the 1950s that major progress really began. Driven in part by chemists such as R. B. Woodward and Vladimir Prelog but also by the development of new techniques. The first of these was X-ray crystallography, which was used to determine the absolute configuration of an organic compound by Johannes Bijvoet in 1951. Chiral chromatography was introduced a year later by Dalgliesh, who used paper chromatography to separate chiral amino acids. Although Dalgliesh was not the first to observe such separations, he correctly attributed the separation of enantiomers to differential retention by the chiral cellulose. This was expanded upon in 1960, when Klem and Reed first reported the use of chirally-modified silica gel for chiral HPLC separation. Thalidomide While it was known that the different enantiomers of a drug could have different activities, with significant early work being done by Arthur Robertson Cushny, this was not accounted for in early drug design and testing. However, following the thalidomide disaster the development and licensing of drugs changed dramatically. First synthesized in 1953, thalidomide was widely prescribed for morning sickness from 1957 to 1962, but was soon found to be seriously teratogenic, eventually causing birth defects in more than 10,000 babies. The disaster prompted many countries to introduce tougher rules for the testing and licensing of drugs, such as the Kefauver-Harris Amendment (US) and Directive 65/65/EEC1 (EU). Early research into the teratogenic mechanism, using mice, suggested that one enantiomer of thalidomide was teratogenic while the other possessed all the therapeutic activity. This theory was later shown to be incorrect and has now been superseded by a body of research. However it raised the importance of chirality in drug design, leading to increased research into enantioselective synthesis. Modern age (since 1965) The Cahn–Ingold–Prelog priority rules (often abbreviated as the CIP system) were first published in 1966; allowing enantiomers to be more easily and accurately described. The same year saw first successful enantiomeric separation by gas chromatography an important development as the technology was in common use at the time. Metal-catalysed enantioselective synthesis was pioneered by William S. Knowles, Ryōji Noyori and K. Barry Sharpless; for which they would receive the 2001 Nobel Prize in Chemistry. Knowles and Noyori began with the development of asymmetric hydrogenation, which they developed independently in 1968. Knowles replaced the achiral triphenylphosphine ligands in Wilkinson's catalyst with chiral phosphine ligands. This experimental catalyst was employed in an asymmetric hydrogenation with