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`TREASURY DEPARTMENT
`
`
`PUBLIC HEALTH
`
`REPORTS
`
`ISSUED WEEKLY
`BY THE
`
`UNITED STATES PUBLIC HEALTH SERVICE
`
`
`CONTAINING INFORMATION ON THE CURRENT
`PREVALENCE OF DISEASE, THE PREVENTION
`AND CONTROL OF DISEASE, AND
`RELATED SUBJECTS
`
`VOLUME 43—PART 1
`NUMBERS 1—26
`
`JANUARY—JUNE, 1928
`
`SE
`
`UNITED STATES
`GOVERNMENT PRINTING OFFICE
`WASHINGTON
`1928
`
`
`
`Elysium Health Exhibit 1015
`Page 1 of 38
`
`
`
` ADDITIONAL COPIES
`
`OF THIS PUBLICATION MAY BE PROCURED FROM
`THE SUPERINTENDENT OF DOCUMENTS
`U.S.t‘.0\'ERNMENT PRINTING OFFICE
`WASHINGTOX. D. C.
`AT
`5 CENTS PER COPY
`
`I I
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`“.HI _..
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`“nirihrfis
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`5"‘.C‘i".| i1.,'TT"f']'i"-'J "."Vl': "7"!
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`Jcan"‘
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`Elysium Health Exhibit 1015
`Page 2 of 38
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`PUBLIC HEALTH REPORT
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`VOL. 43
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`JUNE 8, 1928
`
`NO. 23
`
`A STUDY OF THE BLACKTONGUE-PREVENTIVE ACTION
`OF 16 FOODSTUFFS, WITH SPECIAL REFERENCE TO THE
`IDENTITY OF BLACKTONGUE 0F DOGS AND PELLAGRA
`OF MAN
`'
`
`and R. D. LILLIE
`By JOSEPH GOLDBERGER and G. A. WHEELER, Surgeons,
`{End L. M. ROGERS, Passed Assistant Surgeons, United States Public Health
`i'e-rivicc
`
`
`CONTENTS
`
`Page
`Page
`Introduction ______________________________ ,.
`1385
`Beef....................................... --
`1424
`Methods and criteria..____
`..
`1387
`Pork liver _ _ _ _ . _ _ _ . _
`_ _ .. _ _ .
`l . l _ _ l _ __ _ .-
`1428
`
`1380
`Canned salmon
`Maize (and cornstarch)"
`11130
`143+
`1302
`Eggyolk.
`Wheat,,,,,,,, ,,
`1431
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`Wheat germ. , _
`1394
`Tomatoes
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`(Iowpea._,,
`1438
`1397
`Carrots
`.
`Soy bean _______________________
`1400 Rulahagascnun ,._,,..._...-
`_
`1443
`
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`Relation of blacklongue to pellagra__...__--_ 144G
`Milk _____ __
`1402
`Summary and conclusions,"
`__
`Button“...
`1405
`1447
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`References_________________________________ ..
`Cod-liver oil
`1420
`144s
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`Cottonseed oil.___
`Tables ________ _.-___________________________ _..
`1422
`1440
`
`
`Some of the results of our study of the problem of an experimental
`animal for pellagra were briefly summarized in a communication
`published two years ago (1), and have been presented in detail in
`two recent publications.
`In the first of
`those Goldbergcr
`and
`Wheeler (2) reported the production in the dog, by feeding pellagra-
`producing diets, of a pathological condition considered by them to be
`identical with the spontaneously occurring canine disease known to
`American veterinarians as blacktongue.1 The clinical resemblance of
`this canine disease to pellagra in man was discussed and was consid-
`ered so striking as to be, in itself, practically conclusive of the identity
`of these two conditions.
`In harmony with and supporting this View
`was also the suggestion of a cOmmon etiology indicated by the success-
`ful production of the canine disease by feeding with pellagra—producing
`diets.
`In the second communication, Goldberger, Wheeler, Lillie,
`and Rogers (3) reported a series of feeding experiments with yeast
`from the results of which they concluded that experimental black-
`tongue is due to a deficiency in diet that is capable of being corrected
`by something present in abundance in yeast. This demonstration of
`the presence of the blacktongue preventive in yeast, a substance in
`which the pellagra preventive (factor P—P) was also known to be
`present in abundance (4), Was considered to increase somewhat the
`
`a1
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`Elysium Health Exhibit 1015
`Page 3 of 38
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`June 8, 1928
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`In this connection it is of interest {to note: that Denton
`conditions.
`(5), in a study of the tissue changes in experimental blacktongue, has
`found that the lesions of the skin, mouth, pharyi'ix, esophagus, and
`colonin the canine disease are very similar to those in pellagra, and
`that histologically the lesions in experimental blacktongne duplicate
`those in pellagra.
`In the bodyr of this report reference will be made to differences
`between certain of the results of our study and those of an apparently
`similar study by Underhill and Mendel (6). The divergence in our
`results is of interest, since We have heretofore considered it highly
`probable that the pathological condition experimentally induced in
`the dog by Chittenden and Undcrhill and studied by Dnderhill and
`hieudel was identical with the experimental condition studlcd and
`identified by us as blacktongue (2). The extensive report ofltheir
`work (7) which has just come to our attention presents some clinical
`details which not only seem in themselves significant of a difference
`in the two pathological mnditions, but also suggest that we had here-
`tofore, perhaps, underestimated the significance of certain other clin-
`ical differences. Thus we find in this report that a “troublesome
`skin rash” appears to have been common in the condition with which
`Underhill and hlendid have worked.
`“To have encountered none
`
`such in our dogs. On the other hand, while we have observed a
`pellagra-like dermatitis of the scrotum in some 40 to 50 per cent of
`attacks in our male dogs, there is no mention of the occurrence of
`such an eruption in the condition studied by Underhill and Memlel.
`Again, in the condition studied by 11s%1111111elj,*, blacktongueithcro
`is a definitely marked febrile stage which does not seem to occur in
`the Chittendcn-Underhill syndrome stridied by Underhill and hien-
`del; for they nowhere make mention of it, not even in their fulllrepo'rt.
`These clinical differences seem to us of such importance that, in spite
`of the striking clinical similarity in certain other respects, doubt now
`arises as to the identity of the Chittenden-Underhill “pellagra-hkc’
`syndrome. Until this doubt is definitely resolved one way or another,
`it would seem premature to discuss, and we therefore do not attempt
`to discuss, the differences between the results reported by Underhnl
`and Mendel and those recorded by ourselves in the present and 111 a
`preceding communication (3).
`I
`‘
`f
`In the present communication we present some further i‘csnlt-slo
`our study of experimental blacktrmguc. These results deal With 1. in
`blacktongue preventive potency of cc1*tai1rscler_-rml
`f0?[‘lstllffil, p}
`number, with special reference to the relation of cxlml'lmen '35 b "*5 ‘-
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`1387
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`June 8,1028
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`METHODS AND CRITERIA
`
`The general methods of caring for and feeding our experimental
`animals have already been described (2) (3). We may recall, how-
`ever, that the experimental diets were, as a rule, freshly prepared each
`day. The daily allowance of food was, in general, intended to he no
`more than enough for the maintenance of normal body weight. An
`exception was made in the case of young growing animals, to which
`more than this allowance was offered.
`It may be recalled, too, that
`it has been our practice to use our dogs repeatedly with or without
`intermediate periods of stock feeding as might he demanded by the
`purpose of the experiment.
`In stock feeding, a definite food mixture
`has been used, principally our diet No. 156,
`the composition and
`evidence of the adequacy of which have been given in a preceding
`communication (2).
`In testing for the .blacktongue preventive we have employed both
`the curative and the preventive procedure, singly or in combination.
`Since, as we have in a preceding communication (2), already indicated
`the clinical course of experimen tal blacktonguc, especially in the inva-
`sional stage, may normally be of an intermittent or relapsing char-
`acter, we attach no significance to a seemingly favorable therapeutic
`result in cases in which the treatment is begun early unless confirmed
`by the results of a preventive test. On the other hand, consistently
`unfavorable results of treatment under such favoring circumstances
`have hccn considered trustworthy indications of a poverty in or lack
`of the blacktonguc preventive, provided that the test dose has been a
`liberal one. Our experience with experimental blacktongue has led
`us to consider the rise in temperature which occurs in the advanced
`stage of the disease as a mark of gravity (2). Only very exceptionally
`does the attack normally remit after this temperature rise has taken
`place. We have, therefore, been disposed to consider clinical recovery
`from the attack (that is, disappearance of all manifestations of the
`disease with recovery of appetite) following treatment begun at. this
`advanced grave stage as significant, but have, nevertheless, always
`required confirmation by the preventive test before drawing final
`conclusions with respect
`to the presence of the preventive in the
`substance thus found to be active.
`Isolated cases of the apparent
`failure of treatment under these unfavorable circumstances have been
`considered as without significance.
`In testing the individual foodstuffs, one, or exceptionally both, of
`two types of test diet have been employed.
`In the first the com-
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`Elysium Health Exhibit 1015
`Page 4 of 38
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`June 8, 1928
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`1388
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`I
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`basic diet sh-ould be kept in mind in eValuating and comparing the
`indications of preventive potency, since the results yielded by the
`former may probably be considered as due Virtually entirely to the
`action of the foodstuff tested, whereas those of the latter must be
`considered as a summation effect due to the combined action of the
`basic components and of the test foodstuff.
`So far be our data permit, an appraisal has been made of the
`blacktongue preventive potency of each foodstiifl’.
`In View of the
`lack of a better practicable standard for such purpose, our appraisal
`is simply a judgment, in broad terms, of the preventive adequacy of
`such a quantity as, according to conventional practice, represents
`the daily alloii-‘aiice for an average adult human male.
`.
`The exnerimental disease in the dog and its d1agnos1s have been
`describediin a preceding report
`(2); we need recall only that the
`earliest distinctive buccal signs are a vivid red 1n]cct1.on of
`the
`mucosa of the floor of the mouth or a peculiar reddening of the
`mucosa of
`the upper lip in the form of bilaterally symmetrical
`patches, or of both. We have considered the first appearance of
`these mouth lesions as marking the beginning of the attack of black—
`tongue. We have conformed to this rule in all cases, even'in those
`relatively few instances in which the pellagralilke dermatitis of the
`scrotum appeared in advance of the mouth les10ns._ 'l‘hris marked,
`the beginning of the experimental disease, when this IS‘ induced by
`feeding our basic diet No. 123 (or certain of its modifications, namely
`diets No. 209, No. 195, and N0. 268), is only 'very exceptionally de—
`layed beyond about 60 days after the beginning of the feeding (d).
`We have therefore been inclined to cons1der
`very notable pio—
`longation of this period, particularly when manifested in more tirin
`one of a group of test animals, as Significant of the presence in tie
`test diet of the blacktongiie preventive
`an amount that is spine-
`what larger than that presumably contained in our standaid )flSlO
`diet.1 Since other factors, not yet understood, such, for mistigrce, as
`self-imposed starvation or semistarvation and other possll" ymc:
`existing deficiencies or maladjustments of dietary essentla b; may
`and Probably d0 influence the duration of what for conipipencyecrds);
`be designated as the deprivation period, We have trier
`0 0.
`due caution in the interpretation of such indications.
`
`ontaln,wejiidge,
`r
`r
`-
`-
`_
`n iii-iiifiiiriiiiiiieiiiidtiiifi iiiiiifiidxiiiiifliidd13.3333riftiégfiiiiiiiiii. orlm‘limflr mm
`‘
`.
`_ 1th wlilc'h
`'
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`Jones, 1928
`
`1389
`MAIZE
`The idea that the maize in the diet is in some way concerned in
`the causation of pellagra has, as is wall known, been entertained by
`students of that disease almost from the time of its first recognition.
`It seems to have arisen in part, at least, because maize constituted a
`very large part of the diet of the populations among whom, in the
`Old World, the disease was endemic.
`In the United States, maize
`also is a conspicuous element in the diet of the population in the
`area where the disease is most prevalent. Both in the Old and in
`the New World, therefore, maize is more or less prominently asso—
`ciated with the occurrence of pellagra. While the extreme position
`of certain zcists that there is no pellagra without maize is now no
`longer tenable, the association is no doubt very common. One is
`justified in concluding, therefore, that maize is very poor in or lacks
`the pellagra preventive
`In constructing our experimental diets, based as they are on diets
`foimd in association with the occurrence of pellagra, maize was from
`the first included as a. conspicuous element. The basic dict most
`frequently used by us for the experimental production of blacktonguc
`(diet No. 123, shown in Table 1) contains 400 grams of maize meal
`per 2,400 calorie ration. This is a large amount of cereal, consti-
`tuting as it does two—thirds of the weight of the dry ingredients of
`the diet. Notwithstanding this, however, as has in a preceding coni-
`munication (3) already been set forth, dogs fed this diet (including
`certain of its Inmlilieations) have developed blacktonguc within a
`period which only exceptionally exceeded a duration of about 60
`days. This would indicate that, as measured by the requirements
`of the. dog, maize contains little if any of the blacktongue preveitive.
`Incidentally, it may be noted that cornstarch would also appear to
`he very poor or lacking in the blacktonguc preventive since, as pre—
`viralsly reported (3), two dogs fed a. diet (No. 281) containing 366
`grams of cornstarch per Alton-calorie portion promptly developed the
`disease.
`The maize men] used in our basic diet No. 12-3 (including its modi-
`float-ions) does not, however, represent quite the whole kernel, since
`a small part of the bran is removed by sifting as if for human con-
`sumption.
`It seemed desirable, therefore, to test a meal from which
`nothing had been taken away. But as it did not seem to us probable
`that the difference in the meal represented by the small amount of
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`Elysium Health Exhibit 1015
`Page 5 of 38
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`1391
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`June 8, 1928
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`June 8, 1928
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`EXPERIMENT 1
`
`This was a test of the blacktongue preventive action of Whole white
`maize meal which was incorporated in test diets N0. 149 and N0.
`149A.
`(Table 2.) - These diets, which are identical except that the
`butterfat of one is quantitatively replaced by cod-liver oil in the other,
`are a slight modification of a maize diet studied by hchollum, Sim-
`monds, and Pitz (8), and by them considered complete for normal
`growth of the rat to normal adult size, and for that reason selected
`by us for this study. Each contains 450 grams of whole—maize meal
`in a. ration of slightly less than 2,400 calories. Suitable portions of
`one or the other of these diets were offered daily to each of seven test
`animals, dogs 29, 40, 52, 54, 57, 65, and 73. One of these dogs served
`during two separate periods, so that eight tests in all are to be con—
`sidered. The significant details relating to each of the test animals
`are presented in the following:
`
`Dog ‘29.~Male. Acquired May 9, 1923, between which date and January 11,
`1924, served in a number of experiments and suffered four attacks of blacktongue,
`the latest of which began January 7, 1924. On a miscellaneous stock diet from
`January 11 to February 5, 1924.
`February 5, 1924: In good condition; weighs 11.1 kilograms; begins test diet
`N0. 149.
`(Table 2.)
`On February 17, 1924, at the end of a period of 12 days, pres'cnted the first signs
`of an attack of blacktongue, an injection of the floor of the mouth. Further
`history not relevant.
`Dog- 40.~Male. VVhelped in the laboratory June 26, 1923, and reared on a
`stock diet. Up to February 20, 1924, served in a number of experiments and
`suffered two attacks of blacktongue, the later One of which began February 19,
`1924. On a stock diet for reconditioning from February 20 to March 11, 1924.
`March 11, 1924: In good condition; weighs 9.2 kilograms; begins diet No. 149.
`On April 23, 1924', at the end of a period of 43 days, presented the first signs of
`an attack of blacktongue, an injection of the floor of the mouth. W'cight was
`11 kilograms. Further history not relevant.
`Dog 53.—Bitch. Acquired September 25, 1923. Up to February 20, 1924,
`served in a number of experiments and suffered two attacks of blacktongue, the
`later one of which began February 18:, 1924. On a stock diet for reconditioning
`from February 20 to March 11, 1924.
`March: 11, 1924:
`In- good condition; weighs 9.7 kilograms; begins test diet No. 149.
`On July 31, 1924, at the end of a period of 1—42 days, presented the first signs of an
`attack of blacktongue, an injection of the floor of the mouth. Weighs 10
`kilograms. Further history not relevant.
`Dog 54.—Bitch. Acquired September 25, 1923.. Up to January 11,. I924:
`served in a number of experiments and suffered an attack of blacktongue which
`began November 28, 1923. On reconditioning diets from January 11 to March
`25, 1924.
`March 25, 1924: In good condition; Weighs 8.1 kilograms; begins test diet N0-
`149A.
`(Table 2.)
`_
`On June 5, 1924, at the end of a. period of 72 days, presented the first s1gns 01' an
`
`Dot? §?.—Maic. Acquired September 25, 1923. Up to January 15, 1924,
`served 1n a. number of experiments and sufl'ered two attacks of lilacktongue, the
`latter of which began December 13, 1923. From January 15 to February 5, 1924,
`on 21 miscellaneous stock diet for reconditioning.
`Fellérruer-y 5, 1924: In good condition; weighs 9.7 kilograms; begins test dict
`. o. 149.
`On February 23, 1924, at the end of a period of 18 days, presented the first signs of
`blacktonguo, an injection of the floor of the mouth, of the mucosa of the
`checks, and of the anterior {social pillars. Weighs 10 kilograms. Begins
`reconditioning diet.
`February 25, 1924: Redness of mucosa of the floor and checks is less pronout'lced.
`February 26, 1924: Redness has practically completely faded. Weighs 9.9
`kilograms.
`March 25, 1924: In good condition; weighs 10.1 kilograms; begins test diet N0.
`149A.
`
`On April 11, at the end of a period of 17 days, presented the beginning signs of an
`attack of blacktongue, an injection of the floor of the mouth. Further history
`not relevant.
`-
`
`Dog 65.—Bitch. Acquired January 28, 1924. Kept on a. miscellaneous stock
`diet to February 5, 1924.
`February 5, 1924: In good condition; weights 6.7 kilograms; begins test diet
`No. 149.
`
`April 22: Weighs 7.7 kilograms.
`011 April 27, 1924, at the end of a period of 77 days, presented the first signs of an
`attack of hiaoktongue, a reddening of the mucosa of the floor of the mouth.
`Further history not relevant.
`Dog 23.——Bitch. Acquired March 19, 1924. On stock diet up to April 1, 1924.
`April 1, 1924: In good condition; weighs 7.7 kilograms; begins test diet No. 149A.
`July 8, 1924: Weighs 10.2 kilograms.
`On July. 12, 1924, or 102 days after beginning the test, this animal presented an
`inject-ion of the mucosa of the floor of the mouth suggestive of a, beginning
`attack of blacktongue. Tn'o days later this was no longer perceptible, nor was
`there any reappearance of signs of blacktonguo during a. further period of
`observation of 38 days which ended August 19, 1924, on which date this
`experiment was discontinued.
`
`Results and conclusionsr—Six of the seven dog's developed black-
`tongue in from 12 to 142 days after beghining the test. The. seventh
`(dog 73) presented evanescent evidence very suggestive but not con-
`clusive of blacktongue at
`the end of a period of 102 days. The
`observation of this animal was discontinued at the end of- 140 days,
`so that the possibility is not excluded that a definite attack of black-
`tongue would have developed had the observation period been longer.
`One of the test animals (dog 57) served during two separate periods
`and developed an attack of blacktongue in each. Thus the six
`animals in which definite evidence of blacktongue developed experi-
`enced,
`in all, seven attacks.
`Six of these appeared at the end of
`periods of not over 77 days in duration, and the seventh (dog 52)
`at the end of a period of 142 days.
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`Elysium Health Exhibit 1015
`Page 6 of 38
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`tion period in the latter was but 140 days, suggest, by contrast with
`our evperieuce with basic diet No. 123 (including cert-am of its
`modifications (3)), that the test diets under consideration may have
`poeseeeed slight preventive properties. The difierence is not very
`notable and, such as it is, can not be attributed, altogether at least,
`to the character and increased quantity of the maize, Since one of
`the test diets (No. 149), unlike our standard basic dict (No. 123),
`contained some butter, which, as will precontly be seen, while apoor
`Source is. not, entirely devoid of the preventive factor, a fact. that. was
`not \fully appreciated when this experiment; was planned:
`This
`experiment is {immune not conclusive. Notwithstanding this, hour-
`ever, the evidence quite clearljF indicates that, at boot, this cereal 13
`e ventr poor source of the blackt-ongue preventive.
`Recalling the indications of its poverty in or lack of the pollagra
`preventive it would appcar that maize, if it contains any, is a poor
`source of the preventive for both blacktongue end pellagra.
`WHEAT
`
`The import-ant place among the cereals held by wheel; and a desire
`to compare it with maize led us to test its blacktongue preventive
`potency. The following experiment was accordingly carried out.
`
`
`EXPERIMENT 2
`
`
`
`For the present purpose, wheel; ground in this laboratory into a
`meal was, without oilting, incorporated in e diet, No. 128, the coin-
`poeition of which is she“'11 in Table 3. This, as may be seen by refer-
`once to Table 1, is essentially dictNo. 123, the maize meal of which
`has been quantitatively replaced by the ground wheat, of which there
`are, therefore, 400 grams in. each 2,400-ealorie- portion. Some of Blue
`diet was daily offered to ench of eight test animals—dogs 5, 9, 13, 1.4,
`29, 38, 44, and '47. The significant details relating to each are bl'ltll'ly'
`as follows:
`
`Dog 5.——Bitch. Acquired November 8, 1921._ Has served in a. number-pf
`experiments and has suffered two attache of blacktongue, the Inter one of which
`began August 28, 1923.
`011 stock diet from September 8, 192.1, to January 29,
`1924. Whelped a litter of seven pups November 25, 1923, so: ol‘ wlucll eur-
`vived and were weaned in good condition January 17', 1112-1.
`I
`(Table 3.).
`January 29, 1924: In good condition; begins diet No. 123.
`On August 2, 1924, at the end of a. period of 136 clays, presented the first signs
`of l'Jlncktonguc, a. reddening of the Emotion. of the cheeks.
`lo this there was
`added on August 3 a reddening of the mucosa. of the floor of thcmoutli and of
`that of the upper lip on the leftr side.
`rumm- liiut-orv_ is not relevant.
`I
`I
`Dog {Fr—Male. Acqllired April 1, 192.1. Has served m 9 number of caper-
`merits and has suffered four attacks of blacktong'ue of wluclt the latest began
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`1393
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`Juno 8,1928
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`On July 31, 1924, at the end of a period of 142
`days, presented the first signs of on
`attack of blacktongue, e reddench patch on the mucosa of the upper lip, in the
`region of the canines, on each side, and a slight reddening of the mucosa of the
`floor of thomouth. Further hietory in not relevant.
`Dear IS.——Melc. Acquired April 7, 1923. Up to November 28. 1923, served
`in several expel-fluorite and suffered three attacks of blacktonguo, of which the
`latest began November 2
`-
`4, 1923. On a reconditioning diet from November 28
`
`o pronounced the next day,
`out notable change for some
`:15 normal on February 25.
`142 days, preset: ted renewed
`the mucosa of the upper lip
`o canines coda slight reddening of the floor of the
`_
`mouth. Further hint-cry not relevant.
`Dog 14.—Mn[e. Acquired April 7, 1923. Up to November 23, 1923, served
`in several experiments and suffered four attacks of bleckionguc, of which the
`latest began October 30, 1923. On a reconditioning dict from November 28 to
`December 11, 1923.
`
`Ir‘urt-hcr ln'slrory not relevant.
`of the mouth,
`Dog 2.9.——Mnle. Acquired May 9, 19213.
`Up to November 27, 1923, served
`in several experiments and eulfercd three att
`acks of blacktongue, of which the
`laieat hogan October 18, 1923. On a recon
`ditioning dict from November 27
`To December 11, 1923.
`'
`December 11, 1923: In good condition; begins diet No. 128.
`011 January 7, 1924, at. the end of a period of 27 days, presented the first signs of
`an attack of blacklougue, a reddening of the women. of the floor of the mouth.
`Dag 38_—-\Iaio.
`li’helped in the laboratory Jone 26, 1923. Up to February
`20, 1924-, carved in several experiment-r. and suffered two attacks; of black-tongue,
`the second one of which began Feb'ruery 14, 1924. On a rt-leoudil'inuing dict from
`February 20 to March 11, 1924.
`March 11, 1924: In good condition; begins diet No. 128.
`Orr-June 24, 1924, at the end of a period of 105 cl
`ays, presented the first signs
`of on attack of blacktonguc, a reddening of the
`floor of the mouth. Further
`hintm‘y notrclevanls.
`Degas—Male. Whelped in the laboratory June 26, 1923.
`27, 1923, served in one experimeut'and suffered an atto '
`began October 23, 1923. On a reconditioning diet fr
`to January 29, 1924.
`January 29, 1924: In good condition,- begins diet No. 128.
`On August 13, 1924, 'at the end of a period of 197 days, presented the first signs
`of an attack of blacktonguc, roddcncd patches on the mucosa of the upper
`lip on each side.
`Furl-her history not relevant.
`Dog 4?.——Mn.lc. Acquired August 18, 1023. Up to Non-ember 28, 1923, served
`in an cum-intent cud suffered an attack of blacktongue, which began September
`
`
`
`'
`
`Elysium Health Exhibit 1015
`Page 7 of 38
`
`
`
`
`
`
`
`June 8, 1928
`
`On January 7, 1924, at the end of a period of 18 days, presented the first signs
`of an attack of blacktongue, a reddening of the floor of the mouth. Further
`history not relevant.
`
`Results and concl'u.s'£ons.——As is evident, all eight of the test animals
`developed blacktongue.
`It is noteworthy, however, that in but two
`of the dogs did the attack have its onset at the end of periods shorter
`than 71 days.
`In five of the eight animals the first signs of the attack
`made their appearance at the end of periods varying between 105 and
`197 days—that is, after periods very definitely longer than is the
`rule in the case of dogs fed diet No. 123. This delay in the develop-
`ment of the disease would appear to indicate that diet No. 128 had
`exercised appreciable but incomplete lgalacktongue preventive action
`and, therefore, that whole wheat con tains the hiaektongue preventive,
`but in small amount. Compared with the result of the experiment
`with whole maize, the outcome of the test of whole wheat suggests
`that this is probably a slightly better source of the blacktongue
`preventive than is the maize.
`WHEAT GERM
`
`While the preceding experiment with whole wheat was under way,
`tests were made of the blacktongue—producing potency of a number
`of diets in which were included varying amounts of commercial
`wheat germ as u source of “vitamin B.” The results of one of these
`tests which happened to be with a diet that included an unusually
`large quantity of the wheat germ, suggested rather strongly that this
`germ might possess definite blacktongue-preventive action. This
`led us to carry out the following experiment:
`
`EXPERIMENT 3
`
`the blacktongue—preventive action of ether—
`This was a test of
`extracted wheat germ. The wheat germ was a. commercial product
`from which we had extracted the fat by percolation with ether
`(U. S. P.) at air temperature.1
`It was incorporated in a diet, No.
`197,
`the composition of which is shown in Table 4. As may be
`seen, each 2,400 calorie port-ion contains 180 grams of the extracted
`ge‘rm.
`It may be noted, too, that it contains a considerable amount
`of cornstarch; notably less, however, as was noted in the preceding
`section in connection with maize, than has been found to be lacking
`in appreciable blacktongue-preventive action. This diet is some-
`what similar to our basic diet No. 123 (Table 1), from WhiCh it differs
`notably, however,
`in that the wheat germ and the starch of
`the
`former completely replace the corn meal and cowpeas of the latter.
`
`1395
`
`June 8,1928
`
`ammals, dogs 54, 61, 65, 1’0, 71, 78, 86, 87, and 88. The significant
`details relating to each are presented in the following:
`magi. Elli—Bitch- Acquired September 25, 1923. Up to June 17, 1924 served
`seem 1c: experiments and suflered two attacks of blacktonguc of which the
`.
`it
`egan Juno :1, 1924. On stock diet for reconditioning from June 17 to
`July 23 1924.
`'
`'
`‘
`'
`July 23: 1924' tool;:31: Sgpiggental diet, which included some wheat germ, from-
`3Ia§ 21:, 1925: In good condition; begins wheat-germ diet No. 197.
`(Table 3 )
`n on ember '11}, 1925, at the end of 136 days, this animal g'ircseotcil a slight hut
`suggestive reddening of the mucosa of the floor of the month, which lit-aw-
`Elflcki: I‘ll) longer perceptible 2-1 hours later. No further evidence suggesting
`antler] Mifgagpplrgtrgt
`(11:21:11; the remainder of the period of observation, which
`germ dict.
`,
`..
`..
`good condttum at the and of one year on the wheat-
`Dug. 61,.—l\-Ialc.
`thlped in the Ialmmtory November 4 1923
`Up to May
`27, 1924, served in one experiment and suffered one attack of blacki
`ngue, which
`_
`D
`hogan May 21, 1924-. On rccondi-tionic
`3 dict from May 27 to Joly 23, 192-1.
`From July 23, 192-1, to May 26: 1925
`, on an. experimental diet, which included a
`considerable amount of wheat germ.
`May 26, 1925: In good condition; begins wheat-germ diet No 1!]?
`113n-..1anl‘.1ar,\r 5, 1926, or at the end of a. period of 224 days, there were noted th -
`gist Eight:
`an attack oi: lilaektonguo, which ended in death on .l'armary-‘ZU 1926a
`0m :{il}e1:Lme!:tchr. 1 Acquired January 23,
`.1924. Up to Mny 27. 192-1, smiled oi
`dim t.
`- f
`an suffered an attack of lJl'acktougu'c. On stock diet for recon--
`.
`mug rem May -7 to July 23, 1924. On an experimental diet, which included
`wheat germ from July 23, 192-1, to May 2li, 15-125.
`May 26, 1925: In good condition,- begins wheat-«germ dict No 197.
`On February 3, 1928, at the end of 253 days,
`I
`I
`this sniuml presented a eh i
`l
`“FE-game reddening of the mucosa of the floor of the mouth and of thvgeliiciilit
`w. itch, however, had completely faded 24 hours later. N0 further evidence sl: ‘3
`:liingiflftsfgiligpiiggfd during the remainder of the periml of ohservotioigi-
`,
`-'
`4'33"
`“I.
`In
`"
`I
`l
`Wheat-germ dict.
`,
`good condition at the end of one year on the
`Dog 20,—Ma1c. Whel-ped in the laboratory Novernbcr 25, 1923'. Up to Mar
`14, 192-1, served in one experiment and
`suffered an attack of blacktongl to, which
`began. May 13, 1924.
`(in stock diet for rec
`ondiiioning from May 14 to Julv 23
`1024. On an experimental diet, which ion
`hided wheat germ, from July 23-, 1924;
`to May 26, 1925.
`d‘ -.
`- J
`.
`-
`gIIlB that- o
`Mav 2d, 1925' In good condition- be '
`It: N“. 197-
`On September 15, 1925, or at the'end of
`g ml
`t
`I
`a period of 112 days presented the fi' t
`signs of an attack of blacktonguo, reddcncd lesions on the mucosa of the updfir
`hp pp
`‘
`d
`U
`031“; “la cmlmfi, a.”
`an 1319851011 or the {1001 of
`mull-“1..
`1".“ the:
`
`Dog 71 .-—Ms_le. Whelped in the laboratory November 25, 1923. Hear-ed on
`miscellaneous stock dicta. On an or
`perimcnt-al diet, which included wheat germ,
`from July 23, 192-1, to May 26, 1925.
`I
`May 26 1925- I11 good condiiinn- begi
`9
`,
`.‘
`,
`.nswheat-ermd‘.tN-.
`May 26', 1.923: Completes one year- on the wheat-g
`m
`0 I 7-
`I
`'
`_
`germ diet in good condit'ott‘
`'
`presented no recognisable Britten-cc of blacktoo'gue during the year
`1
`‘ has
`
`
`
`
`Elysium Health Exhibit 1015
`Page 8 of 38
`
`
`
`June 3, 1923
`
`a
`1096
`
`
`
`1397
`
`June 8, 1928
`
`On August 11, 1925, at the end of a period of 77 days, presented the first signs of
`an attack of blacktongue, which ended in death during the night of August
`22—23, 1925.
`I
`Dog 86,—Bitch. Whelped in the laboratory October 12, 1924. On stock diet
`to April 28, 1925. From April 28 to May 26, 1925, 011 an experimental dict; whlch
`included wheat germ.
`.
`'
`I
`MaV 26, 1925:
`In good condition; begins wheat-germ diet No. 197..
`On ‘December 27, 1925, at the end of 215 days, presented a suggestive reddening
`of the mucosa. of the floor of the mouth which gradually faded during the 5:110-
`ceedinv 48 hours. Presented no other evidence of blacktongue at any tune
`I:
`'
`‘
`durinrr a further period of observation which ended May 26, 1926.
`In good
`‘0'
`v
`)
`. -
`.
`diet.
`condItlon at the close of the year 011 the wheat ge1m
`‘
`.
`Dog S7'.—l3itch. Whelped in the laboratory October 12, 1924.
`011 stock diet
`up to April 28, 1925. From April 28 to May 26, 1925, on an experimental (llcl;
`which included wheat germ.
`'
`T.
`197
`.
`,
`May 26, 1925: In good condition; begins wheat—germ diet.1\o.
`May 26, 1926: Completes one year on the wheat-germ diet.
`Is In good eond1-
`tion. Has presented no recognizab