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CLASSIFICATION AND METHODS OF USE OF WAR GASES
[NOTE: The classification employed by the British medical historians (History of the Great War, Based on Official Documents. Medical Services. Diseases of the War, Volume II, Including the Medical Aspects of Aviation and Gas Warfare, and Gas Poisoning in Tanks and Mines. London, His Majesty's Stationery Office; 1923, D. 252) is as follows:
(1) Acute lung irritants; (2) lacrymators; (3) direct poisons of the nervous system or paralysants; (4) sensory irritants of the eyes, nose, and upper respiratory passages (sternutators); vesicants. The paralysant group (hydrocyanic acid and sulphuretted hydrogen) is not included in the classification followed in the present volume, since our troops were not subjected to these gases.]
1. THE LACRYMATORS produced temporary blindness. Liberation of small quantities of a gas of this type made it impossible to carry on without wearing a mask. These gases, while not responsible for many evacuations to the rear, harassed troops engaged in close fighting or in manipulating guns. Practically all of the long list of lacrymators had a bromine base.
2. THE STERNUTATOR gases or nasopharyngeal irritants were nonlethal. They were capable, however, of producing extreme irritation of the nose, throat, and eyes, caused severe headache and nausea. The symptoms were comparatively short in duration, and the gases were not effective when the mask was worn. The inhalation of these gases before the application of the mask made mask wearing very uncomfortable and was apt to cause its premature removal and thus to subject the wearer to the effects of more important gases which usually accompanied or immediately followed the use of the sternutators. This type of gas usually arrived in the nature of a surprise, since it was used in high explosive shells. Because of this it was difficult for the troops to recognize immediately the presence of the gas. A good example of this type of gas is diphenylchlorarsine, which was long and extensively used at the front.
3. THE SUFFOCATING gases were used to kill and contained the most deadly substances employed in chemical warfare. Severe edema of the lungs quickly followed their inhalation, and death from asphyxiation frequently resulted within a few hours. Gases of this character were rather quickly dissipated, however, and it was difficult for the enemy to maintain an effective concentration over a long period of time. Good mask discipline robbed these gases of most of their terror and placed heavy expense on the enemy when they were extensively used. The two gases of this group most widely employed along our front were phosgene and chloropicrin.
Many combinations were made from these gases with other substances intended to assist them in their action.
PHOSGENE, a gas of high density, with an odor much like that of decaying hay or grain, is little, if at all, irritating to the eyes and has no irritant action on the skin. Its presence, therefore, was perceived with difficulty and men were gassed before they were aware of exposure.
CHLOROPICRIN requires a higher degree of concentration to cause a suffocative action than could readily be obtained in field use. It was frequently used in conjunction with phosgene the enemy hoping that the prompt irritant effect of the chloropicrin would prevent the wearing of the gas mask, thus rendering the soldier an easy prey to the accompanying phosgene.
THE VESICANT TYPE of gas made its appearance later than the others mentioned, but soon became the most important in gas warfare. It first came into prominence at Ypres on July 12, 1917, dichlorethylsulphide being the chemical used. It was called by the French soldiers "yperite," by the Italians "yprite," and by the British, "mustard gas." Gas-mask discipline offered ample protection to the eyes and lungs, but very important military results were obtained from skin burns which caused the evacuation of enormous numbers of casualties. The Central Powers considered dichlorethylsulphide their most pernicious gas, and the experience of the Allies certainly confirmed the opinion that it had won this place in military importance. This gas had many features which rendered it especially suitable. It was toxic in concentrations which could not be detected by the sense of smell; the person affected suffered no discomfort at the time of the exposure, and symptoms were not evident until man hours later. Mustard gas penetrated all clothing and was remarkably persistent on the earth or on foliage over which it had been scattered. These factors tended to increase its effectiveness; in addition to the physical action of the gas on the men themselves, the morale of troops was impaired.
Truly speaking, dichlorethylsulphide is not a gas, but a liquid, which slowly vaporizes, and is effective in either state. It volatilizes slowly at ordinary temperatures and dissociates only at high temperatures. This latter fact was taken advantage of in the treatment of contaminated clothing. Furthermore, it is readily oxidized by such substances as chlorine or bleaching powder, and these chemicals were used in purifying dugouts, trenches, and ground or foliage saturated with the gas.
This classification, while eminently practical and convenient, does not imply that some of the gases have no physiological action other than that of their group. This is not true. For instance, bromacetone and chloropicrin, when employed in concentrations too low to affect the lungs, are lacrymators.
In addition to the four groups mentioned, gas officers occasionally reported the use of substances which possessed some of the properties of both the suffocative and vesicant gases. The usual shell filling which produced this result was made of equal parts of ethyldichlorarsine and dichlormethylether. This combination caused a vesicant action of an important nature, if kept in contact with the skin, with the air excluded; under ordinary battle conditions, however, this seldom happened. These gases possessed the properties of the: suffocative type to a greater degree though not so effective as phosgene and chloropicrin. Innumerable combinations of gases were encountered occasionally.
A complete list, in so far as is known, of the gases used by the enemy, includes the following: #2
Acrolein, allylisothiocyanate, arsenic trichloride, arsine, bromacetone, bromacetic ether, bromethylmethylketone,
bromide of benzyl, bromide of xylyl, bromide of toluyl, bromine, carbon monoxide, carbonyl chloride (phosgene),
chloracetone, chlorine, chloropicrin, cyanogen, dichlorethylsulphide (mustard gas), dichlormethylether, dimethylsulphate,
diphenylchlorarsine, diphenylfluorarsine, ethyldichlorarsine, formaldehyde, hydrocyanic acid, hydrosulphuric acid,
iodacetic ether, iodacetone, methylchlorsulphonic acid, monochlormethylchloroformate (palite), nitrogen peroxide,
phenylcarbylamine chloride, phosphine, phosphorus trichloride, sulphur dioxide, sulphur trioxides and trichlormethylchloroformate
(diphosgene or superpalite).
METHODS OF USE
The first gases used by Germany during the war were liberated from charged cylinders secretly installed in their trenches,#3 the success of such a gas attack depending upon a favorable wind which would carry the gas in high concentration slowly over the trenches of the unprotected allied troops. There is no record of the American Army having been exposed to any of the original types of cloud gas attacks from such cylinders.
This method was superseded by the projector attack and trench-mortar firing of gas projectiles.#4 Projectors, during most of the war, were large. smooth-bore cylinders. They were built to receive large drums or bombs of about 18 c. m. diameter. Charges of explosives were put in the bottom of these cylinders and the bomb placed on top. The cylinders were placed in batteries of from six to nine and operated at an angle of 45 degrees in a trench or in some special area that offered protection. Such a plant usually contained from 200 to 800 projectiles, and the batteries were fired by electricity. This permitted the simultaneous discharge of a vast amount of gas on a relatively small target at a range of from 1,000 to 1,500 meters. The gases so used were of the lung irritant type. A successful projector attack produced very serious results, and it could be carried out without much regard to wind direction and velocity. These bombs contained 50 per cent of their total weight in gas, as against 10 per cent in a gas shell. The great advantages were the cheap guns for the delivery of the gas and the enormous sudden concentration of the gas in a small area. Nevertheless, this method of using gas at a relatively short range necessitated great secrecy in installing the projector during the night and in getting off the attack before the allied air service located the line of projectors, else allied artillery would destroy the plant and liberate the gas among the enemy's own troops. Furthermore, the flash and noise produced usually gave the troops sufficient warning to put on masks. This method, at best, was limited to local uses and, although continued throughout the war, it became less and less frequent. During the late months of the war the enemy made an eflort to improve this method by building rifled cylinders and giving the bomb more of a shell contour.#4 This gave a slightly increased range, but did not greatly enlarge the scope of its usefulness.
Hand grenades were employed for delivering gas under certain conditions; but their use was so limited for this purpose that they did not account for many casualties.#4
These methods all proved of relatively little importance, however, as soon as the enemy discovered that gas could be better distributed by shells.
The innovation which placed gas warfare on a very important military plane was the building of the gas shell and the distribution of these shells by the use of artillery.#5 When first employed by the enemy the shells- carried only lacrymator substances. Lethal gases made their appearance in shell about the time of the first battle of the Somme, and this method of gas warfare rapidly developed until, at the close of the war, all types of gases were being used in gas shells, with many of them as a part of the filling in high-explosive shells. Distribution of gas in this manner on a given target was limited only by the number of guns available and the rapidity of their fire. This method of delivering gas was in very small degree limited by weather conditions and had the advantage of long range. It sometimes aflfected the territory even beyond the actual range of the artillery, since with a favorable wind a harmful concentration of gas would float with the air currents well beyond the point of shell burst. Definite tactics were evolved with this use of gas, placing its employment on as definite a plane as were the tactical methods of other arms of the service. After the use of gas shells had been instituted, it was difficult for the troops attacked to determine during a bombardment whether only high explosives were being used or whether a gas attack as well had been launched. For this reason it compelled the wearing of gas masks by the troops as soon as they were subjected to an artillery attack, and this in itself greatly lessened their fighting efficiency.
Their shell were classified by the enemy as pure gas shell and high-explosive gas shell. The pure gas projectile was employed for its lethal and casualty-producing effect by gas alone, since the effect of detonation and fragmentation was very slight. Such shell, when filled with a lung-irritant gas, were marked with a green cross. Various combinations of these fillings were marked green cross 1, green cross 2, or green cross 3, according to the nature of the particular mixture in use. Commonly the suffocative types of shell fillings were referred to as green cross ammunition.#6
Pure gas shells containing dichlorethylsulphide were marked with a yellow cross, and sometimes less important vesicant types received a further mark of identification such as yellow cross 1. This was later changed to green cross 3, the filling then being ethyldichlorarsine and dichlormethylether, the mixture previously described. Gas shell containing lacrymators were indicated by lettering such as " T-Stoff," " K-Stoff," "C-Stoff," and " B-Stoff." #7
High-explosive gas shell usually contained the nasal irritants such as diphenylchlorarsine and were marked with a blue cross.#6 There is reason to believe that very late in the war some mustard gas may have been fired in high-explosive shell. The blue cross shell not only produced a gas effect but also detonation and fragmentation to a marked degree. The amount of gas filling in such a shell was necessarily small, the enemy entertaining the hope that the accompanying high explosive would assist in propelling, vaporizing, and concealing the gas. The burst of this shell, unlike the pure gas shell, could not easily be differentiated from the ordinary high-explosive shell burst.#8
The enemy found the markings mentioned necessary to make it easy for the storage and for artillery troops which handled such ammunition and served the guns. Fortunately, the relationship of these marks to the shell contents soon became known to the Allies. This proved of great value in quickly identifying the nature of gases employed in an attack, since unexploded shell or fragments of shell bearing these marks were found.
Among the tactical programs adopted by the enemy for the use of war gases under different conditions the following are examples:#9
I. Counter battery fire and long-range fire (calibers, 77 mm.,105 mm., 150 mm., howitzers,
10 cm. guns):
| Per cent | |
| Explosive shell | 20 |
| Blue cross gas shell | 70 |
| Green cross gas shell | 10 |
The 15 cm. guns constituting part of the long-range group were provided with high explosive shell only. The rate of fire during the preparation for the attack for the 77 mm. guns was found to be one shot per minute per gun.
II. Fire against infantry-creeping barrage (calibers, 77 mm., 105 mm., 150 mm., howitzers):
| Per cent | |
| Explosive shell | 60 |
| Blue cross gas shell | 30 |
| Green cross gas shell | 10 |
210 mm. howitzers were provided with high-explosive shell only.
III. Fire against infantry-box barrage (calibers, 77 mm., 105 mm., and 10 cm. guns):
| Per cent | |
| Explosive shell | 30 |
| Blue cross gas shell | 60 |
| Green cross gas shell | 10 |
Yellow cross gas does not appear in these orders, since the enemy never attacked immediately through an area that they had shelled with mustard gas.
Allied troops at points selected for attack by the enemy and the artillery supporting such allied troops were subjected, before the enemy infantry advance, to a gas attack with high-explosive shell containing blue cross substances, and this fire was immediately followed by green cross shell. Late in the war it very frequently happened that all areas lateral to the point of attack were neutralized by a saturating fire of yellow cross shell. Reserve troop concentrations in the rear of such points of attack, villages near the scene, roads, wooded areas, ravines, reverse slopes, and other strong points. not intended to be occupied by the enemy were also shelled with mustard gas. In some instances, when an enemy attack failed and an orderly retreat could be made, he used mustard gas to assist in covering the retreat.#10
Thus it can be seen to what extent gas could be used in open warfare and how extremely difficult it was for the medical officer to determine whether one gas or a combination of gases produced the casualties he was called upon to care for. The individual patient might have been exposed to all the gases used in such an operation, or, on the other hand, he might have been in a spot where there was a significant concentration of only one of the gases.
The persistent and insidious character of mustard gas made it effective for several days after the burst of the shell. It made a good weapon, therefore, against wooded areas, billeting spaces, roads, artillery and machine-gun positions, as well as all points of cover. According to the needs of the situation, yellow cross shell could be used for surprise burst of fire, for saturation shoots, or for the area shoot. The last method, when used against inexperienced troops, was apt to cause them to minimize the danger of such concentration.
This method of fire consisted in maintaining a low concentration of mustard vapor in a given locality by slow intermittent shooting directed at that area. Such regions would be fired on frequently enough to keep up a low vapor concentration for days and weeks at a time. The inconspicuous way in which these areas were planted and kept planted with mustard gas resulted in many casualties. Directions for such area shooting are known in one instance to have been as follows: #9
Seventy-seven millimeter guns; 100 rounds per hectare (approximately 2M2 acres):
Target at 1,000 meters, 100 rounds. Target at 5,000 meters, 125 rounds.
Target at 6,000 meters, 125 rounds.
Target at 7,000 meters, 150 rounds.
(1) Monthly Summary of Information, Gas Warfare (British), No. 1, July, 1917.S. S. 184. On file, Medical Division, Chemical Warfare Service.
(2) Warthin, Alfred Scott, and Weller, Carl Vernon: The Medical Aspects of Mustard Gas Poisoning. C. V. Mosby Company, St. Louis, 1919, 21.
(3) Gilchrist, H. L., Col., M. C., U. S. A., and Church, J. R., Col., M. C., U. S. A. Report on Chemical Warfare in France, July 1, 1921, 155. On file, Medical Division, Chemical Warfare Service.
(4) Gas Warfare, Part I. German Methods of Offense. Army War College, February, 1918, War Department Document No. 705, 11.
(5) Gilchrist and Church: op. cit., 156.
(6) Chemical Warfare, Medical Aspects. War Department Chemical Warfare, Medical Division, Washington, D. C., November 1, 1922. On file, Medical Division, Chemical Warfare Service.
(7) Gas Warfare, Part I. German Methods of Offense. Army War College, February, 1918, War Department Document No. 705, 53.
(9) Special Report from the Chief of the Medical Division of Chemical Warfare Service to the Surgeon General, U. S. A., April 13, 1923, 2-3. OII file, Historical Division, S. G. O.
(10) Fries, Amos A., Brig. Gen., C. W. S., and West, Clarence J., Maj., C. W. S.: Chemical Warfare. McGraw-Hill Book Co. (Inc.), New York, 1921, 177.
SECTION II
The peculiar requirements for field use, as contrasted with controlled laboratory administration, was responsible, of course, for the fact that hydrocyanic acid was found almost useless as a war gas, while the commonly handled chlorine, produced industrially in such large amounts every day without accident, proved so very potent in war and the insidious phosgene ten times more so.
Experience showed that, to be valuable as a war gas, a poison must meet certain requirements. It should be a liquid or be easily liquefied, or it might be a solid, though the solids did not prove as effective as liquids. It must be readily volatilized at ordinary temperatures, and the vapor must have sufficient density to remain near the ground and to maintain its concentration for some time. It must be fairly stable in the presence of moisture and under the molecular shock of the detonating charge of the shell. In addition, it must compare favorably with the most toxic compounds known to science. Hydrocyanic acid fails as a war gas because of the low density of its vapor and the fact that the human organism can withstand the gas below certain concentrations without apparent injury. To kill, then, it requires a concentration which it is not practicable to obtain in the field. Gases like chlorine or phosgene injure in proportion to the amount encountered, so that, while a lethal concentration may not be attained at a given point, nevertheless they will cause casualties of greater or lesser extent, depending upon the concentration and time of exposure.
ORGANIC HALOGEN DERIVATIVES
The second outstanding feature of the war gases is the fact that they are practically all organic halogen derivatives. With the exception of hydrocyanic acid, acrolein, and a very few others, all of the gases which appeared to be of even possible value in the field contain chlorine, bromine, iodine, or fluorine in organic combination. The organic groupings impart the necessary volatility; the halogens give added weight to the molecule, increasing the vapor density, in many eases giving an instability in the presence of water sufficient to account for the final toxicity. The organic groups also give to a large number of the war gases their characteristic lipoid solubility. Of the three or four most effective compounds used, all are soluble in alcohol, acetone, fats, and oils, and so are able to penetrate the cells of the body with the facility of the anesthetics and for the same reason.
SPECIFICITY
The third outstanding feature of the war gases is their specificity. This is more apparent than real, perhaps, but it is sufficiently striking to allow of a rough classification based on the physiological attack. All the gases are irritating to all tissues with whi(h they come in sufficient contact, but under field conditions certain tissues and organs are more quickly or obviously injured by a given gas than are others.
1. Brombenzyl cyanide.
2. Benzyl bromide.
3. Bromacetone.
4. Chloracetophenone.
5. Chloropicrin.
6. Xylyl bromide.
7. Dichloretllylsulphide (mustard gas):
1. Chlorine, bromine.
2. Phosgene.
3. Trichlormethylchlorformate.
4. Chloropicrin.
5. Mustard.
1. Diphenylchlorarsine.
2. Mustard.
EYE IRRITANT
Taking up the groups in their order, the lacrymators, are characterized by their instantaneous effect on the corneas nerves. Sudden contact with a very moderate concentration of a good lacrymator is as painful as a sharp blow on the eyes, and, indeed, feels very much like it. Such a concentration is immediately unbearable, the eyes are kept shut and the lacrymatory glands are stimulated to a copious secretion of tears. At very low concentrations the lacrymators are felt as a slight irritation of the eye, causing frequent winking and increased flow of tears. Such concentrations are not detectable by the nerves of taste or smell, and do not produce irritation of the respiratory tract except after exceedingly long exposure. Some substances, even with prolonged exposures, fail to show injury to the respiratory mechanism, while they are distinctly and immediately felt in the eye. For example, a concentration of chloropicrin which is perceptible to the eye in time will injure the lung epithelium, but several days of continuous exposure are required before there is evidence of the development of lung edema. The effect on the eyes, however is instantaneous, suggests a physical or a molecular effect, and is a striking example of specificity. The time element precludes the possibility of hydrolysis or other decomposition, and suggests that this compound is itself a protoplasmic poison with a particular chemical relation to the compounds of the corneal nerve filaments, so that these are stimulated long before other nerve endings or other types of tissue cells are affected. After prolonged exposure, recognizable only in the eye, the respiratory mucosa shows definite injury, and rhinitis, bronchitis, pneumonia, and lung edema develop. At a still later period the kidney also shows injury. Chloropicrin is evidently toxic, therefore, to many tissues. As is well known, it is quite stable chemically, and hydrolyzes only very slowly in water. It is soluble in the fat solvents and the fats. Like chloroform, it is picked up by the blood stream from the lungs, and because of a certain degree of tissue specificity it reaches and damages the kidney more perceptibly than the liver, muscles, nerve cells, or other types of tissues. In this it resembles its chemical relative, chloroform, whose specific action on the liver is well known.
Mustard gas, on the other hand, produces no instantaneous effect on the eye. The individual is usually entirely unaware of its presence unless he detects its odor and recognizes it. Hours after exposure the typical injury to the exposed corneal area appears, with conjunctivitis. There is nothing resembling the instantaneous action of the true lacrymators. It may be concluded that mustard gas has no special affinity for the corneal nerve filaments, and that it is not, itself, in the same sense or degree as are chlorine and chloropicrin, a protoplasmic poison.
LUNG IRRITANTS
A large number of casualties and some the most severe injuries produced by the war gases are to be credited to the lung irritants.
Chlorine is interesting chiefly because of its historic position as the first war gas used, and because of the dramatic sufferings of the first, unprotected, victims. It is a highly reactive element, combining with protoplasm in a very great variety of ways, irritating and killing tissues, therefore, wherever it comes in contact with it. Chlorine gives evidence of instantaneous reactivity along the respiratory tract and in the eyes. Its effect on the nerve endings of the upper respiratory tract is so intense that in high concentrations it causes immediate spasms of the glottis or violent coughing and vomiting. The lungs later develop the usual reaction to injury of the lining epithelium, namely, edema and necrosis.
Chlorine may replace hydrogen in its organic combinations, incidentally producing hydrochloric acid; it may add directly on to unsaturated molecules or form more stable compounds; it may remove hydrogen from water, causing destructive oxidations, with the formation of hydrochloric acid; it may remove metallic ions from protein combination and thus alter the distribution of electric charges and so change the physical properties of the protoplasm; it may combine with the basic organic groups. These are some of the more obvious ways in which chlorine reacts with and alters protoplasm. These alterations are probably irreversible, chemically or physically, and any such change is assumed to be injurious or, if extensive enough, fatal.
The action of chloropicrin on the respiratory tract has already been touched upon. At moderate concentrations it produces lung edema, intense irritation of the whole tract, violent coughing, and retching. The edema comes on with considerable delay after exposure. Chloropicrin hydrolyzes very slowly in water, so that its effect on the respiratory mucosa can hardly be attributed to a production of hydrochloric acid within the cells, though this factor may contribute in the delayed action. A very general injury to the whole organism is suggested in the fact that men exposed to this gas are described as aging quickly, though the kidney lesions may account for part of this general deterioration. Nothing at all definite is known concerning the chemical action of this gas on protoplasm.
Phosgene and its relative, superpalite, are the most effective of the lung irritant group. Phosgene is quite reactive chemically. It dissolves and quickly hydrolyzes in water thus it is readily soluble in oils and fats and the fat solvents. While phosgene may react in a large number of ways, its lipoid solubility and its production of acid in contact with water would appear to be sufficient to account for its great toxicity. The former carries it into the cells like an anesthetic, the latter breaks it up when inside them, with the production of acidity. There is no strong evidence that it is immediately toxic. It produces no striking irritation of the corneal nerves nor, at medium concentrations, of those in the respiratory tract. Diluted, it may be inhaled without discomfort and has, at such times, a rather pleasant odor reminiscent of muscat grapes or of fermenting corn stalks. In more concentrated form the gas produces a sense of shock and a gripping of the chest, but even this immediate sensation passes off and leaves no well defined sense of injury. Some time later the developing injury to the lung tissues and the resulting edema become sufficient to make the patient aware of his condition, and the feeling of malaise rapidly intensifies. Phosgene itself probably gets as far as the lung capillaries. The packing of the corpuscles in these capillaries during the early stages of phosgene gassing has been established and is probably due to the production of acid in the corpuscle membranes. There is no evidence of action to a greater distance, and from the rate of hydrolysis of phosgene it is improbable on theoretical grounds.
Superpalite behaves like phosgene but is still more toxic.
Mustard gas must be classed as a lung irritant. It has no immediate effect but, like phosgene, is absorbed and
hydrolyzes within the cell to produce an acid. It produces, however, a type of reaction in the respiratory tract
quite different from that of phosgene, with the formation of a tenacious membrane in the upper portion of the trachea
and bronchial tree instead of the excessive edema of the alveoli.
NASAL IRRITANTS
The nasal irritants, as a rule, are not, strictly speaking, gases. They are solids which are highly dispersed in the form of smokes, and which are therefore more apt to collect in the upper respiratory passages rather than in the alveoli. Sufficient concentration or deep breathing incident to heavy work, however, will carry the particles into the deeper portions of the respiratory tract. The phenylchlorarsines are the typical examples of this group. These compounds irritate the nerve endings in the nose and throat, producing violent sneezing or vomiting and coughing. The mode of action of these smokes is not known definitely, though they are probably protoplasmic poisons per se, and on decomposition yield phenyl and arsenic groups as well as acid. The fact that they are not gaseous prevents their affecting tissues to any large extent and so limits their field of importance. They ean be rather easily removed from the inspired air by a filtering device attached to the mask.
SKIN IRRITANTS
Next to the lung irritants the skin irritants have proved most effective and Mustard gas was the substance most commonly used. It acts on all the tissues with which it comes in contact-eyes, respiratory tract, and skin. It is a heavy, oily liquid, volatilizing slowly. It dissolves in the ordinary fat solvents, fats, and lipids, but only to a very small extent in water. It penetrates the cells with considerable rapidity and by virtue of its lipoid solubility, tends to collect in the fat droplets and lipids of the cell. In the watery phase of the cell it hydrolyzes to produce hydrochloric acid. The passage from oil solution to water solution, and finally to hydrochloric acid, is slow and may continue for several days in the cells of a tissue exposed to mustard gas. This leads to a slowly developing injury to skin, eye, and respiratory tract, which increases in intensity, at times, for a period of two to three days and is then followed by the removal of the necrotic tissue and the very slow process of repair. There is very little evidence that mustard gas owes its tremendous toxicity to anything more than its ability to penetrate cells and there to produce acidity. Mustard gas has no immediate irritating action on nerve endings or tissues. Its toxicity develops slowly and is presumably the result of its decomposition products. One of these is hydrochloric acid, and while it is quite possible that other toxic fragments are developed in its breakdown, the acid alone can easily account for much of the injury. One of its hydrolytic products, dihydroxethyl sulphide, has been shown by Marshall to be practically nontoxic.
In concluding this chapter it seems appropriate to emphasize again the injury which results from the development of acidity within cells. Aside from the well-known action of phosphorus and perhaps chloroform on the liver cells, few clean-cut examples of this type of reaction had been described prior to the war. It may prove, however, that many types of cell intoxicants owe their action to an indirect development of acidity, which becomes the immediate cause of the injury.
There is considerable evidence to show that acid outside of the cell does very little harm. For example, very large amounts of hydrochloric acid may be injected into the veins of an animal without producing noticeable physiological effects. In this case the acidity is immediately taken care of by the effective buffer system of the circulating medium and the injected acid never reaches the interior of the tissue cells. The mucosa of the stomach is regularly bathed with 0.2 to 0.4 per cent hydrochloric acid, with a hydrogen ion concentration sufficient to indicate with Congo Red, but without damage to the mucosa cells. The neutrality of the cell interior is maintained by the impermeability of its membranes to acid. In the same way the skin resists damage from dilute acids for long periods.
On the other hand, the appearance of acidity within the cell instantly sets in motion the autolytic machinery of the cell, and in direct proportion to the amount of acid developed. Cell proteins are not digested by the cell proteases in the normal reaction of its fluids. When this reaction shifts toward the acid side these proteins become digestible by the enzymes always present. The more acid produced the more protein is rendered available for digestion. These available proteins liquefy and digest away, the structure of the cell is obliterated, the products diffuse out and are transported elsewhere by the blood and lymph, and the cell shrinks or dies and is completely autolyzed. All tissues which have been studied behave in this way toward acidity, but they differ very markedly in the extent of the reaction. Muscle and connective tissues are only slightly digested by their own enzymes, even under the most favorable conditions. They contain relatively large proportions of stroma or skeletal proteins which are not rendered digestible by a physiological or pathological rise in the hydrogen ion concentration. The epithelial tissues, on the other hand, are exceedingly sensitive to increased hydrogen ion concentration. They respond by very rapid and complete autolysis to the optimum increase of acidity. Anything, therefore, which can reach and penetrate epithelial structures and produce acidity within these tissue cells will do the maximum amount of tissue injury. If injury is done to a particularly vital gland or structure, the conditions are right for the maximum disablement of the organism as a whole. Phosgene, superpalite, and " mustard " combine the properties of the anesthetics with rapid hydrolysis to acids. By the strategy of the war they were applied directly to epithelial tissues. With phosgene and superpalite contact is made with the alveolar epithelium, a vital link in the fundamental functions of tissue respiration. Injury to it is like injury to the heart or blood vessels or the blood. It makes precarious the maintenance of the proper oxygen supply to the body as a whole. With mustard gas the skin epithelium is injured, or the upper respiratory tract. While the former injury is not necessarily fatal unless of large extent, it effectually eliminates the man from active service until the wounds are healed.
When such a combination is effected of a penetrating, acid-forming substance coming in contact with epithelial organs-there is a lethal toxicity quite equal to that of hydrocyanic acid and, in addition, injuries grading all the way down to zero, in proportion to the amount of gas received by the epithelium. In spite of its chemical reactivity, chlorine has only a tenth the toxic power of these gases (phosgene, superpalite, and "mustard") because it penetrates only slightly, and in the many combinations which it makes with protoplasm only a few lead to the production of acid.
From: The Medical Department of the United States in the World War, Volume XIV, Medical Aspects of Gas Warfare, prepared under the direction of Maj. Gen. M. W. Ireland, Washington: Government Printing Office, 1926.