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ample, the physiological well-being of man seems to depend in certain regions in large part upon the possibility of assimilating a fraction of a milligram of iodin from time to time. Proteins and fats, carbohydrates and calories assume a minor rôle in the hygienic concern of the individual when his thyroid functions fail to proceed properly, owing to the lack of some seemingly minor essential ordinarily furnished by his food and drink. It is perhaps worthy of emphasis here that more than one fact indicating the large physiological significance of some "little thing" has been derived from the study of milk, Prout's prototype of a perfect food.

The progress of the modern science of bacteriology has directed attention to the microorganisms associated with milk and its products. At first only the baneful bacteria aroused popular interest. The menace of disease-carrying milk should never be minimized; but the fear of germs has long prevented the deserved recognition of the more beneficent part that bacteria in milk may play in nutrition. From a technical standpoint_dairy bacteriology has been of great help to the milk industry. Latterly, the consumer of milk has in many instances had hopes of unusual personal benefit raised by the current propaganda regarding the use of milk products containing acidophilic microorganisms. The fashion of to-day has replaced the Bacillus bulgaricus by the Bacillus acidophilus as the presumably helpful alimentary invader. The current situation has recently been summarized by an expert for the American Medical Association as follows:

Milk soured by acid-producing organisms which are more or less natural to ordinary commercial milk, or by certain types or species which are intentionally added with or without the association of alcohol-producing yeasts (kefir, kumyss), has been used as a food for centuries. This more or less extensive practice is due to the fact that the products were palatable to many, or rested on the assumption among the laity, as well as physicians, that they were beneficial in the correction of certain disorders of the gastro-intestinal tract. A great stimulus to the employment of fermented milks was given by the theories of Metchnikoff regarding intestinal putrefaction. These theories were in part that if the products of so-called "intestinal putrefaction," elaborated chiefly in the large intestine, were absorbed, by their action on the walls of the blood vessels they produced arteriosclerosis and premature senility. He also advanced the theory that the growth of the proteolytic bacteria which elaborated these poisons could be modified or prevented by the presence in the intestines of lactic acid-producing bacteria. For this purpose he advocated the use of Bacillus bulgaricus.

During recent years, reports have been published from different laboratories which indicate that the growth in the intestinal canal of the normally present Bacillus acidophilus may be increased so as to make it the predominating organism, by the administration of lactose (sugar of milk), by milk inoculated and fermented with Bacillus acidophilus, or by the administration of viable cultures of Bacillus acidophilus in conjunction with lactose. Growing out of the claims of favorable therapeutic action which are based on more or less extensive experimental data, the use of so-called Bacillus acidophilus milk and other products prepared with B. acidophilus has become quite widespread in this country. While no one subscribes seriously to-day to the original theories of Metchnikoff, there are many who believe that the regulation of types of bacteria and of the bacterial activities in the intestine is of much importance from the health standpoint. Since B. acidophilus and its very close neighbor, B. bifidus, are very common and as a rule the predominating types in the intestines of breast-fed infants, and, furthermore, since extensive experiments have been made which show these organisms to be of a strictly nonputrefactive and ap77612-24- -29

parently harmless nature, added weight is given by many to the claims made as to actual therapeutic value.

There is evidence that the administration of sour milk is at times beneficial. This is particularly true in pediatrics, in which field fermented milks have found a wide application. Sour milk and sour milk products are used in cases of vomiting, and of acute diarrhea, as well as chronic disturbances of the gastrointestinal tract. On what the particular value of sour milks as such depends is not known at the present time. There can be no doubt that a wide clinical observation gives a basis for the opinion that, for certain types of gastric and intestinal disturbance, fermented milk accomplishes more than sweet milk with a similar fat, sugar, and protein content. No one will, of course, deny the great value of milk as a growth-producing and energy-yielding food, whether the milk is sweet or whether it is soured by any of the so-called "lactic acid bacteria."

Recent observations made at various laboratories seem to indicate that, in contrast with B. acidophilus, B. bulgaricus can not be implanted or made to proliferate in the intestine, even when administered in large numbers. Much doubt is cast, therefore, on any alleged physiologic action that this organism was claimed to have in the intestine. It is for this reason and because B. acidophilus, according to numerous reports, can be successfully implanted, that preference is now given by many in the use of lactic acid bacillus cultures to those prepared with B. acidophilus.

There is little, if indeed any, satisfactory proof that liquid cultures or aqueous suspensions of lactic acid-producing organisms are of real value as local applications to mucous membranes or in arresting putrefaction or suppuration in wounds, abscesses, and sinuses. In such conditions their use appears to be still in the experimental stage.

Sour or fermented milk may be administered in the form of buttermilk or naturally soured skim milk, the lactic acid being produced by Streptococcus lacticus, which occurs commonly in milk and other dairy products and grows readily at ordinary room temperature; also in the form of sour milk produced by Bacillus bulgaricus.

To these may be now added the so-called Bacillus acidophilus milk which is prepared by the inoculation of milk which has been previously sterilized or heated for about an hour, at or near boiling temperature, with a pure starter made by inoculating pressure-sterilized milk with viable B. acidophilus and incubating at from 35° to 37° C. for from 20 to 24 hours. On the completion of proper ripening, which should take place within from 20 to 24 hours at from 35° to 37° C., a product is obtained which is slightly sour to the taste and has a characteristic odor not very unlike ordinary pure buttermilk. There is a slight separation of whey, but on thoroughly mixing the product has a uniform creamy consistency. Acidophilus milk is produced in various laboratories and dairies, though in many instances with partial success only. It may be made from fresh skim milk, whole milk, or from skim milk to which varying amounts of cream have been added. In all milk-culture work, mass inoculation with the use of a sterile pipette is necessary. The preparation of uniform pure acidophilus milk requires adequate facilities, the aid of a trained technician, and close adherence to instructions.

At least four distinct proteins have already been separated from the milk of certain species and demonstrated by biological tests to be individual substances. Among them casein and lactalbumin have long been recognized by physiological chemists. Inasmuch as proteins are at present differentiated and evaluated from a nutritive standpoint on the basis of their comparative amino acid make-up, a recent compilation made for me by Dr. H. B. Vickery of the best determinations at present available may be of interest here. The data regarding several other proteins are presented for comparison with casein and lactalbumin.

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Broadly speaking, these milk proteins are of good nutrient quality. They can supply all, or at any rate very nearly all, of the amino acid factors requisite for nutrition. The biological signficance of the different proportions of the individual proteins in the milk of various species remains a much discussed but little understood problem. The preponderance of casein in cow's milk and of the other proteins in human milk, for example, has long furnished a topic for scientific speculation. Lately attention has been directed to the possible importance of colostrum and its unusual complement of protein constituents. According to the studies of Theobald Smith and his coworkers, colostrum is the chief agent in transferring known anti

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FIG. 1.-Showing the effect of the addition of milk to a cereal food.

bodies to the newborn calf, and seems to have the important function. of protecting the newborn animal of this species against invasion of harmful microorganisms into the intestinal tract during the first few days of life. No such signficance has been demonstrated for colostrum in relation to the human infant.

Feeding experiments conducted in recent years have shown the value of the milk proteins in supplementing some of the albuminous substances which enter the dietary from other sources, notably the cereal grains that play so large a part in the food of man. From a protein standpoint the addition of milk to cereals as is so commonly done in the present day regimen represents an advantageous improvement in the quality of the grain products. An illustration of what this may mean is shown in Figure 1.

With respect to the milk fats per se there is little new to be said. Owing to their somewhat peculiar composition, represented by a relatively large component of glycerides of the volatile fatty acids, they doubtless have certain culinary advantages which have long been recognized. The peculiar rôle of milk sugar in the alimentary tract has already been referred to in reference to lactic acid milks. It is perhaps a signficant fact that milk sugar has been an abundant constituent of experimental diets recently devised with success to prevent intestinal toxemia and consequent tetany in animals deprived of their parathyroid glands. Under such feeding there is a practically complete suppression of bacterial proteolysis in the bowels, the feces become odorless and acid, and the intestinal floral is changed in a striking way.

It is an interesting fact that some of the earliest fundamental observations which led to the appreciation of those essential dietary factors now designated as vitamins were made in relation to milk and its derivatives. Hopkins, in England, had observed that certain animals failed to thrive on mixtures made up of an abundance of protein, fat, carbohydrate and inorganic salts, in the customary proportions of a so-called balanced ration, whereas they promptly improved in nutritive condition, and the young began to grow, when small additions of milk were made to the dietary described. It soon became evident that the successes were not due to calories or the then familiar nutrients.

Similarly the earlier attempts of Osborne and myself to feed mixtures of more or less purified proteins, fats, carbohydrates and inorganic salts ended, like the trials of other investigators, in failure. Sooner or later the animals refused to eat the food mixtures in sufficient amounts and declined in nutritive condition. They could usually be restored by a supply of "natural" foods. We were emboldened, however, to repeat the attempts again and again, because other animals throve on a food as simple as milk seemingly is.

Accordingly we determined presently to supply the mineral ingredients of our artificial diets in the form of what we termed "protein-free milk "-that is, the dried residue of milk after separation of its fats and proteins. Aside from traces of unremoved albuminous ingredients, it contains the milk sugar and inorganic elements along with small amounts of unidentified components.

The protein-free milk, which we first prepared in 1911, proved to hold a secret to success in our experimentation. On mixtures of such protein-free milk, sugar, starch, and purified fats, along with selected isolated proteins, young white rats have grown to maturity and have in turn produced young even in the third generation. Evidently the protein-free milk contained something present in small amounts not represented by the familiar salts and organic nutrients yet essential to adequate nutrition. At first we were inclined to ascribe the good results to a more favorable supply of salts in the protein-free milk component of the mixture of isolated food substances. Presently, however, we were led, in common with other investigators working in different ways, to appreciate that we were dealing with unique factors requisite for physiological well-being. After attaining some success in preparing mixtures of isolated food substances (including protein-free milk with its unrecognized

essential factors), so that animals could be nourished more satisfactorily, it was observed by us that growth invariably ceased after a time, and nutritive disaster ultimately ensued unless certain changes were made in the diet. Osborne and I had kept rats through two generations on a diet consisting of whole milk powder, lard, and starch. When we attempted to grow young animals on a comparable diet of isolated protein, protein-free milk, carbohydrate, and lard, there was a suspension of growth, sometimes quite sudden and usually more gradual, before adult size was reached. The essential difference between the adequate and the inadequate ration just described lies in the absence of the milk fat or cream element of the latter. We found that addition of unsalted butter or of butterfat to the inadequate diets in which lard formed the fat component prevented the suspension of growth in ungrown rats and promptly restored growth when it had failed. Milk fat, which includes all the milk constitutents soluble in the fats proper, therefore contains something essential for the nutrition of growth. Similar observations of the existence of such an unidentified "essential" had been made by McCollum and his collaborators. Since these experiences, published in 1913, comparable "potencies" have been discovered in a number of animal fats, notably the tissue fats, among which liver oils are striking illustrations, whereas they are missing in most other edible fats, particularly those of plant origin.

The effects of the lack of these two dietary essentials discovered in milk is shown in young experimental animals by a retardation of growth and nutritive decline, whereas there is improvement of nutrition when the missing factor is added to an otherwise adequate diet.

Whether and to what extent milk may furnish some additional specific factor requisite for the proper development of the generative organs and the satisfactory fulfillment of their natural functions is being investigated in several laboratories in this country at the present time. The antiscorbutic property of raw milk (now frequently referred to as its content of vitamin C) has long been recognized. This potency can be destroyed by heat, particularly in the presence of air; and this fact has furnished the occasion for considerable familiar controversy, often of an unnecessarily acrimonious character. It apparently has also furnished the basis for many more or less incorrect or illogical statements implying that all vitamins are readily destroyed by heat even under customary conditions of culinary procedure or commercial practice. It is high time that some of these unwarranted generalizations should be corrected, for it is a fact that milk is now being dried by more than one process without serious loss of any of the three familiar vitamin potencies referred to.

In this connection it may be worth while to direct attention to two features respecting the known vitamins in milk that seem not always to be adequately appreciated. In comparison with some other products milk is not extremely "rich" in vitamin A, B, or C. Gram for gram it may be surpassed in this respect by various edible products, few of which, however, show an equally liberal content of all the potencies found in milk. To place dependence on milk alone

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