Kelvin a year later. The origin of chirality itself was finally described in 1874, when Jacobus Henricus van 't Hoff and Joseph Le Bel independently proposed the tetrahedral geometry of carbon. Structural models prior to this work had been two-dimensional, and van 't Hoff and Le Bel theorized that the arrangement of groups around this tetrahedron could dictate the optical activity of the resulting compound through what became known as the Le Bel–van 't Hoff rule. In 1894 Hermann Emil Fischer outlined the concept of asymmetric induction; in which he correctly ascribed selective the formation of D-glucose by plants to be due to the influence of optically active substances within chlorophyll. Fischer also successfully performed what would now be regarded as the first example of enantioselective synthesis, by enantioselectively elongating sugars via a process which would eventually become the Kiliani–Fischer synthesis. The first enantioselective chemical synthesis is most often attributed to Willy Marckwald, Universität zu Berlin, for a brucine-catalyzed enantioselective decarboxylation of 2-ethyl-2-methylmalonic acid reported in 1904. A slight excess of the levorotary form of the product of the reaction, 2-methylbutyric acid, was produced; as this product is also a natural product—e.g., as a side chain of lovastatin formed by its diketide synthase (LovF) during its biosynthesis—this result constitutes the first recorded total synthesis with enantioselectivity, as well other firsts (as Koskinen notes, first "example of asymmetric catalysis, enantiotopic selection, and organocatalysis"). This observation is also of historical significance, as at the time enantioselective synthesis could only be understood in terms of vitalism. At the time many prominent chemists such as Jöns Jacob Berzelius argued that natural and artificial compounds were fundamentally different and that chirality was simply a manifestation of the 'vital force' which could only exist in natural compounds. Unlike Fischer, Marckwald had performed an enantioselective reaction upon an achiral, un-natural starting material, albeit with a chiral organocatalyst (as we now understand this chemistry). Early work (1905–1965) The development of enantioselective synthesis was initially slow, largely due to the limited range of techniques available for their separation and analysis. Diastereomers possess different physical properties, allowing separation by conventional means, however at the time enantiomers could only be separated by spontaneous resolution (where enantiomers separate upon crystallisation) or kinetic resolution (where one enantiomer is selectively destroyed). The only tool for analysing enantiomers was optical activity using a polarimeter, a method which provides no structural data. It was not until