`
` A
`
` Further Study of Experimental Blacktongue with Special Reference to the Blacktongue
`Preventive in Yeast
`Author(s): Joseph Goldberger, G. A. Wheeler, R. D. Lillie and L. M. Rogers
`Source: Public Health Reports (1896-1970), Vol. 43, No. 12 (Mar. 23, 1928), pp. 657-694
`Published by: Sage Publications, Inc.
`Stable URL: http://www.jstor.org/stable/4578755
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`Elysium Health Exhibit 1009
`Page 1 of 39
`
`

`

` PUBLIC HEALTH REPORTS
`
` VOL. 43 MARCH 23, 1928 NO. 12
`
` PREVALENCE OF SMALLPOX IN THE UNITED STATES
`
` The reports indicate that smallpox is more prevalent in the United
` States than it was at this time last year or in 1926. For the week
` ended March 10, 1928, 42 States reported 1,161 cases of smallpox.
` For the corresponding week of 1927 these States reported 876 cases,
` and in 1 926 they reported 864 cases- for the week.
` In 1925 the peak of the smallpox curve was reached about the
` middle of January; in 1926 the greatest number of cases was re-
` ported during the second week of February, and in 1927 the peak
` came after the middle of March. Some decrease in the incidence of
` smallpox is to be expected, but health officers should be constantly
` on the alert.
`
` A FURTHER STUDY OF EXPERIMENTAL BLACKTONGUE
` WITH SPECIAL REFERENCE TO THE BLACKTONGUE
` PREVENTIVE IN YEAST
`
` By JOSEPH GOLDBERGER aInd G. A. WXHEELER, Surgeons, and R. D. LILLIE and
` L. M. ROGERS, Passed Assistan.t Surgeons, United States Public Health Service
`
` CONTENTS
`
` Page Pago
` Introduction- 657 The blacktongue preventive:
` MIethods -65$ Dried brewers' yeast- 667
` Blacktongue-producing loteocy of a basic Yeast extract powder- 672
` experimental dlet and of three of its mnodifl- Seidell's activated solid -674
` cations: Yeast charcoal- 677
` Basic diet No. 123-6- ,9 P-P activaated fuller's earth -681
` Basic diet No. 209 -661 Seven and a half hour autoclaved yeast- 683
` Basic diet No. 195- 663 Identity of the blackiLonigue preventive- 684
` Basic diet No. 8 -66-I Sumnmnary and conclusions -688
` References -6S9
` Tables -690
`
` In a previous communicationi, Goldherger and Wheeler (1) pre-
` sented some oL the results of a study of the problem of an experimental
` animal for pellagra. They reported the production in the dog,
` by feeding pellagra-prodtucing diets, of a condition considered by
` them to be identical with a spontanieously occurring caniine disease
` known as blacktongue or Stuttgart dog epizootic. The similarity
` 875-33'-28--1 (657)
`
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`
`Elysium Health Exhibit 1009
`Page 2 of 39
`
`

`

` Mar el2 23, 1928 658
`
` of this experimental disease to humian pellagra was pornted out, and
` was considered so striking as to be well-nigh conclulsive of the identity
` of the two conditions. This view was supported, they believed, by
` the suggestion of a common etiology iindicated by the successful
` production of the condition (blacktongue) in the dog by feeding
` with pellagra-producing diets. In the present paper we desire to
` report sonie further results of the same study.
`
` METHODS
`
` Our methods of housing, caring for, and feeding the experimenital
` animals have been described in a precedinag commnaunication (1). It
` may be noted that the experimnental ration was offered each animal
` onace a day and, as a rule, freshly prepared. The amouLnlt offered
` -as, in general, all t-hat the dog wouild eat. At first, to insure this,
` tie attempt was made to ofIer an excess; but in order to minimize
` waste this practice was, after a time, nmodified so that, except for a
` vou.ng growing animal, o:nly enough food for the maintenance of
` normual body wxeight was offered. The animals were weighed once
` a week. It may be here recalled, too, that it has been our practice
` to use otur dogs repeatedly. Depending o.n the purp-ose of the exper-
` melnt, the animal was or was not reconditio.ned by a period of stock
` diet feeding between successive e-xnerimnenits, for which purpose our
` stock diet No. 156 (1) was the ore most frequently used. In what
` follows, details of thlis nature wi'll be neoted in coninectioni wvvith the
` presentatiu3on of the pertinentC parts of t'hle history of each experimental
` aniimal. The diagnostic criteria of ex-perimental blacktongue have
` been presented in a preceding article (1). Here we will say only
` that the earliest distinctive buccal lesions are a vivid -ed injectwioni
` of the floor of the mnouth or an erythema of the mutcosa of the upper
` lip in the form. of bilaterally symmetrical patches or both.
`
` BLACKTONGUE-PRODUTCING POTENCY OF A BASIC EXPERIMENTAL
` DIET AND OF CERTAIN OF ITS MODIFICATIONS
`
` Th1ze composition of the diet with which Goldberger and Wheeler
` (1) first successfully induced experimental b1hcktongrue Is shown in?
` T'able 1. This diet was constructed as a som3ewha- c-im-phified replica
` of the type of di-et found' associated witfh, aind, ii-flJcss suita-bly SUp-
` plemnented, beli-eved to be responsible for, the occuirence of pellagra.
` After a numnber of modifications of the diet shown in Table 1 had
` been tested, the diet No. 123, shown i-n T'able 92, .as constructed and
` subsenuently used as the basic blacktosngute-prodluciing odiet in many
` of our experimencts. It seemis desirable, therefwore, to suiimmarize otir
` experience with this (together with certain of its nmodifications) as a
` blacktongue-producing diet. This is done in experimients 1, 2, 3,
` and 4.
`
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`
`Elysium Health Exhibit 1009
`Page 3 of 39
`
`

`

` 659 March 23,1928
`
` Basic Diet No. 123
`
` EXPERIMENT 1
`
` The blacktongue-producing potency of diet No. 123 (Table 2)
` has been tested in a considerable numuber of animals and under
` various conditions. We shall consider here only those tests, however,
` that were carried out either in aniimals after a period of reconditioninig
` following a previous experiment and thus presumably in normal
` condition, or in such as were not previously subjected to experiment
` and were not known to have ever suffered from blacktongue. Such
` tests were performed in a total of 14 dogs, the significanlt details
` relating to each of which are as follows:
` Dog 13.-Male. Acquired April 7, 1923, between which date and Noveimiber
` 18, 1926, served in several experiments and suffered seven attacks of experimllental
` blacktongue, the latest of which began July 31, 1925. Was on stock diet No.
` 156 for reconditioning from November 18 to December 8, 1926.
` December 8, 1926: In good conditioni; weight, 10.1 kilograms; begins test diet
` No. 123.
` On January 25, 1927, at the end of a period of 48 days, noted the first signis of
` blacktongue,l an injection of the floor of the inouth. Weight 9.4 kilogramxs.
` Confirmatory evidence of blacktongue inoted on February 10, 1927. Course of
` the attack.was remittent or relapsing in character, accompanied by self-im-iposed
` partial starvation. Killed with illuminatiing gas April 28, 1927.
` Dog. 14.-Male. Acquired April 7, 1923. Between that date and Septemiiber
` 25, 1923, served in two experiments and suffered a relapsing attack of blacktongue
` beginning May 18, 1923. On stock diet No. 34C, for reconditioning, from Sep-
` tember 25 to October 16, 1923.
` October 16, 1923: In good condition; weight, 9.3 kilograms; begins test diet
` No. 123.
` On October 30, 1923, at the end of a period of 14 davs noted the first signs of
` blacktongtue, an injection of the floor of the mouth and a patch of redness on
` the mucosa of the upper lip opposite the base of the canine tooth on each side.
` Weight, 9.2 kilograms. Further history not relevanit.
` Dog 15.-Male. Acquired April 14, 1923. Between- that date and September
` 2'5, 1923, served in two experiments and suffered a relapsing attack of blacktonigue
` beginning August 7, 1923. OIn stock diet No. 34C, for reconditioilinlg, from
` September 25 to October 16, 1923.
` October 16, 1923: In good conditioni; weight, 9.4 kilograms; begins test diet
` No. 123.
` On October 27, 1923, at the end of a period of 11 days, noted the first signs of
` blacktongue, an injection of the floor of the mouth and slight reddening of the
` mucosa of the upper lip. Weight, 9.3 kilograms. F'urther history not relevant.
` Dog 50.-Male. Acquired September 25, 1923. On stock diet No. 34C to
` October 16, 1923.
` October 16, 1923: In good condition; veight, 9 kilograms; begins test diet
` No. 123.
` On October 27, 1923, at the end of a period of 11 days, noted the first sigIns of
` blacktongue, a definite reddeniing of the floor of the mnouith. Weight, 8.8
` kilograms. Further history niot relevant.
`
` I The experimental disease has been desceribed in a preceding report (1).
`
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`
`Elysium Health Exhibit 1009
`Page 4 of 39
`
`

`

` Marchl 23, 1928 660
`
` Dog 51.-Bitch. Acquired September 25, 1923. On stock diet No. 34C to
` October 18, 1923.
` October 1S, 1923: In good condition; weight, 7.3 kilograms; begins test diet No.
` 123.
` On October 30, 1923, at eind of a period of 12 days, noted first signs of blacktongtue,
` an injection of the floor of the motuth. Weight, 71.8 kilograms. Further history-
` not relevant.
` Dog 52.-Bitch. Acquired Septemiber 25, 1923. On a miscellaneous stock diet
` to October 22, 1923.
` October 22, 1923: Ia good condition; weight, 8.5 kilograms; begins test diet No.
` 123.
` On November 27, 1923, at the end of a period of 36 days, noted the first signs of
` blacktongue, an injection of the floor of the mouth. Weight, 8.5 kilograms.
` Further history inot relevant.
` Dog 53.-Bitch. Acquired Septem ber 25. 1923. On a miscellaneous stoclkc diet
` to October 22, 1923.
` October 22, 1923: In good condition; weight, 5.7 kilogranms; begins test diet No.
` 123.
` November 20, 1923: Weight, 5.8 kilograms.
` Oin November 27, 1923, at the end of a period of 36 days, noted the first signs of
` blacktoingue, an injection of the floor of the mouth and of the mnucosa of the
` cheeks. Further history notu relevant.
` Dog 5.4.-Bitch. Acquired Septenmber 25, 1023. On a miscellaneous stock diet
` to October 22, 1923.
` October 22, 1923: In good condition; weight, 6.2 kilograms; begins test diet No.
` 123.
` On November 28, 1923, at enad of a period of 37 days, noted the first signs of black-
` tongue, anI injection of the Floor of the motuth. WVeight, 6.7 kilogramas. Further
` hiistory not relevant.
` Dog 57.-Male. Acquired September 25, 1923. On stock Cdiet No. 34C to
` October 16, 1923.
` October 16, 1923: In good condition; weight, 7.7 kilograms; begins test diet, No.
` 123.
` On November 2, 1923, at the end of a period of 17 days, noted the first signs of
` blacktonguie, an injection of the floor of' the mouth. Weight, 8.8 kilograims.
` Further history not relevant.
` Dog 5S.-Bitch. Acquired September 27, 1923. On stock diet No. 34C to
` October 16, 1923.
` October 16, 1923: In good condition; weight, 13. 5 kilograms; begins test diet No.
` 123.
` On November 1, 1923, at the end of a period of 16 days, noted the first signs of
` blacktongue, an injection of the floor of the m-outh. Weight, 14.3 kilograms.
` Further history not relevan.
` Dog 79.-Bitch. Acquired June 9, 1924. OIn stock diet No. 156 to December
` 16, 1924, during which period was bred and whelped a litter of five puips wvhich
` were successfully w-eeaned.
` December 16, 1924: In good condition; weight, 5.3 kilograms; begins test diet No.
` 123.
` January 27, 1925: Weight, 5.5 kilograms.
` On February 7, 1925, at the end of a period of 53 days, noted the first signs of
` blacktonguie, a reddeninig o(f the floor of the moouth. Weight, 5.4 kilograms.
` Fu-rthner history niot relevanit.
` Dog 81.-Male. Acqtuired October 13, 1924. Oni stock diet No. 156 to Novem-
` ber 21, 1924.
`
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`Elysium Health Exhibit 1009
`Page 5 of 39
`
`

`

` 661 Marel 23, 1928
`
` November 21, 1924: In good coindition; begins test diet No. 123.
` November 25, 1924: Weight, 9.4 kilograms.
` OIn December 27, 1924, at the end of a period of 36 days, noted the first signs of
` blacktongue, a reddening of the floor of the mouth and of the mucosa of the
` cheeks. Weight, 10.4 kilograms. Further history not relevant.
` Dog 82.-Bitch. Acquired October 13, 1924. On stock diet No. 156 to
` November 21, 1924.
` November 21, 1924: In good condition; weight 10.7 kilograms; begins test diet
` No. 123.
` On December 23, 1924, at the end of a period of 32 days, noted the first signs of
` blacktongue, reddened bands on mucosa of the upper lip on each side; reddening
` of mucosa of the cheeks, reddening of the floor of the mouth. Weight 11.5
` kilograms.
` Treated an-d used in a study of tomato juice from January 3, 1925, to November
` 18, 1926, during which period she had an attack of blacktongue beginning March
` 8, 1925.
` On stock diet No. 156 for reconditioning from November 18, 1926, to December
` 8, 1926. On December 7, 1926, weighed 14.8 kilograms.
` December 8, 1926: In good condition; begins a second period of test diet No. 123.
` December 14, 1926: WVeight, 13.9 kilograms.
` January 18, 1927: Weight, 13.9 kilograms.
` On January 22, 1927, at the end of a period of 45 days, noted the first signs of
` blacktongue, reddened patches on mucosa of the upper lip in region of canine
` teeth of each side; reddening of muicosa of the cheek, and reddening of the
` floor of the mouth. A rapidly progressive attack, untreated, terminating in
` death Janiuary 29-30, 1927.
` Dog 109.-Bitch. Acquired October 29, 1926. On stock diet No. 156 to
` December 8, 1926.
` December 8, 1926: In good condition; weight, 7.1 kilograms; begins diet No. 123.
` December 28, 1926: Weight, 7.9 kilograms.
` On December 30, 1926, at the end of a period of 22 days, noted the first signs of
` blacktongue, an injection of the floor of the mouth-. The attack took a slowly
` progressive, remittenit or relapsing course accoinpanied by self-imposed partial
` starvation; untreated, terminated in death April 20, 1927. Weight on day
` preceding death, 3.3 kilogramzs.
` Thus all 14 of the test arnimals developed blacktongue, the first
` distinctive signs of which appeared within not to exceed 53 days after
` beginning the test diet. Allowed t-o take its course without therapeutic
` interference in two of the dogs, it ended in the deatlh of both aninmals.
` One of the aniimals (dog 82) was subjected to the test during two
` widely separated periods and responded with blacktongue beginning
` at the end of 32 days in the first and at the end of 45 days in the
` seconid period.
`
` Basic Diet No. 209
`
` In diet No. 123 (Table 2) the principal component, quantitatively,
` is white corn meal, which forms 66 per cent of the weight of the dry
` ingredients of the ration. Since yellow' corn has slightly dilfferent
` dietary properties from the white (richer in vitamim A (2)), it seem ed
` desirable to determine what effect, if aniy, the substitution in diet
`
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`
`Elysium Health Exhibit 1009
`Page 6 of 39
`
`

`

` }arch 23, 1M28 662
`
` No. 123 of yellow corn meal for the white would have on the black-
` tongue-producing potency of that diet. Accordingly the following
` test was made:
`
` EXPERIMENT 2
`
` Six dog,s, numbered 44, 52, 60, 63, 64, and 73, were each offered a
` suitable daily portion of diet No. 209, the composition of which is
` shown in Table 3. By comparison with Table 2 it may be seen
` that this differs from diet No. 123 only in that yellow corn meal is
` used instead of white. The si0nlificant facts in relation to each of
` the test animials are briefly as follows:
` Dog 44. -Male. Wheiped in the laboratory June 26, 1923. Up to July 17,
` 1925, served in a inumber of feeding experimients anid suffered two attacks of
` blacktongue, the latest of which began December 27, 1924. On stock diet
` No. 156 for reconditioning from July 17, 1925, to August 11, 1925.
` August 11, 1925: In good condition; weight, 12.9 kilograms; begins test diet
` No. 209.
` On Sepltemiber 1, 1925, at the end of a period of 21 days, noted the first signs
` of blacktongue, a reddening of the mucosa of the upper lip and an injection
` of the floor of the mouth. Weight, 13.3 kilograms. Further history not
` relevant.
` Dog 52.-Bitch. Acquired September 25, l123. Between that date and
` July 17, 1925, served in several experiment-s and had four attacks of blaektongaue,
` the la.test of which began March 24, 1925. O(n Xstock diet No. 156 for recondition-
` ing from July 17, 1925, to August 11, 1925.
` August 11, 1926: In good conditioni; weight, 10.8 kilograns; begins test diet
` No. 209.
` On October 6, 1926, at the end of a period of 56 days, noted the first signs of
` blacktoingue, an injection of the floor of the mouth. Weight, 9.8 kilograms.
` Further history nor relevant.
` DoEg 60.-Male. Whelped in the laboratory November 4, 1923. Up to July
` 17, 1925, served in a feeding experiment and suffeled an attack of blacktongue,
` whiclh began July 14, 1925. On stock diet.- No. 156 for reconiditioning from
` July 17, 1925, to August 11, 1925.
` August 11, 1925: In good condition; weight, 7.2 kilograms; begins test diet
` No. 209.
` On September 13, 1925, at the end of a period of 33 days, noted the first signs
` of blactellongue, an injection of the floor of the mnouth and a flushing of the
` mnucosa of the cheeks. Weight on September 15, 1925, 7.4 kilograMs. Further
` hiistory not relevant.
` Dog 63.-Male. Whelped in the laboratory Novemlber 4, 1923. Up to
` July 17, 1925, served in two experiments and suffered two attacks of blacktongue,
` the later one of which began March 5, 1925. Orn stock diet No. 156 for recoin-
` ditioning from July 17, 1925, to August 11, 192a.
` August 11, 1925: In good condition; weight, 7.1 kilograms; begins test diet
` No. 209.
` On August 29, 1925, at the end of a period of 18 days, noted the first signs of
` blacktoingue, a reddening of the fioor of the mouth. Weiglht, 7.5 kilograms
` Further history not relevarnt.
` Dog 64.-Bitchh. Whelped in the laboratory November 4, 1923. Up to
` July 17, 1925, had suffered o-ne uncertain, but probable, attack of blacktongue
`
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`
`Elysium Health Exhibit 1009
`Page 7 of 39
`
`

`

` 663 March 23, 1928
`
` which was in evidence June 27, 1925. On stock diet No. 156 for reconditionilng
` from July 17 to August 11, 1925.
` August 11, 1925: In good condition; weight, 6.6 kilograms; begins test diet
` No. 209.
` On September 12, 1925, at the end of a period of 32 days, noted first signs of
` blacktongue, a reddening of the faucial pillars, the pharynx, and the floor
` of mouth. Weight, 6.7 kilograms. Further history not relevant.
` Dog 73.-Bitch. Acquired March 19, 1924. Up to July 17, 1925, suffered
` two uncertain, evanescent attacks of blacktongue, the second of which was in
` evidence July 12, 1925. On stock diet No. 156 for reconditioning from July 17
` to August 11, 1925.
` August 11, 1925: In good condition; weight, 10.7 kilograms; beginis test diet
` No. 209.
` On December 17, 1925, at the end of a period of 128 days, noted the first signs
` of blacktongue, a reddening of the miucosa of the upper lip and of that of the
` cheeks. Weight, 8.3 kilograms. Further history not relevant.
`
` All six dogs developed blacktongue, the first distinctive signs of
` which appeared within not to exceed 56 days after beginning the
` test diet in five, and at the end of a period of 128 days in one of themn.
` It would appear, then, that the substitution of yellow for white
` corn meal made no significant difference in the blacktongue-produc-
` ing potency of the test diet.
`
` Basic Diet No. 195
`
` In diet No. 123 and its modification, diet No. 209, sodium chloride
` anid calcium carbonate are used to supplement the inorganic, " ash, "
` constituents furnished by the other components of the ration. It
` was thought desirable to determine what effect, if any, on the black-
` tongue-producirng potency of diet No. 123 would be produced by the
` substitution of a "complete" salt mixture for the sodium chloride
` and the caleiuLm carbonate. For that purpose experiment 3 was
` carried out.
`
` LEXPERIMENT 3
`
` Five dogs, numbered 9, 29, 83, 84, and 85, were each offered a sulit-
` able daily portion of diet No. 195, the composition of which is shown
` in Table 4. As may be seen by reference to Table 2, this differs from
` diet No. 123 only in that the well known "complete" salt mixture
` of Osborne and Mendel (3) replaces the sodium chloride and calcium
` carbonate of the latter diet. The significant facts in relation to each
` of the test animals were, in brief, as follows:
`
` Dog 9.-Male. Acquired April 1, 1923, between which date andc February 28,
` 1925, served in a number of experiments anid suffered seven attacks of black-
` tonigue, the latest of which began February 24, 1925. On stock diet No. 156
` for reconditioninig from February 28 to April 1, 1925.
` April 1, 1925: In good condition; weight, 12.7 kilograms; begins test diet No. 195.
`
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`
`Elysium Health Exhibit 1009
`Page 8 of 39
`
`

`

` March 23, 1928 664
`
` On MTa y 31, 1925, at the end of a period of 60 days, noted the first signs of black-
` tongle, a reddening of the mucosa of tlle uappr lip in tlhe region of the canine
` teeth of each side, and an injection of the floor o' the mouth. Weight, 11.4
` kilogramns. Further history not relevanlt.
` Dog 29 -Male. Acquired May 9, 1923, betweeni which date and February 28,
` 1925, served in a niumber of exp)eriments and suffered nine attacks of blaektongLue,
` the latest of which begaln February 6, 1925. On stock diet No. 156 for recondition-
` ing from February 28, 1925, to April 1, 1925.
` April 1, 1925: In good condition; weight, 11.7 kilograms; begins diet No. 195.
` On April 17, 1925, at end of a period of 16 days, noted the first signs of black-
` tongue, a reddening of the mucosa of the upper lip and of the floor of the moouth.
` Weight, 11.1 kilograms. Further history not relevant.
` Dog 83.-Bitch. Acquired Februiary 20, 1925, fron1 whiich date to April 1,
` 1925, was on stock diet No. 155.
` April 1, 1925: In good condition; weight, 6.8 kilograms; begins test diet No. 195.
` On April 18, 1925, aVt the end of a period of 17 days, noted the first signs of black-
` tongue, a reddeninig of the floor of the mouth. Weight, 7.3 kilograms. Further
` history nor relevant.
` Dog 84t.-fiale. Acquired March 2, 1925, from which date to April 1, 1925,
` was on stock diet No. 156.
` April 1, 1925: In good condition; weight, 7.8 kilograms; begins test diet No. 195.
` On April 23, at the end of a period of 22 days, noted the firL signs of blacktongue,
` reddened patchles on mucosa of the uipper lip opposite the caninie teeth of
` each side. Weight, 9.1 kilograms. Further history not relevant.
` Dog 85.-Male. Acquired March 2, 1925, from which date to April 1, 1925,
` was on stock diet No. 156.
` April 1, 1925: In good condition; weight, 6.9 kilograms; begins test diet No. 195.
` On April 16, 1925, at the enid of a period of 15 days, noted the first signs of black-
` tongule, reddening of mnucosa of the upper lip, of that of the cheeks, and of
` the floor of the mouth. Weight, 6.8 kilograms. Further history not relevant.
` All five test animals developed blacktongue, the first distinctive
` signs of which appeared withiin not to exceed 60 days after beginning
` the test diet.
` The substitution of the "complete" salt mixtUure for the sodiun
` chloride and calcium carbonate of diet No. 123 made, thus, no sig-
` ni ieaiit differeinee in its blacktongue-produeing poteney.
`
` Basic Diet No. 268
`
` Although diet No. 123 (and its modifications, No. 209 and No.
` 195) contains a considerable amount of pro-tein, fully one-hal-L of
` which is from casein, it was thought, ineeivtheless, that the biological
` quality of the proteini mixture ff might, perhaps, be improved by increas-
` ing t,he casein comaponent, a lIew that was stre:ngthened by the results
` of some orrowth test!fs in rats (unpublished). It seemed desirable,
` therefore, to determine, what effect, if any, an increase in the casein
` component of diet No. 123, and thus, presumably, an improvemrent
` in the biologia_ l quality of its protein, would have on its blacktongue-
` producilig poteniey. Experiment 4 was accordingbly carried out.
`
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`
`Elysium Health Exhibit 1009
`Page 9 of 39
`
`

`

` 665 M'arch 23, 1928
`
` EXPEiRIMENT 4
`
` Eight dogs, numbered 62, 69, and 101 to 106, inrclusive, were each.
` offered a suitable daily portion of diet No. 268, the conmposition of
` which is shown in Table 5. As may be seen, this diet differs from
` No. 123 (Table 2) in containing 50 per cent more casein; it differs
` from No. 123 also in that it contains a "complete" salt mixture in
` the place of sodium chloride and calcium carbonate. This experiment
` may be con-isidered, therefore, as a test of the efTect not only of a
` substantial increase in protein, but also of the use, at the samne timeB,
` of a complete salt mixture on the blacktongue-producing potency of
` that diet.
` In this connection, it may be stated that this expeliment was
` planned to serve one other purpose-namely, to secure tissues suit-
` able for histopathological study. Believing that diet N\o. 268 was
` more nearly complete-at least for maintenance-than No. 123 or
` its other modiffications with respect to all known dietary essentials
` except the specific factor or factors related to blacktongue,2 it was
` thought that animals fed with it when killed at suitable intervals
` would furnish tissues which might show a sequence of histopathio-
` logical changes which would thus be relatable to the specific dietary
` defect.
` The significant facts in relation to each of the test animals, except
` as concerns the histopathology, which will form the subject of a
` separate report by Dr. James Denton, are briefly as follows:
`
` Dog 62.-Male. Whelped in the laboratory November 4, 1923. Up to May 26,
` 1926, had one evanesc6nt attack of blacktongue which was in evidence March
` 24-27, 1925. On stock diet No. 156 May 26 to June 12, 1926.
` June 12, 1926: In good conditioni; weight, 8.8 kilograms; begilns test diet No. 268.
` On June 26, 1926, at the end of a period of 14 days, killed with illuminating gas
` for histopathological study. le prescited no signs of blacktonguie. Weight,
` 8.6 kilograms.
` Dog 69.-Male. Whelped in the laboratory November 25, 1923. Up to May
` 26, 1926, served in two experiments, but showed no evidence of blacktongue.
` On stock diet No. 156 from May 26 to June 12, 1926.
` June 12, 1926: Inl good condition; weight, 8.8 kilograms; begins test diet No. 268.
` July 27, 1926: Weight, 8.7 kilograms.
` July 28, 1926, at the enid of a period of 46 days, noted first signs of blacktongue,
` a slight injectioni of the floor of the moouth which became more definite on
` August 6, and on the following day (August 7) there was nioted il addition a
` slight reddening of the mucosa of the cheeks and of the upper lip in the region
` of the canines.
` Animiial killed with illuminating gas for histopathological study on August 7,
` 1926.
` Dog 101.-Male. Whelped in the laboratory Decemiiber 9, 1925, and reared
` on stock diet No. 156.
`
` 2 The dog does not seem to require the antiscorbutic. It is probable that workers who have reported
` scorbutic signs in dogs were dealing with some other condition, at timaes, at least, with blacktongue.
`
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`
`Elysium Health Exhibit 1009
`Page 10 of 39
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`

` March 23, 1928 666
`
` June 12,1926: In good condition; weight, 7.7 kilograms; begins test diet No. 268.
` On July 10, 1926, at the end of a period of 28 days, noted first signs of black-
` tongue, an injection of the floor of the mouth. Weight, 7.9 kilograms. Attack
` slowly progressed. Animal killed with illuminating gas for histopathological
` study on August 7, 1926.
` Dog 102.-Male. Whelped in the laboratory December 9, 1925. Reared on
` stock diet No. 156.
` June 12, 1926: In good condition; begins test diet No. 268.
` June 15: Weight, 6.10 kilograms.
` July 6, 1926: Weight, 6.7 kilograms.
` On July 10, 1926, at the end of a period of 28 days, noted first signs of black-
` tongue, an injection of the floor of the mouth. Attack progressed rapidly.
` Aninlal killed with illuminating gas for histopathological study on July 20, 1926.
` Dog 103.-Male. Whelped in the laboratory December 9, 1925. Reared on
` stock diet No. 156.
` June 12, 1926: In good condition; begins test diet No. 268,
` June 15: Weight, 6.7 kilograms.
` July 6, 1926: Weight, 6.4 kilograms.
` On July 10, 1926, at the end of a period of 28 days, noted first signs of black-
` tongue, an injection of the floor of the mouth. Attack was progressive with
` remissions. Animal killed for histopathological study August 7, 1926.
` Dog 104.-Bitch. Whelped in the laboratory December 9, 1925. Reared on
` stock diet No. 156.
` Junie 12, 1926: In good condition; begins test diet No. 268.
` June 15: Weight, 5.7 kilograms.
` On July 6, 1926, at the end of a period of 24 days, noted first signs of black-
` tongue, a reddening of the floor of the mouth, of the faucial pillars, and of the
` mucosa of the upper lip. Weight, 5.6 kilograms. Ainimal killed for histopatho-
` logical study July 10, 1926.
` Dog. 105.-Bitch. Whelped in the laboratory December 9, 1925. Reared
` on stock diet No. 156.
` June 12, 1926: In good condition; begins test diet No. 268.
` Jun-e 15: Weight, 4.9 kilograms.
` On July 15, 1926, at the enld of a period of 33 days, noted first signs of black-
` tongue, an injection of the floor of the mouth. Weight, 5.2 kilograms. Attack
` mild, relapsing. Animal killed August 7, 1926, for histopathological study.
` Dog 106.-Bitch. Whelped in the laboratory Deceinber 9, 1925. Reared on
` stock diet No. 156.
` June 12, 1926: In good conditioni; begins test diet No. 268.
` June 15: Weight, 4.3 kilograms.
` On June 26, 1926, at the end of a period of 14 days, killed for histopathological
` study. Had presented no signs of blacktongue. Weight, 4.5 kilograms.
`
` Of the eight test animal?, two were killed at the end of a test period
` of 14 days for the purpose of histopathological study. Neithler ani-
` mal had show.n any evidence of blacktongue. The period of obser-
` vation was so brief that these two animals can niot properly be con-
` sidered in appraising the blacktongue-producinig potency of the diet.
` The remaining six animals all developed blacktongue, the first dis-
` tiictive sigins of which appeared within a period of niot to exceed 46
` days.
` It would appear, theni, that the modification of diet No. 123 rep-
` resented by a substantial increase in the protein combined with the
`
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`
`Elysium Health Exhibit 1009
`Page 11 of 39
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`

` 667 M?arch 23, 1928
`
` use of "complete" salt mixture was without significant effect on the
` blacktongue-producing potency of that diet as judged bv the attack
` rate and duration of the feeding period before the appearance of the
` first distinctive signs of the disease.
` In the foregoing series of tests of the pellagra-producing potency
` of diet No. 123 and its modifications, a total of 33 dogs were used as
` test animals, and blacktonigue was induced in all but two of them.
` The two that escaped were the two that were killed at the end of a
` feeding period of 14 days for the purpose of histopathological study.
` Disregardi.rg these as not having had a full opportunity for the