralph Shuckett, to be the new configuration of Utopia. This line-up performed their first show at Central Park on August 25, 1973, sharing the bill with the Brecker Brothers and Hall & Oates. Utopia played more shows throughout November and December, performing material from Something/Anything? and Wizard after a solo opening set by Rundgren on piano playing along to a pre-recorded track. On December 7, Rundgren appeared by himself on The Midnight Special performing "Hello It's Me" while dressed in jarringly flamboyant glam attire to the chagrin of some of his bandmates and Bearsville executive Paul Fishkin, who recalled that Rundgren looked "like a fucking drag queen".

Utopia embarked on their first successful tour between March and April 1974, after which Rundgren produced Hello People's The Handsome Devils and Hall & Oates' War Babies. The band's debut record came in the form of the LP titled Todd Rundgren's Utopia (November 1974). It marked Rundgren's first full-fledged venture into the progressive rock genre. Utopia released several more albums between 1975 and 1985. Although they gradually rebranded toward a rock-pop sound, Todd Rundgren's Utopia remained their highest album chart showing at number 34. Keyboardist Roger Powell recalled that Bearsville wished Utopia would have "just gone away", however, "Todd's contract called for a certain number of albums over a certain number of years, so he decided that every other album would be a solo album and the next one a Utopia album."

Initiation, Faithful, and Hermit of Mink Hollow
A Wizard, a True Star included "Rock N Roll Pussy", a song aimed at former Beatle John Lennon. In 1974, Rundgren and Lennon were embroiled in a minor feud over comments Rundgren made in the February edition of Melody Maker magazine. In the article, he accused Lennon of striking a waitress at the Troubadour in Hollywood and called him a "fucking idiot" proselytizing revolution and "acting like an ass". In September, the magazine published Lennon's response, in which he denied the charges and referred to the musician as "Turd Runtgreen": "I have never claimed to be a revolutionary. But I am allowed to sing about anything I want! Right?" Later, Rundgren said, "John and I realized we were being used and I got a phone call from him one day and we just said: 'Let's drop this now.'"

Initiation (1975) showed more experimentation with synthesizers, and displayed the musical influence of the avant-garde jazz fusion of contemporary acts such as the Mahavishnu Orchestra and Frank Zappa. Once again the original LP issue saw Rundgren pushing the medium to its physical limits, with the side-long suite "A Treatise on Cosmic Fire" clocking in at over 35 minutes.

Released in May 1976, Faithful saw Rundgren celebrating his tenth year as a professional musician. The album featured one side of original songs and one side of covers of significant songs from 1966, including the Yardbirds' "Happenings Ten Years Time Ago", the Beach Boys' "Good Vibrations", and two Lennon-penned Beatles songs. The arrangements of the covers were intended to sound as close to the originals as possible, and Rundgren's original songs were written as a reflection of his 1960s influences. He cited the song "The Verb 'To Love'" as the point in which he made the conscious decision to stop writing superficial love songs and "seek out all other kinds of subject matter to write about". Despite the lack of sales and promotion for Faithful, lead single "Good Vibrations" received regular airplay on American radio.

Following the completion of Faithful, Rundgren spent two months on an eastern spiritual retreat, visiting Iran, Afghanistan, India, Nepal, Sri Lanka, Bali, Thailand, Japan, and Hawaii. He also opened Utopia Sound Studios in Lake Hill, New York, just outside of Woodstock, and bought a home nearby, as well as an adjoining property to be taken over as accommodation for artists who used the studio. The Lake Hill complex on Mink Hollow Road remained Rundgren's base for the next six years. In the interim until his next solo effort, he recorded three albums with Utopia. The first, Disco Jets, was a tongue-in-cheek collection of instrumental disco tracks left unreleased until 2001. Ra (February 1977) was a concept album based on Egyptian mythology, which prefaced a lavish tour involving an extravagant stage set with a giant pyramid and Sphynx head. Oops! Wrong Planet (September 1977), recorded immediately after the tour, signaled the start of a more pop-oriented direction for the group.

By late 1977, Rundgren was in the midst of separating from then-girlfriend Bebe Buell and their infant daughter Liv Tyler. Rundgren recalled leaving his home in New York City and sequestering himself at Mink Hollow, "after I discovered that I didn't want to cohabit any longer with Bebe, in any sense of the word ... A fortunate by-product of being so out of everything all the time and always being the odd man out ... is that you have plenty of time for self-examination." He intended the songs on his next solo album to be performed on piano with minimal arrangements, apart from the bass, drums and voices. In that sense, he stated that the songwriting process appeared to be "fairly conventional".

Hermit of Mink Hollow was released in May 1978. Popularly viewed as his most immediately accessible work since Something/Anything?, it received more public attention and radio airplay than most of Rundgren's efforts since A Wizard, a True Star and was heralded as a "return to form" after the string of prog records with Utopia. In the US, the LP peaked at number 36, while single "Can We Still Be Friends" reached number 29. The song became Rundgren's most-covered, with versions by Robert Palmer, Rod Stewart, Colin Blunstone, and Mandy Moore. To promote the work, Rundgren undertook an American tour playing at smaller venues including The Bottom Line in New York and The Roxy in Los Angeles. These shows resulted in the double live album Back to the Bars, which featured a mixture of material from his solo work and Utopia, performed with backing musicians including Utopia, Spencer Davis, Daryl Hall and John Oates and Stevie Nicks.

In 1980, Utopia recorded a Beatles parody album in the form of Deface the Music. It included "Everybody Else Is Wrong", another song perceived to have been aimed at Lennon. Later that year, Lennon was killed by Mark David Chapman, an obsessive Rundgren fan who was incensed by Lennon's remarks on religion. When he was apprehended, Chapman was wearing a promotional T-shirt for Hermit of Mink Hollow and had left a copy of ''Runt. The Ballad of Todd Rundgren'' in his hotel room. Rundgren was not aware of the connections until "way after the fact". When asked about the Melody Maker feud, Chapman stated he was not aware of the musicians' interactions in the press until years after they occurred.

Healing and Tortured Artist Effect
The year 1981 saw the album-long concept work Healing. His music video for the song "Time Heals" was among the first videos aired on MTV, and a video he produced for RCA, accompanied by Gustav Holst's The Planets, was used as a demo for their videodisc players. Rundgren's experience with computer graphics dates back to 1981, when he developed one of the first computer paint programs, dubbed the Utopia Graphics System; it ran on an Apple II with Apple's digitizer tablet. He is also the co-developer of the computer screensaver system Flowfazer.

Rundgren's Mink Hollow home was burglarized on August 13, 1980. He and his girlfriend (who was pregnant at the time) were tied up while the house was ransacked by a group of armed men. According to Rundgren's account, the men erroneously assumed that he possessed a large quantity of cocaine. Although the family was unharmed, the men stole some valuable items, including a custom-made Alembic bass guitar.

The new wave-tinged The Ever Popular Tortured Artist Effect (1982) included a cover of the Small Faces' hit "Tin Soldier". "Bang The Drum All Day", an album single, was a minor chart hit. It later became more prominent and was adopted as an unofficial theme by several professional sports franchises, notably the Green Bay Packers. Disc Jockey Geno Michellini of KLOS in Los Angeles used "Bang The Drum All Day" as an unofficial kick-off to the weekend on Friday afternoons. "Bang The Drum All Day" was also featured in a Carnival Cruise television advertising campaign. It is now considered one of Rundgren's most popular songs. Tortured Artist marked the end of Rundgren's tenure with Bearsville Records.

1980s–1990s: A Cappella, Nearly Human, and 2nd Wind
Rundgren signed with Warner Bros. Records, who issued his next album, A Cappella (1985), which was recorded using Rundgren's multi-tracked voice, accompanied by arrangements constructed entirely from programmed vocal samples. Rundgren scored four episodes of the popular children's television show Pee-wee's Playhouse in 1986.

Nearly Human (1989) and 2nd Wind (1991) were both recorded live—the former in the studio, the latter in a theater before a live audience, who were instructed to remain silent. Each song on these albums was recorded as a complete single take with no later overdubbing. Both albums marked, in part, a return to his Philly soul roots. 2nd Wind also included several excerpts from Rundgren's musical Up Against It, which was adapted from the screenplay (originally titled "Prick Up Your Ears"), that British playwright Joe Orton had originally offered to the Beatles for their never-made follow-up to Help!.

Rundgren was an early adopter of the NewTek Video Toaster and made several videos with it. The first, for "Change Myself" from 2nd Wind, was widely distributed as a demo reel for the Toaster. Later, he set up a company to produce 3D animation using the Toaster; this company's first demo, "Theology" (a look at religious architecture through the ages featuring music by former Utopia bandmate Roger Powell) also became a widely circulated item among Toaster users.

1990s–2000s: TR-I, PatroNet, and Liars
The mid-1990s saw Rundgren recording under the pseudonym TR-i ("Todd Rundgren interactive") for two albums. The first of these, 1993's No World Order, consisted of hundreds of seconds-long snippets of music, that could be combined in various ways to suit the listener. Initially targeted for the Philips CD-i platform, No World Order featured interactive controls for tempo, mood, and other parameters, along with pre-programmed mixes by Rundgren himself, Bob Clearmountain, Don Was and Jerry Harrison. The disc was also released for PC and Macintosh and in two versions on standard audio CD, the continuous mix disc No World Order and, later, the more song-oriented No World Order Lite. The music itself was quite a departure from Rundgren's previous work, with a dance/techno feel and much rapping by Rundgren. The follow-up, The Individualist (1995), featured interactive video content, that could be viewed or in one case, played; it was a simple video game along with the music, which was more rock-oriented than No World Order.

Rundgren returned to recording under his own name for With a Twist... (1997), an album of bossa-nova covers of his older material. His PatroNet work, which trickled out to subscribers over more than a year, was released in 2000 as One Long Year. In 2004, Rundgren released Liars, a concept album about "paucity of truth", that features a mixture of his older and newer sounds.

As the Internet gained mass acceptance, Rundgren, along with longtime manager Eric Gardner and Apple digital music exec Kelli Richards, started PatroNet, which offered fans (patrons) access to his works-in-progress and new unreleased tracks in exchange for a subscription fee, cutting out record labels. The songs from Rundgren's first PatroNet run were later released as the album One Long Year. Since then, Rundgren has severed his connections with major record labels and continues to offer new music direct to subscribers via his website, although he also continues to record and release CDs through independent labels. As of 2022, the PatroNet.com website was not active.

2000s–2010s
In the aftermath of the September 11 attacks, Rundgren created the score for the film A Face to a Name, directed by Douglas Sloan. The film depicted numerous photographs of missing New Yorkers that were displayed on Bellevue Hospital's 'wall of prayers' following the attacks. The film was part of a special screening at the Woodstock Film Festival in 2002.

In late 2005, the Boston-based band The Cars were planning to re-form despite bassist Benjamin Orr's death and lack of interest on the part of former lead singer Ric Ocasek. Rumors followed that Rundgren had joined Elliot Easton and Greg Hawkes in rehearsals for a possible new Cars lineup. Initial speculation pointed to The New Cars being fleshed out with Clem Burke of Blondie and Art Alexakis of Everclear. Eventually the group completed their lineup with former Rundgren bassist Kasim Sulton and studio drummer Prairie Prince of The Tubes, who had played on XTC's Rundgren-produced Skylarking and who has recorded and toured with Rundgren.

In early 2006, the new lineup played a few private shows for industry professionals, played live on The Tonight Show with Jay Leno and made other media appearances before commencing a 2006 summer tour with the re-formed Blondie. Rundgren referred to the project as "an opportunity ... for me to pay my bills, play to a larger audience, work with musicians I know and like, and ideally have some fun for a year." The New Cars' first single, "Not Tonight", was released on March 20, 2006. A live album/greatest hits collection, The New Cars: It's Alive, was released in June 2006. The album includes classic Cars songs (and two Rundgren hits) recorded live plus three new studio tracks ("Not Tonight", "Warm", and "More")

In April 2011, Todd Rundgren's Johnson, a collection of Robert Johnson covers, which had been recorded more than a year earlier, was released. In another 2011, an album of covers, (re)Production, features Rundgren performing tracks he had previously produced for other acts, including Grand Funk Railroad's "Walk Like a Man" and XTC's "Dear God".

In 2017, Rundgren released White Knight, which features collaborations with Trent Reznor, Robyn, Daryl Hall, Joe Walsh and Donald Fagen.

In December 2018, Cleopatra Press published his self-penned memoir, The Individualist: Digressions, Dreams, and Dissertations. The book contains 181 chapters, each one page long, and each consisting of three paragraphs. He said that "I realized that I have to do this or somebody else will do it. I'm getting to the point where I could at some point not be able to do it myself, and then someone else would do it and I wouldn't be happy with the result." Its coverage ends at Rundgren's 50th birthday in 1998, which was the same time he began writing the book. Since then, he said, "my life has been a lot more boring ... I'm not doing as much record production as I used to, so interesting tales that go along with those projects don't exist anymore." On October 21, 2019, he stopped by the Library of Congress and signed a braille copy—which was produced for him by a fan and National Library Service for the Blind and Print Disabled patron who is blind.

Rundgren toured in late 2019 with Micky Dolenz, Jason Scheff, Christopher Cross and Joey Molland of Badfinger in celebration of the Beatles' White Album on the "It Was Fifty Years Ago Today – A Tribute to the Beatles' White Album".

2020s
Rundgren collaborated with Weezer frontman Rivers Cuomo in 2020, releasing the single "Down With The Ship". In December, he released his English translation of the 1978 song "Flappie", originally by Dutch comedian Youp van 't Hek. That April, he reunited with Sparks 50 years after producing their debut album, releasing a single "Your Fandango". In September 2022, he released the album Space Force.

As a solo artist
Writing for AllMusic, music critic Stephen Thomas Erlewine recognizes Rundgren thus:

"Todd Rundgren's best-known songs – the Carole King pastiche 'I Saw the Light', the ballads 'Hello, It's Me' and 'Can We Still Be Friends', and the goofy novelty 'Bang on the Drum All Day' – suggest that he is a talented pop craftsman ... but at his core, Rundgren is a rock & roll maverick. Once he had a taste of success with his 1972 masterwork Something/Anything?, Rundgren chose to abandon stardom and, with it, conventional pop music. He began a course through uncharted musical territory, becoming a pioneer not only in electronic music and prog rock, but in music video, computer software, and Internet music delivery as well."

As a solo artist from 1972 to 1978, Rundgren scored four US Top 40 singles on the Billboard Hot 100, including one Top 10 hit with "Hello, It's Me", and three US Top 40 albums on the Billboard 200. He is one of the first acts to be prominent both as an artist and as a producer. and he was also influential in the fields of power pop, lo-fi, overdubbing, and experimental music. Rundgren performed in an eclectic variety of styles, so much so that his singles often contrasted with other tracks from the LPs from which they derived, which curtailed his mass appeal. Of his early incorporation of digital technology, he said "I wasn't the first to start recording digitally, because it was so expensive. But once the technology came down to where I could afford it, then I went digital." Rundgren said that adapting his sound to meet commercial expectations was also never an issue for him since he already made "so much money from production", a rare luxury for an artist.

As a producer
Comparisons are sometimes drawn between Rundgren and producer/artists Brian Wilson and Brian Eno. Biographer Paul Myers attributes the recording studio to be Rundgren's "ultimate instrument". Rundgren acknowledged that, in the case of his own records, he does not think "as a producer", but uses the studio to "assist in creating a performance". His recording processes continued in the same tradition as multitrack recording innovator Les Paul as well as the studio experiments of the Beatles and the Beach Boys.

According to biographer Myers, Rundgren himself came to inspire "a generation of self-contained geniuses like Prince ... Ironically, some of his innovations would come to liberate the recording artist in such a way as to lessen the perceived value, or need, for a record producer at all." Rundgren's influence is also cited to Hall & Oates, Björk and Daft Punk. Slate writer Marc Weingarten identified A Cappella as the precedent for Björk's "all vocals, all the time" experiment Medúlla (2004) and said that, overall, "The two [artists] share more common ground than their fans might think."

Rundgren's production work for other artists were largely one-off affairs. Exceptions were Grand Funk Railroad, the New York Dolls, the Tubes, Hello People, and the Pursuit of Happiness. He described his typical function as being a "'songcraft' agitator". In cases where the act's songs were unfinished, he would complete them and decline a writer's credit. Some of his collaborators frequently characterize him as a "genius", but also "sarcastic" and "aloof". His most notorious production was for XTC's 1986 album Skylarking, known for the creative tensions and disagreements that arose during its sessions. The album is sometimes regarded as both the pinnacle of Rundgren's production career and of the career of XTC. He commented that, in spite of the turmoil surrounding its making, the record "ultimately ... sounds like we were having a great time doing it. And at times we were having a good time." All three members expressed admiration for the end product.

The Fool guitar
During the mid-to-late 1970s, Rundgren regularly played the eye-catching psychedelic Gibson SG (known variously as "Sunny" or "The Fool"), which Eric Clapton had played in Cream. After he had stopped using it ca. 1968, Clapton gave the guitar to George Harrison, who subsequently 'loaned' it to British singer Jackie Lomax. In 1972, after meeting at a recording session, Lomax sold the guitar to Rundgren for $500 with an option to buy it back, which he never took up. Rundgren played it extensively during the early years of Utopia before retiring the instrument for a short time in the mid to late 1970s, which in that time he had the guitar restored having a lacquer finish applied to protect the paint and replaced the tailpiece and bridge to stabilize tuning, bringing the guitar back out on tour during the 1980 Deface the Music tour and using it on and off throughout the 1980s until 1993 when he permanently retired the guitar, eventually auctioning it off in 1999; he now uses a reproduction given to him in 1988 by a Japanese fan.

Personal life
Rundgren began a relationship with model Bebe Buell in 1972. During a break in their relationship, Buell had a brief relationship with Steven Tyler, which resulted in an unplanned pregnancy. Buell gave birth to Liv Tyler on July 1, 1977. Buell initially claimed that Todd Rundgren was the biological father and named the child Liv Rundgren. Shortly after Liv's birth, Rundgren and Buell ended their romantic relationship, but Rundgren remained committed to Liv. At age eleven, Liv learned that her biological father was Steven Tyler. According to Liv Tyler, "Todd basically decided when I was born that I needed a father so he signed my birth certificate. He knew that there was a chance that I might not be his, but…" He paid to put her through private school, and she visited him several times a year. As of 2012, Tyler maintains a close relationship with Rundgren. "I'm so grateful to him, I have so much love for him. You know, when he holds me it feels like Daddy. And he's very protective and strong." Buell's stated reason for claiming that Rundgren was Liv's father was that Tyler was too heavily addicted to drugs at the time of Liv's birth.

Rundgren had a long-term relationship with Karen Darvin, with whom he had two sons, Rex (born 1980) and Randy (born 1985). Rex was a minor league baseball player (infielder) for nine seasons. Darvin had previously been in a relationship with Bruce Springsteen.

Rundgren married Michele Gray in 1998. Gray had been a dancer with the Tubes and had performed with Rundgren as a backup singer on the tour for his album Nearly Human which led to a number of appearances on The David Letterman Show as one of "The World's Most Dangerous Backup Singers". Together, they have a son, named Rebop, and an adoptive son, named Keoni.

Paul Myers, in his 2010 book on Rundgren, A Wizard, a True Star: Todd Rundgren in the Studio, reported that Rundgren diagnosed himself with attention-deficit disorder.

Awards and honors

 * 1984: Grammy Award nomination for Best Music Video – "Videosyncracy"
 * 1995: Berkeley Lifetime Achievement Award from the Popular Culture Society at UC Berkeley.
 * 2017: Honorary doctorate from Berklee College of Music, where he delivered the commencement address, and an honorary doctorate from DePauw University.
 * 2018: Nominated for the Rock and Roll Hall of Fame's class of 2019. Since becoming eligible in 1995, he has often been asked about his absence from the Hall of Fame. A 2018 poll conducted by the institution, which is not factored in the final vote, placed Rundgren as the third-most deserving nominee on the ballot. In 2016, Rundgren told an interviewer: "It doesn't have the same cachet as a Nobel Peace Prize or some historical foundation. If I told you about how they actually determine who gets into the Hall of Fame, you'd think that I was bullshitting you, because I've been told what's involved. ... It's just as corrupt as anything else, and that's why I don't care."
 * 2021: Inducted into the Rock and Roll Hall of Fame.

Discography
Solo albums
 * Runt (1970)
 * Runt. The Ballad of Todd Rundgren (1971)
 * Something/Anything? (1972)
 * A Wizard, a True Star (1973)
 * Todd (1974)
 * Initiation (1975)
 * Faithful (1976)
 * Hermit of Mink Hollow (1978)
 * Healing (1981)
 * The Ever Popular Tortured Artist Effect (1982)
 * A Cappella (1985)
 * Nearly Human (1989)
 * 2nd Wind (1991)
 * No World Order (1993) (as TR-I)
 * The Individualist (1995) (as TR-I)
 * With a Twist... (1997) (remakes album)
 * One Long Year (2000)
 * Liars (2004)
 * Arena (2008)
 * Todd Rundgren's Johnson (2011) (covers album)
 * (re)Production (2011) (covers album)
 * State (2013)
 * Global (2015)
 * White Knight (2017)
 * Space Force (2022)

Nazz
 * Nazz (1968)
 * Nazz Nazz (1969)
 * Nazz III (1971)

Utopia
 * Todd Rundgren's Utopia (1974)
 * Another Live (1975)
 * Ra (1977)
 * Oops! Wrong Planet (1977)
 * Adventures in Utopia (1979)
 * Deface the Music (1980)
 * Swing to the Right (1982)
 * Utopia (1982)
 * Oblivion (1984)
 * POV (1985)

Other albums (1980s demos for the musical of the same name) (Japanese-imported compilation of unreleased tracks) (Utopia album recorded 1976) (The New Cars)
 * Up Against It! (1997)
 * Somewhere/Anywhere (1998)
 * Disco Jets (2001)
 * It's Alive! (2006)
 * Runddans (2015) (with Lindstrøm and Emil Nikolaisen)

Selected productions
 * Straight Up (1971) – Badfinger
 * Halfnelson (1971) – Halfnelson/Sparks
 * New York Dolls (1973) – New York Dolls
 * We're an American Band (1973) – Grand Funk Railroad
 * Shinin' On (1974) – Grand Funk Railroad
 * War Babies (1974) – Hall & Oates
 * Bat Out of Hell (1977) – Meat Loaf
 * Remote Control (1979) – The Tubes
 * Wasp (1980) – Shaun Cassidy
 * Forever Now (1982) – The Psychedelic Furs
 * Next Position Please (1983) – Cheap Trick
 * Love Bomb (1985) – The Tubes
 * Skylarking (1986) – XTC
 * Dreams of Ordinary Men (1986) – Dragon
 * The New America (2000) – Bad Religion
 * Separation Anxieties (2000) – 12 Rods
 * Cause I Sez So (2009) – New York Dolls

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

title: Todd Rundgren


text:
User:Robert Dolan

Robert T. Dolan, MD robdolan@yahoo.com

Some of my interests include biomedical science and technology, the history of scientific thought and methods, mathematics, philosophy, military history,computer science, modern architecture, languages, ju-jitsu and other martial arts, scuba diving, sports medicine.

My contributions so far: artery, nitrogen narcosis

Welcome to the 'pedia Robert! If you have the time, could you look at the taxol article I submitted to make sure I didn't make any major (or minor for that matter) errors? I am not an MD so I defer to your expertise. maveric149

Thanks for your kind words on my Talk page. If you ever have a question on how to do something around the 'pedia, don't hesitate to ask. Oh, and most wikipedia users (not all mind you) are choosing to move their user pages to the new format. To do so, just copy the text in Robert Dolan, paste it here, and then delete all the text in Robert Dolan. You can then insert the following: #REDIRECT User:Robert Dolan That way, people visiting your old page will be directed to the new one automatically. You can also move all the messages people write to your Talk page -- otherwise, your user page begins to get a bit messy (see Larry Sanger for an example). Of course, here in the wiki, you don't have to do anything you don't really want to. Isn't it cool! --maveric149

title: User:Robert Dolan


text:
Paclitaxel

Paclitaxel, sold under the brand name Taxol among others, is a chemotherapy medication used to treat ovarian cancer, esophageal cancer, breast cancer, lung cancer, Kaposi's sarcoma, cervical cancer, and pancreatic cancer. It is administered by intravenous injection. There is also an albumin-bound formulation.

Common side effects include hair loss, bone marrow suppression, numbness, allergic reactions, muscle pains, and diarrhea. Other side effects include heart problems, increased risk of infection, and lung inflammation. There are concerns that use during pregnancy may cause birth defects. Paclitaxel is in the taxane family of medications. It works by interference with the normal function of microtubules during cell division.

Paclitaxel was isolated in 1971 from the Pacific yew and approved for medical use in 1993. It is on the World Health Organization's List of Essential Medicines. It has been made from precursors, and through cell culture.

Medical use
Paclitaxel is approved in the UK for ovarian, breast, lung, bladder, prostate, melanoma, esophageal, and other types of solid tumor cancers as well as Kaposi's sarcoma.

It is recommended in National Institute for Health and Care Excellence (NICE) guidance of June 2001 for non-small-cell lung cancer in patients unsuitable for curative treatment, and in first-line and second-line treatment of ovarian cancer. In September 2001, NICE recommended paclitaxel for the treatment of advanced breast cancer after the failure of anthracyclic chemotherapy, but that its first-line use should be limited to clinical trials. In September 2006, NICE recommended paclitaxel should not be used in the adjuvant treatment of early node-positive breast cancer.

, it is approved in the United States for the treatment of breast, pancreatic, ovarian, Kaposi's sarcoma and non-small-cell lung cancers.

Similar compounds
Albumin-bound paclitaxel (brand name Abraxane, also called nab-paclitaxel) is an alternative formulation where paclitaxel is bound to albumin nanoparticles. Much of the clinical toxicity of paclitaxel is associated with the solvent Cremophor EL in which it is dissolved for delivery.

Abraxis BioScience developed Abraxane, in which paclitaxel is bonded to albumin as an alternative delivery agent to the often toxic solvent delivery method. This was approved by the FDA in January 2005 for the treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within six months of adjuvant chemotherapy. It has since been approved for locally advanced or metastatic non-small cell lung cancer and metastatic adenocarcinoma of the pancreas as well.

Synthetic approaches to paclitaxel production led to the development of docetaxel. Docetaxel has a similar set of clinical uses to paclitaxel, and it is marketed under the brand name Taxotere.

Taxanes, including paclitaxel, 10-deacetylbaccatin III, baccatin III, paclitaxel C, and 7-epipaclitaxel, have been found in the leaves and shells of hazel. The finding of these compounds in shells, which are considered discarded material and are mass-produced by many food industries, is of interest for the future availability of paclitaxel.

Restenosis
Paclitaxel is used as an antiproliferative agent for the prevention of restenosis (recurrent narrowing) of coronary and peripheral stents; locally delivered to the wall of the artery, a paclitaxel coating limits the growth of neointima (scar tissue) within stents. Paclitaxel drug-eluting stents for coronary artery placement are sold under the trade name Taxus by Boston Scientific in the United States. Paclitaxel drug-eluting stents for femoropopliteal artery placement are also available.

Side effects
Common side effects include nausea and vomiting, loss of appetite, change in taste, thinned or brittle hair, pain in the joints of the arms or legs lasting two to three days, changes in the color of the nails, and tingling in the hands or toes. More serious side effects such as unusual bruising or bleeding, pain, redness or swelling at the injection site, hand-foot syndrome, change in normal bowel habits for more than two days, fever, chills, cough, sore throat, difficulty swallowing, dizziness, shortness of breath, severe exhaustion, skin rash, facial flushing, female infertility by ovarian damage, and chest pain can also occur. Neuropathy may also occur.

Dexamethasone is given prior to paclitaxel infusion to mitigate some of the side effects.

A number of these side effects are associated with the excipient used, Cremophor EL, a polyoxyethylated castor oil. Allergies to cyclosporine, teniposide, and other drugs delivered in polyoxyethylated castor oil may increase the risk of adverse reactions to paclitaxel.

Mechanism of action
Paclitaxel is one of several cytoskeletal drugs that target tubulin. Paclitaxel-treated cells have defects in mitotic spindle assembly, chromosome segregation, and cell division. Unlike other tubulin-targeting drugs, such as colchicine, that inhibit microtubule assembly, paclitaxel stabilizes the microtubule polymer and protects it from disassembly. Chromosomes are thus unable to achieve a metaphase spindle configuration. This blocks the progression of mitosis and prolonged activation of the mitotic checkpoint triggers apoptosis or reversion to the G0-phase of the cell cycle without cell division.

The ability of paclitaxel to inhibit spindle function is generally attributed to its suppression of microtubule dynamics, but other studies have demonstrated that suppression of dynamics occurs at concentrations lower than those needed to block mitosis. At the higher therapeutic concentrations, paclitaxel appears to suppress microtubule detachment from centrosomes, a process normally activated during mitosis. Paclitaxel binds to the beta-tubulin subunits of microtubules.

Chemistry
The nomenclature for paclitaxel is structured on a tetracyclic 17-atom skeleton. There are a total of 11 stereocenters. The active stereoisomer is (−)-paclitaxel (shown here).

{{multiple image|align = center|image1 = TaxolNomenClature.svg|width1 = 315|caption1 = Position numbering|image2 = TaxolStereochemistry.svg|width2 = 303|caption2 = Absolute stereochemistry|footer = (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-Diacetoxy-15-$($[(2R,3S)-3-(benzoylamino)-2-hydroxy-3-phenylpropanoyl]oxy}-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0~3,10~.0~4,7~]heptadec-13-en-2-yl rel-benzoate }}

Bark processing

From 1967 to 1993, almost all paclitaxel produced was derived from bark of the Pacific yew, Taxus brevifolia, the harvesting of which kills the tree in the process. The processes used were descendants of the original isolation method of Monroe Wall and Mansukh Wani; by 1987, the U.S. National Cancer Institute (NCI) had contracted Hauser Chemical Research of Boulder, Colorado, to handle bark on the scale needed for phase II and III trials. While both the size of the wild population of the Pacific yew and the magnitude of the eventual demand for paclitaxel were uncertain, it was clear that an alternative, sustainable source of the natural product would be needed. Initial attempts to broaden its sourcing used needles from the tree, or material from other related Taxus species, including cultivated ones, but these attempts were challenged by the relatively low and often highly variable yields obtained. Early in the 1990s, coincident with increased sensitivity to the ecology of the forests of the Pacific Northwest, paclitaxel was extracted on a clinically useful scale from these sources.

Semisynthesis
Concurrently, synthetic chemists in the U.S. and France had been interested in paclitaxel, beginning in the late 1970s. As noted, by 1992 extensive efforts were underway to accomplish the total synthesis of paclitaxel, efforts motivated by the desire to generate new chemical understanding rather than to achieve practical commercial production. In contrast, the French group of Pierre Potier at the Centre national de la recherche scientifique (CNRS) addressed the matter of overall process yield, showing that it was feasible to isolate relatively large quantities of the compound 10-deacetylbaccatin from the European yew, Taxus baccata, which grew on the CNRS campus and whose needles were available in large quantity. By virtue of its structure, 10-deacetylbaccatin was seen as a viable starting material for a short semisynthesis to produce paclitaxel. By 1988, Poitier and collaborators had published a semisynthetic route from needles of the European yew to paclitaxel.

The view of the NCI, however, was that even this route was not practical. The group of Robert A. Holton had also pursued a practical semisynthetic production route; by late 1989, Holton's group had developed a semisynthetic route to paclitaxel with twice the yield of the Potier process. The main innovation was "Ojima−Holton coupling", a ring-opening method independently discovered by Holton and Ojima. Florida State University, where Holton worked, signed a deal with Bristol-Myers Squibb (BMS) to license their semisynthesis and future patents. In 1992, Holton patented an improved process with an 80% yield, and BMS took the process in-house and started to manufacture paclitaxel in Ireland from 10-deacetylbaccatin isolated from the needles of the European yew. In early 1993, BMS announced that it would cease reliance on Pacific yew bark by the end of 1995, effectively terminating ecological controversy over its use. This announcement also made good their commitment to develop an alternative supply route, made to the NCI in their cooperative research and development agreement (CRADA) application of 1989.

As of 2013, BMS was using the semisynthetic method utilizing needles from the European yew to produce paclitaxel. Another company which worked with BMS until 2012, Phyton Biotech, Inc., uses plant cell fermentation (PCF) technology. By cultivating a specific Taxus cell line in fermentation tanks, they no longer need ongoing sourcing of material from actual yew tree plantations. Paclitaxel is then captured directly from the suspension broth by a resin allowing concentration to highly enriched powder containing about 40% paclitaxel. The compound is then purified by one chromatographic step followed by crystallization. Compared to the semisynthesis method, PCF eliminates the need for many hazardous chemicals and saves a considerable amount of energy.

In 1993, paclitaxel was discovered as a natural product in Taxomyces andreanae, a newly described endophytic fungus living in the yew tree. It has since been reported in a number of other endophytic fungi, including Nodulisporium sylviforme, Alternaria taxi, Cladosporium cladosporioides MD2, Metarhizium anisopliae, Aspergillus candidus MD3, Mucor rouxianus, Chaetomella raphigera, Phyllosticta tabernaemontanae, Phomopsis, Pestalotiopsis pauciseta, Phyllosticta citricarpa, Podocarpus sp., Fusarium solani, Pestalotiopsis terminaliae, Pestalotiopsis breviseta, Botryodiplodia theobromae, Gliocladium sp., Alternaria alternata var. monosporus, Cladosporium cladosporioides, Nigrospora sp. and Pestalotiopsis versicolor. However, there has been contradictory evidence for its production by endophytes, with other studies finding independent production is unlikely.

Biosynthesis
Taxol is a tetracyclic diterpene, and the biosynthesis of diterpenes starts with an FPP molecule being elongated by the addition of an IPP molecule in order to form geranylgeranyl diphosphate (GGPP). The biosynthesis of Taxol contains nineteen steps. These 19 steps can be considered in several steps, with the first step being the formation of the taxane skeleton, which then undergoes a series of oxygenations. Following the oxygenations, two acetylations and a benzoylation occur on the intermediate. The oxygenation of the taxane core is believed to occur on C5 and C10, C2 and C9, C13 followed by C7, and a C1 hydroxylation later on in the pathway. Later in the pathway, an oxidation at C9 forms a ketone functional group and an oxetane, forming the intermediate baccatin III. The final steps of the pathway include the formation of a C13-side chain which is attached to baccatin III. The biosynthesis of Taxol is illustrated in more detail in the figure, with steps 1-7 all occurring in the enzyme taxadiene synthase (TS on the figure). Taxol's biosynthesis begins with E,E,E-GGPP losing pyrophosphate via an SN1 mechanism (step 1 in the figure). The double-bond attacks the cation via electrophilic addition, yielding a tertiary cation and creating the first ring closure (step 2). Another electrophilic attack occurs, further cyclizing the structure by creating the first 6-membered ring and creating another tertiary cation (step 3). An intramolecular proton transfer occurs, attacking the verticillyl cation (step 4) and creating a double bond, yielding a tertiary cation. An electrophilic cyclization occurs in step 5, and an intramolecular proton transfer attacks the taxenyl cation (step 6). This forms the fused ring structure intermediate known as taxadiene. Taxadiene then undergoes a series of 10 oxidations via NADPH, forming the intermediate taxadiene-5α-acetoxy-10β-ol (multiple steps later in the figure). A series of hydroxylations and esterficiations occur, forming the intermediate 10-deacetyl-baccatin III, which undergoes a further series of esterifications and a side-chain hydroxylation. This finally yields the product taxol.

Total synthesis
By 1992, at least thirty academic research teams globally were working to achieve a total synthesis of this natural product, with the synthesis proceeding from simple natural products and other readily available starting materials. This total synthesis effort was motivated primarily by the desire to generate new chemical understanding, rather than with an expectation of the practical commercial production of paclitaxel. The first laboratories to complete the total synthesis from much less complex starting materials were the research groups of Robert A. Holton, who had the first article to be accepted for publication, and of K. C. Nicolaou who had the first article to appear in print (by a week, on 7 February 1994). Though the Holton submission preceded the Nicolaou by a month (21 December 1993 versus 24 January 1994), the near coincidence of the publications arising from each of these massive, multiyear efforts—11–18 authors appearing on each of the February 1994 publications—has led the ending of the race to be termed a "tie" or a "photo finish", though each group has argued that their synthetic strategy and tactics were superior.

As of 2006, five additional research groups had reported total syntheses of paclitaxel: Wender et al. in 1997, and Kuwajima et al. and Mukaiyama et al. in 1998 with further linear syntheses, and Danishefsky et al. in 1996 and Takahashi et al. in 2006 with further convergent syntheses. As of that date, all strategies had aimed to prepare a 10-deacetylbaccatin-type core containing the ABCD ring system, followed generally by last stage addition of the "tail" to the 13-hydroxyl group.

While the "political climate surrounding [paclitaxel] and [the Pacific yew] in the early 1990s ... helped bolster [a] link between total synthesis and the [paclitaxel] supply problem," and though total synthesis activities were a requisite to explore the structure-activity relationships of paclitaxel via generation of analogs for testing, the total synthesis efforts were never seen "as a serious commercial route" to provide significant quantities of the natural product for medical testing or therapeutic use.

History
The discovery of paclitaxel began in 1962 as a result of a NCI-funded screening program. A number of years later it was isolated from the bark of the Pacific yew, Taxus brevifolia, hence its name "taxol".

The discovery was made by Monroe E. Wall and Mansukh C. Wani at the Research Triangle Institute, Research Triangle Park, North Carolina, in 1971. These scientists isolated the natural product from the bark of the Pacific yew tree, determined its structure and named it "taxol", and arranged for its first biological testing. The compound was then developed commercially by BMS, who had the generic name assigned as "paclitaxel".

Plant screening program
In 1955, the NCI in the United States set up the Cancer Chemotherapy National Service Center (CCNSC) to act as a public screening center for anticancer activity in compounds submitted by external institutions and companies. Although the majority of compounds screened were of synthetic origin, one chemist, Jonathan Hartwell, who was employed there from 1958 onwards, had experience with natural product derived compounds, and began a plant screening operation.

After some years of informal arrangements, in July 1960, the NCI commissioned the United States Department of Agriculture (USDA) botanists to collect samples from about 1,000 plant species per year. On 21 August 1962, one of those botanists, Arthur S. Barclay, collected bark from a single Pacific yew tree in a forest north of the town of Packwood, Washington, as part of a four-month trip to collect material from over 200 different species. The material was then processed by a number of specialist CCNSC subcontractors, and one of the tree's samples was found to be cytotoxic in a cellular assay on 22 May 1964.

Accordingly, in late 1964 or early 1965, the fractionation and isolation laboratory run by Monroe E. Wall in Research Triangle Park, North Carolina, began work on fresh Taxus samples, isolating the active ingredient in September 1966 and announcing their findings at an April 1967 American Chemical Society meeting in Miami Beach. They named the pure compound taxol in June 1967. Wall and his colleague Wani published their results, including the chemical structure, in 1971.

The NCI continued to commission work to collect more Taxus bark and to isolate increasing quantities of taxol. By 1969, 28 kg of crude extract had been isolated from almost 1200 kg of bark, although this ultimately yielded only 10 g of pure material, but for several years, no use was made of the compound by the NCI. In 1975, it was shown to be active in another in vitro system; two years later, a new department head reviewed the data and finally recommended taxol be moved on to the next stage in the discovery process. This required increasing quantities of purified taxol, up to 600 g, and in 1977 a further request for 7000 lb of bark was made.

In 1978, two NCI researchers published a report showing that taxol was mildly effective in leukaemic mice. In November 1978, taxol was shown to be effective in xenograft studies. Meanwhile, taxol began to be well known in the cell biology, as well as the cancer communities, with a publication in early 1979 by Susan B. Horwitz, a molecular pharmacologist at Albert Einstein College of Medicine, showing that taxol had a previously unknown mechanism of action involving the stabilization of microtubules. Together with formulation problems, this increased interest from researchers meant that, by 1980, the NCI envisaged needing to collect 20000 lb of bark. Animal toxicology studies were completed by June 1982, and in November, the NCI applied for the IND necessary to begin clinical trials in humans.

Early clinical trials, supply and the transfer to BMS
Phase I clinical trials began in April 1984, and the decision to start Phase II trials was made a year later. These larger trials needed more bark and collection of a further 12,000 pounds was commissioned, which enabled some phase II trials to begin by the end of 1986. But by then it was recognized that the demand for taxol might be substantial and that more than 60,000 pounds of bark might be needed as a minimum. This unprecedentedly large amount brought ecological concerns about the impact on yew populations into focus for the first time, as local politicians and foresters expressed unease at the program.

The first public report from a phase II trial in May 1988 showed promising effects in melanoma and refractory ovarian cancer. At this point, Gordon Cragg of the NCI's Natural Product Branch calculated the synthesis of enough taxol to treat all the ovarian cancer and melanoma cases in the US would require the destruction of 360,000 trees annually. For the first time, serious consideration was given to the problem of supply. Because of the practical and, in particular, the financial scale of the program needed, the NCI decided to seek association with a pharmaceutical company, and in August 1989, it published a Cooperative Research and Development Agreement (CRADA) offering its current stock and supply from current bark stocks, and proprietary access to the data so far collected, to a company willing to commit to providing the funds to collect further raw material, isolate taxol, and fund a large proportion of clinical trials. In the words of Goodman and Welsh, authors of a substantial scholarly book on taxol, "The NCI was thinking, not of collaboration, ... but of a hand-over of taxol (and its problems)".

Although the offer was widely advertised, only four companies responded to the CRADA, including the American firm Bristol-Myers Squibb (BMS), which was selected as the partner in December 1989. The choice of BMS later became controversial and was the subject of Congressional hearings in 1991 and 1992. While it seems clear the NCI had little choice but to seek a commercial partner, there was also controversy about the terms of the deal, eventually leading to a report by the General Accounting Office in 2003, which concluded the NIH had failed to ensure value for money. In related CRADAs with the USDA and Department of the Interior, Bristol-Myers Squibb was given exclusive first refusal on all Federal supplies of Taxus brevifolia. This exclusive contract lead to some criticism for giving BMS a "cancer monopoly". Eighteen months after the CRADA, BMS filed a new drug application (NDA), which was given FDA approval at the very end of 1992. Although there was no patent on the compound, the provisions of the Waxman-Hatch Act gave Bristol-Myers Squibb five years exclusive marketing rights.

In 1990, BMS applied to trademark the name taxol as Taxol(R). This was controversially approved in 1992. At the same time, paclitaxel replaced taxol as the generic (INN) name of the compound. Critics, including the journal Nature, argued the name taxol had been used for more than two decades and in more than 600 scientific articles and suggested the trademark should not have been awarded and the BMS should renounce its rights to it. BMS argued changing the name would cause confusion among oncologists and possibly endanger the health of patients. BMS has continued to defend its rights to the name in the courts. BMS has also been criticized for misrepresentation by Goodman and Walsh, who quote from a company report saying "It was not until 1971 that ... testing ... enabled the isolation of paclitaxel, initially described as 'compound 17". This quote is, strictly speaking, accurate: the objection seems to be that this misleadingly neglects to explain that it was the scientist doing the isolation who named the compound taxol and it was not referred to in any other way for more than twenty years. Annual sales peaked in 2000, reaching US$1.6 billion; paclitaxel is now available in generic form.

Legal status
Paclitaxel was approved for medical use in the European Union in 2008.

In November 2023, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Naveruclif, intended for the treatment of metastatic breast cancer, metastatic adenocarcinoma of the pancreas and non-small cell lung cancer. The applicant for this medicinal product is Accord Healthcare S.L.U.

In May 2024, the CHMP adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Apexelsin, intended for the treatment of metastatic breast cancer, metastatic adenocarcinoma of the pancreas and non-small cell lung cancer. The applicant for this medicinal product is WhiteOak Pharmaceutical B.V.

Economics
, the cost to the NHS per patient in early breast cancer, assuming four cycles of treatment, was about £4,000 (approx. $6,000).

Research
Caffeine has been speculated to inhibit paclitaxel-induced apoptosis in colorectal cancer cells.

In 2016, in vitro multi-drug resistant mouse tumor cells were treated with paclitaxel encased in exosomes. Doses 98% less than common dosing had the same effect. Also, dye-marked exosomes were able to mark tumor cells, potentially aiding in diagnosis.

Aside from its direct clinical use, paclitaxel is also used extensively in biological and biomedical research as a microtubule stabilizer. In general, in vitro assays involving microtubules, such as motility assays, rely on paclitaxel to maintain microtubule integrity in the absence of the various nucleating factors and other stabilizing elements found in the cell. For example, it is used for in vitro tests of drugs that aim to alter the behavior of microtubule motor proteins, or for studies of mutant motor proteins.

Paclitaxel has also been used in vitro to inhibit insulin fibrillation. In a molar ratio of 10:1 (insulin:paclitaxel), it hindered insulin fibrillation near 70%. Isothermal titration calorimetry (ITC) findings indicated a spontaneous tendency of paclitaxel to interact with insulin through hydrogen bonds and van der Waal's forces. The inhibitory role of paclitaxel is attributed to its impact on the colloidal stability of protein solution, as it was observed that paclitaxel inhibited lysozyme fibrillation by inducing the formation of "off-pathway" oligomeric intermediates, subsequently increasing the colloidal stability.

Paclitaxel is sometimes used for in vivo studies as well. It can be fed to test organisms, such as fruit flies, or injected into individual cells, to inhibit microtubule disassembly or to increase the number of microtubules in the cell. Paclitaxel induces remyelination in a demyelinating mouse in vivo and inhibits human peptidylarginine deiminase 2 (hPAD2) in vitro though its methyl ester side chain. In 1999, Angiotech Pharmaceuticals Inc. began phase II clinical trials of micellar paclitaxel as treatment for secondary progressive multiple sclerosis, but reported in 2002 that the results showed no statistical significance.

title: Paclitaxel