Owing to the uniformity of the bony changes throughout the whole series of meat-fed animals, it was unnecessary to make a histological examination of each subject. Sections were accordingly made from forty out of the hundred meat-fed rats and from an equal number of control bread-and-milk-fed animals. In this examination special attention was directed to the following points: -
(a) Long bones. - The state of their development, by intra-membranous and intra-cartilaginous ossification.
(b) The histological appearances of the cranial bones.
(c) Ribs. - The minute structure of the nodules present in the bony ribs.
The ossification of the long bones of meat-fed rats is delayed and imperfect, the defect involving both the endochondral and periosteal bone formation. The epiphyses are for the most part normal; in some instances there is a slight irregularity in the size and arrangement of the cartilage cells at the bone-forming margin. The minute structure of the epiphyses of the long bones may be normal, even in animals in which pronounced rachitic-like changes are present in the skeleton. The bone-marrow of the meat-fed rats set. six weeks and onwards shows, in some subjects, a great excess of fat.
In the meat-fed rats, ossification, both intra-membranous and intra-cartilaginous, is less advanced than in the control animals, the bony trabecular in the former being less numerous and enclosing a marrow excessively rich in red blood-corpuscles (see Fig. 12, and compare Fig. 13). While intra-membranous and intra-cartilaginous ossification are both affected, the defect is in some cases more pronounced in the periosteal bone-formation.
There is a striking difference in the degree of development of the frontal, malar, and maxillary bones in the bones of the meat-fed animals at birth, the contrast becoming accentuated as age advances. The bones of the jaws in the meat-fed subjects are of a different shape from the controls, the former being wider and more square-shaped. This condition is associated with an extreme thinness of the hones;md a great increase ill the number of cells - red blood-corpuscles and leucocytes - in the medullary cavity in the meat fed rats (see Figs. 12 and 13). In a very few animals at. three weeks, the difference between the development of the bones in meat-fed and bread and-milk-fed animals is very slight The average state of bone development in the two series is further illustrated in Figs. 14 and 15 for animals at. three weeks. The bony trabecule in the meat-fed rats are extremely thin, and the medullary spaces show a great increase in the number of thin-walled vessels, which are distended with red blood-corpuscles. This increase in the number of red blood-corpuscles in the medulla of meat-fed rats is, in the great majority of subjects, a very striking feature (see Figs. 16 and 17).
These nodules present a striking histological picture. They are composed mainly of cartilage cells, which are derived from the periosteum; at the periphery of these nodules the nodules are undergoing transformation into bones (see Fig. 18). It is of interest to note that 1 have recently observed a similar histological appearance in the bones of an infant at. fifteen months, whose mother - a tuberculous subject - was fed during gestation, and for some time prior to it, on a diet containing a great excess of meat (see Fig. 19).
The results show that the bones of animals fed on an excessive meat diet present an appearance of delayed and imperfect ossification, with increased vascularity and an increase in the number of red blood-corpuscles. Associated with this there is in a number of cases the presence in the bony ribs of nodules of cartilage, developed from the periosteum, with direct transformation of these cartilage cells into bone. It is noteworthy that, while the naked-eye appearances of the skeleton may closely simulate those present in advanced cases of rickets in the human subject, the microscopic appearances in the epiphyseal lines of the long bones are quiet distinct from those present in that disease. The thief object of this paper has been to describe the naked-eye and microscopic appearances of the osseous system in young animals - omnivorous feeders - which are fed on a diet containing an excessive amount of meat. The full consideration of how far the facts observed admit any deductions applicable to disease in the human subject is beyond the scope of the present work. I may here, however, refer in some detail to what, so far as I am aware, is a unique record of disease in an infant, in which the facts prove that the results of the present investigation have a real and practical value for the practitioner. The essential facts of this case are as follows: -
The mother of the patient had pulmonary tuberculosis, and made a satisfactory recovery under prolonged treatment along modern lines, one feature of the treatment being the daily administration of a large amount of nearly raw meat. The patient married and continued to take an excessive meat diet. A child was born after eighteen months, and, in view of the family history, was artificially reared under the best hygienic and general conditions. The infant thrived fairly well until a year old, when there was some trouble with delayed dentition, for which the advice of the family practitioner was sought. As the application of simple remedies proved unavailing, and the child became anaemic and further out of condition, a second opinion was obtained. The chief alteration in the treatment was the administration of raw-meat juice, which was continued for six weeks. Under this regime the condition of the child steadily deteriorated, the anemia becoming more pronounced and being associated with marked physical and mental lethargy, fretful-ness on movement, and a few purpuric and petechial spots; there were no other symptoms or physical signs of note. The child was then seen by a distinguished paediatric physician. After repeated examination of the case, which was admittedly puzzling, and examination of the blood, etc., the opinion was arrived at that the case was probably one of latent tuberculosis, probably located in the mediastinum. At this juncture I had the opportunity of seeing the patient in a non-professional capacity, and as the clinical appearances vividly recalled a clinical picture which I had frequently observed in very young rats, I formed the opinion that the state of profound anemia and physical and mental lethargy was dependent on an exhaustion of the functions of the bone-marrow, thyroid gland, and other structures, consequent on the excessive meat consumption by the mother. The child died in a few days. At the postmortem examination no trace of tuberculosis was found, nor other recognised cause of marked anemia in children. A partial post-mortem examination only was allowed, and was conducted by the consultant who had charge of the case, and who kindly gave me pieces of tissue for histological examination. The long bones were unduly soft in consistence, and it is of special interest to note that the histological appearances of the radius of this child (see Fig. 19) are identical in their essential features with those which were present in the ribs of the rats.
Fig. 16. - The Marrow of a Rat xt. three weeks, unweaned. Mother fed on an ox-flesh diet. (x 200.) Note the erythroblastic type of marrow, the red blood-corpuscles being more numerous than the leucocytes. Cf. Fig. 17.
Fig. 17. - The Marrow of a Rat aet. three weeks, unweaned. Mother fed on a bread-and-milk diet. ( x 200).
Note the leucoblastic type of marrow, the white blood-corpuscles being in excess of the red blood-corpuscles. Cf. Fig. 10.
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Fig. 18. - Longitudinal section of the Bony Rib of a Meat-fed Rat (second generation), aet two months, the section taken through one of the nodules described in the text. ( x 50).
Note the area of cartilage cells in the bone. Cf. Fig. 19.
Fig. 19. - Longitudinal section of the Shaft of the Radius of an Infant aet. sixteen months, whose mother was fed on an excessive meat diet. ( x 90.) Note the area of cartilage cells in the bone. Cf. Fig. 18.
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These facts seem to indicate that the results obtained in my experimental investigation here recorded are capable of application to disease in the human subject. The importance of recognising this, both from the point of view of diagnosis and treatment, will be obvious. I desire to draw special attention to the view which is suggested by the record of facts described - viz., that in diseased conditions in early infancy attention should be directed to the dietetic conditions of the parents prior to and during gestation; and, further, that the symptoms should be critically analysed in the light of facts obtained from experimental observations on diet carried out in lower animals. I have pleasure in expressing my indebtedness to Dr A. Dingwall Fordyce for much assistance in this investigation.