Experiments That Changed Nutritional Thinking - TUUM EST

More documents

Recommendations

Info

1032S SUPPLEMENT TABLE 2 Literature Cited Mean 3-wk weight changes of young rats receiving 18% zein Abderhalden, E. (1909) Weiterer Beitrag zur Frage nach der Verwertung von tief abgebautem Eiweiss in Tierischen Organismus. Z. Physiol. Chem. 61: as their protein source1 194–199. Becker, S. (1968) The Emergence of a Trace Nutrient Concept through Animal Feeding Experiments. Ph.D. thesis, University of Wisconsin. University Micro- Amino acid films Inc., Ann Arbor, MI. supplement to diet Mean weight Carpenter, K. J. (1994) Protein and Energy: A Study of Changing Ideas in Nutri- No. rats (g/100 g) change ({SD) tion. Cambridge University Press, New York, NY. Chittenden, R. H. (1938) Lafayette Benedict Mendel, 1872–1935. Natl. Acad. g Sci. Biogr. Mem. 18: 123–155. Fruton, J. S. (1995) Thomas Burr Osborne and chemistry. Bull. Hist. Chem. 17: 1–8. 22 None 020 ({ 5) Henriques, V. & Hansen, C. (1905) Über Eiwessynthese im Tierkörper. Hoppe- 6 0.54% Tryptophan 07 ({ 6) Seyler’s Z. Physiol. Chem. 43: 417–446. 7 0.54% Tryptophan /22 ({ 5) Osborne, T. & Mendel, L. B. (1911) Feeding Experiments with Isolated Food / 0.54% lysine Substances. Carnegie Inst. Washington. Publ. 156. [Normal weight gain on a control diet] [/35] Osborne, T. & Mendel, L. B. (1914) Amino-acids in nutrition and growth. J. Biol. Chem. 17: 325–349. Osborne, T. & Mendel, L. B. (1916) The amino-acid minimum for maintenance 1 and growth, as exemplified by further experiments with lysine and trypto- Data from Osborne and Mendel (1914). phane. J. Biol. Chem. 25: 1–12. Vickery, H. B. (1932) Thomas Burr Osborne, 1859–1929. Natl. Acad. Sci. Biogr. with gliadin as the sole protein, lysine did not seem to be Mem. 14: 261–304. Willcock, E. G. & Hopkins, F. G. (1906) The importance of individual amino acids in metabolism. J. Physiol. 35: 88–102. required for maintenance. However, by 1915, with an improved analytical procedure for lysine, they had found that gliadin did contain about 0.9% lysine, but they assumed that Paper 9: Pellagra Is Not Infectious! the rat’s muscle proteins, like those of animals’ muscles that (Goldberger, 1916) had been analyzed, contained approximately 8% lysine, so that part of the lysine in the rats’ new tissues had to have come from the free amino acid supplement. They did not report any actual calculations to support this point, but Table 1 reproduces the relevant estimates that they could, and perhaps did, make. Lysine could not apparently by synthesized by rats, even though it had no cyclic group. This was an important point because it had been thought it was the amino acids containing cyclic groups that animals would be found to be unable to synthesize. On the other hand, rats could apparently maintain themselves with dietary protein of very different composition from that of their own tissues. This idea was confirmed by their parallel results with zein (from corn), which is completely lacking in lysine and also both tryptophan and glycine (Osborne and Mendel 1916). They showed most of their results with zein as growth curves for individual rats, because they changed their supplements from time to time, but Table 2 summarizes their results from just the first few weeks of feeding. It is clear that without tryptophan the rats did worst. With it, but without lysine, they did better, though on average still losing a little weight. With both amino acids added, they grew fairly rapidly, at about two thirds of the optimal rate. They concluded, as Willcock and Hopkins (1906) had earlier, that perhaps the more rapid loss in the absence of tryptophan meant that this amino acid was needed for some special priority function, requiring tissue loss to provide it, and that in its presence there was at any rate less breakdown of protein. The work clarified the importance of amino acid composition as a determinant of protein quality and demonstrated examples of three types of amino acids: lysine that could not be synthesized and was needed almost entirely for growth, tryptophan needed for maintenance as well as growth, and glycine that could be synthesized so that its supply was not limiting. Osborne and Mendel’s persistence with long-term growth as a measure of nutritional adequacy, in parallel with the work of McCollum’s group in Wisconsin, opened up a new approach to the search for vitamins as well as the discovery of further essential amino acids (Becker 1968, Carpenter 1994). Presented by Leslie M. Klevay, U.S. Department of Agriculture, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58202 and Robert E. Olson, College of Medicine, University of South Florida, Tampa, FL 33606 as part of the minisymposium ‘‘Experiments That Changed Nutritional Thinking’’ given at Experimental Biology 96, April 16, 1996, in Washington DC. Microbiology was transforming medicine at the end of the Victorian era. By the time Funk coined the term ‘‘vitamine’’ in 1912, the causative organism for tuberculosis had been known for 30 years. It is not surprising that infection was considered more likely than dietary deficiency to be the cause of pellagra. Both toxicity and heredity, two other causes of disease known at the turn of the century, had also been suggested. Dementia, dermatitis, diarrhea and finally death associated with a diet of meat, maize and molasses described the pellagra syndrome. Unfortunately, the ‘‘meat’’ consumed by poor people was high in fat and low in protein. The dermatitis is photo- sensitive and confined to the areas of skin exposed to sunlight; Cásal’s (1691–1759) necklace is the eponym attached to ‘‘the area of erythema and pigmentation around the neck in pellagra’’ (Terris 1964). The dementia was usually of the manic- depressive type and severe enough to justify admission to a mental institution. Joseph Goldberger, who contributed extensively to our understanding of the causes of pellagra, was born in Austria in 1874 and immigrated with his parents to the United States in the 1880s. He grew up in New York City and entered the City College of New York as a high school graduate in 1890 to study engineering but changed his field to medicine two years later by enrolling at the Bellevue Hospital Medical College. He obtained his MD degree in 1895 and after interning for one year and practicing medicine in New York and Pennsylvania for three additional years, he joined the U.S. Public Health Service in 1899. He served as a quarantine officer in various ports including New Orleans, Tampico, Veracruz and Havana and studied yellow fever and typhus transmission by mosquitos in those areas. In 1909, he solved the cause of Schamberg’s disease, a pigmented dermatitis, prevalent in crew members / 4p09$$0062 04-07-97 14:02:12 nutras LP: J Nut May Suppl Downloaded from jn.nutrition.org by on June 3, 2010
HISTORY OF NUTRITION 1033S on private yachts and in men living in private dwellings and berger and Wheeler themselves were the first subjects, each boarding houses in the Philadelphia area. Goldberger and receiving 5 mL of the defibrinated blood by intramuscular Schamberg (1909) observed that these men slept on straw injection and also secretions. Three days later, Goldberger ate mattresses, and they finally identified a mite (Pediculoides ventricosus) feces from an acutely ill patient together with the urine and as the vector for the disease. Thus, Goldberger had dermatitis scales from two other patients. As a result, Gold- considerable experience in epidemiology and knowledge of berger developed diarrhea that lasted for about a week, but infectious diseases when he was assigned by the Surgeon Gen- despite this both he and Wheeler joined three other volunteers eral in 1913 to undertake a study of the causation of pellagra. for a similar round of tests with both injections of defibrinated Pellagra was not recognized as a problem in the United blood from three patients and the oral consumption of scales States until early in the 20th century. In 1912, Lavinder of and excreta. To maximize the chance of catching any infection the U.S. Public Health Service estimated that more than from stools, they used fresh fecal material from the rectum of 25,000 cases of pellagra had occurred in the United States in pellagrins by using an enema and then blended material from the previous five years and that the case fatality rate was 40%. five subjects into pills that were consumed by the volunteers. The dominant thinking in the United States at the time Goldberger The volunteers also took sodium bicarbonate before and after began his investigations was that pellagra was an infec- consuming these materials to reduce the acidity of the stomach tious disease. As a result of studies in South Carolina, the to prevent a possible bacteriocidal action of gastric juice. Mrs. Thompson-McFadden Pellagra Commission concluded in Goldberger received one injection of blood. Both Goldberger 1913 that ‘‘1) The supposition that the ingestion of good or and Wheeler felt stiffness after the intramuscular injections, spoiled maize is the essential cause of pellagra is not supported and several volunteers felt nauseous after ingestion of feces. by our study; and 2) Pellagra is in all probability a specific Nonetheless, after five to seven months none showed any sign infectious disease communicable from person to person by of pellagra. Because Goldberger’s group had failed to demonstrate means at present unknown.’’ These conclusions were elaborated any transmissibility of an infectious agent to themselves by Siler et al. (1914). from pellagrins and had demonstrated both the preventative In less than three months after beginning his investigation, and curative action in pellagrins of diets rich in animal foods, Goldberger (1914) published his first paper on pellagra. In a they felt secure in their conclusion that the disease was dietary document of a little over three pages, Goldberger summarized and not infectious. Nonetheless, they conducted another epi- the epidemiology of the disease as follows. Pellagra cannot be demiologic study of seven cotton mill villages in South Carolina communicable. The cause is dietary. Prevention should result beginning in 1916, which showed that the disease was from a ‘‘reduction in cereals and vegetables and canned foods not high in villages with poor sanitation but was high in that enter to a large extent in the dietary of many of the villages with poor diets. people in the South and an increase in fresh animal food In 1920, the question remaining was: What was the agent component such as fresh meats, eggs and milk.’’ In support of in animal foods that prevented pellagra? Because the biological these views Goldberger pointed out that 1) in institutions value of animal protein was in general better than the values where pellagra was prevalent, no case had ever occurred in for proteins in cereals and vegetables, Goldberger and Tanner nurses or attendants; 2) the disease was essentially rural; and (1922) proposed that an amino acid might be the pellagra 3) it was associated with poverty, which in turn was associated preventative factor. Tanner actually conducted a trial of trypwith a diet deficient in animal foods. tophan in one pellagrous patient, which caused marked improvement These conclusions, however, were reached by epidemiologic of the dermatitis but little change in the diarrhea. methods involving the association of variables and did not He reported the finding in a progress report to Goldberger, constitute proof of the etiology of the disease. Goldberger and but the result was not followed up (Tanner 1921, quoted by his colleagues then proceeded to attempt 1) to cure pellagra Hundley 1954). Goldberger also tested various foods in an by changing the diet of pellagrins to one rich in animal foods attempt to cure black tongue, the pellagrous analogue in dogs. and 2) to demonstrate by direct studies the possible infectivity Goldberger died prematurely at age 55 in 1929. He thus of secretions, scales and excreta from pellagrins. A year after didn’t live to see the cure of black tongue with niacin as publishing his first paper on pellagra, Goldberger and his co- reported by Elvehjem et al. in 1937, although Goldberger and workers demonstrated in back-to-back papers (Goldberger et Sebrell (1930) did induce remission of this canine disease with al. 1915, Willets 1915) that pellagra could be prevented in liver extract. His idea that amino acids were critical in the institutionalized patients by a diet that included generous pathogenesis of pellagra was confirmed by a finding by Krehl amounts of milk, eggs, meat, beans and peas and that pellagra et al. (1945), who proved that nicotinic acid could be formed could be successfully treated by the same regimen. from tryptophan. Subsequently Vilter et al. (1949) showed The second part of Goldberger’s plan was to demonstrate that tryptophan would cure pellagra in humans. the nontransmissibility of pellagra by contact with nasophabrilliant In summary, Goldberger was a well-trained physician, a ryngeal secretions, blood and excreta from pellagrins (Goldtor. epidemiologist and an imaginative clinical investiga- berger 1916). In a heroic study on themselves conducted by He studied a variety of infectious diseases and pellagra, Goldberger, Sydenstricker, Tanner, Wheeler, Willets, Goldthat which was not infectious, with a multidisciplinary approach berger’s wife and an additional 10 volunteers, defibrinated included epidemiology. He is still lauded as a exemplar blood, nasopharyngeal secretions, feces, urine and dermatitic of clinical epidemiology (Elmore and Feinstein 1994). scales were administered enterally and parenterally in an attempt to cause pellagra. It must be noted that physicians in the public health service at that time had learned to accept Literature Cited such exposures as the risk of dealing with infectious diseases, Elmore, J. G. & Feinstein, A. R. (1994) Joseph Goldberger; an unsung hero of and in fact Goldberger himself had contracted both yellow American clinical epidemiology. Ann. Intern. Med. 121: 372–375. fever and typhus from his previous work. Various tissues, nasal Elvehjem, C. A., Madden, R. J., Strong, F. M. & Wooley, D. W. (1937) Relation of nicotinic acid and nicotinic amide to canine black tongue. J. Am. Chem. secretions and excreta were obtained from 17 cases of pellagra Soc. 59: 1767–1768. of various grades of severity, including three fatal cases. Gold- Goldberger, J. (1914) The etiology of pellagra: the significance of certain epi- / 4p09$$0062 04-07-97 14:02:12 nutras LP: J Nut May Suppl Downloaded from jn.nutrition.org by on June 3, 2010
Page 1 and 2: Symposium: Experiments That Changed
Page 3 and 4: HISTORY OF NUTRITION 1019S common p
Page 5 and 6: HISTORY OF NUTRITION 1021S 233, he
Page 7 and 8: HISTORY OF NUTRITION 1023S If inorg
Page 9 and 10: HISTORY OF NUTRITION 1025S starvati
Page 11 and 12: HISTORY OF NUTRITION 1027S not ling
Page 13 and 14: HISTORY OF NUTRITION 1029S highly p
Page 15: HISTORY OF NUTRITION 1031S on rice
Page 19 and 20: Downloaded from jn.nutrition.org by
Page 21 and 22: HISTORY OF NUTRITION 1037S TABLE 1
Page 23 and 24: HISTORY OF NUTRITION 1039S Fisher,
Page 27 and 28: HISTORY OF NUTRITION 1043S Folin, O
Page 29 and 30: HISTORY OF NUTRITION 1045S by the o
Page 33 and 34: HISTORY OF NUTRITION 1049S vegetabl
Page 35 and 36: HISTORY OF NUTRITION 1051S further
Page 37: Downloaded from jn.nutrition.org by

Experiments That Changed Nutritional Thinking - TUUM EST

Create successful ePaper yourself

Delete template?

Save as template?