Claims that alcohol consumption caused idiocy were also part of the Teetotalisms message in the 19th century, but such claims, despite some attempts to offer evidence, were ignored because no mechanism could be advanced.The earliest recorded observation of possible links between maternal alcohol use and fetal damage was made in 1899 by Dr. William Sullivan, a Liverpool prison physician who noted higher rates of stillbirth for 120 alcoholic female prisoners than their sober female relatives; he suggested the causal agent to be alcohol use. This contradicted the predominating belief at the time that heredity caused intellectual disability, poverty, and criminal behavior, which contemporary studies on the subjects usually concluded. A case study by Henry H. Goddard of the Kallikak family—popular in the early 1900s—represents this earlier perspective, though later researchers have suggested that the Kallikaks almost certainly had FAS. General studies and discussions on alcoholism throughout the mid-1900s were typically based on a heredity argument.Prior to fetal alcohol syndrome being specifically identified and named in 1973, only a few studies had noted differences between the children of mothers who used alcohol during pregnancy or breast-feeding and those who did not, and identified alcohol use as a possible contributing factor rather than heredity. Recognition as a syndrome
Fetal alcohol syndrome was named in 1973 by two dysmorphologists, Drs. Kenneth Lyons Jones and David Weyhe Smith of the University of Washington Medical School in Seattle, United States.
It is a synthetic tetradecapeptide (14 amino acid peptide) with the sequence CCEYCCNPACTGCY by one-letter abbreviation, or by three-letter abbreviation:H–Cys1–Cys2–Glu3–Tyr4–Cys5–Cys6–Asn7–Pro8–Ala9–Cys10–Thr11–Gly12–Cys13–Tyr14–OH
However, the actual structure of linaclotide is not fully specified without the three disulfide (R-S-S-R) bonds it contains, which are between Cys1 and Cys6, between Cys2 and Cys10, and between Cys5 and Cys13; these are shown in exaggerated fashion in the line-angle graphic showing the chemical bonds within and between each amino acid (and their stereochemistries, see the infobox, above right), and are represented using a one-letter abbreviations in the following additional schematic:

A study in discovery synthesis reported that 2 of 14 strategies available to synthesize linaclotide were successful—the successful ones involving trityl protection of all cysteines, or trityl protection of all cysteines except Cys1 and Cys6, which were protected with tert-butylsulphenyl groups. The study also reported that solution-phase oxidation (disulfide formation) was advisable over solid-supported synthesis for linaclotide, and that the Cys1–Cys6 disulfide bridge was the most favored energetically. History
The drug was discovered at Microbia, Inc, which had been spun out of the Whitehead Institute in 1998 by postdocs from the lab of Gerald Fink to commercialize the labs know-how and inventions related to microbial pathogens and biology. In 2002 the company hired Mark Currie who had worked at the Searle division of Monsanto and then had gone to Sepracor. Currie directed the efforts that led to the discovery of linaclotide, which was based on an enterotoxin produced by some strains of Escherichia coli that cause travelers diarrhea.