early life the heart develops toward the left. You notice that the consensus of opinion is that these hearts are smaller than normal. The orthodiagrams show this. Again, I found that a large number of these people have a sinus arrythmia. Of course, that is natural with young people, and many older people who develop neurasthenia or nervous depression have a reversion to this type of rhythm. This question is very interesting in detail. I have heard quite a number of discussions in many societies on it, and this paper is one of the best résumés I have heard, for it covered a great subject in a short time. The idea I would like to bring to you is that these people present either congenitally defective hearts or a reversion to the infantile. type.

The Physiology and Experimental Treatment of Poisoning with the Lethal War Gases.

FRANK P. UNDERHILL.

(Recently Lieutenant-Colonel, Chemical Warfare Service, United States Army)

Professor of Experimental Medicine, School of Medicine, Yale University

From the viewpoint of the military purpose for which gases were employed in warfare they may be divided into two large groups-(a) the Lethal Gases, and (b) the Neutralizing Gases. Under the term of Lethal Gases are included all those gases used in warfare for the object of killing the enemy. The principal substances comprising this group are chlorine, phosgene (carbonyl chloride), and chlorpicrin (nitrochloroform). On the other hand, extensive use was made of a large variety of gases the main purpose being not to kill the enemy but to make him work under difficulties, in other words to neutralize his military efficiency. Hence this group of substances received the name of Neutralizing Gases and included the lachrymators (as xylyl and benzyl bromide), the sneezing gases (as diphenylchlorarsine) and the vesicants (as yperite or mustard gas).

In general the neutralizing gases produce effects upon the human organism of a nature which cause discomfort rather than serious injury, although in sufficient concentration many of these substances may produce death. Grave effects by the neutralizing gases were not especially prominent in producing casualties in the field and hence the serious influences these gases are capable of inducing have not been extensively investigated.

The Lethal Gases.

Of special importance in warfare have been the lethal gases, chlorine, phosgene and chlorpicrin. These substances are alike in that each contains chlorine as an essential part of the molecule and one might assume at first glance that the physiological effects produced by phosgene and chlorpicrin are due to the action of the free chlorine or hydrochloric acid formed as a result of the

hydrolysis or other decomposition of the gases. This is an interesting hypothesis but from the pathologist's findings can hardly be true inasmuch as the lesions produced in the three cases are quite distinct and specific.

Pathology of Gas Poisoning.

Chlorine produces injury to the organism by causing immediate death of the epithelium lining the upper respiratory tract. The destruction of the epithelium permits the invasion into the bronchioles of pathogenic bacteria from the mouth resulting in a pneumonia. In animals that survive there may be a persistence of a chronic bronchitis and a bronchiolitis with scarring of the lung. Edema of the lungs, trachea and bronchi is the most striking feature of acute death from chlorine poisoning.

With phosgene poisoning edema and congestion of the lungs are prominent. Phosgene acts more especially upon the epithelium of the smaller bronchi and bronchioles whereas that of the trachea and larger bronchi is not damaged. A typical lobular or pseudo-lobar pneumonia may be present.

Chlorpicrin injures the epithelium of the entire respiratory tract but all portions of the tract are not equally affected. The trachea and largest bronchi, though irritated, suffer only transient injury. The medium-sized and small bronchi are most affected. An overwhelming edema of the lungs follows exposure to suitable concentrations of gas.

A comparative study of the pathology of the three gases shows that chlorpicrin in its action on the respiratory tract occupies a position somewhere between chlorine and phosgene.

An Interpretation of Gas Poisoning.

In the time allotted it would be impossible to describe in detail the character of the various types of work carried through in our investigation on the war gases. It will suffice to say that under carefully controlled conditions the influence of the lethal gases upon the organism of the dog has been studied both intensively and extensively. In this investigation several thousand animals were employed. As a result of this work it may be stated that

pulmonary edema is the prominent feature of the effects induced by these gases. In addition to pulmonary edema gassing has a definite influence upon the respiration, heart beat, temperature, the concentration of the blood, the water content of the lungs and other tissues, the chloride content of the blood and tissues with resulting changes in chloride excretion by way of the kidney, the number of the red and white cells of the blood, and the respiratory function of the blood leading to dyspnoea and partial asphyxia. Acidosis is present at times and there is a distinct influence upon protein metabolism. Some of these effects are of course dependent upon the development of pulmonary edema but others are not so readily explained in this way. It should be stated that so far as can be determined by experimental methods the lethal gases act specifically upon the respiratory tract which action results in edema. Little or none of the gas is absorbed. Hence whatever influence is exerted upon the organism by these gases must be explained by an interpretation of the effects induced in the respiratory tract.

The effects of gassing as enumerated above are so various that an attempt at correlation or the assignment of cause and effect seems at first glance well nigh impossible. Further study of the problem, however, brings to light one significant feature which stands out clear and distinct from all the other effects induced by exposure to gas. This is the well-defined curve of changes in blood concentration. Upon the basis of alterations in blood concentration quite definite stages in gas poisoning may be outlined. These stages stand out most clearly with phosgene and therefore the picture presented by this gas will be considered first.

Stages in Phosgene Poisoning.

First Stage. In the first few hours (5-8) after phosgene poisoning there is a notable decrease in the concentration of the blood.

Second Stage. The period of blood dilution is followed by an interval during which the blood rapidly becomes concentrated to a point far above the normal value and remains near this level for several hours.

Third Stage. After the period of increased concentration the blood gradually becomes more dilute until it is slightly under the normal value, which is eventually gained, and the animal

recovers.

The interpretation which may be placed upon the different stages of phosgene poisoning is as follows: In the first stage there is marked dilution of the blood. There are at least two ways in which this dilution may be explained. In the first place it may mean an increased blood volume, the excess fluid finding its way into the blood from the tissues in response to the strong irritation stimulus exerted by the gas upon the respiratory tract. Or secondly, a diluted blood would result if the red cells were removed in part and deposited in some organ or tissue. In the present investigation no studies have been made to determine actual changes in blood volume. Reports by Eyster and Meek, however, who have made such estimations, tend to the conclusion that in the stage of phosgene poisoning under discussion blood volume is not increased, and they account for the dilution of the blood on the hypothesis that red cells are stored in the lungs, at least temporarily. Whichever explanation is correct it is certain that during this first stage two features may be quite prominent, namely, edema of the lungs and dilatation of the heart. Edema can be explained very readily on the hypothesis of increased blood volume and it is also possible that such a condition might lead to a dilated heart. On the other hand, the deposition of corpuscles in the lungs, by causing an obstruction in the circulation, would lead to a dilated heart. The relatively large transport of fluid to the lungs during this period is, however, not so easily explained by this hypothesis. Whichever hypothesis is accepted, edema of the lungs prevails and there may be a dilated right heart.

In the second period edema has reached its maximum development and here also blood concentration is at its height. The latter state is undoubtedly induced by the withdrawal of fluid which finds its way into the lungs. During the interval of blood concentration the blood volume is definitely decreased and the heart may be noticeably diminished in size (Eyster). This would