`
`TREASURY DEPARTMENT
`
`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
`
`PUBLIC HEALTH
`REPORTS
`
`Page 1 of 22
`
`
`
`
`
`VOLUME 48— PART 1
`NUMBERS1-26
`
`JANUARY-JUNE, 1928
`
`
`
`|
`
`UNITED STATES
`
`GOVERNMENT PRINTING OFFICE
`WASHINGTON
`1928
`
`Elysium Health Exhibit 1013
`Page 1 of 22
`
`

`

` ADDITIONAL COPIES
`
`OF THIS PUBLICATION MAY BE PROGURED FROM
`THE SUPERINTENDENT OF DOCUMENTS
`U.8.GOVERNMENT PRINTING OFFICE
`WASHINGTON, D, C.
`AT
`4 CENTS PER COPY
`
`cypri
`
`WATT YS MmVyi[Ssion
`
`Ww.
`Wi
`Py
`
`14
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`Elysium Health Exhibit 1013
`Page 2 of 22
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`
`PUBLIC HEALTH REPORTS
`
`VOL. 43
`MARCH 23, 1928
`NO. 12
`
`PREVALENCE OF SMALLPOX IN THE UNITED st!rEs
`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 1926 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 GoLvBERaeEn and G. A. WHEELER, Surgeons, and R. D, Liviand
`L. M. Roamnrs, Passed Assistant Surgeons, United States Public Health Service
`
`
`CONTENTS
`
`
`
`
`
`Pago
`Page
`Introduction... 4ule il asl Te 657|The blacktongue preventive:
`
`Mctltods: Was 22 _ 0 Sie i ie8) 658
`Dried brewers’ yeast_._.-.__.-......___-
`667
`Blacktongue-producing potency of a basic
`Yeast extrach powders. asses! som a 672
`experimental diet andof three of its modifi-
`Seidell’s activated solid_._...---________.
`674
`cations:
`Yeast charcoal__._---.---__-2.2--2---_-.-
`677
`Basie diet No, 123_--___---_2.222--2
`P-Pactivated fuller’s earth.______._____
`681
`659
`Seven and a half hour autoclaved yeast..
`683
`661
`
`
`Basic diet No, 195_____ 663|Identity of the blacktongue preventive. __.__ 684
`
`
`Basic diet No, 268_...-.--.-.--__---____. 664|Summary and conelusious.____-.________..__ 688
`References(et pee pees eseesens |
`689
`Dables< -. Apseeaeveaeegseae easee lee 690
`
`
` Basic diet No. 209__
`
`In a previous communication, Goldberger and Wheeler (1) pre-
`sented some of theresults of a studyof the problemof an experimental
`animal for pellagra. They reported the production in the dog,
`
`Elysium Health Exhibit 1013
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`
`
`659
`
`
`Basic Diet No. 123
`
`March 28, 1928
`
`658
`Mareh23, 1928
`of this experimental disease to human pellagra was pointed out, and
`was considered sostriking as to be well-nigh conclusive of the identity
`of the two conditions. This view was supported, they believed, by
`the suggestion of 2 common etiology indicated 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 some further results of the same study.
`METHODS
`Our methods of housing, caring for, and feeding the experimental
`animals have been described in a preceding communication (1).
`It
`may be noted that the experimental ration was offered each animal
`once a day and, as a rule, freshly prepared, The amount offered
`was, in general, all that the dog would eat. At first, to insure this,
`the attempt was made to offer an excess; but in order to minimize
`waste this practice was, after a time, modified so that, except for a
`young growing animal, only enough food for the maintenance of
`normal body weight was offered. The animals were weighed, once
`a week.
`It may be here recalled, too, that it has been our g#actice
`to use our dogs repeatedly. Depending on the purposeof the experi-
`nent, the animal was or was not reconditioned by a period of stock
`diet feeding between successive experunents, for which purpose our
`stock diet No. 156 (1) was the one most frequently used.
`In what
`follows, details of this nature will be noted in connection with the
`presentation of the pertinent parts of the history of each experimental
`animal. The diagnostic criteria of experimental blacktongue have
`been presented in a preceding article (1). Here we will say only
`that the earliest distinctive buccal lesions are vivid red injection
`of the floor of the mouth or an erythema of the mucosa of the upper
`lip in the formof bilaterally symmetrical patches or both.
`BLACKTONGUE-PRODUCING POTENCY OF A BASIC EXPERIMENTAL
`DIET AND OF CERTAIN OF ITS MODIFICATIONS
`The composition of the diet with which Goldberger and Wheeler
`(1) first successfully induced experimental blacktongue is shown m
`Table 1. This diet was constructed as a somewhat simplified replica
`of the type of diet found associated with, and, unless suitably sup-
`plemented, believed to be responsible for, the occurrence of pellagra.
`After a number of modifications of the diet shown in Table 1 had
`been tested, the diet No. 123, shown in Table 2, was constructed and
`subsequently used as the baste blacktongue-producing diet in many
`of our experiments.
`It seems desirable, therefore, to summarize our
`experience with this (together with certain of its modifications) as a
`
`
`
`
`
`
`
`EXPERIMENT 1
`
`The blacktongue-producing potency of dict No. 123 (Table 2)
`has. been tested in a considerable number of animals and under
`various conditions. Weshall considerhere only those tests, however
`that were carried out either in animals after a period of Pacthinelinine
`following & previous experiment and thus presumably in foetal
`condition, or in such as were not previously subjected to experiment
`and were not knownto have ever suffered from blacktoneue. Such
`tests were performed in a total of 14 dogs,
`the significant details
`relating to each of whichare as follows:
`Dog 13.—Male. Acquired April 7, 1923, between which date and November
`18, 1926, served in several experiments and suffered seven attacks of experimental
`blacktongue, the latest of which began July 31, 1925. Was on stock diet No
`156 for reconditioning from November 18 to December8, 1926.
`event 8, 1926: In good condition; weight, 10.1 kilograms; begins test dict
`No.
`123,
`.
`On January 25, 1927, at the end of a period of 48 days, noted thefirst signs of
`OEE an. injection of the floor of the mouth. Weight 9.4 kilograms
`Confirmatory evidence of blacktongue noted on February 10, 1927. Course of
`the attack was remittent or relapsing in character, accompanied byself-imposed
`partial starvation. Killed with illuminating gas April 28, 1927.
`apne 14.—Male. Acquired April 7, 1923. Between that date and September
`ay 1923, he in two experiments and suffered arelapsing attack of blacktongue
`yeginning
`May 18, 1923. On stock diet No. 34C, for reconditioni
`;
`‘
`tember 25 to October16, 1923.
`SSSREy TAREE”
`October 16,
`-ondition;
`weigh
`cd
`i
`ass 5
`n good condition; weight,
`9.38 kilograms; begins test diet
`On October 30, 1923, at the end of a period of 14 days noted thefirst signs of
`blacktongue, an injection of the floor of the mouth and a patch of redness on
`the mucosa of the upperlip opposite the base of the canine tooth on eachside
`,
`Weight, 9.2 kilograins. Further history not relevant.
`4 Dog 15.—Male. Acquired April 14, 1923. Between that date and September
`25, 1928, servedin two experiments andsuffered a relapsing attack of blacktongue
`beginning August 7, 1928. On stock dict No.
`384£C, for reconditioning from
`September 25 to October 16, 1923.
`'
`October 16,
`1923: I
`ition;
`ie ant
`3:
`In good condition; weight, 9.4 kilograms; begins test diet
`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
`
`mua oftt upperlip. Weight, 9.3 kilograms.
`furtherhistory not relevant
`og 80.—Male. Acquired September 25,
`1923. On stock
`diet
`N.
`340to
`Pie. vcs
`;
`3
`stock
`diet No. 384C to
`a os 923:
`In good condition; weight, 9 kilograms; begins test dict
`On October 27, 1923, at the end of a period of 11 days, noted thefirst signs of
`blacktongue, a definite reddening of
`the floor of the mouth. Weight
`3.8
`kilograms. Further history not relevant.
`manatee,
`
`
`
`i
`
`i
`
`1923: I
`
`wei
`
`4
`
`ki
`
`October
`
`16,
`
`1923:
`
`dition;
`
`weight
`
`i
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`Elysium Health Exhibit 1013
`Page 4 of 22
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`

`

`March23, 1928
`
`660
`
`March 23, 1928
`
`
`661
`November 21, 1924: In good condition; begins test diet No. 123.
`November 25, 1924: Weight, 9.4 kilograms,
`On December27, 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
`checks. 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 December23, 1924, at the endof a period of 32 days, noted the first signs of
`blacktongue, reddened bands on mucosa of the upperlip oneach side; reddening
`of mucosa of the cheeks, reddening of the floor of the mouth. Weight 11.5
`kilograms.
`Treated and usedin 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.
`Onstock diet No. 156 for reconditioning from November 18, 1926, to December
`81926. On December 7, 1926, weighed 14.8 kilograms.
`December8, 1926: In good condition; begins a second period of test diet No. 123,
`December 14, 1926: Weight, 13.9 kilograms.
`January 18, 1927: Weight, 13.9 kilograms.
`On January 22, 1927, at the end of ® period of 45 days, noted the first signs of
`blacktongue, reddetied patches on mucosa of the upper lip in region of eanine
`teeth of each side; reddening of mucosa of the cheek, and reddening of the
`floor of the mouth.
`A rapidly progressive attack, untreated, terminating in
`death January 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, 7:0 lslograms.
`On December30, 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, remittent oy relapsing course accompanied by self-imposed partial
`starvation; untreated, terminated in death April 20, 1927, Weight on day
`preceding death, 3.3 kilograms.
`Thus all i4 of
`the test animals developed blacktongue, the first
`distinctive signs of which appeared within not to exceed 53 days after
`beginning the testdiet. Allowed to take its course without therapeutic
`interferencein two of the dogs, it ended in the death of both animals.
`One of the animals (dog 82) was subjected to the test during two
`widely separated periods and respondedwith blacktongue beginning
`at the end of 32 days in the first and at the end of 45 days in the
`second period.
`
`Basic Diet No. 209
`
`7
`
`In dict No. 123 (Table 2) the principal component, quantitatively,
`is white corn meal, which forms 66 per cent of the weight of the dry
`
`Dog &4.—Bitch. Acquired September 25, 1923. On a miscellaneous stock die
`
`,
`
`Deg 51.—Bitch. Acquired September 25, 1923. On stock diet No. 34C to
`October 18, 1923.
`dt
`Phe
`ined
`ye
`October 1s, 1923: In good condition; weight, 7.3 kilograms; begins test diet No.
`125.
`;
`OnOctober30, 1923, at endof a period of 12 days, notedfirst signs cf blacktongue,
`an injectionof the floor of (he mouth. Weight, 7.8 kilograms. Further history
`not relevant.
`ne
`Dog 52.—Bitch. Acquired September 25, 1923. Ona miscellaneous stock die
`to October 22, 1923.
`rie,
`October 22, 1923: In good condition; weight, 8.5 kilograms; begins test dict No.
`123.
`'
`"he
`On November 27, 1923, at the endof a periodof 36 days, noted the first signs of
`blacktongue, an injection of the floor of the mouth. Weight, 8.5 kilograms.
`Further history not relevant.
`itl veh
`
`Dog 53.—Bitch. Acquired September 25. 1923. Ona miscellaneous stock die
`to October 22, 1923.
`October 22, 1923: In good condition; weight, 5.7 kilograms; begins test dict No.
`123.
`|
`%
`
`November 20, 1923: Weight, 5.8 kilograms.
`4
`On November 27, 1928, at the end of a period of 36 days, notedthe ‘first signs o
`blacktongue, an injection of the floor of the mouth and of the mucosa of the
`cheeks.
`I'urther history not relevant.
`.
`alt
`to October 22, 1923.
`ues ale
`October 22, 1923: In good condition; weight, 6.2 kilograms; begins test diel
`No.
`is
`f black
`i
`On November 28, 1923, at end of a period of 37 days, noted the first signs of black-
`tongue, an injection of the floor of the mouth. Weight, 6.7 kilograms. Further
`history not relevant.
`:
`a
`re
`Dog 57.—Male. Acquired September 25, 1923. On stock diet No. 34C to
`October 16, 1923.
`October 16, 1923: In good condition; weight, 7.7 kilograms; begins test dict No.
`123.
`‘pitt
`On November 2, 1923, at the end of a period of 17 days, noted the first signs of
`blaektongue, an injection of the floor of the mouth. Weight, 8.8 kilograms.
`Further history not relevant.
`;
`abi
`Dog 58.—Bitch. Acquired September 27, 1923. On stock diet No. 34C to
`October 16, 1923.
`an
`;
`October 16, 1923: In good condition; weight, 18. 5 kilograms; begins test diet No.
`125.
`i
`thay
`On Neve 1, 1925, at the end of a period of 16 days, noted the first signs of
`hlacktongue, an injection of the floor of the mouth. Weight, 14.3 kilograms.
`Further history not relevant.
`5
`ceo
`al
`Dog 79.——Bitch. Acquired June 9, 1924. On stock diet No. 156 to December
`) a
`e
`16, 1924, during which period was bred and whelpeda litter of five pups which
`were successfully weaned,
`\
`'
`_ ane
`December 16, 1924: In good condition; weight, 5.3 kilograms; begins test diet No.
`123.
`=
`i
`;
`January 27, 1925: Weight, 5.5 ki ograms.
`On Farspeucti 7, 1925, at the end of a period of 53 days, noted the first signs of
`
`
`
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`Page 5 of 22
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`

`

`
`
`
`
`
`March 23, 1928
`
`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 dogs, numbored 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 mealis
`used instead of white. Thesignificant facts in relation to each of
`the test animals are briefly as follows:
`Dag 44.—Male. Whelped in the laboratory June 26, 1923. Up to July 17,
`1925, served in a number of feeding experiments and 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 eondition; weight, 12.9 kilograms; begins test diet
`No, 209.
`On September 1, 1925, at the end of a period ‘of 21 days, noted the
`t signs
`of blacktongue, a reddening of the mucosa of the upperlip and ae
`of the floor of the mouth. Weight, 13.3 kilograms. Further history not
`relevant,
`Dog 62.—Biteh. Acquired September 25, 1923. Between that date and
`July 17, 1925, servedin several experiments and had four attacks of blacktongue,
`thelatest of whieh began March 24,1925. On stook diet No. 156for reeondition-
`ing from July 17, 1925, to August 11, 1925,
`August 11, 1926: In good condition; weight, 10.8 kilograms; begins test diet
`No, 209,
`On. October 6, 1926, at the end of a period of 56 days, noted the first signs of
`blacktongue, an injection of the floor of the mouth. Weight, 9.8 kilograms:
`Further history nor relevant.
`Dog 60.—Male. Whelped in the laboratory November 4, 1923. Up to July
`17, 1925, served in a feeding experiment and suffered an attack of blacktongue,
`which began July 14, 1925. On stock diet No. 156 for reconditioning 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 blacktongue, an injection of the floor of the mouth and a flushing of the
`mucosa of the cheeks, Weight on September 15, 1925,.7.4 kilograms. Further
`history not relevant.
`Dog 63.—Male. Whelped in the laboratory November 4, 1993. Up to
`July 17, 1925, served in two experiments and sufferedtwo attacks of blacktongue,
`the later one of which began Mareh 5, 1925. Gn stock diet No. 156 for recon-
`ditioning from July 17, 1925, to August 11, 1925,
`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 thefirst signs of
`blacktongue, a reddening of the floor of the mouth. Weight, 7.5 kilograis
`
`
`
`663
`March 23, 1928
`which was in evidence June 27, 1925. On stock diet No. 156 for reconditioning
`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, nated 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.—Biteh. 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; begins test diet
`No. 209.
`On December 17, 1925, at the endof a period of 128 days, notedthefirst signs
`of blacktongue, a reddening of the mucosa of the upperlip 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 endof a period of 128 days in one of them.
`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 andits modification, diet No. 209, sodiumchloride
`and 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-producing potency of diet No. 123 would be produced by the
`substitution of a “complete” salt mixture for the sodium chloride
`and the calcium carbonate.
`Forthat purpose experiment 3 was
`carried out.
`
`EXPERIMENT 3
`Iive dogs, numbered 9, 29, 83, 84, and 85, were each offered a suit-
`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:
`Deg 9—Male. Acquired April 1, 1923, between which date and February 28,
`1925, served in a number of experiments and suffered seven attacks of black-
`tongue, the latest of which began February 24, 1925. On stock diet No. 156
`
`
`
`Elysium Health Exhibit 1013
`Page 6 of 22
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`

`
`
`Match 23, 1928
`
`664
`
`On May31, 1925, at the end of a period of 60 days, noted the first signs of black-
`tongue, a reddening of the mucosa of the upper lip in the region of the canine
`teeth of cach side, and an injection of the floor of the mouth. Weight, 11.4
`kilograms.
`further history not relevant.
`Dog 29.—Male. Acquired May 9, 1928, between whieh date and February 28,
`1925, served in a number of experiments and suffered nine attacks of hlacktongue,
`the latest of which began Tebruary 6, 1925. On stock diet No, 156 for recondition-
`ing from February 28, 1925, to April 1, 1925,
`April 1, 1925; In good eondition; 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 upperlip andof the floor of the mouth.
`Weight, 11.1 kilograms. Further history not relevant.
`Dog 83.—Bitch. Acquired February 20, 1925, from which date to April 1,
`1925, was on stock dict No. 156.
`April 1, 1925: In good condition; weight, 6.8 kilograms; begins test diet No. 195.
`On April 18, 1925, at the end of a period of 17 days, noted the first signs of black-
`.
`tongue, 2 reddening of the floor of the mouth. Weight, 7.3 kilograms. Further
`history nor relevant.
`' Dog 84.—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, 7.8 kilograms; begins test diet No. 195.
`Qn April 23, at the end of a period of 22 days, notedthe first signs of blacktongue,
`reddened patehes on mucosa of the upper lip opposite the canine teeth of
`each side. Weight, 9.1 kilograms. Turther history not relevant.
`Dog 85.—Male. Acquired Mareh 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 endof a period of 15 days, notedthefirst signs of black-
`tongue, reddening of mucosa of the upper lip, of that of the checks, 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 within not to exceed 60 days after beginning
`the test diet.
`ia
`The substitution of the “complete” salt mixture for the sodium
`chioride and calcium carbonate of diet No. 123 made, thus, no sig-
`nificant difference in its blacktongue-producing potency.
`Basic Diet No. 268
`
`Although diet No. 123 (and its modifications, No. 209 and No.
`195) contains a considerable amount of protein, fully one-half of
`whichis fromcasein, it was thought, nevertheless, that the biological
`qualityof the protein mixture might, perhaps, be improved byincreas-
`ing the casein component, a view that was strengthened bythe results
`of some growth tests in rats (unpublished).
`It seemed desirable,
`therefore, to determine what effect, if any, an increase in the casein
`ecinponentof diet No. 123, and thus, presumably, an improvement
`
`
`
`665
`
`March 23, 1928
`
`EXPERIMENT 4
`Hight dogs, numbered 62, 69, and 101 to 106, inclusive, were each
`offered a suitable daily portion of diet No. 268, the composition 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 sodiumchloride andcalcium carbonate. This experiment
`may be considered, therefore, as a test of the effect not only of a
`substantial increase in protein, but. also of the. use, at the same time,
`of acomplete salt mixture on the blacktongue-producing potency of
`that diet.
`In this connection, it may be stated that this experiment was
`planned to serve one other purpose—namely, to secure tissues suit-
`able for histopathological study. Believing that diet No. 268 was
`more nearly complete—at least for maintenance—than No. 123 or
`its other modifications with respect to all known dietary essentials
`except the specific factor or factors related to blacktongue,? it was
`thought that animals fed with it when killed at suitable intervals
`would furnish tissues which might show a sequence of histopatho-
`logieal changes which would thus be relatable to the specific dietary
`defect.
`Thesignificant 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. Whelpedin the laboratory November4, 1923. Up to May 26,
`1926, had one evanescent attack of blacktongue which was in evidence March
`24-27, 1925. On stock diet No, 156 May26 to June 12, 1926.
`June 12,1926: In good condition; weight, 8.8 kilograms; begins test diet No. 268.
`On ime 26, 1926, at the end of a period of 14 days, killed with illuminating gas
`for histopathological study. He presented no signs of blacktongue. 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: In good condition; weight, 8.8 kilograms; begins test diet No. 268.
`July 27, 1926: Weight, 8.7 kilograms,
`.
`July 28, 1926, at the end of a period of 46 days, notedfirst signs of blacktongue,
`a slight injection of the floor of the mouth which became more definite on
`August 6, and on the following day (August 7) there was noted in addition a
`slight reddening of the mueosa of the cheeks and of the upperlip in the region
`of the canines.
`Animal killed with illuminating gas for histopathological study on August 7,
`1926.
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`Elysium Health Exhibit 1013
`Page 7 of 22
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`March23, 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.
`Animal 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 dict No. 156.
`June 12, 1926: In goad condition; begins test diet No. 268.
`June 15: Weight, 5.7 kilograms,
`On July 6, 1926, at the endof 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 upperlip. Weight, 5.6 kilograms, Animalkilledfor histopatho-
`logieal 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.
`June 15: Weight, 4.9 kilograms.
`On July 15, 1926, at the end 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 December 9, 1925. Reared:en
`stock diet No. 156.
`5
`June 12, 1926: In good condition; 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 animals, two were killed at the endof a test period
`of 14 days for the purpose of histopathological study. Neither ani-
`mal had shown any evidence of blacktongue. The period of obser-
`vation was so brief that these two animals can not properly be con-
`sidered in appraising the blacktongue-producing potency of the diet.
`The remaining six animals all developed blacktongue, the first dis-
`
`EXPERIMENT 5
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`
`
`667
`March 23, 1928
`use of “complete” salt mixture was without significant effect on the
`blacktongue-producing potency of that diet as judged bythe attack
`rate and duration of the feeding period before the appearance of the
`first distinctive signs of the disease,
`Tn the foregoing series of tests of the pellagra-producing potency
`of diet No. 123 and its modifications, a total of 38 dogs were used as
`test animals, and blacktongue wasinduced 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 purposeof histopathological study.
`Disregarding these as not having hada full opportunity for the devel-
`opment of the disease, blacktongue was induced in every one of the
`other 31 test animals.
`In each of twoof these the disease was induced
`on two separate occasions, so that 33 separateattacks of black tongue
`were induced in the 31 animals under consideration in this series of
`experiments. These 33 attacks developed at the end of feeding pe-
`riods that varied between 11 and 128 days in duration, but only one
`of the attacks developed at the end of a period of over 61 days.
`THE BLACKTONGUE PREVENTIVE
`
`Dried Brewers’ Yeast
`If may be recalled that Goldberger and Wheeler's first success in
`experimentally inducing blacktonzue was with a diet that differed
`from that previously tried without success by Goldberger and Lake
`in that it included no milk and was not supplemented withyeast (1),
`The difference in outeome led us to suspect that this might be related
`to the difference in the diets used. There was alreadyreasonto believe
`that milk possessed pellagra-preventive properties (4) (5) and thus,
`possibly, also blacktongue-preventive properties; but, as the amount
`of milk contained in the diet tested by Goldberger and Lake was very
`small, it seemed improbable that their faihire was attributable, at
`least to an important degree, to the milk. Up to this time we had had
`no suspicion that yeast might possess pellagra-preventive properties;
`but in seeking for the explanation of the difference in results under
`consideration it seemed much more likely that,
`if Goldberger and
`Lake's failure was due to the preventive action of either food,
`this
`failure was due to the action of the yeast rather than to that of the
`milk, Reasoning thus, it was decided to test this view; and after
`some preliminary trials which it seems superfluous to detail, the fol-
`lowing experiments were performed:
`
`Elysium Health Exhibit 1013
`Page 8 of 22
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` 669 March 23, 1928
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`attack. Treated veésh yeast this attack rapidly cleared up and the
`animal’s condition returned to normal and remained so during a
`
`
`further period of 104 days, at the end of which time the experiment
`was discontinued.
`
`
`
`Dog 80.—Male. Acquired August 1, 1923, between which date and October
`29, 1923, served in two experiments and suffered two mild attacks of black-
`tongue. Between October 29, 1928, and March 11, 1924, was subjected to some
`preliminarytests of yeast.
`March 11, 1924: In good condition; weighs 11.4 kilograms; begins test dict
`No. 155.
`February 24, 1925: In good condition; weighs 10.5 kilograms.
`On February 28, 1925, dict No. 155 was replacedby diet No. 123, supplemented
`with a daily dose of 18 grams of yeast separately administered in gelatine cap-
`sules. The dose of yeast thus administered was approximately the same as
`that ingested in the daily ration of diet No. 155, so that diet No. 123 so supple-
`mented was essentially equivalent to diet No. 155.
`May19, 1925: This animal has nowfor upward of 14 months been onthe yeast-
`containing test diet No. 155 or its equivalent basic diet No. 123 supplemented
`with yeast. The dog has shown no recognizable evidence of blacktongue at
`any time during this period. He has been and is in good condition; weighs
`10.7 kilograms.
`Effective to-day the yeast supplement to basic dict No. 123 is discontinued.
`On July 2, 1925, or 44 days after discontinuing the yeast, there were noted the
`first signs of an attack of blacktongue, erythematous patches on the mucosa
`of the upperlip in the region of the canine teeth. The further history of this
`animal belongs to another experiment.
`Dog 35.—Bitch. Acquired August 6, 1923, between which date and March
`11, 1924, served in a numberof experiments including a preliminary test of yeast
`and suffered three attacks of hlacktongue, the latest of which began December
`22, 1923.
`March 11, 1924: In good condition; weighs 5.8 kilograms. Begins test diet
`No. 155.
`
`On March16, 1924, the animal was found to have developed an ulcerative, infec-
`tive stomatitis. Verylittle or none of the ration was eaten between March 1