Template Theories, the Rule of Parsimony, and Disregard for Irreproducibility—The Example of Linus Pauling’s Research on Antibody Formation

In 1940, Linus Pauling proposed his template theory of antibody formation, one of many such theories that rejected Paul Ehrlich’s selective theory of preformed “receptors” (antibodies), assuming instead a direct molding of antibody shapes onto that of the antigen. Pauling believed that protein shapes—independently of amino acid sequences—determined antibody specificity and biological specificity in general. His theory was informed by his pioneering work on protein structure, and it was inspired by the intuitive “rule of parsimony” and simplicity. In 1942, Pauling published his alleged success in producing specific artificial antibodies through experiments based on his 1940 theory. However, his experiments could not be reproduced by prominent immunochemists at the time, and, later, it became generally accepted that antibody specificity was not generated according to Pauling’s and others’ “instruction” template theories. A citation analysis shows that Pauling’s papers on antibody generation continue to be cited as, among other things, pioneering studies of a chemical technology called “molecular imprinting.” The examples of Pauling and other protein chemists are used in this paper to demonstrate that scientific belief, philosophical concepts, and subjective theory preferences facilitated the occurrence of irreproducibility in immunochemistry and beyond. The article points to long-term consequences for the scientific community if irreproducible results are not acknowledged. It concludes by arguing that despite the risks, e.g., for the occurrence and perpetuation of irreproducible results that they entail, subjectivity and a commitment to scientific convictions have often been pre-requisites for the generation, and holding on to, scientific innovation in the face of doubt and rejection from the scientific community.

A Critical Look at Linus Pauling’s Influence on the Understanding of Chemical Bonding

The influence of Linus Pauling on the understanding of chemical bonding is critically examined. Pauling deserves credit for presenting a connection between the quantum theoretical description of chemical bonding and Gilbert Lewis’s classical bonding model of localized electron pair bonds for a wide range of chemistry. Using the concept of resonance that he introduced, he was able to present a consistent description of chemical bonding for molecules, metals, and ionic crystals which was used by many chemists and subsequently found its way into chemistry textbooks. However, his one-sided restriction to the valence bond method and his rejection of the molecular orbital approach hindered further development of chemical bonding theory for a while and his close association of the heuristic Lewis binding model with the quantum chemical VB approach led to misleading ideas until today.

The Importance and Challenges for Analytical Chemistry in Proteomics Analysis

Although Linus Pauling had an exceptional scientific contribution to the study of chemical bonds, reported in his book The Nature of Chemical Bond, the lousy image he got for the X-ray diffraction drove him to an unstable structure with an unreal DNA triple helix publication. Oppositely, for the consecration of James Watson & Francis Crick, they had the opportunity to enter science history using the right image of X-ray to propose the famous DNA double helix structure correctly. This chapter of science is an excellent example of how analytical chemistry performance affects horizons and scientific advances. Today the complexity of the systems is more significant and understanding how all proteins truly work into cells and organisms is the current challenge from proteomics. Comprehending how analysis is carried out and how instruments work could promote new insights to improve the analytical performance in proteomics. Here we described an overview based on our expertise on the analytical chemistry toolkit for proteomics analysis: shotgun, bottom-up, middle-down, top-down, and native proteomics, and their inherent instrumentation technologies. In addition, a detailed discussion of the analytical figures of merit in proteomics analysis is provided. We also address the limitations in multidimensional liquid chromatography and tandem mass spectrometry platforms. Furthermore, we present some perspectives in bioinformatics, mathematical modeling simulations, and chemometrics tools, as well.

Valence Bond Theory—Its Birth, Struggles with Molecular Orbital Theory, Its Present State and Future Prospects

This essay describes the successive births of valence bond (VB) theory during 1916–1931. The alternative molecular orbital (MO) theory was born in the late 1920s. The presence of two seemingly different descriptions of molecules by the two theories led to struggles between the main proponents, Linus Pauling and Robert Mulliken, and their supporters. Until the 1950s, VB theory was dominant, and then it was eclipsed by MO theory. The struggles will be discussed, as well as the new dawn of VB theory, and its future.

The legacy of Charles Oliver Ingamells (1916–1994)

Charles Oliver Ingamells passed away in April 1994 at age 77. Ingamells received his BA at the University of Western Ontario and his MS at the University of Minnesota. During his later years in his retirement home in Florida he was a faithful representative of a group of well-known world experts in Sampling Theory, such as Pierre M. Gy, Francis F. Pitard, Jan Visman, Paul Switzer at Stanford University and J.C. Engels at the US Geological Survey and the Linus Pauling Institute in Menlo Park, California. His association with Francis F. Pitard during several years at Amax Extractive Research & Development in Colorado has added to a unique combination of different experiences in the field of geochemical analysis. His pioneering work in the field of geological sampling led to collaboration with the above experts.

Lawrence Bragg and Linus Pauling: Comparisons and Rivalries

W. L. Bragg and L. C. Pauling were among the most famous scientists in the world for much of the twentieth century. Each was a Nobel Laureate, and each was admired, not only for their fundamental achievements in X-ray crystallography, but also as exemplary popularizers of science. In the fields of mineralogy (especially the structure of silicates) and protein structures, their interests overlapped. They admired their respective technical virtuosities, but there was deep-seated rivalry between them. It irked Bragg that Pauling had formulated simple stereochemical rules to account for the multiplicity of structures exhibited by vast numbers of silicates, and also that Pauling had proposed the existence of the alpha-helix and pleated sheets as motifs in the structure of proteins like keratin. The details of their rivalry, bordering on envy, is described through specific examples.