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Huygens Institute - Royal Netherlands Academy of Arts and Sciences (KNAW) Citation: Eijkman, C. & Hoogenhuyze, C.J.C. van, The influence of feeding and of starvation on thedevelopment of polyneuritis gallinarum, in:KNAW, Proceedings, 18 II, 1916, Amsterdam, 1916, pp. 1467-1480 This PDF was made on 24 September 2010, from the 'Digital Library' of the Dutch History of Science Web Center (www.dwc.knaw.nl)

> 'Digital Library > Proceedings of the Royal Netherlands Academy of Arts and Sciences (KNAW), http://www.digitallibrary.nl'

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pencil consists of the intersection of two of tJle planes c, c', c" and a cubic lying on CP3. SA the P on tp3 is determined by a pencil of conics (J~, of which three base-points SI' S~, S3' lie on t~3. A qua­dratic transformation with prineipal points Sic tmn'3fol'ms t!J3 mto a curve XJ passing through Sk and the peneil ((J2) into a plane peneil, of whielt the vertex SI lies outside X3 • The 5ix tangents sent by XJ

throngh IS"'" are the images of six conics (J2 touchmg at 'l~3; thc plane tp is therefore touched by si.')] curves Q3. The congmence [1'J of tlle tangents at the curves Q3 has therefore the class six.

If a plane tI' is laid thl'ough the singular point 0, the involution P degenerates into an involution T, the pairs of whieh are com­pleted into triplets by C. Of the six tangents l' four pass through P; the remaining two are replaeed by the straight line touching the curve n 3 in C.

§ 6. Tbe eongruenee [1'J has the planes (Jk of the conics Q2Jr as singula1' planes. The tangent plane (Jo in C at cp3 is also sinfJula1', for every' straight line of the pencll (0, (Jo) is tangent at a QJ. ° is of course at the same time singulal' point of [r J.

Throllgh a point P of w3 pass five tangents 1', viz. the four tangents of n 3

, having P as tane;ential point, aud the straight line 1', whieh touches the Q3 laid through P; this tangent must be eounted twice. -The ol'de1' of' [1'J amounts therefore to si,v.

The straight line f1 is intersected in the pairs of an P by the curyes Q3; it is therefore tangent for two of these curves, sa that the oseulating plan es ro of the two points of contact pass through f1' The line f1 flll'ther bears the plane (JI> which must be considel'ed as osculating plane of the conic Q/. As each of the thl'ee planes mentioned must be counted twice, we may eonelude that the osculat­ing planes of the curves Q3 envelop a sU1:face ,Q of class sim. - For the tig'ure (Q1 2, gl) the straight 1ine hl> touching Ql ~ in its

intersection with gl> is triple class axis, ,Q contains consequently the si.v st1'a~qltt lines ltk.

Pathology. --=:.. "Tlte infhtence of feeding and of stal'vation on the development of polynew'itis ,qallinantm". By Prof. Dr. O. EIJK1I1AN and Dr. O. J. O. VAN HOOGENHUYZE.

(Communicated in the meeting of Febl'uary 26, 1916.)

As communieated by me in 1896 Dr. A. G. VORDERi\1AN undertook an investigation, into the re1ationship of the natnre of a rice-dieL with the OCCllrrence of beri beri in the pl'isons of Java. These researches had been suggested by my studies of polyneuritis galli-

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narum, a disease that bears a close resemblance, clinically as weU as patho-anatomically, to beri bed and could be developed in fowls and pigeons through a diet of polished rice. If the animals were fed on unhuskcd rice (gabba) or undermilled rice, i. e. rice denuded o11ly of the coarse outer skin, not of the so-called "silrerlayer", the inner layer of the periearpium, the disease did not decIare itself, nay, diseased allimals could even be cured by snch a diet. UIlder­milled rice IS still the staple food of the Javanese, especially in the country-distl'icts, where instead of modern machinery, pl'imitive implements are used for husking. VORDERMAN'S investigation showed, , in accordance with my researches on polyneuritis gallinarum, that bed bed occurred frequently in those prisons wh ere polished rice was the staple artiele of diet, and r~rely in those where nnder­milled rice was the ordinary food.

Thenceforth many researchers have oecupied themselyes with the experimental study of this bird's disease and have also applied theil' reiSults to the ben beri problem to good purpose.

As we intend to contine ourselves, in th is paper, to the etiology of polyneuritis gallinarum, we wish to point out beforehand that students of the diseaE.e are still dlvided in their opinion about the influence of diet in its causation. The pl'esumed existence of a poison, operatmg in the diet, has already by some been assigned as the probable etiologie factor, just as heretofore in the case of beri beri. This VIew implies that the protective and cnrative effeet of l'ice-poHshings and other iSimilarly aeting natural products, such as katjang idjo, yeast, egg-yolk, meat and the like, proceeds from a constituent th at aets as an antidote. Over againElt the poison-

\

hypothesis, whieh still has many snpporters, is anothel' "iew, first clearly fOl'mulated by Dr. G. GRIJNS 1), viz. that the constituent alluded to does liot act as an antidote but as a so-called acres­sory food-stuff, which together with protein, fats, carbohydrates and salts is essential for the diet, to meet the physiological requirements, and thttt the disease develops itself when tlle said constituent is adminisrered more sparingly than is reqnired by the organism. Tt htts not yet been defined ehemically with suffjcient certttinty, nor has it been made out whether we have to do with 011e or with more substances. This must be remembered when we use the sy110nyms "curative", "protective" or "antineuritic" sllbstttnce or substanees.

Also other diseases, sueh as SClll'vy, Bar]ow's disease, pellagra and the like are with more or less probability caused by a deficiency

1) Geneesk. Tijdschr. v. Ned. Tnd. Deel,41, p. 47, 1901.

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in special unknown accessory ,food-stuffs, which FUNK 1) has included

under the general name of vitamins, while the diseases themselves are classed as "deficiency diseases" or "avitaminoses". _ rhe foundations on which the deficiency-hypothesis has been built were furnished by the evidence of my own experiments, showing that not only rice-polishings of themselves, but also an extract from them, possesses prophylactic and l'emedial properties again5t polynen­ritis gallinarum,2) and showing also that neithel' deficiency of protein, nor of fat, or salt produced the disease 3). This, however, did not eject the poison-hypothesis, w hich, aftel' all on the basis of the facts had also to as&mne a deficiency in the diet, notably a diet defective in a substance (or substances) that rende red a poison innocuous or prevented its formation. Oonsidering the poison­hy po thesis to be merely a basis for further researches I suggested in my earlier publications 3) tbl'ee possibilities, viz. a poison ingested with the food, or a poison evolved from the food in the alimentary canal (through the agency of micro-organisms ?), or a poison produced by a disturbed metabolism in the tissues. Elsewhere 4) 1 have demonstrated elaborately why the first possibility may be rejected as clashing with indubitable facts, and also that though the sec(}Dd and the third could not be excluded, positive evidence could not be addllced. It is the analogy to the neuritis, incited by common poisons, su eh as lead, arsenie, alcohol, ergot and some bacterial toxins, that proves fOl' an intoxication; however the qllestion cOllld not be settled as in spite of numerous attempts no one lIas succeeded as yet in aSbigning a poison as the etiological factor of polynelll'itis gallinarum, .

'rhe following may serve to illustrate how interpretations of experimental data, obtained in this field, vary with the view-point of the experimenter.

FUNK 5) and likewise BRADDON and OOOUR 6) believing the detlciency-hypothesis to be correct, arl'ive at 1,he conclusion that it is especially the cal'bohydrate metabolism that causes a more abundant consumption of antineuritic matter. By increasing tbe content of carbohydrate in a mixed diet, they succeeded in. hastening

1) J ourn. of State Medecille, Vol. 20, p. 341, 1',)12. 2) Arch. f. Hygiene, Bnd. 58, S. 150, 1906. 3) Gen. Tijdschr. v. Ned. Indië, Vol. 36, p. 213, 1896. Virchow's A.rchiv.

Bd. 148, S. 523, 1897. 4) XVIIth Intern. Congress of Med. London 1913, section XXI. 6) HOPPE SEYLER'S Z. f. physiol. Chemie, Bnd. 89, S. 378, 1914. 6) Journ. o. Hyg. Vol. 14, p. 331, 1914.

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the outbreak of the dlsease. This eaIls to mind my old experiencè that fowls, suffering from polyneuritis, l'ecovered aftel' the admini­&traiion of meat on1y, whi1e healthy annuals, fed on meat and stareh, developeel tbe disease, from which I c6ncluded then that its Ol'igin i& associalec1 w!th a starch (het. OASPARl and lVIOSZKOWSRY 1) al&o found that pigeol1s fed on 11en's eggs, dextrose anel salt 1'emaiuee! healthy and gamed in weight, bnl were attacked by polyneuritis wllen this diet was supplemented vi'ith pohshed rice; howeve1', they declal'ed it to be intoxwation, emanating from the 1'lCe ancl even attached to these tests the vnlue of an experunentmIl crllci& in support of theil' view.

Aftcl' what has been said above it is neediess to add th at we ('annot accept lhis view withont furthel' consldel·ation. We, therefo1'e; sOllght for an expel'imentum cl'ucis relatIve to the questioll: 1I01son­hypolhesis or deficiency-hypothesis, in anotber du'ection, and sup­posed to have detected it in abnndantly drenching the stal'vmg ol'ganism with water.

lf the neuritis were caused by a poison, the disease couid not be expected to manifest Hself, ingesüon 9f poison being exclnded in stal'vation, whil~ an occasional endogenous poison (product of a distnrbed meta,bolism) wonid most hkely not accumulate in the body, but would be removed together wJth the water along the intestine and olher excretory ol'gans. For the same renson, howeve1', the body wonlel to some degree be deprived of viLamins, and if polyneuritis wel'e associated with tl1lS dcficiency alone, t11e disease woule! p1'esumably break out.

Our d1'enchin~' experiments Vi'el'e rondllcted in tIle following way : Fowls had the crops filled w ith water, instead of food t wice daiIy; besides this they weJ.'e given subcuLaneously three times a day 10 c.c. physiological salt solution (or RINGER'S fluid without glucose).

lt now appeared that fasting in conjnnction with dl'enc11ing prodnced polynellritis, as established clmically by 0111' diagndsis as weU as thl'Ollgh micl'oscopical examination of tbe nerves that had beell tl'eated aftel' MARcm's method. It was remal'kable thai, jllSt as wilh a l'ice diet, the crop when filled vI,ith water, did not empty dllring tbe last days oej O1'e the onset of the disease, so that the supply of watet' bad to be discolltinued. Af tOl' all the ttspect of the disease was in every rcspect like tbat appearing aftel' a one-sided cliet, only in the latter case the emaciation is nót so considerabie.

A positive result was also achieved in the foll~wing' experüu<2nts,

,

1) Derl. Klin. W. Bnd. 50, S. 1515, 1913. I I

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tending to show sepal'ately t11e intluence of dl'enching and that of subcutaneous iujection upon the development of the disease in starving ani mals.

Onl' researches were controlled by simple starvation expel'iments. Befol'ehand it is desiraule to observe that such eÀpenments have been cal'ned out by many previolls workel's, who apparently had all been struck by the fact that with a monotonous diet (e.g. pohshed l'lce) most fowls showed a dlsinclmation to eai and lost gremly in weigh t. Several observers al'gued that the animals under dlScllssion do not, in some cases, show the typlcal dlsease conditions, but sllccumb throllgh pure manition. Likewise tbe special starva.tion experiments of a nnmber of experimenters on polyneuritis yielded, till recently. only negative I'esults. (EIJKMAN l.c., SAKAKr 1), Ho IJST 2), SHIGi\ and KUSAl\f \ 3), FRASER and S'l'ANTON 4), BRADDON and COOPER l.c., FUNK 5), TASAWA G), l\1ASAYO SEGAIVA 7)

Years ago already GRIJNS l.c., in view of my experiments, accounted fol' the non-appearance of polyneu1'itis in consequence of deprivation of food by asserting that starvation callses the protem of the m~lscles to be katabolized and that, togethér wlih this pro'tein, pl'otective sllbstances are liberated fol' the benefit of t11e nerves. Feeeling, on the other hanel, prodllces a higher degl'ee of metabolism, alld exalts the consnmption of the said snbstances; lf, therefo1'e, the food is pOOl' in snch substances; lt càimot meet tbe greater demand and the disease consequentl)' declares itself.

Om drenching experiments rested on the statement cOl'l'oboratec1 by many researches, that mel'e deprl\'ation'lof food does not lead to polyneuritis. N evertheless, when entering upon OUI' investigation, we unc1ertook some contl'Ol-expel'iments. This, aftel' all, _tul'l1ed Ollt to be all the more l'equisite as, iu the meantime, I hacl taken ('ogniza~n(.e of' the ~'es~arc~les of CHAlIIBERtJATN, BLOOl\~BImGH and rÜr,130URNE 8), \vbich 11ad escapèd . my notice t1il'ougli having been published . in a periodiöal rlifiicult to get hold of. Contrill'y to the experiments _refe~'l'ed to above, theil' researches yicldeel some, I

- : \ . \ - \ -1) Sei-i·Kwai, 31-q-1903. ~) Journ o. Hyg. Vol. 7, p. 619, 1907. S) Mllteil. d. Beriberi:Sluche~-KomI?issiol?' Toky?, 1911. I.' _ , ,

'1) StudIes from the Iustilute for medic. research Federated MaTay States NO. 12, Smgapore, 1911.

5) Z. f. physiol. éhemie, Bud. 89, S. 378, 1914. n)' Z. f. expo Path. u. Ther., BmI. 17, S 27, 1914. 7) VIRCIIOW'S, Al'chiv, Bud. 215, S 404, 1914. 8) PIIILIPP. Jouw. of Sciencc, Sect. 13, vol. 6, p. 177, 1911.

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positive reslllts. Two of their fow]s fed on gradnally smaller quan-tities of unhllsked rice, developed po]yneuritis. Eight fow]s, snpplied with water only, not with food, presented three positive, two dOllbtful and th ree negative cases.

The resnlt, flOW, of Dur control-expel'iments was that out of eight fow]s that had been gi ven drinking-water only two died of typical inanition, the othel' six de\'eloped polyneul'itis. There was no mista­king the symptoms, and the diagnosis cOllld be sllbstantiated by the exumination of the nel'ves. We are not able to say why previously only negative !'eslüts were obtained. CHAl\fBERLAIN c. R. attribute them to the circumstance that the symptoms manifest themselves onI}' a very short time before death and, at this juncture, escape Dur notice in consequence of the general weakness. I cannot enter in their view, first of all becallse, in my previous cases no degenerath'e changes were found in the nerves.

MOl'eover the weakness and emaciation, which occur frequently with a one-sided diet (emaciation being in this case even sometimes detected by (;HA)1BERLAIN c. s: in as high a degree as in stal'ving animaIs) do not prevent the detection of pal'eses and paralyses.

The following tàble gives the l'esults of our stal'vation and drenching expel'iments:

A

B

C

D

E

TABLE J •

.... 1/)

Mean Mean CIJ-.0::: Polyneuritis a.g original loss of Particulars ::: weight welght I), after z't;

4 1459 grOl. 42.9 proc. 14-27 aver. 19 d. 2Xd. 125 e.c. water in the erop,

3Xd. 10 e.c. phys. water subc.

3 1497 "

35.2 "

18-28 " 22 " lXd. 125 e.c. water in the erop,

injection as above.

2 1670 "

44.3 11 18-34 " 26 11 2Xd. 125 e.c. water in the erop.

4 1740 "

43.8 11 28-33 " 31 " 3Xd. 10 e.c. phys. water subc.

6 1656 " 44.7 "

18-43 " 30 11 only drinking·water

I) From the beginning of the experiment till the outbreak of the disease.

The5e figures seem to justify the conjectllre that the drenching and especially the fOl'ced supply of an abundance of water in the crop has qnickened the olltbreak of the disease. However, it is difficult in Ihis case to dl'ttw a positive conclusion from them,

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considering }he marked individnal deviations exhibited by the animals even wh en treated similarly. One of the factors causing these differences seems to be the body weight. The greater ihis is at the beginning of the experiment the longer the period of incubation will generally beo

Aftel' the statement that polyneuritis gallinarum can be /produced apart from an)' dietary inflllence, the poison hypothesis has to be for the greater part relinqui5hed as being incompatible with our evidence and we may be justified in concluding that the influence of the diet according as its composition varies, plays a principal part in tlle I p1'evention of the disease, but an inferior part in Us development. A similar view has all'eady been put forward Iby me with regm'd io beri-bel'i in an earher publication 1). The supporters of the poison hJ' pothesis could at best still adhere to an endogenous poison as resuItmg ft'om a distUl'bed metabolism, admissible in star­vation; still, the results of the drenching experiments do not support this view of the poison hypothesis either.

As regal'ds the influence of diet in the causation of polyneuritis, th ere is some reason to suppose that its deficient composition aids tIle onset of the disease indirectly in the manner first expounded by GRIJNS, as stated before.

On the other hand it 5eems hardly permissible LO ho1d with OHAMBERLAIN (' .s. on the basis of tlle positi ve findings in their star­vation experiments th'i:tt not partial but general inanition is answerable for the disease. We are ab1e to furnish direct evidence for the view that, aftel' fasting just as wel! as aftel' a defective diet, polyneuritis depends llpon a parlial deficiency, as has been shown in a number of cases in WhlCIl the stal'\'Îng animaIs, dil'ectly aftel' the detection of the disease, were given 8 LO 10 grms of yeast for two or three consecntive days and in which the symptoms of polyneuritis we re seen to recede despite a p1'og1'essive loss of body weigltt. The fi:tvouJ'­able effect of yeast, then, pl'oved the same as in the ('ase of poly­neuritis produced aftel' a vitamin-poor diet.

When we consider the neuritis in starved fowls relative to the neuritis developing through a {ree one-sided diet, we shall see that, in the latter case, in consequence of the 10ss of appetite allllded to before, a condition may be evoked approximating the condition reslllting from fOl'ced fasting. They agl'ee also in th at the disease OCCUl'S less regularly than aftel' a forced one-sided diet, in which

1) Neet Tijdschr. v. geneesk., 1898, I p. 18ti.

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case we may reasonably assume with GRIJNS' that a larger 'qu'antity of pl'otecti ve substances have been consumed.

With a view to its more constant results we had reCOUl'se to fOl'ced feeding, whenevel' the appetite decreased appreciably. However, fr om my lndian experiments, with a feee diet of polished rice Ol' stareh, it appeared that, unlike the expel'ience of OHAl\IBERLAIN c. s. the 108s of weight was nevel' so considerable (28 0/ 0) as with depl'ivation of food (40-53,7 0/0)' As could be expected, a still gl'eater difference with our starvation expel'iments is found when fowls are fed fOl'cibly (with 50-60 grms of polished rice daily), viz. a loss of weight on the aYel'age of 18.2 0/0' -as against 44,7 percent wUh our starving animals. Some bil'ds lose weighi ahnost fl'om the beg'inning, also when fed forcibly; others however, maintain their weight, or even increase it, befol'e, towards the end, a retrogression reveals itself in consequence of the digestion being intel'fel'ed with, when thö Cl'Op does not readily discharge itself. In this case the disease eau break out, when the body weight is about equal to or greater than that at the beginning of the experiment. This was [the case with 7 out of 57 fowls, weighed at regular intervals, all being fed forcibly with polished rice, and Iikewise with 5 out of 44 pigeons fed in the same way. Other researchers (VEDDER and CLARK 1), GmsoN ~), TASAWA 1. C., MASAYO SEGAWA l.c.), report similar cases. '

For all this, the onset of the disease is not infreqllently preceded by considerabIe emaciation, especially with a free diet of polished l'ice or simple starch, whereas, on the othel' hand, beri-beri

. most often attacks people, apparently in a favourable conelition of nutdtion. As early as 1890 I pointed to this, as it seemed, character­istic difference betwe~J~ beri-beri anel polyneuritis gallinal'um 3), which also attracted the attention of later observers. In my sub­sequent reports, however, I 'was in a position to point out that emaciation is not an essential feature of expel'imental polyneuritis, as it was shown that, wheri snpplementing the rice with a quantity' of meat, or of rice-polishings, not sufficient to prevent the ontbl'eak of the disease, but sufficient to retard it, at the same time a favour­able nutritive conditioll was maintained. This has, evidently, escaped most investigators who still stick to emaciation as a constant symptom of polyneuritis gallinarum. Only in recent years have othel' writel's,

1) PHILIPP. Journ. of Scienee, Seet. B, vol. 7, p. 423, 1912.

2) PHILIPP. Journ. of Scienee, Seet. B, vol. 8, p. 351, 1913.

3) Geneesk. Tijdsehl'. v. Ned. Ind., Dl. 30, blz. 295, 1890.

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TZUZUKl 1), TASAWA l.C., COOPlm 2

), also l'ecorded a similar experience. Nor must it be forgotten that in the case of developing beri-beri

the diet is nevel' so exclusive as the food (l'ice or sago) from which in fowls and pigeons generaIly emaciation ensues. If, therefore, we wish to make a compal'ative study of beri-beri anel polyneuritis gallinarum, we_ are flllly justified in watching the neuritis, as developed in animals that have been given some accessory diet, rather than the aspect of the disease as prodncecl in animals aftel' a simple diet, say polished rice Ol' sago.

OHAMBERLAIN and VEDDER 3) have pointeel out that, whel'eas starving fowls are liable -to develop polyneuritis, beri-beri, nor anything like it was never observed in long-fasting men. 'l'hey maintain, however, that th is does not go against the conception that, etiologi­cally, the two diseases are on a par. They argue that the period of incllbation in beri-beri lasts at least 87 days and th at it is contrary to all reasonable expectation for a man to live without food 1'01'

that length of time. In addition tb this argnment we should also like to caIl attention to the undeniable fart that it is far easier to produce polyneuritis in bircjs than in mammaIs. Birds al'e evidently far more pl'eelisposeel, which, accol'ding' to some, is due to their higher metabolism, and, consequently, to a severer drain llpon their vitamin store. Howevel', Ihe hJPothesis propoundeel here, is in Ollr opion inconsistent with the fact, that fowls, for such' small animaIs, can persist in fasting for a remarkably lo.ng time.

Pursuing my Jine of research, a numbel" of investigatol's have endeavoUl'eel to produce expel'imentally polyneul'ites in monkeys by the aelministration of a one-sideel eliet (commonly polished rice). Some of therp., as MARCHOUX and SALll\1BENI 4), SCHAUMANN 6), GmsoN l.c., SHfGA anel KUSAl\fA l.c., TSUZUKI l.c., NAGAYO and FUJIl 0) succ~eeled in some, but by no meant> in all cases. TSUZUKI, for instance, failed with Japanese anel Singapore monkeys and arcOl'eling to N AGAYO the \ occlIrt'ence of a beri bel'i-like affection in monkeys on l'ice is ver)' !'are. Others,

. as NoË 7), also OH Al\lBERLAIN, Br.OOMBERGH allel KILBOUHNE 1.('., moreovel'

FRASER and STANTON l.c., obtaineel, like rn)'self, onl)' negative l'esults in spite of expel'Îments extended over a series of months. The only

1) Mitteil. d. Beriberi·Studien·Kommission, Tokyo, 1911, S. 289. !) Journ o. Hyg. Vol. 12, p. 436, 1912. S) PHILIPP. Journ. of Science, Sect. B, Vol. 6 p. 177, 1911. .t) Bulletin Soc. Patl!. exot. 31 Oct. 1903. Iî) Transactions Soc. trop. Med. and Hyg. Vol. 5, No. 2, p. 59, 1911. G) Verhandl. d. Japan. pathol. Gesellsch., H Tagung 1913. 7) Bulletin Soc, Path. exot., p. 315, 1911.

Proceedings Royal Acad. Amsterdam. Vol. XV lil.

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case of polynellritis in a monkey, observed by me and for which 1 am indebted (0 VORDl~Rl\IAN, I repol'ted as long since as 1888 1

).

The animal had, indeed, been fed chiefly on boiled rice and bananas, but it moved about among suffel'ers from bel'i-bel'i. This experience, , therefore, did not yield decisive evidence to establish the inflllence of feeding.

Man also is natllrally lesR liable to polynellritis than bÏt'ds, so th at, besides the diet, other unknown, or insufficiently known, f[t('tors generally come into rlay to produce beri-beri. Nevel'theless it has been shown, by othel' experimenters also, th11t thel'e is Sllffirient likeness in polynellritis gallinarum to beri-bel'i, to apply with dlle calltion the results obtained in the study of the one disease 111so to the other.

We next have to consider the qllestion in how [[tl' the feeding inflllences the consumption of antinelll'itic slIbstances, and, in ronse­quenee of this, also modifies the demand for theRe substanres in the ol'ganism. As al ready stated, FUNK, as well as BRADDON and COOPER al'rived at the conclnsion that it is especially t11e carbohydrates of the food [hat heighten tile demand for a sllpply of vitaminE. in the body. N ow it is a fact, as we observed befol'e, that _an increase of carbohyd!'ates in the food helps on the olltbreak of the disease. The question, -h0wever is, whether an increment of the amollnt of fat or protein, without a propol'tionate increase of the amollnt of vitamins, does not eqllally pl'omote the outbreak of polyneuritis. In view of his experiments on this head, FUNK believes that, in this respect, the effect of casein and of fat is less unfavourable than that of starch and sngar; if, however, we look at his data, and if we consider the lllarked individllal diffel'ences, occlll'l'ing with the S!lme food, we can accede to this view at the fal'thest for the fat.

Ovel' against FUNK, SCHAUMANN~) obsel'ves that polyneuritis ean be produced throllgh food, rich in protein and pOOl' in cal'bobydrate, provided there be not any or hardly any vitamins in it.

We have made feeding-experiments with aleuronat, ä powderlike protein prepal'ation, a waste-product fl'om wheatstal'ch factories. The Pl·ocednre of its pl'epal'ation involves a thorollgh washing' ) with water, so that it may be expected to be vitamin-pool', if not vitamin-free, as for all we kllow about them, vitamins are highl,)' soluble in watel'. Our pl'epar ation stiJl contained some amylum; howevel' 90 % of the dry subs(ance was made up of protein, as

1) Geneesk. Tijdschr. v. Ned: Indië, Dl. 28, 1888. 2) Arch. f. Schiffs· u. Tropenhyg. Bnd. 19, S. 393, H1l5.

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eomputed from the nitrogen-content. Ta two hens, weighing respectively 1110 grms and 1960 grms, 30-40 gl'ms of aleuronn.t was passed into the erop daily, exeepting the Jast days, wh en the erop did not discharge itself reg lllarly, The one showed, al ready on the 17th day, unmistakable signs of the disease, its body-weight feIl 29,7 %

; the other only on the 37111 day, with a loss of 33,7 %

in weight, 'l'he compaeatively long period of incubation i':l the latter case, may be assoeiated again with the considerable original body-weight. As to tlle first case, howevel', the resnlt ean hardIy be deemed less unfavourable than with a polished-riee or with a starrh-diet.

FUNK'S interpretation (in our opinion somewhat one-sided) that vitamins play an aetive part in the carbohydrate-metabolism, a much more important part than in the metabolism of othel' foodstuffs, is perhaps best refuted by the starvation experiments, During starvation the bQdy is thrown upon its ovm resources fOl" fat and fol' protein, the stOl'e of carbohydrates being soon exhausted, Now, if \l\Je bear in minel that starvation may pave the way fol' polyneuritis gallina­rum, we ean realize that the consumption of proteetive snbstauees may be gl'eater than can be met by the shl'inking fat- and muscle­tissues, so that the organism is g..adually getting poorer in these substanees not only absolutely, but al80 relati vely,

Next we wish to report some experimenls eanied ont wilh a view to ascertain whether the emaciation that, with a one-sided diet aften pre­cedes the outbreak of a disease, is, like the disease itself, attributable to a deficiency of special substanres, or to an unfavourable ratio of the principal food-stuffs: protein, fat, and earbohydrates, For protein wus -given ovalbumin siccum, fol' fat oleum olivarum, and polished rice or marantha-starch repl'esented the carbohydrates, The oil had been pl'evi­ously shaken np ,'vith a dilute soda-solution, the albumin dissolved in an excess of salt-solution, preeipitated with alcohol and evaporated to dl'yness, all which was done to remo\'e oceasional proiectÎ\'e con­!:ltituents in these foodstuffs.

The l'esults of these experiments have been brollght togethel' in Table I1, (See p, 1478).

The l'esnlts al'e ineonelnsive. Whereas those wit.h a simple rice diet and with a simple amylum mal'anthae-diet ag'l'ee fairly weIl - which is sumewhat surprisin/1; eonsidel'ing the fal' simplel' compositioll of the latter - the otber data seem 10 teach us that, when pari of the rice is exchanged for all appl'oximately iso-dynamie quantity of alhllmin Ol' of f~ü, the period of in~ubation l'emains about lhe same, but the l'elative loss in body-_weight fllightly decreases, On

~5~'

/

- 13 -

\

/ -1478

TABLE II.

.... en -.... Mean Cl)- I::~.c .0::= E<E

(Ij._ b.() loss of Polyneuritis af ter : Diiily food (forced). Cl) b.()'-

::I .... :a c ~ weight Zo 0

4 1506grm . . 24.4 proc. I 14-22 gem. 18 d. 70 grms. of pol. rice

5 1533 "

25.6 "

14-'--23 " 17.8" 60

" " " + 10 grms. of lactose

4 1395 "

18.3 "

18-19 "

18.5 JI 60 " " " +10 "

albumin

4 1365 "

18.8 "

14-20 " 17.5 " 60

" IJ ., +5 " of ol. oliv.

~

5 1550 "

23.7 "

14-23 " 18.8 " 70 grms. amyl. maranthae

3 1377 "

23.5 "

24-25 " 24.7" 60

" IJ " + 10 grm.ofalb.

3 1430 "

27.4 ,,' 23-26 " 24.7 " 60

" " " + 5 " 01 oliv.

-

tbe other hand the same exchange in the arnylum-diet ex erts only little influence upon the percentage of the 10ss in weigIJt, but lengthens ihe period of incubation.

Anyhow, it is evident that the deficiency alone of fat Ol' of protein in the polished rice and in the starch camlot exclnsively be responsible for the 10ss in weig-ht dnring the period of ineubation. As observed before, there is no mistake about it tbat an important factor in this procE'ss is tlle incidental distlll'bance in the mechanism of the digestion viz. the retarded and ultimately checked discharge of the Cl'Op j also, as far as freely-fed animals are concerned, tlle loss of appetite. Now the former can be set, to rights again by supplying rice-polishings, yeast and the likE', as we and many other investigators have made out. In so far the emaciation is indirectl)' dependent on a deficiency of antinel11'itic substances.

Regarding the possibility of any chemical anornaly of the digestion we noticed the fol/owing. We found that uncooked polished ri ce was digested badly !'rom t.he very' beginning. A microscopical examination made out that tile faeces of the animals contained much undigested stul'ch and consequently, when stained with iodin, exhibited, even for the unaided eye, au intense bll1e coloration. It did not bbcome better when finely ground l'ice was given j cooked 1'ice contrariwise yielded starch-poor faeces. This was the case also, when the fowls wel'e fed on l'aW unhusked rice or on raw l1ndermilled rice j macroseopicallJ~

the faeces did not then show any starch-l'eaction with iodin j mÏCl'os­copically no or hardly an)' starch was detected. The question, thel'e­fore, arose whether the defective digestion of' the uncookecl polished

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1,*79

rice was to be ascribed to its small content of cellulose, or to its deficiency of vitamins. The fiest seemed to be the case, as starch­rich faeces again resulted from _ a mixture of ground polished l'lce and an antineul'itic extract of rice-polishings. lf tbe ground rice was mi.xed with washed rice-polishings, saw-dust, or ground filter­paper, tlie digestion was, on the othel' hand, very satisfactory, the' faeces, just as in a simple diet of raw undel'milled rice, being then mostly a white mass Ol' a mass coloured pale green by bile, which, however, appeared to consist for the greater pat't of paper-ti bres.

We now tabulate the reslllts of these experiments:

TAB LE lIl.

, - I Polynou'itis aft",

1-00 bI).J::

~~ .- bi) Mean S'ä)

E..E Os:: ~ 1055 of Daily food (forced) ::l CIl- weight Zo Q)o:!

::E .S

4 1439grms 20.1 perc. 17-41 mean 27 1/4 d. 50 grms ground, polished rice

6 1503 11 13 "

15-24 " 19.3 " As above + 3 grms. ground paper.

Th-ollgh the admixtUl'e of cellulose seemed to have acted favourably with respect to the loss of weight, this did not retard the ol1tbreak of the disease, it l'ather accelerated it. This again favoul's the view that polyneuritis gallinarum is not a consequence of general inanition.

SUMMARY.

1. OUI' experiments lend sllpport to CHAl\IBERLAIN, Br.oOl\fBERGH and KILBOURNE'S expel'ience that general deprivation of food may fllrthel' a developrnent of polynel1ritis. The ol1tbl'eak of the disease is then ql1ickened by abundantly drenching the organism witb water.

Starvation-polynel1ritis, j ust as feeding-polyneuritis is engendered tbrongh a det1ciency of "antineuritir" substances, or so-called vita­mins. An addition of the latter exerts a cul'ative effect upon eithero

2. Etiologically there is in feeding;-polyneuritis no direct relation with the i,nanition that often attende it, in sueh a sen se that the former should result fJ'om the latter. In oue sen se, indeed, the l'evel'se is (he case. Loss of body-weight may occhr from the begin­ning of the experiment w1Lh a one-sided diet; however it OCClll'S con­stantly only towal'ds the outbl'eak of tile disease Gin consequence of a motol'Ïal distUl'bance in the digestion) and may even be pl'eceded ~by an inet'ease of bodyweight in spite of the one-sidedness of the diet.

II is doubtflli l whetlwl' a, tavolll'Çtble effect on (hé congitiQl1 Qf

- 15 -

1480'

nlltrition and the period of incub::ltion is produced by ralsmg the protein· and the far-content or the diet that evolves polyneuritis.

3. On the gl'Ollnd of the {h'st concillsion the hypo thesis of a­nenritic poison in the cliet, or a toxin, originating from the food in the inlestinal canal, as probable callsative factors of feeding'-poly­neuritis, must be abandoned, while probably na endogenous neuritic poison is in opel'ation.

4. A.ccording as the food is composed it plays the principal part in preventmg, but an infel'Ïor part in pl'oducing tlle disease.

5. Feeding, most likely causes an incl'eased consumption of anti- ~

neuritic substances. It seems hardly permissible to con~1 ude with BRADDON and COOPER and with FUNK that carhohydrates promote the katabolism mllch more than, for instance, proteins do.

6. 1'he rligestion of polished rice in fowls is aided throngh the admixtllre of cellulose to the food, not however, thl'ough the nddition of the antlnellt'itic extract from rieepolishings. The admixture of cellulose ma)' exel't a favourable influence upon the condition of nutrition; it would seem, on the othel' hand, that the outbl'eak of the disease is accelerated by it l'ather than retal'ded.

7. The ('onclusions l'egardillg the causative Ol' the prophylactic agency of certain factors in polyneuritis gallinal'llm, are, in so far as they al'e based upon a shortening or a lengthening of the l'el'iod of incubation, more or less doubtful on account of the considerabie individllal differences, exhibited by the animals expel'Îmented upon, even with a uniform treatment.

Utrecht, Januarj' 1916. The Instihtte of Hypiene of the Uü'ec/d University.

PhYsics. -- On tlte B1'ownian ~Movement in Gases" . 'BJ Miss A. SNBTHLAGE. (Commnnicated by Prof. J. D. VAN: DER WAALS).

(Communicated in the meeting of February 26, 1916).

Among the different derivations of the deviation which a particle sllspended in - a gas or liquid obtains in a time t, there is one of VON SMOIJUCHOWSKl 1

), in which only kinetic considerations al'e made nse of. L\.ccording to VON Sl\IOWCHOWSKI this deri vation wW onJy hold for gases, and th at only wh~n the climensions of the pal'ticle are smal! with respect to the mean free path of the surrounding molecules. As the Wl'iteL' himself observes, there is still something

1) VON SMOLUCliOWSl\I. Ann. der Phys. 21 p. 769 (1906).