Chapter III: Appendix: 81 (2)

By having thus presented to you the results of my experiments and explained my epidemiological views, I have not really deviated from the subject of the suppression of tuberculosis. We have seen that the tubercle bacilli which gain access to the system through the alimentary tract in infancy constitute the important etiological factor in the production of the tubercular infection which leads to consumption, and I believe that the realization of this great fact will supply us with a rational plan for combating tuberculosis. It will be necessary to strive more than ever to secure a suitable milk diet for new-born and very young children, one based on sound experimental investigations. The as yet unsolved problem, that of a rational milk hygiene in the suppression of tuberculosis, coincides with the problem of milk-feeding of infants in general. The mode of infection is everywhere the same, but the infectious agents are of great variety. Most of them excite acute diseases which end either fatally or in entire recovery; in the latter case with a simultaneous development of immunity. The virus of tuberculosis, however, behaves quite differently, creeping in most insidiously, all unnoticed, and being in this respect analogous only to the virus of leprosy, of syphilis, or possibly of malaria in tropical countries. It may be months, years, or decades before the infection leads to manifest disease. This depends on the virulence of the virus, which is generally much greater in the virus of bovine tuberculosis than in that of human tuberculosis. It also depends on the number of bacilli introduced per stomach, and whether such introduction is single or oft repeated. In the human being months and years may elapse before the infection is followed by any sensitiveness to tuberculin injections in the usual dose. If, then, at the time of puberty, or after an exhausting puerperium, after too great a demand on the milk secretion (especially with insufficient food), after so-called colds and other unfavorable meteorological conditions, after muscular over-exertion, under conditions unfavorable to life, such as improper nourishment, confinement in insufficiently or badly ventilated rooms, etc., if, after any of these, pulmonary disease develops whose tubercular nature we cannot doubt, then we are dealing with the _beginning of consumption_; the _beginning of tubercular lesions_ is much further back; and the first introduction of the disease germs, in other words, the _beginning of the infection_, is far back in earliest infancy. This must be so, for we see many individuals, though subject to the most unfavorable conditions, for example, those confined in unsanitary prisons, wholly escape tuberculosis.

The results of all these scientific investigations lead us back to the old folk belief in family tuberculosis and hereditary consumption, with this difference, however, that now we believe the germs of consumption to be transmitted _postgenitally_ from parents, relatives, or house-companions. If a coughing consumptive lives together with a new-born child, especially if cleanliness leaves much to be desired, it is impossible for this child to avoid infection with tubercle bacilli. They are present in the particles of sputum which are scattered about everywhere, and they thus gain access to the mouth and nose of the infant. From there they reach the intestinal mucous membrane, which they penetrate, and so they invade the body juices. Not alone infants, but older persons as well, are endangered in the home of the consumptive. In these, however, there must previously have been pathological changes in the alimentary tract, or an overwhelming dose of the infectious agent, in order to effect an intestinal infection. Pathological changes, accompanied by the shedding of epithelium, occur especially in the exanthemata, and particularly after measles. The laity has long noticed this close relation between measles and tuberculosis. In the infant, the disposition to intestinal tubercular infection is entirely physiological and normal. The healthiest and strongest infant is exposed fully as much as the weak, sickly one, and perhaps more so, for in the latter other parasites are contending for the cells on which they feed.

I have now given you a general idea of the origin and spread of the tubercular infections ending disastrously. This brings us at once to certain practical points in dietetic hygiene which, though never entirely neglected, are now brought into prominence.

It is unnecessary for me to further emphasize the necessity, in infant feeding, to insist under all circumstances on milk absolutely free from tubercle bacilli; nor, what is equally obvious, that it is absolutely necessary to keep coughing consumptives away from infants. But I should like to observe that not only infants but also older persons should be protected against the possibility of infection, if we have any reason to fear that the alimentary tract is anywhere deficient in its protective epithelial covering. I have already pointed out the importance of the exanthemata in this respect, and I need only remind you of the many other disturbances associated with the shedding of epithelium, disturbances due to catching cold, to indigestion, or the after-effects of certain diseases associated with intestinal ulceration, etc. There is one other condition which I must not fail to mention, namely, the temporary exacerbations of a tubercular process, in which one cannot be too careful in ordering the diet. For that large class of individuals threatened with consumption, I believe we have a valuable healing agent in the dietetic therapy made prominent during the past decade, especially by von Leyden and his pupils. In the same sense we must regard the temporary residence of tuberculous individuals in sanitaria as most valuable, for even if the lesions do not heal there, the progressive downward course of the disease is checked and the patients learn for the rest of their lives to appreciate what will benefit and what will harm them. In many cases, therefore, these sanitaria will prove themselves homes for the prevention of consumption, even if they are not homes for the cure of tuberculosis.

My own efforts in the field of tubercular therapeutics do not, to be sure, concern themselves with sanitarium treatment. _Their last aim is to make all homes for the prevention of consumption, all sanitaria, etc., unnecessary by means of a protective agent similar to that by which Jenner made smallpox pest-houses unnecessary._ Institutions for persons bodily wrecked are like those for persons morally wrecked; they are products of our civilization, but not desirable products. At best they are necessary evils.

OBSERVATIONS CONCERNING THE STUDY OF PHTHISIOGENESIS IN MAN AND IN ANIMALS.

1. It is possible in experiments on guinea-pigs to produce pulmonary phthisis by infecting these animals from the oral cavity in such a manner that every direct infection of the lungs (alveolar infection through the trachea = aerogenous infection of the lung) is excluded.

(_a_) Infection through the parenchyma of the tongue.

(_b_) Feeding of tubercle bacilli with milk.

2. Ascribing the pulmonary phthisis which I succeeded in producing experimentally to a lymphogenous or hæmatogenous infection of the lung following previous scrofulous disease. Definition of the term “scrofula”: multiple, caseating areas of disease in lymph-glands and in other organs, caused by Tb. infection. Concerning the etymology of the word “scrofula” (Greek = choeraden), see Virchow’s “Geschwülste,” Vol. II, p. 558.

3. Other varieties of experimental phthisiogenesis;

(_a_) v. Baumgarten’s experimental method of causing pulmonary
phthisis by means of primary infection of the urogenital
apparatus.

(_b_) The experiments of Troje and Tangl with tubercle bacilli
artificially weakened in virulence.

4. Critical analysis of the so-called “Inhalation Tuberculosis” of guinea-pigs and rabbits.

(_a_) My own experiments, in which the typical picture
heretofore regarded as that of an inhalation tuberculosis, in
the sense of an aerogenous alveolar infection, was produced by
lymphogenous or hæmatogenous introduction of tubercle bacilli,
with the complete exclusion of a primary alveolar or bronchial
infection.

(_b_) The experiments of Weleminsky (Hüppe).

(_c_) Signs distinguishing tubercular pulmonary consumption
from so-called inhalation tuberculosis.

5. Improbability, so far as importance as a phthisiogenetic factor is concerned, of a primary bronchial, or even primary alveolar Tb. infection following aerogenous introduction of Tb. into the mouth and nose, through the inhalation of dust or droplets containing tubercle bacilli.

6. Proof for my assumptions,

(_a_) That inhaled tubercle bacilli under circumstances
occurring in nature are taken up by the lymphatic receptive
apparatus without exciting, at the point of entry into the
lymph-channels, any tubercular disease.

(_b_) That inhaled tubercle bacilli, after they have entered
the lymph-channels of the throat, take the following courses:
some find lodgment in the submental glands and glands of the
neck; some are transported to the mediastinal (bronchial?)
glands; some gain the circulation and thus cause hæmatogenous
infections, especially at the peripheral (sub-pleural) endings
of the pulmonary artery, from which then the lung parenchyma
can be infected; finally, some are carried through the stomach
to the lowest portions of the intestines, from where they can
reach the mesenteric lymph-glands, the portal vein, and the
peritoneum.

(_c_) That the introduction of Tb. into the lymph-channels is
accomplished primarily by the leucocytic wandering cell, which
takes up the tubercle bacillus.

7. In the herbivora the Tb. are most commonly carried from the cæcum to the mesenteric lymph-glands. In man, the agminated lymph-follicles of the small, and the solitary lymph-follicles of the large intestine also serve as points of entry (cf. Carl Hof, “Ueber primäre Darmtuberculose,” Kieler Dissert., 1903. Compare also v. Hansemann, “Ueber Fütterungs Tuberculose,” _Berl. klin. Wochenschr._, 1903, No. 7).

8. Reference to the peculiar features of the stomach of ruminants and remarks on primary tuberculosis of the stomach (Schottelius).

9. The primary development of localized foci in the lesser omentum after infection through the stomach in early nursing period.

10. Peculiarities of the infection of nurslings through the alimentary tract, experimentally and statistically determined.

(_a_) Feeding experiments with anthrax bacilli and other
bacteria.

(_b_) Feeding of spores.

(_c_) Tubercular virus behaves in many ways more like the
resistant form [spore form] of anthrax virus, especially when
the Tb. virus is present in cheesy pus.

(_d_) The observations of Adalbert Czerny and Paul Moser on the
occurrence of bacteria in the blood of living human nurslings
(1894).

(_e_) Carl Weigert’s statements concerning the penetrability,
for Tb. virus, of the intestinal apparatus of very young
children. (From 1883, cited in _Deutsche medizin. Wochenschr._,
1903, No. 41.)

(_f_) Raw’s communication (_British Med. Journ._, 1903)
concerning 300 cases of _tabes mesenterica_, not one of which
was found to have developed in a child nursed exclusively at
the breast, but rather in those who had been nourished for a
considerable time on cow’s milk.

11. It is probable that in thickly populated countries practically every person is at some time or other infected with tuberculosis. Aside from the quantity and quality of the Tb. virus, the outcome of the tubercular infection is dependent to a high degree on the physiological state of the infected individual and on accidental conditions of infection. (Intercurrent pathological factors; endogenous and exogenous conditions of infection.)

12. Not a single unexceptionable case has been brought forward to show that under the conditions of life usually present in civilized lands, an adult person has ever contracted pulmonary, bronchial, tracheal, or laryngeal tuberculosis without having previously been infected and thus rendered oversensitive to the tubercular poison.

13. Against the action of tubercle bacilli entering the intestinal apparatus, healthy, full-grown persons apparently possess sufficient protection in the character of the mucous surfaces and the anti-bacterial action of the digestive juices. It has, too, still to be proved that healthy, full-grown persons become ill with tuberculosis as a result of eating food (milk, butter, meat) derived from tuberculous cattle.

14. Very probably adult persons frequently acquire intestinal tuberculosis through food containing tubercle bacilli, if the epithelial covering of the intestinal mucosa is defective, or if perhaps there exist ulcers which extend down to the parenchyma of the wall of the alimentary tract. (Exanthematic diseases, typhoid, dysentery, carcinoma, etc.)

15. Whether adult persons in whom the conditions are favorable for an intestinal infection with Tb. will develop primary tubercular lesions in the intestinal wall, or in the mesenteric glands and the peritoneum, will depend mainly on the circumstance whether or not, owing to a previous infection, they have become oversensitive to tuberculin. _Individuals oversensitive to tuberculin are inclined to develop lesions at the point of entry of the tubercular virus_, if opportunity is given for the introduction of the virus by means of leucocytic wandering cells. This opportunity is lacking in the virile infecting period at such places where the lymphatic receptive apparatus is destroyed [verödet]. (Mucous surfaces of the faucial ring of consumptives?)

16. In order to explain the mode of origin of cheesy pneumonias and tubercular broncho-pneumonias it is necessary at autopsy to regard most carefully the possible direct extension of the infection from cheesy mediastinal and bronchial glands to the bronchi and their branches, before thinking of aerogenous or hæmatogenous pathogenesis. (Compare [Ribbert] Sievers, “Marburg Dissertation,” Aug. 14, 1902.)

17. Critical analysis of several statistical statements which seek to show that alveolar pulmonary tuberculosis is referable directly to inhaled tubercle bacilli; especially the statement of Knopf (New York) cited by Mitulescu (_Zeitschrift für Hygiene_, 1903), that in Lansing, Mich., twenty employés of a library became consumptive through handling Tb. laden books.[5] Probability of the correctness of my assumption that Knopf was misled by unscientific communications from Lansing. Proof that Mitulescu again misunderstood Knopf.

18. It has not yet been proved that persons cutaneously infected with human or bovine Tb. have as a result of this developed phthisis. (My own observations on cases of infection on the hand in persons working with tubercle bacilli of various origins.)

19. Justification of the statement by Virchow in his “Phymatie, Tuberculose und Granulie,” that “the history of phthisis is concerned much more with cheesy hepatization than with tubercles” (Virchow’s “Tuberkel,” Begriff).

20. The analysis of the origin of pulmonary consumption must begin with the primary attack (primary regionally as well as chronologically) of the Tb. introduced into the organism.

21. _As a rule we can regard as points of primary infection polynuclear leucocytes in the blood and lymphatic receptive apparatus; next in order are the muscular elements in the walls of the smallest blood-vessels._ Endothelium and epithelium may become carriers of Tb. through the action of polynuclear leucocytes which have wandered into these tissues.

22. In studying the results of an infection with tubercular virus, aside from the degree of virulence, from the dosage, the single or repeated Tb. inoculation, and the primary point of attack (regional and cellular), we have particularly to consider the age at which the primary infection occurs. I distinguish four periods:

(_a_) Infantile period of infection;
(_b_) Puerile ” ” ”
(_c_) Virile ” ” ”
(_d_) Senile ” ” ”

23. It seems to me that in the epidemiological origin of pulmonary consumption the infantile Tb. infection, followed by latent or manifest scrofula in the puerile period, is of great significance, so that we can formulate the following doctrine: “_An infantile tubercular infection predisposes to tubercular pulmonary consumption_.” Under “scrofula” I here include the alteration in the muscle of the blood-vessels, caused by the Tb. infection, which finds its expression in the increased sensitiveness to tuberculin, and which in general is equivalent to “scrofulous diathesis” of the older authors.

24. The primary infection from the mouth or nose with tubercular virus derived from food or even from inhalation, in the small quantities that under ordinary conditions of life are concerned, is followed after the bacilli have entered the circulation, by alterations in the walls of the smallest vessels. These manifest themselves as follows:

(_a_) Microscopically, by a loosening of the vessel wall,
between whose elements, shortly after the infection, tubercle
bacilli can be found. These bacilli, brought here by the
wandering cells, are set free on the destruction of the cells.

(_b_) In primary functional disturbances which can be
recognized by the temperature curve and the heart action.

(_c_) In secondary tuberculin hypersensitiveness.

25. Following mild infections the alterations in the vessel walls may retrogress with a suppression [Beseitigung] of the tubercle bacilli. Without exception, however, the hypersensitiveness to tuberculin remains, varying in degree and length of time according to the virulence of the infecting Tb. and to their more or less locally limited action on the vascular system.

26. After a moderately severe infection there is a formation of transparent, submiliary eruptions (nowadays our “gray miliary tubercle”), especially about the smallest vessels of serous membranes. _These eruptions are capable of becoming organized. In fact, when they have healed they form a tissue entirely identical with the tissue in which they originated._ (Bichat, Lebert, Empis, and many other older investigators.) Aufrecht, _Deutsch. Arch. f. klin. Med._, Vol. LXXV.

27. The introduction of a tubercular virus so strong as to cause the smallest vessels to become occluded, especially Cohnheim’s terminal arteries of the spleen, lungs, and kidneys, results in the exudation of a coagulable fluid and in necrobiosis of the extra-vascular region supplied by those vessels. (Aufrecht, _Arch. f. klin. Med._, Vol. LXXV.) Into this dead area tubercle bacilli are dragged by the wandering cells. These bacilli multiply and cause chemical changes which manifest themselves first in a fatty (steatomatous) and then in a cheesy metamorphosis. (Cf. Koch, Volume II of the _Mittheilungen aus dem Kaiserlich. Gesundheitsamt_, p. 21, and Plate IX, Figs. 45 and 46); my own observations; Aufrecht, 1. c.; compare also the critical reference by Virchow to the works of older authors, such as Vetter, Gendrin, Lobstein, Cruveilhier, Bayle, Baillie, Laënnec, Rilliet and Barthez, Vulpian, Craigie, etc., in “Phymatie, Tuberculose und Granulie,” and in Vol. II of “Die Krankhaften Geschwülste.”

28. We may enumerate as the result of primary tubercular focal disease

(_a_) Anatomically demonstrable residues.
(_b_) Functional alterations.

29. Functional alterations may remain without any anatomically demonstrable residues of the primary infectious processes. I divide functional alterations into

(_a_) Alterations which leave behind them an immunity against
living Tb. virus, probably to be sought for in the peculiar
condition of the vessel musculature and, in the beginning at
least, always associated with hypersensitiveness to the soluble
tubercular poisons.

(_b_) Scrofulous diathesis, consisting in such changes in the
vascular system and the lymphatic apparatus that a renewed Tb.
infection very readily causes cheesy tubercular lesions.

30. As scrofulous infectious processes, I regard

(_a_) Lupus, which I interpret as a cutaneous additional effect
of a tubercular infection.

(_b_) Gland scrofula,[6] inclusive of tuberculosis of the
mediastinal, bronchial, and mesenteric glands.

(_c_) Bone scrofula and joint scrofula.

(_d_) Scrofula in the domain of the external body covering, of
the mucous membranes, and of the lymph-channels.

(_e_) Cheesy metamorphosis in internal organs, inclusive of the
organs of sense, and the vessel intima.

31. The acute miliary tuberculosis in man, which can be clinically diagnosticated, is to be regarded as a provocative secondary infection, resulting from scrofula of the blood-vessels’ intima when, on the disintegration of cheesy intima tubercles, a great many tubercle bacilli are thrown into the circulation at once. (Weigert-Ponfick.)

32. Disease of the lung apices occurring in the virile period of infection and, because of its important bearing on the origin of consumption, considered separately, is preceded by the consequences of an infantile infection. Foremost among these is the secondary hypoplasia of the smooth muscle tissue (of vessels, bronchi, and intestinal wall); next in order come wasting [Veröding] of the lymphatic apparatus (quantitative and qualitative reduction of the follicular receptive apparatus of the _tubus alimentarius_); destruction of lymph-glands; and the secondary hypoplasia of other primary points of attack for Tb. action (in the spleen, bone-marrow cavities, on serous surfaces of the large body cavities, and of the joints). The predilection of the thoracic dome for immobilizing changes can probably be ascribed to its exposure to the Tb. infection in connection with precedent mediastinal-gland scrofula; while the predilection of the lung apices for caseating lesions can again be brought into causal relation with secondary ossifying processes, of scrofulous origin, in the joint structures of the thoracic dome (cf. Aufrecht, 1. c.).

33. In my experiments on tubercular cattle I succeeded in producing eruptions of gray, non-caseating tubercles, running an acute course, by means of injections of tuberculin. At the same time it was noticed that not infrequently after the intercurrent exacerbation had subsided, the old infectious process had been favorably influenced.

34. Even when caseating lesions are present, the simultaneously developing submiliary transparent eruptions (granulie, of the older authors) are to be regarded as capable of being organized and spontaneously cured. They are much more numerous in man than has heretofore been assumed. This is shown, for example, by the fact that upon opening the abdominal cavity of such young individuals as showed no clinically diagnosticated symptoms of a miliary tuberculosis, these eruptions were by chance demonstrated.

It is of the highest interest to determine the fate of such individuals with a healed miliary tuberculosis of the peritoneum, that is, whether in virile period of life the disposition in them to pulmonary consumption is increased or diminished.

35. The clinical picture of scrofula in the puerile period of infection is etiologically complicated by other infectious processes, especially in the domain of the outer body covering. The functional alterations in the vascular system, due to an infantile Tb. infection, find their expression not only in the organism’s increased sensitiveness to tuberculin, but also in a marked instability [labilität] of the dynamic equilibrium of the circulation (lymphatic constitution). In consequence of this, eczematous eruptions due to parasitic and toxic agents result much more readily in these individuals than in those who have not suffered such an infantile Tb. infection (one incompletely healed).

36. The symptoms of the so-called “inclination to consumption” are the expression of a defective overcoming of the infantile and puerile infectious periods. The hindered development and weakness of the organs made up of smooth muscle fibres (muscles of the blood-vessels, intestinal wall, and bronchi) are comprehensible when we remember the great share that the smooth muscle tissue has in the reaction against the Tb. circulating in the blood. The question whether the weakened conditions and hindered development in the domain of the striped muscles are due directly or indirectly to the Tb. infection cannot be answered without further investigations. Similarly, we do not yet know the mechanism of the origin of the chest anomalies seen in candidates for consumption. A partial impoverishment of the intestinal lymphatic receptive apparatus is presumably accountable for the fact that even a plentiful supply of food is unable to increase the accumulation of fat.

37. The possibility must also be considered that in the course of the puerile period of infection the development of a caseating tubercle may proceed in the joint tissues between costal cartilage and breast-bone, and that such a scrofulous thoracic affection is clinically much less readily diagnosed than a similar affection in bones of the extremities. Further, that such a lesion in the lower extremity is much more readily recognized than one in the upper extremity, since even slight alterations in the bony tissues of the lower extremity, because of functional disturbances in walking and running, make themselves manifest.

38. For a detailed analysis of the origin of pulmonary consumption, beside the results of infantile and puerile infections, there must still be considered

(_a_) Additional virile Tb. infections (cf. Romberg, _Deutsch.
Arch. f. klin. Med._, 1903).

(_b_) Combined action of a complicating infection.

(_c_) The co-action of general hygienic and dietetic injuries.

39. For my plans for suppression of tuberculosis, therefore, the following points are essential:

(_a_) Prevention of the introduction of Tb. with food,
especially with milk, during infantile life.

(_b_) Introducing Tb. anti-bodies with the milk in earliest
infancy in order to render innocuous any inhaled tubercle
bacilli.

40. I have made separate communications regarding feeding with Tb.-free milk. The production of such a milk will be very easy if my method of cattle immunization in practice fulfils the hopes, which I have for it; and these hopes I am convinced are fully justified.

41. In order to produce immunity by means of anti-bodies it is probable that anti-bodies derived elsewhere will have to be added to the milk given to infants.

SUGGESTIONS CONCERNING THE HYGIENE OF COW-STABLES AND THE PRODUCTION OF MILK FOR INFANT-FEEDING, WITH SPECIAL REFERENCE TO TUBERCULOSIS.

THE BONN RULES.

1. Until it has been definitely decided whether or not my protective cattle inoculation protects cattle against tuberculosis when these are kept in stalls or herds strongly infected with Tb. virus, it should be sought to reduce the danger of infection as much as possible by following Ostertag’s recommendations and segregating all the cattle with an open tuberculosis.

2. The milk of cows which react positively to tuberculin must not be used for feeding calves, nor, of course, for infant-feeding.

3. Whenever the circumstances permit, the separate housing of the protectively inoculated animals in a stable free from tuberculosis is to be recommended. In constructing new stables it is strongly urged that in place of _one large_ stable, several small ones be erected; besides this, attention should be paid to the placing of the animals. They should be placed with the heads toward the lateral walls, and not head to head, facing a common feeding-trough along the middle of the stable.[7]

4. Particular attention should be paid to the cleanliness of the feeding-troughs. Every fourteen days they are to be filled with hot water and freed from any adherent dirt by mechanical means. The feeding-buckets are to be similarly cleansed from time to time.

5. The drinking-water supplied to cattle should meet essentially the same requirements as are demanded of water supplied to dwellings.

6. In maintaining the health of the young cattle an important factor is the pasturage. For larger dairies an arrangement used at our Marburg experimental station, consisting of a lightly constructed shelter within a large enclosed pasture, is to be recommended.

7. The disinfecting of infected stables is to be done in accordance with the government regulations.[8] [This refers to the German regulations of June 23, 1880, and May 1, 1894.] Here it is to be remarked that disinfection of the stables by means of formaldehyde generation is not even then accomplished when one far exceeds the requirements formulated by Flügge for the Breslau method. Utilizing the opportunity presented by a number of courses given at Marburg in the method of making protective inoculations, etc., we have found that even in the stable of the pest laboratory here, which is very easily closed off, the above-mentioned formaldehyde fumigation is ineffectual; for by treating the disinfected objects with ammonia water it was found that neither anthrax virus nor cocci, in the dry state, were certainly destroyed by the fumigation.

8. More important than the disinfection by means of chemicals is the prevention of the accumulation of infectious materials on the stable utensils, in the food, on the body surface of the cattle, on the body and clothing of the stablemen. Training the stablemen to the use of warm or hot water and soap; the use of towels and dishcloths which have been rendered germ-free by means of hot water or dry heat before throwing them among the soiled clothes; special regard to a rational care of the milker’s hands, including the removal of the dirt under the nails; all of these are the most important measures for the prevention and suppression of stable infection.

9. If it is desired to secure a milk as free from dirt and germs as possible (not over 400 germs per c.c.), the following additional measures must be taken:

I. Presupposing that the milk is to be used for infant-feeding, the same is to be filled into bottles holding 250 to 500 c.c. All parts of the bottle, including the air-tight and germ-tight closing contrivance, must be constructed so as to be readily cleansed, and further, so that they can, without injury, be sterilized by heat.

II. In order to meet all the requirements for cleansing and sterilizing milk-bottles, the following rules are recommended. The bottles returned by the consumers are in a soiled condition and contain fluid remnants of milk:

(_a_) The cleansing of the bottles should be undertaken in a
well-ventilated room which can readily be kept clean and which
may also serve as the bottling room. This room is to be so
separated from the stables that the stable odors cannot gain
access.

(_b_) The following manipulations are required to clean the
bottles:

(α) Energetic rinsing with 10% warm soda solution.

(β) Rinsing with quartz gravel by means of a stream of hot
water.

(γ) Cold rinsing.

(δ) Sterilization in the dry chamber. These cleansing
manipulations occupy about forty-five minutes.

III. The stable itself should be so built that it can readily and thoroughly be cleansed, with special regard to the following points:

(_a_) Draining of the fluid excreta, etc., by means of drains
with sufficient pitch.

(_b_) Ready removal of solid refuse without raising dust.

(_c_) A plentiful supply, by means of pipes, of pure, wholesome
water. Also a hot-water supply for cleansing purposes.

(_d_) Good ventilation for the high lying stalls.

(_e_) Broad alleys separating the rows of stalls.

(_f_) Each stall to be constructed in such manner that the cow
is obliged after feeding to step back, thus compelling her to
empty her excreta into an open drain connected with the main
drain. This is effected by means of the so-called “drop-railing
contrivance.”

(g) Water-tight flooring.

IV. The spreading of peat instead of straw to keep the stalls dry.

10. Another deciding factor in the production of a pure milk for infant-feeding is the cleanliness of the stable and dairy attendants, the milkers, the cows, and the stable and dairy utensils.

I. Aside from general body cleanliness, particular attention is to be given to a healthy condition of the milking person’s hands. Before proceeding to milk, these persons are to don a clean gown made of white linen.

II. The cows are to be kept scrupulously clean. The udders and tails are to be so clean that they can be touched with white-kid gloves without causing appreciable amounts of dirt or of odorous substances to soil them. In order to keep the udder and teats clean the following is recommended:

Just before milking, the udder, which should always be kept dry, is to be rubbed off with a clean flannel cloth which has been greased with a little lard. By this means dirt and odorous substances are most readily removed. Following this, the parts are rubbed dry with the aid of a little bran.

III. The milk vessels should be of tinned sheet iron.

IV. The milk should be strained through aluminium-nickel gauze or brass gauze, which is then to be cleaned and disinfected.

V. All the milk of one milking period is pumped high into the bottling room and conducted into a collecting reservoir. This passage to the reservoir, during which it is cooled and aired, occupies only a few minutes and the milk reaches the reservoir at a temperature of 4°-5° C.

VI. From this reservoir the milk is bottled without delay by means of a bottling-machine, the milk having a temperature of about 5°-7° C. on bottling. _A temperature of less than 2° C. has an injurious influence on the anti-bacterial substances in the milk, and should therefore be avoided._

11. If the milk hygienic rules above mentioned are carefully followed, and if attention is paid to the experiences regarding a rational method of feeding milch cows, it is possible, without any further method of preserving the milk, to have the same capable of being transported and kept for sixteen hours without losing its adaptability as infant food. In Berlin I saw such a milk reach the consumer with a germ-content of not over 1000 germs per cubic centimeter. On the other hand, I have seen milk derived from dirty cows and collected without particular hygienic precautions, after being transported six hours, contain a hundred to a thousand times as many germs. In such cases, soon after milking, the milk often contains from 30,000 to 100,000 germs per cubic centimeter.

In the strictly fresh milk from my own cows the number of germs per cubic centimeter varies from 10 to 50 to 200. Such milk kept at room temperature does not coagulate until after three to five days.

At present I regard 1000 germs per cubic centimeter at the time of feeding to be a safe limit for milk fed to infants.

12. If a milk collected in accordance with the preceding regulations is to be made capable of being transported and kept for three days (in which case coagulation factors must be reckoned with) without losing its qualifications as an infant food, the addition of formaldehyde in the proportion of 1:40,000 (B. f. milk) is to be recommended.

The following manipulations are then to be carried out:

I. Preparing a formaldehyde stock solution containing 0.5% formaldehyde. (One part of commercial formaldehyde and 79 parts of boiled water.) This solution will keep for two or three days.

II. Pouring 50 c.c. of this 0.5% stock solution (= .25 gramme formaldehyde) into an empty tin pail in which a mark has been made at the 10-liter level.

III. Milking into this pail up to the mark.

IV. Straining, airing, cooling, etc., according to paragraph 10, IV, V, and VI.

13. In order not to conflict with the government sanitary regulations the milk producers at present delivering this B. f. milk have agreed to supply it only to certain private institutions designated by me.

14. Should the authorities later decide to allow the sale of this B. f. milk, it is recommended that licenses be issued, out of the proceeds of which veterinary physicians be appointed to see that this B. f. milk is produced in accordance with these regulations.

15. Containers for B. f. milk should have trademarked labels indicating that the milk has been produced in conformity with the requirements. Beside this the label should bear in clear figures the time and date of milking.

16. Whenever for any reason it is impossible to raise a calf directly on the udder, B. f. milk should be preferred to milk sterilized by heat. In the production of B. f. milk tubercular and suspected tubercular cows are to be excluded on principle.

17. Where it is desired to suppress an infectious process in the digestive system of cattle, the temporary employment of a stronger formaldehyde milk (1:25,000 to 1:16,000) under the direction of a veterinary physician is recommended.

18. In the suppression of “_Kälbersterbe_,” beside the increased requirements regarding the cleanliness of attendants’ clothing and body, of stable and stable utensils, the proper care of the navel with the aid of ⅖% aqueous solution of formaldehyde is recommended.

19. The radical suppression of bovine tuberculosis by means of my protective inoculation is to be sought for.

20. The following article shows the method of making these inoculations at present in use at Marburg.

SYNOPSIS FOR PROTECTIVE INOCULATION OF CATTLE IN AGRICULTURAL PRACTICE.

GENERAL CONSIDERATIONS.

For the protective inoculation carried out by us in practice we make use of “Mxt. Tb.” in the form of our “Culture No. 1,” which has been studied by us for years and which we have minutely described in the _Beiträge_, Nos. 5 and 6. The accumulation of orders for this virus on the one hand and the multitudinous experimental labors in the institute here on the other, compelled us to rid ourselves of the technical labor of manufacture, weighing off and shipping of the virus, which accordingly has been undertaken by the local firm of Drs. Siebert & Ziegenbein. The virus, however, continues to be tested as to purity, virulence, etc., in the scientific department of the institute at Marburg.

The virus is accompanied by directions for use which have already appeared in the _Zeitschrift für Thier-medicin_. These are as follows:

I. SELECTION OF THE ANIMALS TO BE INOCULATED.--As a rule only animals without external evidences of disease, from three weeks to three months (for the first inoculation) should be inoculated. In healthy animals of this age a previous tuberculin test is unnecessary, even if the animal comes from a notoriously tubercular herd.

II. NUMBERING THE INOCULATED ANIMALS.--Every inoculated animal must be marked with a running number. The marking must be of such a character as to be distinct, not liable to be mistaken for some other, and to last the lifetime of the animal. (Ear-marking, tattooing, etc.) If necessary, the marking is to be repeated should the first mark become indistinct.

III. KEEPING OF RECORDS.--See under “Conditions governing the distribution of the virus, etc.,” p. 75.

IV. TECHNIQUE OF TAKING THE TEMPERATURE.--The body temperature is determined by means of a self-registering thermometer completely inserted into the rectum. Before introducing it, the rectum is to be cleared of any hard fecal masses. A tape about a foot long, having a clamp at its end, is tied to the neck of the instrument. The thermometer is left in the rectum for four minutes, the clamp meanwhile being fastened to the hairs at the root of the tail. In order to save time, thermometers are introduced into a number of animals (about six) consecutively. When the last thermometer has been inserted it will usually be time to extract and read the first. In this way one can take the temperature of fifty head of cattle in 1-1½ hours.

V. THE VIRUS.--The inoculating virus consists of living tubercle bacilli whose action has been accurately tested in the Marburg Institute for Experimental Therapy. The tubercle bacilli have been dried without losing their vital powers in any way. These dry tubercle bacilli (Trocken Tb.), kept in sealed glass tubes, will retain their action on cattle unchanged for a period of thirty days. If, therefore, a tube of Tb. bears the date VII-1-02, the contents can be used for cattle immunization until VIII-1-02. After thirty days, although the immunizing power is not entirely lost, it is so far decreased as to render it ineffective in the dosage recommended.

VI. DOSAGE OF THE VIRUS.--For the first inoculation, one immunizing unit, 1 I. E. [= 1 Immun Einheit] is used for each calf; for the second inoculation, which is not to be undertaken until at least twelve weeks after the first, five units (5 I. E.) are used for each calf. As a rule the dose of 1 I. E. is 0.004 gramme dry Tb., that of 5 I. E. for the second inoculation is therefore 0.02 dry Tb.

If the tube contains the quantity requisite for the first inoculation of twenty cattle, it will bear the label 20 I. E. In order at all times to control the manner of production of the dry Tb. each tube also bears in Roman numerals the consecutive laboratory number thus:

+-------------+
| Op. No. IV. |
| 20 I. E. |
| VII-17-02 |
+-------------+

This label is interpreted as follows:

Dry Tb., which in the records of the Marburg Institute bears
the laboratory number IV, contain on the day of delivery, i.e.,
on VII-17-02, twenty immunizing units, and retain this strength
until VIII-17-02.

For the inoculation the virus is uniformly mixed with 1% salt solution which has previously been boiled and cooled. The procedure is as follows:

The entire contents of the tube are placed in a small mortar and crushed with the pestle. Then 2 to 3 c.c. salt solution are added and the whole rubbed into a uniform mixture or emulsion, after which it is poured into a graduated cylinder holding 50 c.c. A little more salt solution is then added to the mortar, and thus the remaining particles of virus are added to the previous mixture. The fluid in the graduate is then made up to 30 c.c. with salt solution, and then poured into a sterile wide-mouthed bottle holding 100 c.c. Any remaining emulsion is then washed out of the graduate with an additional 10 c.c. salt solution and added to the 30 c.c. in the bottle. The bottle thus contains virus ready to inoculate, and each 2 c.c. will be the dose for the first inoculation of a calf, provided that the tube originally contained 20 I. E. The dose for a second inoculation would then be contained in 10 c.c. of this fluid.

VII. INSTRUMENT CASE.--In order to carry out the inoculations in agricultural practice, the instrument case constructed by W. Holzhauer, Marburg, is to be recommended. It contains the following:

(_a_) Two bottles for the virus, each 100 c.c., made of colored
glass.

(_b_) One bottle lysol.

(_c_) One bottle alcohol.

(_d_) One Erlenmeyer flask (for 1% salt solution).

(_e_) One mortar and pestle.

(_f_) One graduated cylinder 50 c.c.

(_g_) One graduated cylinder of 10 c.c.

(_h_) One basin to hold disinfectant solutions.

(_i_) Six thermometers with tapes and clamps. (Price 10.50
marks or 1.75 marks each.)

(_k_) Two virus syringes with two strong canulas. (Price 11
marks.)

(_l_) One small hand-scale and weights.

(_m_) One alcohol stove and cover.

(_n_) Sterile cotton.

(_o_) One wire basket.

The entire box is supplied with a canvas cover and a leather handle. The lid, which bears four movable legs, can, when the same is removed from the box, be set up like a saucepan and used as a sterilizer. For this purpose the vessels and instruments are placed into the wire basket, the sterilizer half-filled with 2% lysol solution, and the whole heated just to boiling by means of the alcohol stove.

The price of the complete outfit is 85 marks. By omitting the thermometers and syringes the price is reduced to 63.50 marks.

VIII. METHOD OF MAKING THE INTRAVENOUS INJECTION.--The injection is best made by means of a 5-c.c. glass syringe with an asbestos plunger (paragraph VII, _k_), which is cleaned by means of the lysol solution and rinsed in sterile salt solution. The canula attached to the syringe is cleaned in the same manner. One immunizing unit (1 I. E.) is then drawn up into the syringe and any air-bubbles are expelled, care being taken that any drops of fluid expelled in this manner do not fall on the floor but are caught up in the basin. The filled syringe, together with the canula, which is now detached, is then placed on the previously mentioned basin. The virus is injected into the left jugular vein. When possible the cattle should be inoculated, each in its own stall, so as to avoid exciting them. After washing the left side of the neck with 2% lysol solution, the operator, by pressing his thumb on the jugular vein, stops the circulation, causing a distinct, sausage-shaped, fluctuating swelling to appear. With his right hand he now takes the canula from the basin and thrusts it, just above the compressing thumb, upward into the vein at an angle of 45°. One recognizes that the vein has been entered, by the blood that at once flows through the canula. If no blood flows, the vein has not been entered. In that case the canula is withdrawn slightly but not completely, and again thrust into the fluctuating swelling. As soon as blood flows, the left hand ceases making pressure and grasps the canula, whilst the right hand fits the syringe thereto. Then the virus is slowly and uniformly injected into the vein. When the syringe is emptied, the skin at the site of injection is pressed together and the syringe and canula withdrawn. As a rule, bleeding ceases almost at once. The region is then rubbed over with 2% lysol solution and the inoculation is completed.[9]

CONDITIONS GOVERNING THE DISTRIBUTION OF THE VIRUS PROTECTIVE AGAINST TUBERCULOSIS.

1. The virus is supplied by the firm of Drs. Siebert & Ziegenbein in Marburg a. d. Lahn, Germany.

2. This firm supplies the virus in packages containing 5 I. E. and 20 I. E. The price for the former at present is 40 pf. per I. E. and for the latter 25 pf. per I. E. In ordering, the style of package is to be specified.

3. The recipients bind themselves to fill out and return the following records:

A. Temperature charts: The temperature is to be recorded as a curve.

B. Other data as per blank herewith enclosed (see next page).

+---+--------------------------------------+-------------------+
| A | Consecutive Marburg Number. | |
+---+--------------------------------------+-------------------+
| B | Consecutive Inoculation Number. | |
+---+--------------------------------------+-------------------+
| C | Breed, Herd and Designating Number. | |
+---+--------------------------------------+-------------------+
| | | I.|Owner. | |
| | +----+-----+---+----------------+-------------------+
| | | | | A |At Birth. | |
| |Natio-| II.|Loca-+---+----------------+-------------------+
| D |nali- | |tion.| B |At Time of | |
| |ty. | | | |Inoculation. | |
| | +----+-----+---+----------------+-------------------+
| | |III.|Breed. | |
| | +----+--------------------------+-------------------+
| | | IV.|Sex. | |
+---+--------------------------------------+-------------------+
| | | I.|Natural (Suckling Calf). | |
| | |----+------+--+----------------+-------------------+
| E |Manner| | |a |With Non- | |
| |of | |Arti- | |sterilized Milk.| |
| |Rai- | II.|fi- +--+----------------+-------------------+
| |sing. | |cial. |b |With Sterilized | |
| | | | | |Milk. | |
+---+--------------------------------------+-------------------+
| | | I.|Laboratory Number of | |
| |Pro- | |the Virus. | |
| |tec- +----+--------------------------+-------------------+
| F |tive | II.|Dose in Grammes or in c.c.| |
| | +----+--------------------------+-------------------+
| |Inno- |III.|Date and Manner | |
| |cula- | |of Inoculation. | |
| |tion. +----+--------------------------+-------------------+
| | | IV.|Degree of Reaction. | |
+---+--------------------------------------+-------------------+
| |Tuber-|Date. | |
| G |culin +-------------------------------+-------------------+
| |Test. |Degree of Reaction. | |
+---+--------------------------------------+-------------------+
| H | |Weights. | |
+---+--------------------------------------+-------------------+
| I | |Special Remarks. | |
+---+--------------------------------------+-------------------+

DIRECTIONS FOR FILLING THIS BLANK.--Column A is to be left
blank by the attending physician; column B contains the running
number of the animal inoculated; C is to be recorded only in
fitting cases; D, on the other hand, is never to be omitted;
under E the fitting column is to be marked thus: “!”; in column
F, IV, the degree of reaction following the inoculation is to
be noted by signs, thus: O = Failure of any reaction whatsoever
(R = O); I = short febrile reaction; II = 2-4 days of fever;
III = 5-8 days of reaction associated with other disturbances
of health (cough, loss of weight, diminution of appetite,
diarrhœa, etc.).

In the same manner the degree of the reaction to a later
tuberculin test is to be recorded (column G). In column H the
weight is always to be accompanied by the date.

_The returns are to be made as soon as the data for about 100
cattle have been secured._

C. General report: This includes a report on the manner of keeping the inoculated cattle, the hygienic conditions of the stables, previous occurrence of _perlsucht_ in the cattle of the herd, previous use of other means of suppression of tuberculosis and their result, etc., etc.

4. The owners of the cattle must see to it that the inoculations are properly made and they themselves must bear all consequences resulting from defective inoculation. Drs. Siebert & Ziegenbein can in no way accept responsibility for this.

* * * * *

The preceding conditions are still adhered to in many large dairy farms. To a number of smaller dairies we have allowed easier conditions. An example is afforded in the following order of the Ministry of the Interior of the Grandduchy of Hesse.

MINISTRY OF THE INTERIOR OF THE GRANDDUCHY OF HESSE,

DEPARTMENT OF PUBLIC HEALTH.

To the Grandducal County Veterinarians:

Whereas, following the proclamation of the Ministry of the Interior dated Aug. 19, 1902, a large number of replies has been received from the farmers, it is ordered that the inoculations be hereafter made in accordance with the following principles:

1. The protective inoculation consists in the intravenous
injection of a _single_ immunizing unit of tubercle germs
(derived from man), rubbed up with sterile salt solution; and
in a second intravenous injection, three months later, of
_five_ immunizing units of the same germs.

2. The germs in question can be obtained in glass tubes
containing 5 or 20 units.

3. As a rule only cattle without external manifestations of
disease, aged from three weeks to four months (at the first
inoculation) should be inoculated. With healthy animals of this
age it is unnecessary to test them previously with tuberculin,
even if they belong to a notoriously tubercular herd.

4. In exceptional cases older animals (from four months to two
years) may be inoculated with the virus, but only when they are
entirely free from disease, _and when a tuberculin test made on
them results without any reaction whatsoever_.

5. The inoculated animals are to be kept in their stalls two
days before and two weeks after the inoculation.

6. In all cases in which the owners can manage the rectal
temperatures, the same are to be taken two days before the
inoculation (morning and evening) and again on the morning of
the inoculation. After this they are taken once more in the
evening and then once daily for the next five days. If, after
this, the animals still have temperatures above 39.2° C., the
temperatures are to be taken daily until the same reach 39.2° C.

7. In animals not over four months old at the time of the first
inoculation, the temperature may be omitted if there be any
difficulties in taking it. In those, however, which are over
that age at the time of the first inoculation, the temperature
must invariably be recorded according to paragraph 6. Even
when inoculating animals in infected herds the above-mentioned
measurements should be taken whenever practicable.

8. If possible, the inoculated animals should be weighed every
fourteen days on a cattle scale.

9. Owners of cattle are to keep record of all the temperatures
and weights. You are to collect the records concerning
temperatures as soon as they have been completed; the records
of the weights, however, only after three months. The results
noted in the temperature returns are to be entered by you on
the charts herewith provided, and a temperature curve plotted.
These charts are to be made in duplicate, one copy to be
sent to our representative and the other to the Experimental
Division of the Hygienic Institute, Marburg.

10. The inoculated animals are all to be permanently marked.
Those on which temperature and weight observations have been
made should also be numbered.

The method of thus marking and numbering the animals is left to
your judgment.

11. Should you not be informed in regard to the previous
notifications respecting the inoculations, kindly place
yourself in communication with the grand-ducal “Kreis Amt.”
Following this, as soon as you have informed yourself regarding
the age and health of the animals to be inoculated, notify our
representative as to the number of these animals suitable for
inoculation. The reports for each village are to be made out
separately.

12. The necessary virus and utensils, as well as explicit
directions for use, will be furnished by us.

13. We shall see that your first inoculation is attended by our
representative.

(Signed) ----

DARMSTADT, Nov. 16, 1903.