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Alexander Shulgin

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This article is about the scientist. For the musician, see Alexander Shulgin (musician).

Alexander Shulgin
Shulgin sasha 2011 hanna jon.jpg
Alexander and Ann Shulgin at book signing in Oakland, California in December 2011
Born
Alexander Theodore Shulgin

(1925-06-17)June 17, 1925
Berkeley, California, US
DiedJune 2, 2014(2014-06-02) (aged 88)
Lafayette, California
CitizenshipUnited States
Alma mater
Known for
Spouse(s)Nina Shulgin (deceased)
Ann Shulgin
ChildrenTheodore (Ted) A. Shulgin (died of cancer May 15, 2011)[1]
Awards
DEA Awards (numerous)
Scientific career
FieldsChemistry, psychology, philosophy, biology
Institutions

Alexander "Sasha" Theodore Shulgin (June 17, 1925 – June 2, 2014) was an American medicinal chemist, biochemist, organic chemist, pharmacologist, psychopharmacologist, and author. He is credited with introducing 3,4-methylenedioxymethamphetamine (commonly known as MDMA, "ecstasy", "mandy" and "molly") to psychologists in the late 1970s for psychopharmaceutical use and for the discovery, synthesis and personal bioassay of over 230 psychoactive compounds for their psychedelic and entactogenic potential.

In 1991 and 1997, he and his wife Ann Shulgin compiled the books PiHKAL and TiHKAL (standing for Phenethylamines and Tryptamines I Have Known And Loved), from notebooks that extensively described their work and personal experiences with these two classes of psychoactive drugs. Shulgin performed seminal work into the descriptive synthesis of many of these compounds. Some of Shulgin's noteworthy discoveries include compounds of the 2C* family (such as 2C-B) and compounds of the DOx family (such as DOM).

Due in part to Shulgin's extensive work in the field of psychedelic research and the rational drug design of psychedelic drugs, he has since been dubbed the "godfather of psychedelics".[2]

Life and career[]

Shulgin was born in Berkeley, California,[3] to Theodore Stevens Shulgin (1893–1978)[4] and Henrietta D. (Aten) Shulgin (1894–1960).[4][5] His father was born in Chelyabinsk, Russia; his mother was born in Illinois. Theodore and Henrietta were public school teachers in Alameda County.[6]

Shulgin began studying organic chemistry as a Harvard University scholarship student at the age of 16. In 1943 he dropped out of school to join the U.S. Navy. While serving on USS Pope during World War II, a nurse gave Shulgin a glass of orange juice prior to surgery for a thumb infection. Shulgin drank the juice and, assuming that the powder at the bottom of the glass was a sedative, fell asleep rapidly. Upon waking he learned that the powder was undissolved sugar. The experience made him aware of the influence of placebos over the human mind.[7][8]

After serving in the Navy, Shulgin returned to Berkeley, California, and in 1954 earned his PhD in biochemistry from the University of California, Berkeley. Through the late 1950s Shulgin completed post-doctoral work in the fields of psychiatry and pharmacology at University of California, San Francisco. After working at Bio-Rad Laboratories as a research director for a brief period, he began work at Dow Chemical Company as a senior research chemist.[7]

At this time he had a series of psychedelic experiences that helped to shape his further goals and research, the first of which was brought on by mescaline.[9] "I first explored mescaline in the late '50s ... Three-hundred-fifty to 400 milligrams. I learned there was a great deal inside me."[9]

Shulgin later reported personal revelations that "had been brought about by a fraction of a gram of a white solid, but that in no way whatsoever could it be argued that these memories had been contained within the white solid ... I understood that our entire universe is contained in the mind and the spirit. We may choose not to find access to it, we may even deny its existence, but it is indeed there inside us, and there are chemicals that can catalyze its availability."[7]

Zectran-containing pesticide manufactured by Dow; photo taken at the Farm on July 26, 2009.

Shulgin's professional activities continued to lean in the direction of psychopharmacology, furthered by his personal experiences with psychedelics. But during this period he was unable to do much independent research. His opportunity for further research came in 1961 after his development of Zectran, the first biodegradable pesticide, a highly profitable product. In his book PIHKAL, Shulgin limits his pesticide days at Dow Chemical to one sentence in 978 pages. Dow Chemical Company, in return for Zectran's valuable patent, gave Shulgin great freedom. During this time, he created and patented drugs when Dow asked, and published findings on other drugs in journals such as Nature and the Journal of Organic Chemistry. Eventually, Dow Chemical requested that he no longer use their name on his publications.[7]

In late 1966, Shulgin left Dow in order to pursue his own interests. He first spent two years studying neurology at the University of California, San Francisco School of Medicine, leaving to work on a consulting project. He set up a home-based lab on his property, known as "the Farm", and became a private consultant. He also taught classes in the local universities and at the San Francisco General Hospital. Through his friend Bob Sager, head of the U.S. DEA's Western Laboratories, Shulgin formed a relationship with the DEA and began holding pharmacology seminars for the agents, supplying the DEA with samples of various compounds, and occasionally serving as an expert witness in court. In 1988, he authored a then-definitive law enforcement reference book[10] on controlled substances, and received several awards from the DEA.[7]

Independent research[]

In order to work with scheduled psychoactive chemicals, Shulgin obtained a DEA Schedule I license for an analytical laboratory, which allowed him to synthesize and possess any otherwise illicit drug. Shulgin set up a chemical synthesis laboratory in a small building behind his house, which gave him a great deal of career autonomy. Shulgin used this freedom to synthesize and test the effects of potentially psychoactive drugs.

In 1976, Shulgin was introduced to MDMA by a student in the medicinal chemistry group he advised at San Francisco State University.[11] MDMA had been synthesized in 1912 by Merck and patented in 1913 as an intermediate of another synthesis in order to block competitors, but was never explored in its own right. Shulgin went on to develop a new synthesis method, and in 1976, introduced the chemical to Leo Zeff, a psychologist from Oakland, California. Zeff used the substance in his practice in small doses as an aid to talk therapy. Zeff introduced the substance to hundreds of psychologists and lay therapists around the nation, including Ann (born Laura Ann Gotlieb), whom Alexander Shulgin met in 1979, and married in 1981.[7] It was her fourth marriage, and she had four children.[12]

Shulgin at the home-based lab on his property, known as "the Farm", 2009

After judicious self-experiments, Shulgin enlisted a small group of friends with whom he regularly tested his creations, starting in 1960. They developed a systematic way of ranking the effects of the various drugs, known as the Shulgin Rating Scale, with a vocabulary to describe the visual, auditory and physical sensations. He personally tested hundreds of drugs, mainly analogues of various phenethylamines (family containing MDMA, mescaline, and the 2C* family), and tryptamines (family containing DMT and psilocin). There are a seemingly infinite number of slight chemical variations, which can produce variations in effect — some pleasant and some unpleasant, depending on the person, substance, and situation — all of which are meticulously recorded in Shulgin's lab notebooks. Shulgin published many of these objective and subjective reports in his books and papers.[7]

In 1994, two years after the publication of PIHKAL, the DEA raided his lab. The agency requested that Shulgin turn over his license for violating the license's terms, and he was fined $25,000 for possession of anonymous samples sent to him for quality testing. In the 15 years preceding the publication of PIHKAL, two announced and scheduled reviews failed to find any irregularities.[13] Richard Meyer, spokesman for DEA's San Francisco Field Division, has stated that, "It is our opinion that those books are pretty much cookbooks on how to make illegal drugs. Agents tell me that in clandestine labs that they have raided, they have found copies of those books."[7]

Prior to his 2010 health issues, Shulgin had been working on a series of N-allylated tryptamines including 5-MeO-DALT and 5-MeO-MALT.[14]

Declining health and death[]

Shulgin spent most of his later life at the Farm in Lafayette, California. On April 8, 2008, at the age of 82, he underwent surgery to replace a defective aortic valve.[15] On November 16, 2010, he suffered a stroke, from which he largely recovered.[16] Also at the close of 2010, a skin-grafting surgery saved his left foot from being amputated. Around this time, Shulgin began showing early signs of dementia, mostly severe loss of short-term memory. With progression of the dementia since 2010, his wife Ann Shulgin had been trying to sell part of their property to raise more money to cover care costs.

On April 17, 2014, Ann Shulgin reported on Facebook that her husband had developed liver cancer, and in a May 31 update on Facebook she said that, although appearing frail, he seemed to be experiencing his last moments in peace and without pain.[17] On June 2, 2014, Shulgin died at home in bed surrounded by family, fifteen days before his 89th birthday.[18]

Legacy[]

In a 2014 review of the synthesis of designer drugs, the effects of Shulgin's work were described as "by far the most far-reaching" effects associated with the cultural climate of interest at the time in hallucinogenic compounds generally and mescaline in particular, with which various artists and writers had experimented. Shulgin said that mescaline made him aware of a world submerged in human spirit, whose "availability" was "catalyzed" by such chemicals; the consequences of his insights were called "devastating" by the reviewers. In the same review, an example of his insights was given by his description of MDMA as "his low-calorie Martini".[19]

Societies[]

Shulgin was a member of Mensa International and frequently attended Mensa events in California.[20]

Alexander was a Bohemian Club member.[21][22][23] The Bohemian club is located in California where Alexander lived. Alexander refers to "The Owl Club" in chapter 11 of PiHKAL:

One evening in the late 1950’s, I was invited to a musical soiree at an old comfortable home in the Berkeley Hills. I brought my viola with me... The only person I can remember from that evening was a handsome, proper gentleman with a small grey moustache and the residues of an English accent. During coffee, after the music was over, he struck up a conversation. He asked me if I had ever heard of The Owl Club in San Francisco? I had not, so he began painting a picture of a rather fascinating group, with many interests in all sorts of art, drama and music. He mentioned that there was need for a viola player, and would I be interested in sitting in for a couple of evenings? ... The Club proved to be a group of gentlemen from a broad array of political and professional backgrounds, leaning somewhat toward the political right and the well-to-do. ... At my first evening at the Club... Andrew was appointed my Pater Familias ...”

— PiHKAL, First Printing, Eleventh Edition, Chapter 11, pp. 60-65[24]

Bibliography[]

Books[]

  • Controlled Substances: Chemical & Legal Guide to Federal Drug Laws. Berkeley, Calif.: Ronin Publishing (1988). ISBN 091417150X.
  • PiHKAL: A Chemical Love Story, with Ann Shulgin. Berkeley, Calif.: Transform Press (1991). ISBN 0963009605.
  • TiHKAL: The Continuation, with Ann Shulgin. Berkeley, Calif.: Transform Press (1997). ISBN 0963009699.
  • The Simple Plant Isoquinolines , with Wendy Perry. Berkeley, Calif.: Transform Press (2002). ISBN 0963009621.
  • The Shulgin Index, vol. 1: Psychedelic Phenethylamines and Related Compounds, with Tania Manning and Paul Daley. Berkeley, Calif.: Transform Press (2011). ISBN 978-0963009630.
  • Alexander Shulgin (2021). The Nature of Drugs. Berkeley, California: Transform Press. ISBN 9780999547212.

Book contributions[]

Laboratory notebooks[]

Other notable publications
  • 1960–1979. Lab notebooks of Dr. Shulgin
  • 1963. "Psychotomimetic agents related to mescaline". Experientia 19: 127. 19
  • 1963. "Composition of the myristicin fraction from oil of nutmeg". Nature 197: 379. 20
  • 1963. "Concerning the pharmacology of nutmeg". Mind 1: 299–302. 23
  • 1964. "3-methoxy-4,5-methylenedioxy amphetamine, a new psychotomimetic agent". Nature 201: 1120–1121. 29
  • 1964. "Psychotomimetic amphetamines: methoxy 3,4-dialkoxyamphetamines". Experientia 20: 366. 30
  • 1964. with H. O. Kerlinger. "Isolation of methoxyeugenol and trans-isoelemicin from oil of nutmeg". Naturwissenschaften 15: 360–361. 31
  • 1965. "Synthesis of the trimethoxyphenylpropenes". Can. J. Chem. 43: 3437–3440. 43
  • 1966. "Possible implication of myristicin as a psychotropic substance". Nature 210: 380–384. 45
  • 1966. "The six trimethoxyphenylisopropylamines (trimethoxyamphetamines)". J. Med. Chem. 9: 445–446. 46
  • 1966. with T. Sargent, and C. Naranjo. "Role of 3,4-Dimethoxyphenethylamine in schizophrenia". Nature 212: 1606–1607. 48[25]
  • 1967. with T. Sargent, and C. Naranjo. "The chemistry and psychopharmacology of nutmeg and of several related phenylisopropylamines". In D. H. Efron [ed.]: Ethnopharmacologic search for psychoactive drugs. U. S. Dept. of H. E. W., Public Health Service Publication No. 1645. Pp. 202–214. Discussion: ibid. pp. 223–229. 49
  • 1967. with T. Sargent. "Psychotropic phenylisopropylamines derived from apiole and dillapiole". Nature 215: 1494–1495. 50
  • 1967. with Sargent, T. W., D. M. Israelstam, S. A. Landaw, and N. N. Finley. "A note concerning the fate of the 4-methoxyl group in 3,4-dimethoxyphenethylamine (DMPEA)". Biochem. Biophys. Res. Commun. 29: 126–130. 52
  • 1967. with Naranjo, C. and T. Sargent. "Evaluation of 3,4-methylenedioxyamphetamine (MDA) as an adjunct to psychotherapy". Med. Pharmacol. Exp. 17: 359–364. 53
  • 1968. "The ethyl homologs of 2,4,5-trimethoxyphenylisopropylamine". J. Med. Chem. 11: 186–187. 54
  • 1969. with T. Sargent and C. Naranjo. "Structure activity relationships of one-ring psychotomimetics". Nature 221: 537–541. 57
  • 1969. "Recent developments in cannabis chemistry". J. Psyched. Drugs 2: 15–29. 58
  • 1969. "Psychotomimetic agents related to the catecholamines". J. Psyched. Drugs 2(2): 12–26. 59
  • 1970. "Chemistry and structure-activity relationships of the psychotomimetics". In D. H. Efron [ed.]. "Psychotomimetic Drugs". Raven Press, New York. Pp. 21–41. 60
  • 1970. "The mode of action of psychotomimetic drugs; some qualitative properties of the psychotomimetics". Neur. Res. Prog. Bull. 8: 72–78. 61
  • 1970. "4-alkyl-dialkoxy-alpha-methyl-phenethylamines and their pharmacologically-acceptable salts". U. S. Patent 3,547,999, issued Dec. 15, 1970. 63
  • 1971. with T. Sargent and C. Naranjo. "4-bromo-2,5-dimethoxyphenylisopropylamine, a new centrally active amphetamine analog". Pharmacology 5: 103–107. 64
  • 1971. "Chemistry and sources". In S. S. Epstein [ed]. "Drugs of abuse: their genetic and other chronic nonpsychiatric hazards". The MIT Press, Cambridge, Mass. Pp 3–26. 65
  • 1971. "Preliminary studies of the synthesis of nitrogen analogs of Delta1-THC". Acta Pharm. Suec. 8: 680–681. 66
  • 1972. "Hallucinogens, CNS stimulants, and cannabis. In S. J. Mulé and H. Brill [eds.]: Chemical and biological aspects of drug dependence". CRC Press, Cleveland, Ohio. Pp. 163–175. 67
  • 1973. "Stereospecific requirements for hallucinogenesis". J. Pharm. Pharmac. 25: 271–272. 68
  • 1973. "Mescaline: the chemistry and pharmacology of its analogs". Lloydia 36: 46–58. 69
  • 1973. "The narcotic pepper – the chemistry and pharmacology of Piper methysticum and related species". Bull. Narc. 25: 59–1974. "Le poivre stupéfiant – chemie et pharmacologie du Piper methysticum et des espéces apparentées". Bull. Stupéfiants 25: 61–77. 70
  • 1973. with T. Sargent and C. Naranjo. "Animal pharmacology and human psychopharmacology of 3-methoxy-4,5-methylenedioxyphenylisopropylamine (MMDA)". Pharmacology 10: 12–18. 71
  • 1974. with Kalbhen, D. A., T. Sargent, G. Braun, H. Stauffer, N. Kusubov, and M. L. Nohr. "Human pharmacodynamics of the psychodysleptic 4-bromo-2,5-dimethoxyphenylisopropylamine labelled with [82]Br". IRCS (Int. Res. Comm. Sys.) 2: 1091. 73
  • 1975. with Sargent, T., D. A. Kalbhen, H. Stauffer, and N. Kusubov. "A potential new brain-scanning agent: 4-[77]Br-2,5-dimethoxyphenylisopropylamine (4-Br-DPIA)". J. Nucl. Med. 16: 243–245. 74
  • 1975. with M. F. Carter. "Centrally active phenethylamines". Psychopharm. Commun. 1: 93–98. 75
  • 1975. with Sargent, T., D. A. Kalbhen, G. Braun, H. Stauffer, and N. Kusubov. "In vivo human pharmacodynamics of the psychodysleptic 4-Br-2,5-dimethoxyphenylisopropylamine labelled with [82]Br or [77]Br". Neuropharmacology 14: 165–174. 76
  • 1975. "The chemical catalysis of altered states of consciousness. Altered states of consciousness, current views and research problems". The drug abuse council, Washington, D. C. Pp. 123–134. 77
  • 1975. "Drug use and anti-drug legislation". The PharmChem Newsletter 4 (#8). 79
  • 1975. with D. C. Dyer. "Psychotomimetic phenylisopropylamines. 5. 4-alkyl-2,5-dimethoxyphenylisopropylamines". J. Med. Chem. 18: 1201–1204. 80
  • 1975. with C. Helisten. "Differentiation of PCP, TCP, and a contaminating precursor PCC, by thin layer chromatography". Microgram 8: 171–172. 81
  • 1975. with Helisten, C. "The detection of 1-piperidinodydlohexanecarbonitrile contamination in illicit preparations of 1-(1-phenylcyclohexyl)piperidine and 1-(1-(2-thienyl)cyclohexyl)piperidine". J. Chrom. 117: 232–235. 82
  • 1976. "Psychotomimetic agents". In M. Gordon [ed.] "Psychopharmacological agents", Vol. 4. Academic Press, New York. Pp. 59–146. 83
  • 1976. "Abuse of the term 'amphetamines'". Clin. Tox. 9: 351–352. 84
  • 1976. "Profiles of psychedelic drugs. 1. DMT". J. Psychedelic Drugs 8: 167–168. 85
  • 1976. "Profiles of psychedelic drugs. 2. TMA-2". J. Psychedelic Drugs 8: 169. 86
  • 1976. with D. E. MacLean. "Illicit synthesis of phencyclidine (PCP) and several of its analogs". Clin. Tox. 9: 553–560. 87
  • 1976. with Nichols, D. E. "Sulfur analogs of psychotomimetic amines". J. Pharm. Sci. 65: 1554–1556. 89
  • 1976. with Sargent, T. and N. Kusubov. "Quantitative measurement of demethylation of [14]C-methoxyl labeled DMPEA and TMA-2 in rats". Psychopharm. Commun. 2: 199–206. 90
  • 1976. with Standridge, R. T., H. G. Howell, J. A. Gylys, R. A. Partyka. "Phenylalkylamines with potential psychotherapeutic utility. 1. 2-amino-1-(2,5,-dimethoxy-4-methylphenyl)butane". J. Med. Chem. 19: 1400–1404. 91
  • 1976. "Profiles of psychedelic drugs. 3. MMDA". J. Psychedelic Drugs 8: 331. 92
  • 1977. "Profiles of psychedelic drugs. 4. Harmaline". J. Psychedelic Drugs 9: 79–80. 93
  • 1977. "Profiles of psychedelic drugs. 5. STP". J. Psychedelic Drugs 9: 171–172. 94
  • 1977. with Nichols, D. E., and D. C. Dyer. "Directional lipophilic character in a series of psychotomimetic phenethylamine derivatives". Life Sciences 21: 569–576. 95
  • 1977. with Jacob, P. III, G. Anderson III, C. K. Meshul, and N. Castagnoli Jr. "Mononethylthio analogues of 1-(2,4,5-trimethoxyphenyl)2-aminopropane". J. Med. Chem. 20: 1235–1239. 96

References[]

  1. ^ Shulgin, Ann. "CaringBridge Journal Entry for May 24, 2011 5:04pm". CaringBridge. Retrieved April 5, 2014.[permanent dead link]
  2. ^ "DIRTY PICTURES" – Alexander Shulgin documentary movie trailer, SXSW 2010 on YouTube
  3. ^ Ancestry.com. California Birth Index, 1905–1995 [database on-line]. Provo, Utah: Ancestry.com Operations Inc, 2005. Original data: State of California. California Birth Index, 1905–1995. Sacramento, California: State of California Department of Health Services, Center for Health Statistics.
  4. ^ a b Ancestry.com. California Death Index, 1940–1997 [database on-line]. Provo, Utah: Ancestry.com Operations Inc, 2000. Original data: State of California. California Death Index, 1940–1997. Sacramento, California: State of California Department of Health Services, Center for Health Statistics.
  5. ^ Lawrence, Alberta Chamberlain (1952). Authors Biographical Monthly Service. Golden Syndicate Publishing Company.
  6. ^ Ancestry.com. 1930 United States Federal Census [database on-line]. Provo, Utah: Ancestry.com Operations Inc, 2002. Year: 1930; Census Place: Berkeley, Alameda, California; Roll 111; Page: 1B; Enumeration District: 320; File: 1029.0.
  7. ^ a b c d e f g h Bennett, Drake (January 30, 2005). "Dr. Ecstasy". New York Times Magazine. Archived from the original on November 17, 2011. Retrieved July 8, 2006.
  8. ^ Mike Power (January 29, 2014). "The Drug Revolution That No One Can Stop". —Matter — Medium. Archived from the original on April 29, 2016. Retrieved May 11, 2016. (The article is illustrated with a picture of the wrong USS Pope.)
  9. ^ a b Romero, Dennis (September 5, 1995). "Sasha Shulgin, Psychedelic Chemist". Los Angeles Times. Archived from the original on March 26, 2007. Retrieved July 8, 2006.
  10. ^ Shulgin, Alexander (1988). Controlled Substances: Chemical & Legal Guide to Federal Drug Laws. Ronin Publishing. ISBN 0-914171-50-X.
  11. ^ Brown, Ethan (September 1, 2002). "Professor X". Wired. Archived from the original on June 25, 2015. Retrieved January 4, 2015.
  12. ^ "Ann Shulgin". Shulginresearch.org. Archived from the original on May 14, 2016. Retrieved May 11, 2016. Detailed biography of Ann Shulgin
  13. ^ "DEA Raid of Shulgin's Laboratory". Erowid. January 8, 2004. Archived from the original on March 26, 2007. Retrieved July 8, 2006.
  14. ^ Morris, Hamilton; Smith, Ash (May 2, 2010). "Vice Magazine – The Last Interview With Alexander Shulgin". Archived from the original on July 22, 2016. Retrieved August 24, 2017.
  15. ^ Brown, David Jay (June 19, 2008). "MAPS News: June 2008 – First legal dose of LSD administered!". MAPS News. Archived from the original on March 2, 2012.
  16. ^ "Sasha Shulgin". Psychedelic Research. November 18, 2010. Archived from the original on February 22, 2015.
  17. ^ Pescovitz, David (June 1, 2014). "Psychedelic hero Alexander Shulgin nearing death / Boing Boing". Boingboing.net. Archived from the original on November 17, 2015. Retrieved November 17, 2015.
  18. ^ Calamur, Krishnadev (June 3, 2014). "Alexander Shulgin, The 'Godfather Of Ecstasy,' Dies At 88 : The Two-Way". NPR. Archived from the original on May 2, 2015. Retrieved November 17, 2015.
  19. ^ Appendino G, Minassi A, Taglialatela-Scafati O (July 2014). "Recreational drug discovery: natural products as lead structures for the synthesis of smart drugs". Natural Product Reports. 31 (7): 880–904. doi:10.1039/c4np00010b. PMID 24823967. Archived from the original on September 28, 2020. Retrieved September 3, 2019.
  20. ^ with Shulgin, Ann (1991). PIHKAL: A Chemical Love Story. Berkeley: Transform Press. ISBN 0-9630096-0-5.
  21. ^ "Professor X". Wired. September 1, 2002.
  22. ^ "Chemist Alexander Shulgin, Popularizer of the Drug Ecstasy, Dies at 88". MAPS.
  23. ^ "The Last Interview With Alexander Shulgin". www.vice.com.
  24. ^ with Shulgin, Ann (1991). PiHKAL: A Chemical Love Story. Berkeley: Transform Press. ISBN 0-9630096-0-5.
  25. ^ Shulgin, Alexander T.; Sargent, Thornton; Naranjo, Claudio (1966). "Role of 3,4-Dimethoxyphenethylamine in Schizophrenia". Nature. 212 (5070): 1606–7. Bibcode:1966Natur.212.1606S. doi:10.1038/2121606a0. PMID 21105535. S2CID 4266452.

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