[38] A maximum count of 35 was formulated, representing the highest degree of clinical scurvy. This includes three grades of beading of the ribs, four of tenderness of each knee and wrist joint, and four of swelling of each of these joints. It is apparent from the clinical curve (Fig. 10) that an animal may have developed a marked degree of scurvy (20 points), and gained rather than have lost in weight.

[Ill.u.s.tration: FIG. 10.--Hay, oats, and water _ad libitum_ during period I resulted in a lack of gain in weight, and in a development of scurvy.

During period II, 1.5 c.c. of orange juice were given daily, and as will be seen there was a marked gain in weight and disappearance of the s...o...b..tic signs, although, as is generally the case, they continue to develop for a short while after an antis...o...b..tic is given. When the orange juice was discontinued in the third period, the weight once more fell and the scurvy redeveloped. The broken line represents the course of the scurvy, and is a composite formed on the basis of the aggregate of the s...o...b..tic signs. Each square represents a 2-day interval.]

Guinea-pigs generally die of scurvy after having lost about one-third of their body weight; occasionally the loss is greater, reaching almost 50 per cent. This loss is due partly to the s...o...b..tic condition, but to a greater extent to starvation occasioned by a marked lack of appet.i.te. In this connection it may be noted that guinea-pigs frequently lose for a few days following the addition of an antis...o...b..tic to the dietary (Fig.

11). This reaction is evident from a perusal of the weight charts of other investigators, and occurs likewise in human scurvy. This loss is accompanied, as Gerstenberger has pointed out, by diuresis, which may be so marked that it is evident to the casual observation of those caring for the animals.

[Ill.u.s.tration: FIG. 11.--These guinea-pigs developed scurvy in spite of receiving a large quant.i.ty of the water in which young carrots had been cooked for only 20 minutes. It will be noted, however, that although the pigs developed scurvy they did not lose weight, as is usually the case.

After they had developed definite scurvy they were given in addition the equivalent of 80 c.c. of a dried milk prepared by being heated to about 116 C. for a few seconds. The addition of this milk to the diet cured the scurvy, showing that it had largely retained its antis...o...b..tic vitamine.]

Exophthalmos may be mentioned again in this connection as a very rare sign of guinea-pig scurvy. Haematuria also occurs at times; it is not known how frequently it is present, whether it is an early manifestation in the guinea-pig as in the infant, or whether the source of the blood is the kidney or the bladder.

The superficial lymphatic glands are frequently palpable in scurvy, especially those in the inguinal region. This sign is emphasized by some pathologists. It has seemed to us attributable less to the nutritional condition than to the infections which so frequently complicate the disorder.

According to Jackson and Moore a rise of temperature does not accompany scurvy in the guinea-pig. As the result of an examination of nine guinea-pigs they conclude that "experimental scurvy is a non-febrile disease in the majority of affected animals." Nor did they find a leucocytosis, the average leucocyte count of eight s...o...b..tic pigs being about 8000.

As the data are meagre, a consideration of the chemical alterations a.s.sociated with the scurvy of guinea-pigs and monkeys will be taken up in conjunction with the metabolism of human scurvy. The therapy of animal scurvy will also be deferred (chapter VI), as the reaction to dietetic measures is practically the same in man and in animals. In concluding this chapter we would call attention to the following interesting statement contained in the recent paper by Delf and Tozer: "In other experiments, however, where a liberal supply of an antis...o...b..tic was given and where the fat-soluble A growth factor was known to be deficient, the resulting histological changes in the rib-junctions of the animals examined were found to resemble closely those of 'Definite' or of 'Definite Chronic' scurvy. In these test cases the antis...o...b..tic chosen was, we believed, deficient in the fat-soluble A growth factor (for example, orange juice). This fact is mentioned because in the case of an animal not receiving an adequate supply of fat-soluble A the resulting changes in the junctions are not dissimilar from, and are likely to be confused with, those caused by scurvy alone."

If this observation is confirmed, it emphasizes the necessity in nutritional experiments, of constructing a dietary which is complete in every respect except the one under investigation; it also suggests the development of new pathologic ent.i.ties in relation to other nutritional disorders resulting from a lack of the accessory food factors.

CHAPTER VI

ANTIs...o...b..TIC FOODS

=Historical Review.=[39]--It is impossible to state when and how the knowledge of the value of antis...o...b..tic foodstuffs came to be appreciated. It is probable that the potency of herbs and fruits in scurvy was known empirically to individuals and groups of people long before the fact gained general recognition. A most interesting history of antis...o...b..tics is given in the excellent work of Hirsch and in our great cla.s.sic on scurvy by Lind. The first realization of the value of lemons and oranges seems to have been the result of a chance discovery.

Budd tells us that in the sixteenth century sailors of a Dutch sailing vessel laden with these fruits were attacked with scurvy, and that, when they partook of the lemons and oranges in the cargo, a miraculous cure resulted. He narrates also the following striking incident, which is mentioned likewise by Lind:

[39] It is of interest that John Hall, the son-in-law of Shakespeare, and a prominent physician of Warwickshire, was one of the first to urge the use of antis...o...b..tics. In a quaint work ent.i.tled, "Select Observations on English Bodies, or Cures both Empericall and Historical"

(1657 London), he describes how he cured scurvy by means of brewing a beer or ale from "s...o...b..tick hearbs, _viz._: scurvy gra.s.s, water-cresses and brook lime." This book, which ran through at least two editions, has not achieved the popularity of the works of the father-in-law.

In the year 1600 four sailing vessels left England for the East Indies.

The sailors on three of these ships did not receive lime juice, whereas those on the fourth received their daily quota. The men of the first three ships suffered severely from scurvy, but those on the fourth escaped.

In an excellent work on "Scorvey," published in 1685, Harvey wrote: "Wherefore most acids, especially spirit of salt marine, juice of sorrel, limons, citrons, etc., are so deservedly extolled in some s...o...b..tic distempers and seconded with good success." Thus we see that even at this early date it was taken for granted that citrous fruits possessed virtue in curing scurvy. Bachstrom (Observationes circa s...o...b..tum, 1734) evidently was well-acquainted with the antis...o...b..tic value of scurvy gra.s.s, and relates the story of a sailor severely disabled from scurvy who was put ash.o.r.e to perish on Greenland, and crawled on the ground, grazed on scurvy gra.s.s like a beast of the field, and was able to return home perfectly recovered. (Cited from Lind.)

The credit for forcing a general acceptance of the antis...o...b..tic value of fresh food belongs to Lind. He did not, however, have an easy task, and in 1747, in order to convince those who still were skeptical, he resorted to an experiment on human beings. Twelve patients in his hospital were given the same diet, except that some received sea-water in addition to their dietary, others vinegar, or elixir of sulphuric acid, or a daily portion of cider, or oranges and one lemon daily. The last two groups, as we should expect, recovered quickly; one man who received cider improved, but in no other case was any alleviation noted.

Lind extols the value of lemons and oranges, of berries, of sour cabbage, of cider, and of all fresh fruits and vegetables. In spite of the fact, however, that Lind's teaching was based on an experience with thousands of patients suffering from scurvy in the naval hospital, his ideas did not take root. It required an event which came directly under the official eye to bring about radical changes in the diet of the sailors. In 1795 the English Fleet suffered from a severe epidemic of scurvy, which was finally controlled by giving the sailors fresh vegetables and fruit. This therapeutic result was so convincing that thenceforth a daily ration of lime juice was ordered for the sailors and a regular issue provided for the navy. This marks the cessation of scurvy as a scourge of the British navy. From this time the disease appeared only sporadically. The sharp decrease in the incidence can be appreciated by Budd's statement that 1457 cases of scurvy were admitted to the Royal Naval Hospital in 1780, whereas in 1810 an English physician reported that in the seven preceding years he had not treated a single patient in this hospital suffering from scurvy. In another marine hospital, between the years 1806 and 1810, only two cases of scurvy were admitted.

Nothing was done for the British merchant service until over half a century later, although scurvy continued to make its appearance among the sailors with varying severity. Smith states in the article on this subject in Allb.u.t.t's System of Medicine: "In 1864 it was pointed out by Doctor Barnes that during the twelve years following 1851, 1058 cases of scurvy had been admitted into the hospital ship _Dreadnought_." In 1854 a law was pa.s.sed requiring every vessel to carry an adequate supply of lime juice. This law, however, failed in effect, due to the fact that a large part of the lime juice was adulterated. A new shipping-act was pa.s.sed, therefore, in 1867, with the object of preventing adulterations, at the same time increasing the daily quota for each seaman from half an ounce to one ounce.

It may be of interest to add a few words concerning certain antis...o...b..tics which have been under discussion or recognized for so many years that they have acquired an historical aspect. One of these foodstuffs is sauerkraut, which was recognized by Lind in 1772 as having particular potency in this disease. It is interesting to note, in this connection, that this writer appreciated the close relationship of acidity to antis...o...b..tic virtue. "One quality," he writes, "entering the most perfect antis...o...b..tic composition is a vegetable accescency." He prized sauerkraut for its inherent value, and particularly, because he found that "sour cabbage will keep for an East-India voyage."

The famous navigator Cook, whose voyages were remarkable for the freedom from illness which his sailors enjoyed and the absence of scurvy, always kept a large supply of sauerkraut on hand. It was believed by many that the immunity of the Dutch seamen to scurvy was due to their large consumption of this vegetable. As the result of this empirical knowledge, the English navy in 1780 introduced the use of sauerkraut into its ration. As just noted, however, this antis...o...b..tic was supplanted some few years later by an issue of lime juice.

It is common knowledge that outbreaks of scurvy follow closely upon a failure of the potato crop. This has been particularly the case in Ireland, where it was especially evident in relation to the great epidemic of scurvy in 1847. Holst and Froelich inform us that "all scurvy epidemics in Norway in the nineteenth and beginning of this century followed failure of the potato crop." Nor is this danger past.

In an article ent.i.tled "The Role of Antis...o...b..tics in Our Dietary," the author recently reported that the partial failure of the potato crop in the eastern part of the United States led to the development of scurvy in numerous inst.i.tutions, in one of which over 200 cases of definite scurvy developed in the spring (1916).

The occurrence of scurvy in the navy and on sailing vessels has been a.s.sociated in the minds of many with the large amounts of salted meat which necessarily was included in the dietary. It was evident that meat that was salted had no antis...o...b..tic value, but the query has been raised whether eating a considerable amount of salted meat did not induce scurvy. Lind mentions "flesh long salted" as leading to the development of scurvy. The question of the value of meat as an antis...o...b..tic is of importance at the present time, chiefly in connection with Polar expeditions and army rations. As the result of an outbreak of scurvy in the Polar expedition of 1875-6, a British Arctic Survey Committee was appointed to make an investigation. In 1877 it reported that "although the scurvy was due to the absence of lime juice from the sledge dietaries, meat in large amounts is able to prevent the disease." Stefansson also emphasized the value of meat in preventing scurvy in the Polar regions. In his expeditions he has found that raw meat, if taken in sufficient quant.i.ty, is able to afford complete protection. Jackson, who lived for some years among the Samoyeds, tells us that this tribe, owing to the fact that they consumed considerable reindeer meat, never suffered from scurvy in spite of the fact that they ate no vegetables or fresh fruit during the winter.

The following account, a personal communication from Dr. Harrison J.

Hunt, who spent four years in the Arctic regions, is of interest in this connection:

"For some four years I was with the Smith Sound Eskimos, on the northwest coast of Greenland. These people get nothing but animal food normally, and have lived that way for many generations, yet are healthy, of good physique, and are normal in other ways. Scurvy was unknown to them as far as I could ascertain; certainly there was none while I was among them. Much of their meat is eaten raw, and the rest only partly cooked; that is, 'rare done.'

"Whalers who were accustomed to winter in Hudson Bay practically always had scurvy in the crew. It was common knowledge among the captains that fresh meat was curative of scurvy, and it was their practice to obtain meat from the Eskimos whenever possible for that purpose. The last English expeditions to the South Polar regions were afflicted with scurvy which was entirely and quickly eradicated by the use of fresh seal meat in the place of salt meats and canned foods. They do not state that this meat was eaten raw or even rare cooked. On the Danish coast of Greenland, during seasons poor in game, scurvy is quite common, but the natives there live largely on breadstuffs (very coa.r.s.e rye bread).

Personally, during my four years in the Arctic, I took no fresh vegetables whatever, or other commonly-called antis...o...b..tics, relying solely on rare or raw meat. I never was stronger or more healthy in my life. I did have dried fruits and vegetables, and usually plenty of fresh bread. Usually the Eskimos eat their raw meat in a frozen condition, and I can attest that it is extremely palatable in that condition."

We do not wish to discuss, in this place, the value of meat as an antis...o...b..tic; in pa.s.sing, however, it may be said that, as in the case of the other antis...o...b..tics, its efficacy will depend largely upon the amount consumed. The British Mesopotamia Commission Report of 1917 shows that scurvy can develop on a ration which includes 28 ounces of meat a week. We must remember, however, that this refers to cooked meat, whereas in the Polar expeditions meat generally was eaten in a raw state.

Recently an historical inquiry has appeared in an article by Chick, Hume and Skelton as to the antis...o...b..tic virtue of limes and lemons. This sketch is of exceptional interest because it treats of the oldest and most cherished antis...o...b..tics, and particularly because it has unearthed a peculiar fallacy in their connection. As they state, there would appear to be every reason for believing "that the use of so-called lime juice was responsible for the disappearance of scurvy from the British navy in the first decade of the nineteenth century." It would seem, however, that the lime juice which gained this great reputation in the navy some 125 years ago was in reality lemon juice, and that it was not until about 50 years ago that lime juice was really used. These authors show--by one of those striking human experiments which, occasionally, is available--that in a Polar exploration which was organized in 1850 lemon juice was issued to each man, and that no case of scurvy developed, whereas in a similar expedition which went out in 1875 lime juice was issued and scurvy developed the following spring with great severity among the sledge crews. This investigation, therefore, seems to prove that lime juice, the prototype of antis...o...b..tics, has been accorded a false position; that in reality the sailors of the past have been protected by lemon juice.

=Antis...o...b..tic Foods.=--As far as has been ascertained, the antis...o...b..tic food factor exists in all fresh vegetable and animal tissues, being present to a far greater degree in the former than in the latter. It is distinguished by being a.s.sociated in nature with cells which are the seat of active metabolism, just as the water-soluble vitamine is a.s.sociated mainly with cells which are in an inactive or dormant state. Vegetables or fruits may be mildly or highly antis...o...b..tic; there is indeed a remarkable difference in their content of antis...o...b..tic factor or vitamine. They vary widely also in the degree to which their potency is affected by physical or chemical conditions.

In this chapter the most common animal and vegetable antis...o...b..tic foodstuffs will be considered and the effect which processes such as drying, canning, change of reaction, etc., exert on their specific value. Their therapeutic application in the prevention and cure of scurvy will be considered in a subsequent chapter. Until recently our knowledge of this subject was empirical and inaccurate; as the result of scientific work, however, carried out during the past few years in different parts of the world, quant.i.tative and comparative figures of antis...o...b..tic food values have been evolved.

=Milk.=--It is important to have as accurate an idea as possible of the value of milk as an antis...o...b..tic, as the infant depends on it during the first months of its life for a supply of this essential factor.

Considerable attention has been paid to this question in the last few years, and recent reports tend to confirm the former estimations which had been overlooked and forgotten. In 1847 Curran wrote that in the Irish epidemic of this year they had admitted to the Dublin Union Hospital 80 cases of scurvy which had been on a diet which included one pint of milk daily, but was deficient in vegetables. From this experience he realized that milk was not rich in the principles which protect against scurvy. In the following year Parkes came to the same conclusion, stating that 500 to 750 c.c. of raw milk did not always suffice to prevent scurvy. In addition to these opinions concerning adults, similar conclusions have been drawn from clinical experience with infants. Barlow (1894) realized that a small amount of milk was insufficient to protect against scurvy. Still writes: "The antis...o...b..tic power of fresh, unboiled milk is evidently slight." In 1914 Hess and Fish pointed out that "milk must not be considered as having potent antis...o...b..tic properties." Nevertheless, when this question was raised recently by the experimental work of Jackson and Moore, and that of McCollum and Pitz, it was not appreciated that, like other antis...o...b..tics, milk must be regarded from a quant.i.tative standpoint, and that, as it is a weak antis...o...b..tic, its effect must depend largely on the quant.i.ty consumed.

The first laboratory work on this subject was that of Froelich in 1912, who showed that guinea-pigs could be protected by an exclusive diet of fresh milk, and that raw milk is more effective than heated milk. In his work, the amount of milk taken by the animals was not measured, so that it is impossible to glean from it more than these general conclusions.

In the following year, as a result of some quant.i.tative experiments, Funk stated that he was able to protect guinea-pigs with 50 c.c. of fresh milk in addition to an oat diet. This estimate, as subsequent workers showed, is too low. Chick, Hume and Skelton were the first, however, to investigate the antis...o...b..tic potency of milk in a systematic and convincing manner. They demonstrated that if the daily consumption of fresh milk was less than 50 c.c., a guinea-pig died almost as quickly as if it received no milk; if the daily quota varied from 50 to 100 c.c., a greater or less protection from scurvy was observed, varying proportionately with the amount consumed; if 100 to 150 c.c. were taken daily, which practically amounts to a complete milk diet, satisfactory growth and development occurred, and no symptoms of scurvy were observed. This represents in a general way the present conception of the antis...o...b..tic power of milk. In pa.s.sing, it may be remarked that it is not altogether clear why 50 c.c. of milk do not afford partial protection, and prolong the life of the animal for a definite length of time. The authors conclude that "milk is evidently a food poor in the antiscurvy accessory factor, and a ration large in comparison with that of other antis...o...b..tic materials is necessary to afford satisfactory protection from scurvy." The error must be avoided, however, of regarding milk as a standard article of diet containing a definite and specific amount of vitamine per cubic centimetre. It will be shown later that this point of view cannot be taken in regard to vegetables, and it is probable that it cannot be a.s.sumed for milk.

A general conception of the antis...o...b..tic potency of cow's milk may be gleaned from the fact that it requires a minimum of about sixteen ounces (500 c.c.) daily to protect an infant from scurvy or to cure it. Twelve ounces have failed to effect a cure in several instances, although the milk was raw and of the best grade. If it is pasteurized, a larger quant.i.ty is required, depending upon various conditions connected with the heating process and upon the age of the milk, circ.u.mstances fully discussed in relation to etiology. Thus it becomes evident that pasteurized milk a.s.sumes a two-fold role, acting as an antis...o...b..tic if little of its vitamine content has been destroyed and if a large quant.i.ty is consumed, or leading to the development of scurvy when one or both of these conditions is unfavorable. The same holds true for milk which has been boiled for a short period. If the milk has been heated twice, it tends to produce scurvy; if it is condensed, the greater part of its antis...o...b..tic value is destroyed.

It seems necessary to emphasize again the important fact that _dried milk_ may possess marked antis...o...b..tic potency, depending on the method of preparation (Fig. 11). As stated, sixteen ounces of milk dried by the Just-Hatmaker process cured scurvy promptly, in spite of the fact that the milk had been dried six months previously. Here, therefore, is a food of high caloric value, compact, antis...o...b..tic, and stable. The fact that milk, in spite of drying, retains this labile vitamine for so long a period, demonstrates that it is available in the most remote parts of the world, and that the possibilities of its transportation are unlimited.

Little is known regarding the antis...o...b..tic content of the milk of the various domestic animals. Some claim that goat's milk is notably rich in this particular, but experiments with it are too few to warrant conclusions. Lind writes: "Goats, of all animals, afford the richest whey, possessed of the greatest antis...o...b..tic virtue ... which in a singular manner restores the const.i.tution when weakened and impaired by scurvy." Human milk possesses about the same potency as cow's milk, as mentioned in the discussion of the occurrence of infantile scurvy in countries where the adult form is endemic. Twelve ounces of human milk, from a woman on a liberal and varied diet, barely sufficed to alleviate the symptoms of a case of moderate intensity.

FRUIT JUICES

=Orange and Lemon Juice.=--The most thoroughly studied antis...o...b..tic foods are orange and lemon juice, which have been singled out because they contain the antis...o...b..tic factor in the highest concentration. It has been ascertained through the work of various investigators that guinea-pigs require about 3 c.c. daily of either of these juices to protect them from scurvy, but that about half this amount is sufficient to prevent the manifestation of clinical signs.

Both of these juices withstand heat remarkably well. Orange juice can be boiled for 10 minutes without noting any diminution of its antis...o...b..tic value, and lemon juice heated to 110 C. without appreciably losing its efficacy. However, orange juice undergoes some change as the result of being heated in an autoclave for 45 minutes at a temperature of 110 under 10 to 15 pounds pressure. Although 6 c.c. of this heated preparation were able to prevent the development of scurvy, the guinea-pigs did not gain nearly as well as those which received 3 c.c.

of the unheated juice. It seemed as if there was a destruction of some factor apart from the antis...o...b..tic principle.

In spite of the fact that these juices withstand heat well, they are sensitive to some other conditions. Orange juice which had been stored in the cold for three months was unable to protect guinea-pigs in the dosage of 3 c.c. per animal, resembling in its action the autoclaved juice. When this orange juice was six months old, double this quant.i.ty failed to protect; throughout this period it was kept in the ice-box and covered with a layer of oleum petrolatum to avoid the access of air or possible contamination. Harden and Zilva met with a similar experience, and state that "after storing treated (concentrated) lemon juice for about a fortnight in a cold room, a marked loss can be observed in its potency."

These authors reported also that when orange juice is _rendered slightly alkaline_ it loses its antis...o...b..tic potency. This question was investigated in relation to canned tomato juice, as well as to orange juice, and it was found that shortly after having been rendered 0.05 N alkaline to phenolphthalein, neither of these foods had lost an appreciable amount of its antis...o...b..tic factor. Five cubic centimetres per capita daily of freshly-alkalized orange juice were able to cure a group of pigs which had developed scurvy on another diet. If, however, 24 hours were allowed to elapse instead of only one-half to one hour, between the alkalization and the feeding, then a considerable amount of the antis...o...b..tic factor was lost. The same general rule seems to hold for alkalization as for heating, _i.e._, the length of time the antis...o...b..tic food is subjected to the deleterious influence is fully as important as the intensity of the process. Advantage has been taken of the fact that freshly-alkalized orange juice retains its potency, in using it intravenously in the treatment of infantile scurvy.

_Subcutaneous injections_ of neutralized orange juice failed to cure scurvy in guinea-pigs; Harden and Zilva were equally unsuccessful with large doses of their concentrated lemon juice. This is of interest in view of the marked therapeutic result which Shiga obtained with subcutaneous injections of the water-soluble vitamine in pigeons suffering from polyneuritis. It should be added that Holst and Froelich (1912) failed to cure scurvy in guinea-pigs by intraperitoneal inoculations of orange juice.

_Lemon juice or orange juice may be dried_ and lose little of its antis...o...b..tic power. In their paper of 1912 Holst and Froelich reported the efficacy of lemon juice evaporated in a vacuum, and recently Harden and Zilva published experiments which proved that "by evaporating the treated lemon juice to dryness in an acid medium an active dry residue is obtained." Still more recently Givens has shown that orange juice reduced to a powdered form by means of a spraying process has lost little of the antis...o...b..tic factor. These results prove that under certain conditions the antis...o...b..tic factor withstands drying; one of these favorable influences is an acid reaction, and another, rapidity of desiccation.[40]

[40] Preserved mulberries which had been sugared and cooked for one-quarter to one-half an hour were found by Holst and Froelich (1912) to possess good antis...o...b..tic power three months later.