Experiments That Changed Nutritional Thinking - TUUM EST

1034S
SUPPLEMENT
demiological observations with respect thereto. Public Health Rep. 29: 1683– anemic animals by dietary methods, however. In the preceding
1686.
Goldberger, J. (1916) The transmissibility of pellagra: experimental attempts
paper in their series, data were presented showing that iron
at transmission to the human subject. Public Health Rep. 31: 3159–3173. salts of great purity were ineffective in correcting an anemia
Goldberger, J. & Schamberg, J. F. (1909) Epidemic of an urticarioid dermatitis of rats confined to a diet of cow’s milk. However, an equal
due to a small mite (Pediculoides ventricosus) in the straw of mattresses.
amount of iron fed as ash of lettuce, corn or beef liver (an
Pub. Health Rep. 24: 973–975.
Goldberger, J. & Sebrell, W. H. (1930) The black tongue preventive value of acid extract of ash) was very potent in restoring normal hemo-
Minot’s liver extract. Public Health Rep. 45: 3064–3070.
globin.
Goldberger, J. & Tanner, W. F. (1922) Amino acid deficiency probably the etio-
The seventh paper (Hart et al. 1928) in their series establogic
factor in pellagra. Public Health Rep. 37: 462–486.
Goldberger, J., Waring, C. H. & Willets, D. G. (1915) A test of diet in the prevention
of pellagra. South. Med. J. 8: 1043–1044.
were modest, concluding only that the experiments ‘‘point to
lished copper as an essential nutrient. Although the authors
Goldberger, J., Wheeler, G. A. & Sydenstricker, E. (1918) A study of the diet
the need for a more intensive study of the rôle of small amounts
on nonpellagrous and of pellagrous households in textile mill communities in
South Carolina in 1916. J. Am. Med. Assoc. 71: 944–949.
of inorganic substances in the diet,’’ McCollum (1957) suggests
Krehl, W. A., Tepley, L. J., Sarma, P. S. & Elvehjem, C. A. (1945) Growth re- that this experiment and other similar ones on trace elements
tarding effects of corn in nicotinic acid–low rations and its counteraction by ‘‘broadened immensely the outlook of physiologists, biochemtryptophan.
Science 101: 489–491.
Siler, J. F., Garrison, P. E. & MacNeal, W. J. (1914) Pellagra, a summary of the
ists, and pathologists.’’
first progress report of the Thompson-McFadden Commission. J. Am. Med. Figure 1 contains charts on six rats of some 50 presented.
Assn. 62: 8–12.
Each chart showed both rat weight and hemoglobin plotted
Tanner, W. F. (1921) Progress report to Goldberger (unpublished and cited by
Hundley in Sebrell, W. H. & Harris, R. S. (1954) The Vitamins: Chemistry,
against time. Intakes of 0.3 g of Cohn’s liver preparation (ap-
Physiology, Pathology, Volume II, page 553. Academic Press, New York, NY. proximately equivalent to 1.7 g of dried beef liver) produced
Terris, M. (1964) Goldberger on Pellagra. Louisiana State University Press, a ‘‘marked growth response’’ in rat 597 without much improve-
Baton Rouge, LA.
ment in hemoglobin. Cohn et al. (1927) fractionated livers
Vilter, R. W., Mueller, J. F. & Bean, W. B. (1949) The therapeutic effect of trypto
produce extracts more efficacious than whole liver in curing
tophan in human pellagra. J. Lab. Clin. Med. 34: 409–413.
Willets, D. G. (1915) The treatment of pellagra by diet. South. Med. J. 8: 1044– anemia. Rat 596 responded with improved hemoglobin when
1047.
given 0.5 mg of iron. Thus bioassay confirmed that the liver
preparation was low in iron as shown by chemical analysis.
Paper 10: Copper as a Supplement to The response of rat 615 was similar to that of rat 596 when
ash of the liver preparation was fed with iron, thereby exclud-
Iron for Hemoglobin Building in the Rat
ing ‘‘the existence of an organic factor’’ being of benefit in
(Hart et al., 1928)
these experiments.
Because several types of ash had been found ‘‘very potent
Presented by Leslie M. Klevay, U.S. Department of Agriculture,
in restoring to normal the hemoglobin,’’ an attempt to frac-
Grand Forks Human Nutrition Research Center, Grand Forks,
tionate the ash was made ‘‘quite early in our experiments.’’
ND 58202 as part of the minisympsosium ‘‘Experiments That
All experiments were done with the same iron intake. Rat
Changed Nutritional Thinking’’ given at Experimental Biology 95,
620 had improved hemoglobin with an acid extract of ash,
April 11, 1995, in Atlanta, GA.
indicating that the effective ‘‘substance (or substances)’’ were
Although Hopkins (1906) and Funk (1912) shrewdly pretionation
‘‘more dramatic,’’ they treated this acid extract with
soluble in hydrochloric acid. Deciding to make their ash fracdicted
early in the 20th century that some diseases occurred
because of dietary deficiency of accessory or essential food hydrogen sulfide. The hemoglobin of rat 690 was restored by
factors, the observations they cited were ‘‘unknown to medical the ‘‘small but distinct precipitate of sulfides.’’ After this premen
and chemists of that period’’ (McCollum 1957). Physiolonia
and ammonium sulfide; rat 688 died without improvement
cipitate was ‘‘filtered off,’’ the filtrate was treated with ammo-
gists, biochemists and even the public (Allen 1931) caught
up by 1928. Many important discoveries on the role of organic of hemoglobin when given this second precipitate. Thus, it
nutrients were made in the 1920s because Hopkins and Funk was found that the active element had an acid-insoluble sul-
had opened their eyes (McCollum 1957).
fide; other elements besides copper were possible (Sorum
The 1926 edition of Osler’s influential textbook (Osler and 1949). Acid ‘‘extracts of the ash of lettuce . . . could not
McCrae 1926) listed two classes of anemia. The secondary or be separated sharply into an active and inactive fraction by
symptomatic class included those due to blood loss, infection precipitation with ammonia.’’
or intoxication. The primary or essential class included only The chronology of these experiments is not obvious. Perhaps
chlorosis, pernicious anemia and sickle cell anemia. Of these the rat number can be a guide. ‘‘Shortly before the time’’ that
three, only chlorosis had an effective treatment. Osler referred the fractions of the Cohn preparation were studied, a trial of
to the treatment of chlorosis by iron therapy as ‘‘one of the copper was made. Figure 2 shows the response of rat 621, the
most brilliant instances—of which we have but three or rat from which the essentiality of copper can be inferred. When
four—of the specific action of a remedy’’ and stated ‘‘It is a supplemental iron with copper was begun, growth had ceased
minor matter how iron cures chlorosis.’’ Osler did not infer the and hemoglobin was 2.68 g/dL. Growth resumed and hemoglobin
existence of iron deficiency anemia (chlorosis was of unknown increased to 9.35 in 2 wk, 10.9 after 6 wk and then reached 13.3
cause). Anemias from deficiency of ascorbic acid, cobalt, folate, g/dL. ‘‘Without the copper addition, the rise in hemoglobin would
niacin, pantothenic acid, pyridoxine, riboflavin, thiamine, via
single animal but the effect was so convincing and helpful’’
not have occurred.’’ ‘‘This preliminary experiment was with but
tamin E, etc., were unrecognized (Wintrobe 1967).
Hart, Steenbock, Waddell and Elvehjem certainly were well that the chart is recorded ‘‘if for no other reason than its historical
informed about nutritional opportunities and contemporary interest.’’ A dozen other rats were studied at three doses of copper.
nutritional knowledge; they may have been somewhat ahead Response to 0.01 mg of copper was less rapid than the response
of physicians who read Osler. Their experimental design refound
in the ash of the liver preparation.
to 0.05 or 0.1 mg. The intermediate dose was similar to that
sembled that of Whipple et al. (1920), who used phlebotomy
to make dogs anemic and then measured blood regeneration to The authors knew that copper occurs in plant and animal
assay dietary components for nutritional value. They produced tissues, but ‘‘no definite function has been assigned to it except
/ 4p09$$0062 04-07-97 14:02:12 nutras LP: J Nut May Suppl
Downloaded from jn.nutrition.org by on June 3, 2010