removal of the acid thus removes the greater part of the toxicity. The continued intracellular production of acid from the reserve of lipoid-bound "mustard" renders the compound, once it has penetrated the cell, extremely persistent in its action and difficult to counteract.

The toxic action of "mustard gas" has a prolonged latency, a fact in accordance with the above conception. Fertilized starfish eggs treated for a few minutes (up to eight minutes) with a freshly prepared weak solution of "mustard" continue to cleave for some hours, at first regularly; later the cleavage becomes irregular and the eggs break down and disintegrate. If acid derived from the progressive hydrolysis of "mustard" contained as reserve in the cell-lipoids is chiefly responsible for the toxic effect, the long latent period of action is readily understood. An experiment with adult fish (Fundulus) illustrates both the long latent period and the necessity that the "mustard" should be absorbed by the living cells while it is still in the intact or non-hydrolyzed state. Four fish were placed in each of the following solutions: (A) Filtered solution of "mustard" kept at room temperature five days; (B) a similar solution kept at room temperature one day; (C) the same solution as B, but kept at 0° C. and brought to 20° C. one half hour before using; (D) the same solution kept at 0° C. until immediately before using.

Solutions A and B were almost non-toxic; three of the four fish remained alive after five days in the solution; in C all fish were living after three hours, three were dead in eighteen hours, and all in twenty-six hours; in D two were dead and a third dying within three hours. The toxicity is thus an inverse function of the time during which the 66 tard" is undergoing hydrolysis.

mus

While the loss of toxicity of an aqueous "mustard" solution corresponds roughly with the decomposition of "mustard" as determined by titration, a lag in loss of toxicity at the end of the curve suggests that in those extremely dilute solutions the organism takes up a larger proportion of the poison than

would be anticipated, possibly as a result of adsorption.

The velocity of the toxic action exhibits a high temperature-coefficient similar to that of chemical reactions in general. In one experiment freshly fertilized starfish eggs were placed in two portions of the same mustard" solution, one (A) kept at 9 to 10°, the other (B) at 21°. From each solution eggs were transferred to normal sea-water after exposures of 1, 2, 4 and 8 minutes. It was found that an exposure of 2-4 minutes at 21° had almost the same effect in preventing development as one of 8 minutes at 9°-10°. All eggs were killed by 8 minutes' exposure at 21°, while most survived this exposure at 9°. The rate of toxic action at 9°-10° is thus about one third of that at 21°. This result suggests that cold, in conjunction with the other methods of treatment, may prove to be of service in treating the skin-burns caused by "mustard gas," i. e., it indicates that the temperature of the skin should be kept as low as possible during the treatment (e. g., washing with icecold kerosene is suggested).

Experiments on the counteraction of the toxic action by subsequent treatment with weak basic substances which readily penetrate protoplasm (ammonia, aniline) have not yielded very conclusive results. In several experiments fertilized eggs exposed to "mustard" solutions for some minutes and then brought for three or four hours into sea-water containing a little ammonia n/2000 (NH, in sea-water) showed on the whole a more favorable development than eggs returned directly from the "mustard" solution to sea-water (i. e., larvæ showed less irregularity and more active ciliary movement). This favorable effect of ammonia was distinct but somewhat slight. In other experiments Arenicola larvæ treated for some minutes with solutions of aniline in sea-water (of the anesthetizing concentration, ca. 1/8 saturated), and then exposed to "mustard" solution, proved distinctly more resistant to its toxic action than the control. This effect is probably to be regarded as an example of the general protective or antitoxic action which anæsthetics exhibit

with this organism. It is possible, however, that the basicity of aniline may be favorable; larvæ anesthetized with alcohols showed some degree of protection, but less marked than with aniline. The after-treatment of poisoned larvæ with aniline solutions proved ineffective. Treatment with basic substances appears to us to offer the most promising means of counteracting the action of this poison. A substance whose physical properties, solubilities, and rate of hydrolysis resemble those of "mustard," but which yields on hydrolysis a base, e. g., ammonia, instead of an acid, ought theoretically to counteract the action of "mustard" within the cell. Such a compound could be introduced into the lungs in the form of a spray, or applied to the skin in the usual manner. High lipoid-solubility or surfaceactivity, favoring rapid penetration of cells, would be essential in such a substance. We recommend a systematic search for an organic compound having these properties. Physiological experimentation with such a compound, if it is obtainable, should in our opinion yield important results.

By the use of intravitam staining, and by the injection of aqueous "mustard" solution directly into the body of the starfish egg, strong evidence was afforded that free acid is liberated within the cell.

The intravitam stain used was neutral red. Eggs were treated with solutions of "mustard" oil (in sea-water) sufficiently concentrated to cause subsequent abnormal development, and were then transferred to an extremely dilute solution of neutral red in sea-water. Normal eggs were simultaneously treated with the neutral red solution. For a period of at least half an hour controlled and treated eggs were colored to about the same degree. The treated eggs later became progressively more intensely stained, so that in an hour after the treatment the greater intensity in color of the "gassed" eggs over that of the control was easily recognizable.

The effect of "mustard" and its decomposition-products on the cell-interior was tested by the introduction of a drop of the gas solution into the body of the fertilized egg by

means of a micro-pipette. The following results were obtained:

1. Eggs injected with distilled water quickly recover and continue their normal development.

2. Eggs injected with a freshly made saturated aqueous solution of "mustard gas show no immediate injurious effects but subsequently are inhibited in their development.

3. Eggs injected with a saturated solution which has been allowed to stand at room temperature for over two hours undergo cytolysis, the immediate destructive effect being more marked than that following the injection of the undecomposed solution.

4. Eggs injected with an aqueous solution of hydrochloric acid of the same strength as the decomposed gas solution exhibit approximately the same effect, viz., a more or less extended cytolysis.

These experiments lend substantial support to the view, previously expressed by Marshall and Smith, that mustard gas, in virtue of its lipoid-solubility, penetrates rapidly into the cell-interior where it liberates hydrochloric acid which, in the free state, is relatively incapable of penetrating the cell.

R. S. LILLIE,

G. H. A. CLOWES,
R. CHAMBERS

THE MARINE BIOLOGICAL LABORATORY,
WOOD'S HOLE, MASS.

SPECIAL ARTICLES

ON HERSCHELL'S FRINGES

HERSCHELL'S fringes, as produced by the familiar apparatus consisting of a rightangled prism reposing with its broad face on a plate of obsidian, present the well-known group of achromatic fringes running parallel to the arc or limit of total reflection. Observation is made in a direction normal to the edge of the prism.

It occurred to me that the phenomenon could be made much more striking and of wider scope, if a long 60°prism were used and observation made in a plane of symmetry parallel to the edge of the prism. In the interest of variety, moreover, it is preferable not to em

ploy strictly accurate surfaces; so that the prisms with which grandfather used to decorate his gas fixtures will, as a rule, suffice admirably. In the figure P is such a prism (truncated) on a plate of obsidian Q, the long edges being normal to a white window curtain at L near by, illuminated with sun light or day light; or any light toward the front, overhead, is good.

The rays that are wanted, s, will enter symmetrically at a mean angle of about 30° to the vertical and after reflection at the base of the prism and the plate, reach the eye in the direction E. The rays totally reflected, t, come from a greater angle to the vertical and are not wanted.

P

Q

L

The limit of total reflection here (also easily recognized) is usually a sharp parabolic or cuspidal apex. The light seen through either face enters by the opposed face. On looking down from a steeper angle and with properly selected faces, brilliant groups of complete confocal ellipses (major axis one half to over two inches), of confocal hyperbolae may be seen in each of the roof faces. To find advantageous combinations, the three faces of each prism should be examined in succession, and it is well to rub P on Q to improve the contact. On moving the eye fore and aft or using different pressures, any type of ellipse with white or colored disc may be produced at pleasure. It is usually preferable to use a shorter plate Q than is given in the figure, about one half the length of the prism.

When well produced the ellipses may also be

seen by side light, with different patterns in the two roof-faces.

The type of interference figure clearly depends on micrometric differences of the faces in contact. The ellipses are Newton's rings modified by the color dispersion of the glass. The hyperbolae, however, are about equally frequent; but their character is less easily stated. They probably originate in cylindrics. The case of the 45°-90° prism, with the right angled faces respectively horizontal (on the plate) and vertical, is also interesting; for here the ellipses are apt to be circles with each of the two groups seen after two reflections, one in each of the orthogonal faces. The light should enter nearly normal to the oblique face. As it leaves in the same way, one should observe through a horizontal slot in a white screen.

I may add a similar observation: If a cylindrical lens (say 1 diopter) is placed on a plate and illuminated with homogeneous light, the interference pattern consists of a succession of equidistant arrow heads along the line of contact, all pointing in its direction. Now these are the very forms observed in the interferences of reversed spectra along the line of coincidence of spectra, except that the latter are apt to be far narrower than the former. It seems therefore, as if the effect of color variation in one case and of the cylindric increase of thickness of air film, in the other, were formally capable of like treatment.

Cornell University

Medical College

IN THE CITY OF NEW YORK

Admits graduates of approved Colleges presenting the required Physics, Chemistry and Biology.

Instruction by laboratory methods throughout the course. Small sections facilitate personal contact of student and instructor.

Graduate Courses leading to A.M. and Ph.D., also offered under direction of the Graduate School of Cornell University.

Applications for admission are preferably made not later than June.

For further information and catalogue address The Dean, Cornell University Medical College

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Johns Hopkins University

Medical School

The Medical School is an Integral Part of the University and is in close Affiliation with the Johns Hopkins Hospital

ADMISSION

Candidates for admission must be graduates of approved colleges or scientific schools with at least one year's instruction, including laboratory work, in physics, chemistry, and biology, and with evidence of a reading knowledge of French and

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Each class is limited to 90 students, men and women being admitted on the same terms. Except in unusual circumstances, applications for admission will not be considered after July 1st. If vacancies occur, students from other institutions desiring advanced standing may be admitted to the second or third year, provided they fulfill all of our requirements and present exceptional qualifications.

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The next academic year begins September 30, 1919 and closes on the second Tuesday in June. The course of instruetion occupies four years, and especial emphasis is laid upon practical work in the laboratories, in the wards of the Hospital and in the Dispensary.

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The charge for tuition is $250 per annum, payable in three instalments. There are no extra fees except for rental of microscope, certain expensive supplies, and laboratory breakage.

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Washington University

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REQUIREMENTS FOR ADMISSION Candidates for entrance are required to have completed at least two full years of college work which must include English, German, and instruction with laboratory work in Physics, Chemistry and Biology.

INSTRUCTION

Instruction begins on the last Thursday in September and ends on the second Thursday in June. Clinical instruction is given in the Barnes Hospital and the St. Louis Children's Hospital, affiliated with the medical school, the St. Louis City Hos pital, and in the Washington University Dispensary.

COURSES LEADING TO ACADEMIC
DEGREES

Students who have taken their premedical work in Washington University, are eligible for the degree of B.S. upon the completion of the first two years of medical work.

Students in Washington University may pursue study in the fundamental medical sciences leading to the degree of A.M. and Ph.D.