that the high temperature which they used for sterilizing their culture liquids destroyed to a certain extent the activity of the substance which produced immunity, just as in our experiments a still lower temperature had such an effect. If doses of 1 cc. of filtered serum repeated seven or eight times are sufficient to produce immunity in an animal of the size of a guinea pig, which weighs from 400 to 500 grammes, it is not surprising that an equal dose of sterilized culture liquid repeated twice should be sufficient to produce immunity in a pigeon which only weighs from 200 to 250 grammes. Roux also succeeded in producing immunity in guinea pigs against symptomatic charbon by doses of 1 cc. of filtered serum repeated from ten to twelve times. With these experiments before him we are surprised that Duclaux should raise this objection as to the size of the doses of sterilized culture used in our experiments.

The final objection raised by Duclaux is that this method of vaccination had failed with the more susceptible animal species; that it succeeded only with the pigeon, a species on the marginal line of immunity, and that this mode of vaccination succeeded better in winter than in summer, and that even in winter there are some failures. It is true that our experiments failed with large animals like pigs, which are more susceptible to the disease, but this has no bearing on the demonstration of the principle. With these large animals, and especially in this disease, there are other difficulties to be overcome. The large size of the animal requires a great increase in the amount of the material used, an amount for the determination of which, sufficient experiments have not been made. Again the manner in which the virus is introduced into the body under natural conditions has a very important influence. Indeed it is doubtful if the immunity of pigs can be artificially raised to such a degree as to prevent the multiplication of the germs on the mucous surface and within the walls of the intestines and the formation of those large ulcers which are characteristic of the malady and are usually fatal. It is not to be forgotten that M. Roux has not published any experiments in which he has succeeded by this method in conferring immunity on cattle or sheep against symptomatic anthrax; but I have not heard of this being urged as an objection to the conclusions from the experiments on immunity with guinea pigs which he has published.

Duclaux is wrong in supposing that our experiments only succeeded with pigeons in winter. We did not make this statement. Pigeons are more susceptible to the virus of hog cholera in winter than in summer; consequently we selected winter for the experiments because at that time our control experiments with unprotected birds were successful. It is true that some of our experiments failed, but I imagine no principle has been worked out experimentally in which all the experiments from the beginning were successful. It was necessary for us to determine experimentally the dose which was to be given to produce immunity and the number of times it was necessary to repeat the dose. We also endeavored to learn the effect of a boiling temperature on the soluble substances produced in the cultures of this germ, and the high degree of heat is re

sponsible for the failure of some of the experiments. It also required some experimenting to learn that pigeons are more susceptible in winter that in summer. We published all of our experiments. M. Roux avoids the charge of failure by publishing only successful experiments. Taking all these facts into consideration, it must be admitted that our experiments published in 1886 were successful, and that they demonstrated the production of immunity by soluble substances contained in the culture liquids in which the germ of hog cholera had multiplied. I therefore continue to claim priority for this important discovery.

SOME NEW EXPERIMENTS IN PRODUCING ANESTHESIA WITH NITROUS OXIDE AND AIR, AND NITROUS OXIDE AND OXYGEN IN CONDENSED AIR-CHAMBERS, ILLUSTRATED BY EXPERIMENTS ON AN ANIMAL. By Dr. E. P. HOWLAND,' of Washington.

THERE are forty-seven substances mentioned and described as anæsthetics in the latest works on anæsthesia. Four of them, nitrous oxide, nitrous oxide in mechanical combination with oxygen, ether and chloroform, are the anesthetics that have received the sanction of the medical and dental professions, as the best and safest means of producing insensibility to pain during surgical and dental operations.

The cause of anesthesia and the action of anesthetics are still subjects of dispute between those who have had the largest experience in their administration, and who have made the most critical experiments on animals and man; but the best methods of administering and the effects of anæsthetics on the mental organism are subjects that can be demonstrated by experiment and practical experience.

Nitrous oxide has now been administered to millions of persons, and it has been proved to be almost absolutely safe as an anesthetic for short operations, but has proved to be dangerous and unpractical for prolonged operations on account of its effects and the want of acquired skill and experience in its administration.

Dr. Goodwillie of New York, and myself, and a few others have been successful in its administration for surgical operations; but the successful administrators in the United States can be numbered on your fingers. Dr. J. Marion Sims in a letter to Johnston Bros., dated Jan. 25, 1872, says, "Since last September I have performed a great many operations on patients under the influence of nitrous oxide. Many of these took the gas for twenty, twenty-five, thirty and thirty-five minutes. One took it for fifty minutes, and I saw no reason why she could not have safely taken it twice that length of time. Dr. Goodwillie has given the gas in two ovar

1 Dr. Howland died suddenly on his way home from the Cleveland meeting.- EDITOR.

iotomy cases for me; one for twenty-seven minutes, and the other for thirty-one minutes. In these it was all that I could wish."

I have administered nitrous oxide in many thousand dental operations, and several hundred surgical operations in the city of Washington, the longest time being thirty-five minutes for a capital operation performed by Dr. Bliss, assisted by Dr. Stuart. If nitrous oxide had been proved a safe and practical anaesthetic for prolonged operations, ere this it would have been in universal use, and would have taken the place of all other anæsthetics. The reason why it is not safe, is, because the blood is not oxygenated dur ing its administration, and the patient will die of asphyxia in two and half minutes if compelled to breathe pure nitrous oxide.

If nitrous oxide is mixed with five per cent or more of oxygen, or atmospheric air, the gas is so diluted that it will not produce insensibility, and it takes a much larger quantity of oxygen or air than five per cent to prevent its being fatal to the patient from asphyxia. Prolonged anæsthesia is produced by breathing pure nitrous oxide from one-half to three-fourths of a minute till the patient is anæsthetized, and then breathing air from onefourth to one-half a minute to partially oxygenate the blood and then breathing nitrous oxide again before the return of consciousness; recovery or death of the patient occurring within the limits of one and a half minutes. In my experiments on warm-blooded animals, death has generally occurred within two and a half minutes, the animal in a few cases living four minutes. The non-oxydation of the blood during the breathing of nitrous oxide is proved by the livid appearance of the face of the patient, the examination of the blood of animals after death, and the chemical analysis of the expirations of persons under its influence.

From a large number of experiments, I have found that all of the nitrous oxide taken into the lungs during three-fourths of a minute of inhalation is not exhaled in this time, but as much is exhaled as of pure hydrogen or nitrogen when they are breathed for three-fourths of a minute, and no more carbonic acid is found in the exhaled nitrous oxide than in the exhaled hydrogen or nitrogen, proving conclusively that the blood is not oxygenated from the decomposition of the nitrous oxide in the circulation. Some of our most eminent men and practical chemists and physiologists are in error in relation to the decomposition of anaesthetics in the circulation and their elements forming new compounds.

We have a new anesthetic that should claim our earnest attention. Nitrous oxide and oxygen mixed in the proportion of thirty-five parts of nitrous oxide and fifteen parts of oxygen, and administered in a condensed air chamber under a pressure of five pounds per square inch, will produce perfect anæsthesia for any length of time required, and the blood at the same time being perfectly oxygenated by the free and uncombined oxygen there is no danger or injury to the patient from a partial or entire asphyxia, as there is from nitrous oxide alone, or the still greater danger and injury from ether and chloroform.

In my experiments on animals with a mixture of equal quantities of nitrous oxide and atmospheric air, in comparison with a mixture of eighty

five parts of nitrous oxide and fifteen parts of oxygen, I find that they are equal in their anesthetic effects; but the pressure in the condensing chamber has to be fifteen pounds to the square inch with nitrous oxide and air, and only five pounds pressure to the square inch with nitrous oxide and oxygen.

From the thousands of operations performed in France under the influence of nitrous oxide and oxygen in condensed air-chambers, and from my own experiment on animals similarly anæsthetized, I believe that nitrous oxide and oxygen will be the anaesthetic of the future, and I think that greater facilities in administering this agent, regulating the pressure and purifying the air from infectious germs in a chamber that I have devised, will greatly facilitate its introduction.

This anesthetic is going to be of great service to the dentist as well as the surgeon. By increasing the pressure of air in the chamber, a large quantity of gas is administered, and the patient remains a much greater length of time anæsthetized after ceasing inhalation of nitrous oxide and oxygen, than with pure nitrous oxide as ordinarily given, thereby enabling the dentist to extract a large number of teeth before recovery. Refractory patients and those that do not readily become anesthetized under pure nitrous oxide, become perfectly passive and quickly insensible under nitrous oxide and oxygen. The operator is not at all affected by the escape of nitrous oxide in the chamber, and he experiences no unpleasantness or injury as is often the case with the administration of ether and chloroform. The dangerous point of all anæsthetics is when the toxic effect of the substance taken into the system, paralyzes the nerve centres, and they are on the point of ceasing to control and direct vital action, or when the substance as a vapor or gas is taken into the lungs in a quantity that excludes the required amount of oxygen to arterialize the blood, and death may occur from asphyxia. The toxic point of danger from nitrous oxide, I have proved by experiments on animals to be beyond five hours of continued anæsthesia when the blood is perfectly oxygenated with free oxygen, and the danger point from asphyxia is when the volume of oxygen with the nitrous oxide is below ten per cent of the mixture.

The danger point is therefore entirely under the control of the administrator.

If a greater amount of oxygen than fifteen parts to eighty-five of nitrous oxide is administered, perfect anesthesia is not produced unless the pressure of the chamber is increased just in proportion to the amount of oxygen added. When the oxygen is added it makes the whole quantity equal to the nitrous oxide, the pressure of the chamber has to be fifteen pounds to the square inch, the same as with equal quantities of nitrous oxide and air. Prolonged administration of this mixture is injurious, the same as prolonged administration of pure oxygen, causing super-oxidation of the blood and inflammatory action.

I have kept animals perfectly anæsthetized for two hours in a mixture of eighty parts of nitrous oxide and twenty of oxygen under a pressure of ten pounds to the square inch without any apparent injury. The time

of the dangerous toxic point of anesthesia, and also the time of the danger point from asphyxia in all of my experiments with ether and chloroform have proved to be uncertain and unreliable, and the danger point to be beyond the control of the operator, death often occurring without apparent cause. Many professional men declare it criminal to use chloroform instead of ether as there are ten deaths from the former to one from the latter; while to those who survive the effects of these anesthetics, positive injury results from chloroform in still greater proportion.

From statistics by Professor E. Andrews in the Chicago Medical Examiner, the death rate from the administration of chloroform is one in 2,723, from sulphuric ether, one in 23,404, from mixed ether and chloroform, one in 5,588, while during the year 1887, in the United States and Europe, nitrous oxide was administered to over one million persons and not a single death occurred from its use.

Is it not the duty, therefore, of every professional man to lend his influence to bring into use in every city and hospital an anæsthetic that is a hundred thousand times safer than are ether and chloroform?

I am happy to say that in my endeavors to introduce the new anesthetic, I am meeting the almost universal approbation of the medical and dentalprofessions.

Experiment. An animal was placed in an anesthetic chamber under pressure, and remained perfectly anesthetized while the pressure was at five pounds to the square inch, but when reduced below this pressure showed signs of recovery. When the pressure was raised again, the animal became quiet; when taken from the chamber, the animal was insensible to pain but soon recovered as well as ever.

A PHASE OF EVOLUTION. BY DR. E. LEWIS STURTEVANT, South Framingham, Mass.

[ABSTRACT.]

BOTANICAL varieties, the unit of evolutionary progress under vegetable culture, as evidenced by a study of the cultivated and wild dandelion. Drawings (colored) and herbarium specimens exhibited, demonstrating the substantial identity of garden varieties with wild varieties, and conversely showing the types for new varieties of the future.

[Published in full in Proceedings of the Society for the Promotion of Agricultural Science, 1888, p. 77.]

A STUDY OF THE HYDRANGEA, AS TO THE OBJECTS OF CROSS-FERTILIZATION. By Prof. THOMAS MEEHAN, Germantown, Philadelphia, Pa.

[ABSTRACT.]

THE author details a number of facts connected with the structure and development of allied species of Hydrangea, and argues that on no theory