The Joseph McPartlin Selection

Courtesy of Joseph McPartlin 1. In the age of nanofluidics, the 24-hour urine collection may seem a curiosity, though much depends in metabolic studies on the accuracy of collecting these specimens. In an account worthy of Italian satirist Dario Fo, the authors Turner and Merlis1 recount the sources of errors during collections. They also compare working with human subjects to an enormous game of chess, and quote George Eliot's Felix Holt: Fancy what a game of chess would be if all the chess men had passions and intellects, more or less small and cunning; if you were not only uncertain about your adversary's men, but a little uncertain also about your own .... You might be the longest headed of deductive reasoners, and yet you might be beaten by your own pawns .... Yet this imaginary chess is easy, compared with a game a man has to play against his fellow-men with other fellow-men for his instruments. 2. No such problems arose for the late Victor Herbert, the New York hematologist who experimented on himself. To understand folate deficiency, Herbert ate foods thrice boiled to extract folate,2 and he almost died from potassium deficiency. Nevertheless, he resumed self-experimentation and described the most fully documented sequence of laboratory and clinical events in dietary folate deficiency. 3. On one black day for rational thinking, Nature decided to publish a paper3 that seemed to validate homeopathy by claiming that water could 'remember' substances once dissolved in it, but diluted beyond a dilution of 10-24. The catch: The water could remember only when shaken vigorously, not stirred, between each dilution (perhaps explaining James Bond's ability to distinguish between martinis that had been shaken rather than stirred). 4. Unlike the facile solutions offered by alternative medicine, the exhaustive business of elucidating the basis and treatment of disease is exemplified by work conducted by University of Michigan enzymologists on top of their game.4 This paper provides a glimpse of how a public health measure--universal folate fortification--may offset the deleterious effects of a genetic variant. The integrated and painstaking endeavor displayed here also is a reminder that the application of the high-throughput technology of genome sequencing to proteomics is like the high-altitude bombing of an unfamiliar country. 5. In recognition of the new terminology, Watson and Crick should be called the original (gn)omes. The discovery of the double helix of DNA5 is described with the arrogant concision of genius, a paper of similar length as Einstein's Annalen der Physik paper in 1905. No one paid much heed at first, and many were dismayed at the manner in which key players in this drama were portrayed in Watson's book The Double Helix, which goes to show that if you climb on the shoulders of giants, you cannot avoid sometimes stepping on their toes. --Joseph McPartlin, Department of Clinical Medicine, Trinity College, Dublin References 1. W.J. Turner, S. Merlis, "Vicissitudes in research: the twenty-four hour urine collection," Clin Pharmacol Therapeut, 12:163-6, 1971. 2. V. Herbert, "Experimental nutritional folate deficiency in man," Trans Assoc Amer Phys, 75:307-20, 1962. 3. E. Davenas, "Human basophil degranulation triggered by very dilute antiserum against Ig," Nature, 333:816-8, 1988. 4. B. Guenther et al., "The structure and properties of methyl-enetetrahydrofolate reductase from Escherichia coli suggest how folate ameliorates human hyperhomocysteinemia," Nat Struct Biol, 6:359-65, 1999. 5. J.D. Watson, F.H.C. Crick, "Molecular structure of nucleic acids. A structure for deoxyribose nucleic acid," Nature, 171:737-8, 1953.

The Joseph McPartlin Selection

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