Tetanus toxin, one of the most potent poisons known, is prepared by growing the tetanus bacillus in bouillon or blood serum un der anaerobic conditions. The bacillus is re moved by filtration and the filtrate constitutes the toxin. It is of delicate nature and is easily destroyed by both physical and chemical agents. Light and air rapidly render it inert. Even in filtration of the culture both light and air should be excluded. According to Kitasato, exposure to sunlight completely destroys the toxin within from 15 to 18 hours. Other investigators have reported the time as only half of this. Oxidizing agents such as dilute solutions of potassium permanganate, mineral and vegetable acids, destroy it promptly. From its solution in the filtered cultures tetanus toxin is thrown down on the addition of ammonium sulphate, and by dialysis and evaporation in vacuo it can be obtained in dry form, notpure but mixed with the proteins carried down with it by the reagent. The purest preparations yet made still give the protein reactions and there are those who claim that the toxin is an albumose, but this does not necessarily follow. According to•Brieger and Cohn, the fatal dose for a mouse is about 0.0000005 gram and for a man, about 0.00023 gram. It requires 2,000 times as much of the poison per kilo of body-weight to kill a rabbit as it does to kill a horse, and the chicken is 100 times less susceptible than the rab bit. It is highly poisonous when introduced sub cutaneously or intravenously, but is most potent when administered subdurally or in tracerebrally. This is due to the fact that it has a predilection for nervous tissues. It has been shown quite conclusively that when in jected subcutaneously the toxin Is conveyed to the nerve centres through the axis cylinders of the motor nerves, and that symptoms of tetanus first develop when the anterior horns of the spinal cord are reached. This explains why there is always a period of incubation, both after subcutaneous injection of the toxin and as a result of wound infection with the bacillus. It also makes plain the observation so frequently recorded that the period of incubation is shorter the nearer the site of in oculation is to the central nervous system. That tetanus toxin does combine with certain constituents of the central nervous system was demonstrated some years ago by Wassermann who found that when the toxin is rubbed up in a mortar with brain or spinal cord tissue it is completely fixed and neutralized. In other words, it forms a compound with some con stituent of this tissue. This is probably what happens when the poison is generated by the bacillus in the animal body and as a result of the injury thus caused to the nervous tissue tetanic spasms occur. A tetanus antitoxin is prepared in a manner similar to that employed in the preparation of diphtheria antitoxin. Un fortunately, however, the brillant practical re sults obtained in the treatment of diphtheria have not been secured in the treatment of tetanus. The value of tetanus antitoxin as a protective agent has been recognized for many years and has been fully confirmed in the treatment of the wounds of the World's War. Before the United States entered the war, American laboratories were busy supplying the armies of the Allies with this material. Sol diers received a protective dose before they went into battle and all wounded were treated with this agent as soon as possible. In this way a high death rate from tetanus has been avoided, notwithstanding the fact that a large proportion of the wounds are infected with the bacillus. If one waits until symptoms of tetanus have developed the administration of the serum fails in a large proportion of the cases to effect a cure. However, even under this condition the treatment is not wholly with out value. The cessation of trench warfare was followed by a notable decrease in the num ber of wounds infected with the organism of this disease.
In certain parts of Germany, especially in Wiirttemburg and neighboring parts of Baden and Bavaria, where sausage, a favorite article of diet, has been imperfectly cured and eaten raw, poisoning from this article of food has long been known. Rarely, similar cases have
occurred among those in the United States who persisted in the Old World method of preparing and eating sausage. As a rule, food which produces this form of intoxication has been prepared for a long time before it is eaten. The disease thus produced is known as "botul ism* and it should be clearly' understood that this does not include the ordinary form of food poisoning which leads to vomiting and purging and generally ends in recovery. In 1885, some 30 cases of botulism developed in a small Belgian village and were studied by Van Ermengem of Ghent. In this instance, the food was a ham which had been kept in dilute brine. It was from a sound animal, other por tions of which had been eaten while fresh with out harm. In fact the companion ham, from the same brine, had been eaten without dis turbing those who had partaken of it. The sound ham lay near the surface and was not wholly covered by the brine while the faulty piece lay on the bottom of the vat and was completely excluded from the air. It was not noticeably decomposed, but was marked by soft colored spots and gave off the odor of butyric acid. In this meat the bacillus botulinus was found. An aqueous extract of the ham was injected into animals and proved to be intensely poisonous. In cats it caused dilatation of the pupils and abundant mucous secretion in the mouth and pharynx, prolapse of the tongue, roughness of the voice followed by complete aphonia, difficulty in swallowing and paralytic symptoms resulting in death within from four to eight days. Mice and guinea pigs, rabbits and apes were affected in much the same way. The apes were found to be equally susceptible when fed by mouth, while cats, rats, dogs and chickens were not susceptible when fed. Other outbreaks due to the same cause have been re ported from time to time in this and other countries.
The bacillus botulinus is strictly anaerobic, except when grown with other organisms which consume the air. It grows only feebly at animal temperature, but at lower tempera tures and when the air is excluded it develops its toxin. It will be seen that it does not cause an infection but an intoxication. Indeed, the bacillus does not multiply in the animal body, or does so only to a slight extent. It is a toxicogenic, rather than a pathogenic, organism. A striking characteristic of this toxin is that it affects some animals, including man, when taken by the mouth. It also has a predilection for nervous tissue. According to Marinesco and others it induces marked changes in the cells of the anterior horns, leading to chroma tolysis, and disintegration of Nissl's granules. Like tetanus toxin, it combines in vitro with nervous tissue, forming an inert compound. An effective antitoxin has been prepared and has proved efficient in animal experimentation. The writer is not aware that this antitoxin has been used in the treatment of botulism in man. This toxin may occur in canned vegetables as well as in meats. There was quite a scare in the United States in 1917 concerning the possibility of botulism being widely prevalent on account of the new methods of preserving food pro posed at that time by the Agricultural Depart ment. This fright has not been justified by subsequent events. Apparently the bacillus botulinus is not widely distributed. So far, it has been found only once except in food and that was in the feces of hogs. As has been stated, it grows only in the absence of air or in association with other organisms which con sume the air, and it has been found in canned foods. In such, it produces gas which bulges the ends of the can and food from such con tainers should not be eaten. In brine of more than 10 per cent strength it will not grow. It is of special interest because it is essentially a saprophytic organism producing in food in the absence of air a most potent poison which affects man when taken into the stomach.