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Laboratorios Syntex SA (later Syntex Laboratories, Inc.) was a pharmaceutical company formed in
Mexico City Mexico City ( es, link=no, Ciudad de México, ; abbr.: CDMX; Nahuatl: ''Altepetl Mexico'') is the capital and largest city of Mexico, and the most populous city in North America. One of the world's alpha cities, it is located in the Valley o ...
in January 1944 by Russell Marker, Emeric Somlo, and Federico Lehmann to manufacture therapeutic
steroid A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and a ...
s from the Mexican yams called ''cabeza de negro'' (''
Dioscorea mexicana ''Dioscorea mexicana'', Mexican yam or ''cabeza de negro'' is a species of yam in the genus ''Dioscorea''. ''Dioscorea mexicana'' is a caudiciform dioscorea having either a partly to completely above-ground dome-shaped caudex with a thick, ...
'') and ''Barbasco'' (''
Dioscorea composita ''Dioscorea composita'', or barbasco, is a species of yam in the genus '' Dioscorea'', native to Mexico. It is notable for its role in the production of diosgenin, which is a precursor for the synthesis of hormones such as progesterone. Russel ...
''). The demand for barbasco by Syntex initiated the Mexican barbasco trade. As the American Chemistry Society later explained: “In early 1944, the new Mexican company was chartered and named Syntex, S.A. (‘Synthesis and Mexico’). Russell Marker, shortly thereafter, left Syntex on account of his ruthless cofounder.
Luis E. Miramontes Luis Ernesto Miramontes Cárdenas (March 16, 1925 – September 13, 2004) was a Mexican chemist known as the co-inventor of the progestin norethisterone used in one of the first three oral contraceptives. Miramontes was born in Tepic, Nayarit. H ...
, George Rosenkranz and
Carl Djerassi Carl Djerassi (October 29, 1923 – January 30, 2015) was an Austrian-born Bulgarian-American pharmaceutical chemist, novelist, playwright and co-founder of Djerassi Resident Artists Program with Diane Middlebrook, Diane Wood Middlebrook. He is b ...
's successful synthesis of norethindrone (also known as norethindrone) — which was later proven to be an effective pregnancy inhibitor — led to an infusion of capital into Syntex and the Mexican steroid pharmaceutical industry. George Rosenkranz and
Carl Djerassi Carl Djerassi (October 29, 1923 – January 30, 2015) was an Austrian-born Bulgarian-American pharmaceutical chemist, novelist, playwright and co-founder of Djerassi Resident Artists Program with Diane Middlebrook, Diane Wood Middlebrook. He is b ...
went on to synthesize cortisone from
diosgenin Diosgenin, a phytosteroid sapogenin, is the product of hydrolysis by acids, strong bases, or enzymes of saponins, extracted from the tubers of ''Dioscorea'' wild yam species, such as the Kokoro. The sugar-free (aglycone) product of such hydrolys ...
, the same phytosteroid contained in Mexican yams used to synthesize progesterone and norethindrone. The synthesis was more economical than the previous Merck & Co. synthesis, which started with
bile acids Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Diverse bile acids are synthesized in the liver. Bile acids are conjugated with taurine or glycine residues to give anions called bile salts. Primary b ...
. In 1959, Syntex moved its operating headquarters to
Palo Alto, California Palo Alto (; Spanish language, Spanish for "tall stick") is a charter city in the northwestern corner of Santa Clara County, California, United States, in the San Francisco Bay Area, named after a Sequoia sempervirens, coastal redwood tree kno ...
, United States, and evolved into a transnational corporation. Its foreign scientists had become frustrated with bureaucratic delays on the part of the
Mexican government The Federal government of Mexico (alternately known as the Government of the Republic or ' or ') is the national government of the United Mexican States, the central government established by its constitution to share sovereignty over the republi ...
in granting work visas and approving necessary imports of pharmaceutical materials for their work. After 1959, Syntex was incorporated in Panama; its administration, research and marketing were conducted from Palo Alto; its manufacturing of bulk steroid intermediates remained in Mexico; and it also manufactured finished drugs at plants in Puerto Rico and the Bahamas. Syntex agreed to be acquired by the Roche group in May 1994. After the acquisition closed, Roche downsized Syntex's research and development facilities in the
Stanford Research Park Stanford Research Park (SRP) is a technology park established in 1951 as a joint initiative between Stanford University and the City of Palo Alto. It has more than 150 companies, including Hewlett-Packard, Tesla Motors, TIBCO and VMware; previous ...
and finally shut down what was left of Syntex in September 2008. In 2011,
VMware VMware, Inc. is an American cloud computing and virtualization technology company with headquarters in Palo Alto, California. VMware was the first commercially successful company to virtualize the x86 architecture. VMware's desktop software ru ...
moved into the former Syntex campus in Palo Alto.


Prominent researchers

* Russell Marker co-founded the company in 1944. In May 1945, realizing that he was being left out of the company's profits, he left the company. When Marker took his notebooks with him, production was severely hampered because he had done the synthesis himself and had coded the reagent bottles. * George Rosenkranz had studied at the Swiss Federal Institute of Technology and was conducting pharmaceutical research in Cuba.Rosenkranz had fled Nazi Germany to avoid the eventual Holocaust; while in Cuba en route to South America, the Japanese attack on Pearl Harbor stranded him there. He was able to work there for the duration of the war. He joined Syntex in 1945 to replace Marker. He hired Djerassi in 1949. *
Carl Djerassi Carl Djerassi (October 29, 1923 – January 30, 2015) was an Austrian-born Bulgarian-American pharmaceutical chemist, novelist, playwright and co-founder of Djerassi Resident Artists Program with Diane Middlebrook, Diane Wood Middlebrook. He is b ...
went to work at Syntex in 1949 as the associate director of chemical research. He remained there through 1951, leaving to join the faculty of the Chemistry Department at Wayne State University (Detroit, Michigan) starting in 1952. He later returned to the company in 1957, was involved in the company's move to Palo Alto (where he had become a professor of chemistry at Stanford in 1960), and stayed around this time until 1972. * Alejandro Zaffaroni developed procedures for identifying and separating steroids using paper chromatography while studying at the University of Rochester, and joined Syntex as a research biochemist in 1951. He became vice-president in 1956, and was appointed president of Syntex's U.S. subsidiary in Palo Alto, California in 1962. *
Luis E. Miramontes Luis Ernesto Miramontes Cárdenas (March 16, 1925 – September 13, 2004) was a Mexican chemist known as the co-inventor of the progestin norethisterone used in one of the first three oral contraceptives. Miramontes was born in Tepic, Nayarit. H ...
moved from
UNAM The National Autonomous University of Mexico ( es, Universidad Nacional Autónoma de México, UNAM) is a public research university in Mexico. It is consistently ranked as one of the best universities in Latin America, where it's also the bigges ...
to Syntex in 1950 as a researcher under Djerassi. Under the direction of Djerassi and Rosenkranz, he performed the last step of the first synthesis of an orally highly active
progestin A progestogen, also referred to as a progestagen, gestagen, or gestogen, is a type of medication which produces effects similar to those of the natural product, natural female sex hormone progesterone in the body. A progestin is a ''synthetic co ...
on 15 October 1951. The semi-synthetic steroid, norethisterone (19-Nor-17-alpha-ethynyltestosterone), was the first orally highly active progestin, which led to the development of the first oral contraceptive pills. * Albert Bowers joined Syntex, in 1956 as research group leader; went on to publish more than 90 scientific papers on steroid research and originated more than 120 U.S. patents. Bowers became president of Syntex in 1976, was chief executive officer from 1980 to 1989 and had served as chairman of the board, 1981-1990. * Jerzy Rzedowski worked as an explorer botanist. He later became the most prominent plant scientist in Mexico. * Ralph Dorfman Joined the company as a consultant in 1960, eventually serving as President of Syntex Research from 1967–1973


Birth control pill

Syntex submitted its compound to a laboratory in
Madison, Wisconsin Madison is the county seat of Dane County and the capital city of the U.S. state of Wisconsin. As of the 2020 census the population was 269,840, making it the second-largest city in Wisconsin by population, after Milwaukee, and the 80th-lar ...
, for biological evaluation, and found it was the most active, orally-effective progestational hormone of its time. Syntex submitted a patent application in November 1951. In August 1953, G.D. Searle & Co. filed for a patent for the synthesis of the double-bond isomer 13 of norethindrone called noretynodrel. Noretynodrel is converted into norethisterone under acidic conditions, such as those in the human stomach, and the new patent did not infringe on the Syntex patent. Searle obtained approval to market noretynodrel before Syntex received its approval. By 1964 three companies, including Syntex,
G.D. Searle G.D. Searle, LLC is a wholly owned subsidiary of Pfizer. It is currently a trademark company and subsidiary of Pfizer, operating in more than 43 countries. It also operates as a distribution trademark for various pharmaceuticals that were devel ...
, and
Johnson & Johnson Johnson & Johnson (J&J) is an American multinational corporation founded in 1886 that develops medical devices, pharmaceuticals, and consumer packaged goods. Its common stock is a component of the Dow Jones Industrial Average and the company i ...
under the Ortho Pharmaceutical brand, were marketing 2-mg doses of the Syntex norethindrone.


Scientific misconduct

Syntex's submission of a fraudulent toxicology analysis of naproxen largely led to the
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
's uncovering of extensive scientific misconduct by
Industrial Bio-Test Laboratories Industrial Bio-Test Laboratories (IBT Labs) was an American industrial product safety testing laboratory. IBT conducted significant quantities of research for pharmaceutical companies, chemical manufacturers and other industrial clients; at its h ...
in 1976.


References


Further reading

*
Carl Djerassi Carl Djerassi (October 29, 1923 – January 30, 2015) was an Austrian-born Bulgarian-American pharmaceutical chemist, novelist, playwright and co-founder of Djerassi Resident Artists Program with Diane Middlebrook, Diane Wood Middlebrook. He is b ...
''Steroids''. 1994 Jan;59(1):58-9 *
Max F. Perutz Max Ferdinand Perutz (19 May 1914 – 6 February 2002) was an Austrian-born British molecular biologist, who shared the 1962 Nobel Prize for Chemistry with John Kendrew, for their studies of the structures of haemoglobin and myoglobin. He went ...
''I Wish I’d Made You Angry Earlier: Essays on Science, Scientists, and Humanity''. Cold Spring Harbor Laboratory Press 1998 *
Carl Djerassi Carl Djerassi (October 29, 1923 – January 30, 2015) was an Austrian-born Bulgarian-American pharmaceutical chemist, novelist, playwright and co-founder of Djerassi Resident Artists Program with Diane Middlebrook, Diane Wood Middlebrook. He is b ...
''This Man's Pill: Reflections on the 50th Birthday of the Pill''. Oxford University Press 2001 *Lara V. Marks ''Sexual Chemistry: A History of the Contraceptive Pill''. New Haven, Conn., Yale University Press, 2001 *
Carl Djerassi Carl Djerassi (October 29, 1923 – January 30, 2015) was an Austrian-born Bulgarian-American pharmaceutical chemist, novelist, playwright and co-founder of Djerassi Resident Artists Program with Diane Middlebrook, Diane Wood Middlebrook. He is b ...
''Steroids Made It Possible''. American Chemical Society, Washington DC, 1990 {{Authority control Roche Pharmaceutical companies of Mexico Manufacturing companies based in Mexico City Companies of Panama Life sciences industry