CHAPTER VIII

POISONOUS PRODUCTS FORMED IN FOOD BY BACTERIA AND OTHER MICRO-ORGANISMS

In close relation to the cases of infection with animal or plant parasites which have been discussed, there are certain well-established instances of poisoning by substances that have been generated in food while it is still outside of the body. This is the common type of food poisoning in popular estimation, but in point of fact the proved cases of this class are much less frequent than the instances of true infection with bacteria of the _paratyphoid-enteritidis_ group (chapter vi). Thus far the best-known examples of poisoning by the products of micro-organisms are botulism and ergotism.

ERGOTISM

Ergotism or ergot poisoning is due to the use of rye that has become diseased through the attack of a fungus, _Claviceps purpurea_. It occurred frequently in the Middle Ages when in times of famine the ergot or spurred rye (O.Fr. _argot_, "a cock's spur") was often used in default of better food. In Limoges in 922 it is said that forty thousand persons perished from this cause. Improvement in the facilities for transportation of food into regions where crops have failed, and the use of special methods for separating the diseased grain from the wholesome have greatly reduced the prevalence of ergotism. In Western Europe poisoning from this cause has practically ceased, although Hirsch recorded some twenty-eight outbreaks in the nineteenth century; in parts of Russia the disease is said still to occur in years of bad harvest.[95]

The poison ergot itself has long been used as a drug in obstetrics, but its composition is complex and is still not completely understood. Several constituents of ergot have been extracted, and these have been shown to possess different physiological effects.[96] The symptoms observed in the outbreaks of ergotism of mediaeval times are not wholly reproduced experimentally by the drug and are thought to have been in part due to the semi-starvation engendered by the use of rye from which the nutritious portions had been largely removed by the growth of the fungus.

BOTULISM

The best established case of poisoning by means of bacterial products taken in with the food is the serious malady known somewhat inappropriately as botulism (botulus, sausage).[97] This kind of food poisoning, which has a characteristic set of symptoms, seems to have been first recognized and described in 1820 by the German poet and medical writer Justinus Kerner. In two articles (1820-22) he enumerates 174 cases with 71 deaths occurring in Wuerttemberg between 1793 and 1822 and apparently in most cases connected with the use of insufficiently smoked sausage. Mayer[98] tabulates about 600 additional cases observed in various parts of Germany down to the end of 1908, the total mortality in the 800 cases being about 25 per cent. In France botulism is said to be very rare.[99] In Great Britain Savage[100] declares that he has been unable to trace the occurrence of a single outbreak. In the United States several instances of botulism poisoning are on record (Sheppard,[101] 1907, 3 cases, 3 deaths, canned pork and beans; Peck,[102] 1910, 12 cases, 11 deaths; Wilbur and Ophuels,[103] 1914, canned string beans, 12 cases, 1 death; Frost,[104] 1915, 3 cases, 3 deaths). Professor Stiles[105] has given a graphic description of his own attack of probable botulism due in all likelihood to minced chicken.

_Symptoms._--The description of a case seen by Wilbur and Ophuels,[106] is so typical that it may be cited:

Girl, aged 23, Tuesday evening, Nov. 23, 1913, ate the dinner including the canned string beans of the light green color together with a little rare roast beef. The following day she felt perfectly normal except that at 10:00 in the evening the eyes felt strained after some sewing. Thursday morning, thirty-six hours after the meal, when the patient awoke, the eyes were out of focus, appetite was not good, and she felt very tired. At night she had still no appetite, was nauseated, and vomited the noon meal apparently undigested. Friday morning, two and one-half days after the meal, the eyes were worse, objects being seen double on quick movement, and it was noticed that they had a tendency to be crossed. A peculiar mistiness of vision was also complained of. She was in bed until late in the afternoon, when she visited Dr. Black. She had had some disturbance in swallowing previous to this time and stated that it felt as if "something came up from below" that interfered with deglutition. The fourth day she remained in bed, was much constipated, and noticed a marked decrease in the amount of urine voided. There was at no time pain except for occasional mild abdominal cramps, no headache, subnormal temperature, and a normal pulse. The fourth and fifth days the breathing became difficult at times and swallowing was almost impossible. The patient complained of a dry throat with annoying thirst. The sixth day there were periods of a sense of suffocation with a vague feeling of unrest and as if there might be difficulty in getting the next breath. The upper lids had begun to droop. The voice was nasal. When the attempt was made to swallow liquids they passed back through the nose. The patient felt markedly weak.

Physical examination at this time showed ptosis of both upper eyelids, dilatation of the right pupil, sluggish reaction to light of both pupils, apparent paralysis of the internal rectus of the left eye, normal retina, inability to raise the head, control apparently having been lost of the muscles of the neck, inability to swallow, absence of taste. The tongue was heavily coated and the throat was covered with a viscid whitish mucus clinging to the mucous membrane. The soft palate could be raised but was sluggish, particularly on the right side. The exudate on the right tonsil was so marked that it resembled somewhat a diphtheritic membrane. The seventh day there was some change in the condition; occasional periods occurred when swallowing was more effective, and there was less tendency to strangle. On the eleventh day there was some improvement of the eyes, still strangling on swallowing, sensation of taste was keener, and the general condition improved. The twelfth day the patient was able to move her head, but was unable to lift it except when she took hold of the braids of her hair, and pulled the head forward. The eyes could be opened slightly, speech was less nasal and more distinct, and improvement in swallowing was marked. At the end of two weeks the patient was able to take soft diet freely, and at four weeks she was up in a chair for a couple of hours complaining only of general weakness and inability to use her eyes. At the end of five weeks she was able to leave the hospital and return to her home and later to resume her regular work.

In all cases the nervous system is strikingly affected in this form of food poisoning. Dizziness, double vision, difficulty in chewing and swallowing, and other symptoms of nervous involvement occur with varying intensity and may persist for a long time after the first signs of the attack. Temperature, pulse, and respiration remain practically normal. In contrast with the traditional type of food poisoning gastro-intestinal symptoms may be slight or altogether lacking. Freedom from abdominal pain is usually noted; diarrhea is the exception and constipation the rule; vomiting sometimes occurs, but may be absent. In the cases described by Sheppard there was "an entire absence of the usual gastro-intestinal symptoms from first to last, no pain or sensory disturbance and no elevation of temperature." The visual disturbances are very characteristic. Stiles relates his own experiences as follows:

Vertigo and nystagmus developed [a few hours after eating] in a startling degree, the car [in which he was being taken to his house] seemed to be ascending an endless spiral, the stars made circles in the sky, and the houses by the wayside reeled. The lighted doorway of my house seemed to approach and surround me as I was carried in. My bed for the moment presented itself as a vertical surface which I could not conceive to be a resting place.... Whenever I opened my eyes on this day [the next day] the impression of gyration of the room was appalling.... To turn my head even very slowly from one side to the other brought an accession of the overpowering giddiness.... [eight days after the beginning of the attack]. The nystagmus now became limited to momentary onsets, but in its place I became aware of a peculiar diplopia. The image of one retina was not merely displaced from the position of its fellow but was tilted about 15 degrees from parallel.... This fantastic diplopia gradually gave place to the familiar variety and this occurred less and less often as my convalescence proceeded. From [this date] my recovery pursued a course which was dishearteningly slow but free from any setbacks. Among the persistent symptoms were ... the visual difficulties mentioned. The left pupil was usually smaller than the right and I thought I detected a slight failure to relax accommodation with the left eye. Reading was difficult for several weeks and the ability to write, as requiring closer fixation, was still longer in returning.

In the cases reported by Sheppard visual symptoms were the initial signs of trouble, double vision, mistiness, and inability to hit the mark in shooting being the first complaint.

The time elapsing between eating the implicated food and the onset of the earliest symptoms is usually between twelve and forty-eight hours, but may be much less. In Stiles's case the interval was apparently less than three hours.

_Anatomical lesions._--In fatal cases no characteristic gross changes are observed in the various organs. It has been stated by some writers that microscopic degenerative changes occur in the ganglion cells, involving especially the so-called Nissl granules, but in the carefully studied case reported by Ophuels[107] the Nissl granules were quite normal in size, arrangement, and staining qualities. There was, in fact, no evidence to substantiate the hypothesis of a specific action of the toxin on the nerve-cells. On the other hand, Ophuels found numerous hemorrhages in the brain-stem and multiple thromboses in both the arteries and veins. He holds, consequently, that the indications of severe disturbances of brain circulation associated with hemorrhages and thrombosis in medulla and pons are sufficient to explain the symptoms of botulism poisoning without having recourse to the assumption that the poison has a specific action on certain ganglion cells.

_Bacteriology._--The cause of botulism poisoning was discovered by Van Ermengem to be the toxin produced by a bacillus which he named _B. botulinus_. This organism was isolated from portions of a ham that had caused fifty cases of poisoning (1895) at Ellezelles (Belgium), and also from the spleen and gastric contents of one of the three fatal cases. The bacillus grows only in the absence of oxygen (strict anaerobe), stains by Gram's method, forms terminal spores, and develops best at 22 deg.C. Unlike most bacteria dangerous to man, it appears unable to grow in the human body, and its injurious effect is limited to the action of the toxin produced in foodstuffs outside the body. Botulism is an intoxication--not an infection. The fact that the bacillus can grow in nature only when the free oxygen supply is cut off explains in part at least the relatively rare occurrence of botulism since all the conditions necessary for the production of the botulism toxin do not commonly concur. Next to nothing is known as to how widely _B. botulinus_ is distributed. Except in connection with the cases of poisoning it has been reported but once in nature.[108] The botulism poison is a true bacterial toxin, chemically unstable, destroyed by heating at 80 deg.C. for 30 minutes, capable of provoking violent symptoms in minute doses, and possessing the property characteristic of all true toxins of generating an antitoxin when injected in small, non-fatal doses into the bodies of susceptible animals. In animal experiments the toxin formed by _B. botulinus_ has been found capable of reproducing the typical clinical picture of this form of food poisoning. Symptoms of paralysis are produced in rabbits, guinea-pigs, and other animals by the injection of so small a dose as 0.0001 c.c. of a filtered broth culture.

_Epidemiology._--The conditions under which _B. botulinus_ occurs and is given opportunities for multiplying are not completely known. It is possible that there are localities where this bacillus is particularly abundant in the soil or in the intestinal contents of swine or other domestic animals, but on the whole it seems more probable that the organism is widely distributed, but that it does not often find suitable conditions for entrance into, and multiplication in, human food. Practically all the reported cases of botulism have been caused by food which has been given some sort of preliminary treatment, as smoking, pickling, or canning, then allowed to stand for a time, and _eaten before cooking_. Since both the bacillus, including the spore stage, and its toxin are destroyed by relatively slight heating, it is clear that a rather unusual set of factors must co-operate in order that botulism poisoning shall take place. These are evidently: (1) the presence of the bacilli in sufficient numbers in a suitable foodstuff; (2) the initial preparation of the food by a method that does not destroy the _B. botulinus_--inadequate smoking, too weak brine,[109] or insufficient cooking; (3) the holding of this inadequately preserved food for a sufficient length of time under the right conditions of temperature and lack of oxygen; (4) the use of this food, in which conditions have conspired to favor the production of toxin by _B. botulinus_, without final adequate cooking. It seems as reasonable to suppose that the infrequency with which these several factors coincide is responsible for the relative uncommonness of botulism as to suppose it due to the rarity of the specific bacillus. In the Belgian outbreak studied by Van Ermengem the poisonous ham had lain at the bottom of a cask of brine (anaerobic conditions) while the other ham of the same animal lay on top of it but was not covered with brine, and was eaten without producing any poisonous effect. In this instance the presence or absence of favorable conditions for anaerobic growth seemed to be the decisive factor.

_Prevention and treatment._--The food in which _B. botulinus_ has grown does not seem to be altered in a way that necessarily arouses suspicion. In the case described by Roemer the incriminated ham showed bluish-gray areas from which _B. botulinus_ could be isolated, but this condition does not seem to have attracted attention before the poisoning occurred and was an observation made only after the event. So far as can be learned the meat that has caused botulism has always come from perfectly sound animals. In some cases the accused article of food is said to have had a rancid or acrid taste (due to butyric acid?), but there is nothing definitely characteristic about this, as the majority of anaerobes produce butyric acid. If, as in the Darmstadt[110] and Stanford University[111] epidemics, the food (canned beans) is served with salad dressing, a sour taste might pass without notice or even add to the relish. In the instance reported by Sheppard the canned beans were good in appearance, taste, and smell.

The obvious precaution to take against poisoning of this sort is first the use of adequate methods of food preservation. To judge from the recorded outbreaks, domestically prepared vegetables and meats are more likely to give rise to botulism than those prepared commercially on a large scale. The general use of steam under pressure in the large canning factories affords a high degree of protection against the anaerobic bacteria and their resistant spores. Whatever the method of treatment, all canned or preserved food having an unnatural appearance, taste, or odor should be rejected. Reheating of all prepared foods immediately before use is an additional safeguard. Foods, such as salads, composed wholly or in part of uncooked materials should not be allowed to stand overnight before being served.

If symptoms of botulism, such as visual disturbances, become manifest, the stomach should be emptied with a stomach pump, cathartics administered, and strychnine and other stimulants given as required. Since one of the noteworthy features of this disease is the paralysis of the intestinal tract by the toxin absorbed, the guilty food may lie for a long time in the stomach (cf. Stiles, _loc. cit._). Consequently, measures to empty the stomach should be taken even if the patient does not come under observation until several days after the poisonous food has been eaten.

An antitoxic serum has been prepared at the Koch Institute in Berlin. This serum has given successful results in animal experimentation, but has not been used, so far as I can learn, in any human outbreak. It is not available at any point in this country.

OTHER BACTERIAL POISONS

The interesting case reported by Barber[112] shows that there are other possibilities of food poisoning by formed bacterial poisons. Acute attacks of gastro-enteritis were produced in several individuals by the use of milk containing a poisonous substance elaborated by a white staphylococcus. This staphylococcus occurred in almost pure culture in the udder of the cow from which the milk was derived. The milk when used fresh was harmless and the poison was generated in effective quantities only when the milk stood some hours at room temperature before being used. The symptoms were similar to those usually ascribed to "ptomain poisoning."

SPOILED AND DECOMPOSED FOOD

There is a general belief that food is unwholesome whenever the evidence of the senses shows it to be more or less decomposed. This opinion finds expression in civilized countries in many legal enactments forbidding traffic in decomposed meats, vegetables, and fruits. There is unfortunately lack of evidence as to what kinds or degree of visible decomposition are most dangerous. In fact, some foods of high nutrient value, notably cheeses, are eaten only after somewhat extensive decomposition processes (termed ripening) have taken place. The characteristic flavors or aromas of the various hard and soft cheeses are due to the substances formed by certain species of molds and bacteria and are just as properly to be regarded as decomposition products as the unpleasant stenches generated by decomposing eggs or meat. Indeed, some of the decomposition products formed in the ripening of Brie, Camembert, or Limburger are similar to, if not identical with, those which are associated with spoiled foods. Sour milk, again, is recommended and commonly used as a food or beverage for persons in delicate health, and yet sour milk contains many millions of bacteria and their decomposition products. Some of the bacteria commonly concerned in the natural souring of milk are closely related to pathogenic types. The partial decomposition of meats and game birds is often considered to be advantageous rather than otherwise. Even eggs, a food whose "freshness" is marred for most persons by the initial stages of decomposition, are ripened in various ways by the Chinese and eaten as a delicacy after the lapse of months or years. The preserved ducks' eggs known as pidan are stored for months in a pasty mixture of tea, lime, salt, and wood ashes. "They are very different from fresh eggs. The somewhat darkened shell has numerous dark green dots on the inner membrane. Both the white and yolk are coagulated; the white is brown, more or less like coffee jelly...."[113] Increase of ammoniacal nitrogen has taken place to an extraordinary degree in these eggs, indicating much decomposition of the egg protein. The ammoniacal nitrogen in pidan is considerably higher than in the eggs known by egg candlers as black rots.

It is evident, therefore, that bacterial growth in substances used as food is not necessarily injurious and may in some cases increase the palatability of food without destroying its wholesomeness. Little or nothing is known about the correlation of visible signs of decomposition with the presence of poisonous products, and it is at present impossible to say at what point in the process of decomposition a food becomes unfit to use owing to the accumulation of poisonous substances within it. There seems to be no connection between the natural repugnance to the use of a food and its unwholesomeness. Under ordinary conditions the nauseous character of very stale eggs is proverbial, and yet few nitrogenous foods have so clear a health record as eggs or have been so infrequently connected with food poisoning outbreaks.

It might seem tempting to conclude on the basis of the available evidence that spoiled or decomposed foods possess poisonous qualities only when certain specific bacteria, like the _B. botulinus_ already discussed, have accidentally invaded them and formed definite and specific poisons. But we have no right to assume that the everyday decomposition products of the banal bacteria are in all cases without injurious effects. Even though no sharply defined acute form of poisoning may be laid at their door, it does not follow that an irritating or perhaps slightly toxic action of the ordinary decomposition products is altogether absent. Our present knowledge of the nature and degree of danger to be apprehended from the use of spoiled food is imperfect and unsatisfactory. That fact, however, does not release us from the obligation to continue measures of protection based even to a limited extent on experience.

FOOTNOTES:

[95] Another species of _Claviceps_ (_C. paspali_) which attacks the seeds of a wild grass is believed to be responsible for certain outbreaks of poisoning among cattle and horses (_Science_, XLIII [1916], 894).

[96] Barger (_Jour. Chem. Soc._, XCV [1909], 1123) has shown that parahydroxyphenylethylamine is present in ergot and is in some degree responsible for the physiological action of the drug.

[97] Although some of the early outbreaks were traced to the use of sausage, particularly in Wuerttemberg, the proportion of recent botulism poisoning attributed to this food is no greater than of sausage-conveyed infections with the paratyphoid bacillus (chap. vi), and a number of the most completely studied outbreaks of botulism have been traced to ham, beans, and other foods.

[98] _Deutsche Viertelj. f. oeffentl. Ges._, XLV (1913), 8.

[99] E. Sacquepee, _Progres med._, XXVI (1910), 583.

[100] _Report to Local Govt. Board on Bacterial Food Poisoning and Food Inspection_, N.S. No. 77, 1913, p. 27.

[101] _Southern Cal. Pract._, XXII (1907), 370.

[102] _Ibid._, XXV (1910), 121.

[103] _Arch. of Int. Med._, XIV (1914), 589.

[104] _Amer. Med._, X (1915), 85.

[105] _Jour. Amer. Med. Assoc._, LXI (1913), 2301.

[106] _Loc. cit._

[107] _Loc. cit._

[108] In the feces of a healthy pig (Kempner and Pollock, _Deutsche med. Wchnschr._, XXIII [1897], 505).

[109] _B. botulinus_ does not develop in media containing over 6 per cent of salt and should not be able to grow in meat properly covered in brine made with 10 per cent of salt (Roemer, _Centralbl. f. Bakt._, XXVII [1900], 857).

[110] G. Landmann, _Hyg. Rundschau_, XIV (1904), 449.

[111] Wilbur and Ophuels, _Arch. of Int. Med._, XIV (1914), 589.

[112] _Phil. Jour. of Science_, IX (1914), B6, p. 515.

[113] K. Blunt and C. C. Wang, _Jour. Biol. Chem._, XXVIII (1916), 125.