DR. KOCH ON THE CHOLERA.

An important and influential conference[[1]] upon cholera was opened in Berlin at the Imperial Board of Health on the evening of July 26. There were present Drs. v. Bergmann, Coler, Eulenbrg, B. Fränkel, Gaffky, Hirsch, Koch, Leyden, S. Neumann, Pistor, Schubert, Skreczka, Struck, Virchow, and Wollfhügel. The conference had been called at the instance of the Berlin Medical Society, whose President, Prof. Virchow, explained that it was thought advisable Dr. Koch should, in the first instance, give a demonstration of his work before a smaller body than the whole society, so that the proceedings might be fully reported in the medical press. He mentioned that Herr Director Lucanus and President Sydow had expressed their regret at being unable to be present, as well as many others, including Drs. Von Lauer, Von Frerichs, Mehlhausen, and Kersaudt. Before the meeting Dr. Koch exhibited microscopical specimens and drawings of the cholera bacillus, and demonstrated the method of its preparation and cultivation. The preparations included specimens of choleraic dejections dried on covering glasses, stained with fuchsin or methyl-blue, and examined with oil immersion, one-twelfth, and Abbe's condenser; also sections of intestine preserved in absolute alcohol, and stained with methyl-blue. There were also cultures in gelatin, etc.

Dr. Koch commenced by remarking that what was required for the prevention of cholera was a scientific basis. Many and diverse views as to its mode of diffusion and infection prevailed, but they furnished no safe ground for prophylaxis. On the one hand, it was held that cholera is a specific disease originating in India; on the other, that it may arise spontaneously in any country, and own no specific cause. One view regards the infection to be conveyed only by the patient and his surroundings; and the other that it is spread by merchandise, by healthy individuals, and by atmospheric currents. There is a like discrepancy in the views on the possibility of its diffusion by drinking water, on the influence of conditions of soil, on the question whether the dejecta contain the poison or not, and on the duration of the incubation period. No progress was possible in combating the disease until these root questions of the etiology of cholera are decided.

Hitherto the advances in knowledge upon the etiology of other infective diseases have done little toward the etiology of cholera. These advances have been made within the last ten years, during which time no opportunity—at least not in Europe—has occurred to pursue researches; and in India, where there is abundant material for such research, no one has undertaken the task. The opportunity given by the outbreak of cholera in Egypt last year to study the disease before it reached European soil was taken advantage of by various governments, who sent expeditions for the purpose. He had the honor to take part in one of these, and in accepting it he well knew the difficulties of the task before him, for hardly anything was known about the cholera poison, or where it should be sought; whether it was to be found only in the intestinal canal, or in the blood, or elsewhere. Nor was it known whether it was of bacterial nature, or fungoid, or an animal parasite—e.g., an amoeba. But other difficulties appeared in an unexpected direction. From the accounts given in text-books he had imagined that the cholera intestine would show very slight changes, and would be filled with a clear "rice-water" fluid. He had not fully recollected the conditions met with in post-mortem examinations had formerly made, and was therefore at first surprised to meet with quite a different state of things. For he soon found that in a large majority of cases remarkably severe lesions were present in the intestines. In other cases the changes were slighter, and eventually he met with some which, to a certain extent, corresponded with the type described in text-books. But it was some time, and after many inspections, before he was enabled to correctly interpret the varied changes met with. In spite of a most careful examination of all other organs and of the Mood, nothing was found to establish the presence of an infective material, and attention was finally concentrated on the intestinal conditions.

There were cases in which the lower segment of the small intestine, most marked immediately above the ileocæcal valve, extending thence upward, was of a dark reddish-brown color, the mucous membrane being covered with superficial hæmorrhages. In many cases the mucous membrane appeared to be superficially necrosed, and covered with diphtheritic patches. The intestinal contents in such cases were not colorless, but consisted of a sanguinolent, ichorous, putrid fluid. Other cases showed a gradual transition to a less marked change. The redness was less intense, and was in patches, while in others the injection was limited to the margins of the follicular and Peyerian glands, giving an appearance which is quite peculiar to cholera. In comparatively few cases were the changes so slight as to consist in a somewhat swollen and opaque condition of the superficial layers of the mucous membrane, with delicate rosy-red injection, and some prominence of the solitary follicles and Peyer's patches. In such cases the intestinal contents were colorless, but resembling meal-soup rather than rice-water. In only a solitary instance were the contents watery and mucoid. Microscopical examination of the intestine and its contents revealed, especially in the cases where the margins of Peyer's patches were reddened, a considerable invasion of bacteria, occurring partly within the tubular glands, partly between the epithelium and basement membrane, and in some parts deeper still. Then he found cases in which, besides bacteria of one definite and constant form, there were others also accumulated within and around the tubular glands, of various size, some short and thick, others very fine; and be soon concluded that he had to do here with a primary invasion of pathogenic bacilli, which, as it were, prepared the tissues for the entrance of the non-pathogenic forms, just as he had observed, in the necrotic, diphtheritic changes in the intestinal mucosa and in typhoid ulcers.

Passing to speak of the microscopical character of the contents of the bowel, Dr. Koch said that owing to the sanguinolent and putrescent character of these in the cases first examined, no conclusion was arrived at for some time. Thus he found multitudes of bacteria of various kinds, rendering it impossible to distinguish any special forms, and it was not until he had examined two acute and uncomplicated cases, before hæmorrhage had occurred, and where the evacuation had not decomposed, that he found more abundantly the kind of organism which had been seen so richly in the intestinal mucosa. He then proceeded to describe the characters of this bacterium. It is smaller than the tubercle bacillus, being only about half or at most two-thirds the size of the latter, but much more plump, thicker, and slightly curved. As a rule, the curve is no more than that of a comma (,) but sometimes it assumes a semicircular shape, and he has seen it forming a double curve like an S, these two variations from the normal being suggestive of the junction of two individual bacilli. In cultures there always appears a remarkably free development of comma shaped bacilli. These bacilli often grow out to form long threads, not in the manner of anthrax bacilli, nor with a simple undulating form, but assuming the shape of delicate long spirals, a corkscrew shape, reminding one very forcibly of the spirochaete of relapsing fever. Indeed, it would be difficult to distinguish the two if placed side by side. On account of this developmental change, he doubted if the cholera organism should be ranked with bacilli; it is rather a transitional form between the bacillus and the spirillum. Possibly it is a true spirillum, portions of which appear in the comma shape, much as in other spirilla—e. g., spirilla undula, which do not always form complete spirals, but consist only of more or less curved rods. The comma bacilli thrive well in meat infusion, growing in it with great rapidity. By examining, microscopically, a drop of this broth culture the baccilli are seen in active movement, swarming at the margins of the drop, interspersed with the spiral threads, which are also apparently mobile. They grow also in other fluids—e. g., very abundantly in milk, without coagulating it or changing its appearance. Also in blood serum they grow very richly.

Another good nutrient medium is gelatine, wherein the comma bacilli form colonies of a perfectly characteristic kind, different from those of any other form of bacteria. The colony when very young appears as a pale and small spot, not completely spherical as other bacterial colonies in gelatine are wont to be, but with a more or less irregular, protruding, or jagged contour. It also very soon takes on a somewhat granular appearance. As the colony increases, the granular character becomes more marked, until it seems to be made up of highly refractile granules, like a mass of particles of glass. In its further growth the gelatine is liquefied in the vicinity of the colony, which at the same time sinks down deeper into the gelatine mass, and makes a small thread-like excavation in the gelatine, in the center of which the colony appears as a small white point. This again is peculiar; it is never seen, at least so marked, with any other bacterium. And a similar appearance is produced when gelatine is inoculated with a pure culture of this bacillus, the gelatine liquefying at the seat of inoculation, and the small colony continually enlarging; but above it there occurs the excavated spot, like a bubble of air floating over the bacillary colony. It gives the impression that the bacillus growth not only liquefies the gelatine, but causes a rapid evaporation of the fluid so formed. Many bacteria also have the power of so liquefying gelatine with which they are inoculated, but never do they produce such an excavation with the bladder-like cavity on the surface.

Another peculiarity was the slowness with which the gelatine liquefied, and the narrow limits of this liquefaction in the case of a gelatine disk. Cultures of the comma bacillus were also made in agar-agar jelly, which is not liquefied by them. On potato these bacilli grow like those of glanders, forming a grayish-brown layer on the surface. The comma bacilli thrive best at temperatures between 30° and 40° C., but they are not very sensitive to low temperatures, their growth not being prevented until 17° or 16° C. is reached. In this respect they agree with anthrax bacilli. Koch made an experiment to ascertain whether a very low temperature not merely checked development but killed them, and subjected the comma bacilli to a temperature of 10° C. They were then completely frozen, but yet retained vitality, growing in gelatine afterward. Other experiments, by excluding air from the gelatine cultures, or placing them under an exhausted bell jar, or in an atmosphere of carbonic acid, went to prove that they required air and oxygen for their growth; but the deprivation did not kill them, since on removing them from these conditions they again began to grow.

The growth of these bacilli is exceptionally rapid, quickly attaining its height, and after a brief stationary period as quickly terminating. The dying bacilli lose their shape, sometimes appearing shriveled, sometimes swollen, and then staining very slightly or not at all. The special features of their vegetation are best seen when substances which also contain other forms of bacteria are taken—e. g., the intestinal contents or choleraic evacuations mixed with moistened earth or linen and kept damp. The comma bacilli in these conditions multiply with great rapidity so as to far outnumber the other forms of bacteria, which at first might have been in far greater abundance. This state of affairs does not last long; in two or three days the comma bacilli began to die off, and the other bacteria began to multiply. Precisely the same thing takes place in the intestine, where, after the rapid initial vegetation is over, and when exudation of blood occurs in the bowel, the comma bacilli disappear and putrefactive bacteria predominate. Whether the occurrence of putrefaction is inimical to the comma bacilli has not been proved, but from analogy it is very probable. At any rate, it is important to know this for certain, for if it be so, then the comma bacilli will not thrive in a cesspit, and then further disinfection would be unnecessary. These bacilli thrive best in fluids containing a certain amount of nutriment. Experiments have not yet shown the limits in this respect, but Koch has found them capable of growing in meat broth diluted ten times.

Again, if the nutrient medium become acid in reaction their growth is checked, at least in gelatine and meat infusion; but singularly enough, they continue to grow on the surface of a boiled potato which has become acid, showing that all acids are not equally obnoxious to them. But here, as with other substances which hinder their growth, they do not kill the bacilli. Davaine has shown that iodine is a strong bactericide. He experimented with anthrax bacilli in water to which iodine was added, and the bacilli were destroyed. But practically the organisms have to be dealt with in the alkaline contents of the bowel, or in the blood or fluids of the tissues, where iodine cannot remain in the free state. Koch found that the addition of an aqueous solution of iodine (1 in 4,000) to meat infusion, in the proportion of 1 in 10, did not in the least interfere with the growth of the bacilli in that medium. He did not pursue this line of inquiry, seeing that in practice larger quantities of iodine than that could not be given. Alcohol first checks the development of the comma bacilli when it is mixed with the nutrient fluid in the proportion of 1 in 10, a degree of concentration which renders it impracticable for treatment. Common salt was added to the extent of 2 per cent. without influencing the growth of the bacilli. Sulphate of iron, in the proportion of 2 per cent., checks this growth, probably by precipitating albumimites from the fluids, and possibly also by its acid reaction; certainly it does not seem to have any specific disinfecting action—i.e., in destroying the bacilli. Indeed, Koch thinks that the admixture of sulphate of iron with fæcal matter may arrest putrefaction, and really remove what may be the most destructive process to the comma bacilli. Hence he would distinguish between substances which merely arrest putrefaction and those which are bactericidal; for the former may simply serve the purpose of preserving the infective virus. Among other substances which prevent the growth of the comma bacilli may be mentioned alum, in solutions of the strength of 1 in 100; camphor, 1 in 300; carbolic acid, 1 in 400; oil of peppermint, 1 in 2,000; sulphate of copper, 1 in 2,500 (a remedy much employed, but how much would really be needed merely to hinder the growth of the bacilli in the intestine!); quinine, 1 in 5,000; and sublimate, 1 in 100,000. In contrast with the foregoing measures for preventing the growth of these bacilli is the striking fact that they are readily killed by drying. This fact is proved by merely drying a small drop of material containing the bacilli on a cover-glass, and then placing this over some of the fluid on a glass slide. With anthrax bacilli vitality is retained for nearly a week; whereas, the comma bacillus appears to be killed in a very short time. Thus it was found that although vitality was retained—depending largely upon the number of bacilli—for a short time, yet withdrawal of the nutrient fluid for an hour or even less often sufficed; and it never happened that the bacilli retained vitality after a deprivation lasting twenty-four hours. These results would seem to point to the fact that the comma bacillus does not, like the organisms of anthrax and vaccinia, pass into the resting state (Daner-zustande) by drying; and if so, it is one of the most important facts in the etiology of cholera. Much, however, remains to be done, especially with regard to the soiled linen of cholera patients being kept in a damp state. He found that in soiled articles, when dried for a time, varying from twenty-four hours and upward, the comma bacilli were quite destroyed. Nor was the destruction delayed by placing choleraic excreta in or upon earth, dry or moist, or mixed with stagnant water. In gelatine cultures the comma bacilli can be cultivated for six weeks, and also in blood serum, milk, and potato, where anthrax bacilli rapidly form spores. But a resting state of the comma bacilli has never been met with—a very exceptional thing in the case of bacilli, and another reason why the organism must be regarded rather as a spirillum than a bacillus, for the spirilla require only a fluid medium, and do not, like the anthrax bacilli, thrive in a dry state. It is quite unlikely that a resting state of the comma bacillus will ever be discovered; and, moreover, its absence harmonizes with our knowledge of cholera etiology.—The Lancet.

[1]

A detailed report is published in the Berliner Klinische Wochenschrift Aug. 4.


[THE MEDICAL RECORD.]

MALARIA.—THE NATURAL PRODUCTION OF MALARIA, AND THE MEANS OF MAKING MALARIAL COUNTRIES HEALTHIER.[[1]]

By Conrad Tommasi Crudeli, M.D., Professor of Hygiene, University of Rome, Italy.

Before entering upon my subject, I must crave the indulgence of those of my colleagues whose language I have borrowed for any italicisms that I may use, as well as for the foreign accent which must strike their ears more or less disagreeably. Desiring to respond as well as lay in my power to the invitation with which I have been honored to discuss the hygienic questions relating to malaria, I have chosen the French language as being the one in which, apart from my mother tongue, I could express myself with the greatest ease and precision.

I shall be pardoned also, I hope, for having employed the terms "malaria" and "malarial districts" in place of the more commonly used expressions "paludal miasm" (miasme paludeen) and "marshy regions" (contrées marécageuses). The substitution is not a happy one from a literary point of view, but I have made it deliberately and for the following reason: The idea that intermittent and pernicious fevers are engendered by putrid emanations from swamps and marshes is one of those semi-scientific assumptions which have contributed most to lead astray the investigations of scientists and the work of public administrations. This idea, so widespread and so well established by the traditions of the school, is radically false. The specific ferment which engenders those fevers by its accumulation in the atmosphere which we breathe is not exclusively of paludal origin, and still less is it a product of putrefaction. Indeed, in every region of the globe between the two Arctic circles there are swamps and marshes, steeping-tanks of hemp and flax, large deltas where salt and fresh waters mix, and yet there is no malaria there, although putrid decomposition is on every side. On the other hand, in the same parts of the globe there are places which are not and never were marshy, and in which there is not the least trace of putrefaction, but which, nevertheless, produce malaria in abundance. I reject, therefore, wholly the paludal assumption, and in order to express this view in the title of my paper, have been forced to employ terms which to my hearers may sound like italicisms.

The Italians generally have not this paludal notion, for experience taught them long ago that malaria is produced nearly everywhere—in marshy districts as well as in those which might almost be called arid; in a volcanic soil as well as in the deposits of the Miocene and Pliocene periods and the ancient and modern alluvia; in a soil rich in organic matters as well as in one containing almost none; in the plains as well as on the hills or mountains. The word malaria (bad air), which it is the sad privilege of Italy to have lent to all languages to express the cause of intermittent and pernicious fevers, represents, then, among the majority of our rural populations, the idea of an agent which may infect any sort of country, whatever may be its hydraulic and topographical conditions, and whatever may be its geological formation. This word, therefore, is the one best suited to designate this specific ferment in question, and I have on this account, employed it and its adjectival derivatives in order not to resuscitate the idea of the exclusively paludal origin of the morbific agent.

I shall not tarry long to speak of the nature of this ferment, for the studies bearing upon that point, although far advanced, are not yet completed. I may remark, however, that the idea that the ferment is formed of living organisms is a very old one, and has not arisen suddenly because of the modern theories of the parasitic nature of disease. From the time of Varrar (who believed that malaria was made up of invisible mites suspended in the atmosphere) to our own day this theory has been several times advanced by hygienists. Independently of the general considerations which led Rasori, and later Henle, to formulate the doctrine of the contagium vivum of infection (long before the progress of microscopical science had revealed the existence of living ferments), there were peculiar circumstances as regards malaria which should have impelled minds to look in that direction, even in times long past.

Some of these circumstances are of a nature to strike every serious observer, and deserve a few moments' attention. How could one maintain, for example, that this ferment is a product of chemical reactions taking place in the ground, when it is seen to remain constantly the same whatever may be the composition of the soil from which it emanates! As long as the paludal theory held sway, the chemical interpretation of this identity of the product in every latitude was easy. Rica does not hesitate to admit that when a swampy tract is heated by the sun's rays to the necessary point for the putrid decomposition of the organic matters contained in it, the "chemical ferment," or rather the "mephitic gases," to which is attributed the morbific action, are developed, whatever may be the distance from the equator at which this marshy region lies. But since it has been ascertained that malaria is produced in soils of the most varied chemical composition, the persistent identity of this product has become chemically inexplicable; while it is however readily conceivable, if one admits that malaria is an organized ferment which easily finds the necessary conditions for its life and multiplication in the most varied soils, as is the case with millions of other organisms vastly superior to the rudimentary vegetables which constitute the living ferments.

The same thing may be said of the progressive intensity of the morbific production in abandoned malarious districts. This fact has been historically proved in several parts of the earth, and especially in Italy. A large number of Grecian, Etruscan, and Latin cities, even Rome itself, sprang up in malarious territories and attained a high state of prosperity. First among the reasons for this success must be placed the works undertaken with a view of rendering these places more salubrious, and which lessened the evil production, but almost never extinguished it completely. After the abandonment of these localities, the production of malaria recommenced in a degree which went on increasing from age to age, and which has rendered some of these places actually uninhabitable. This was seen, in the time of the ancient Romans, in Etruria, when it was conquered and laid waste, and in several parts of Magna Græcia, and of Sicily. From the fall of Rome even to the present day, this phenomenon has been manifested in a very evident manner in the Roman Campagna, in certain parts of which, even up to the time of the Renaissance, it was possible to maintain pleasure houses, but which are now unhabitable during the hot season. In many cases the physical conditions of the soil have undergone no appreciable change during centuries, so that it is impossible to attribute so enormous an augmentation of malaria to an increase in its annual production, itself increased by a progressive alteration of the chemical composition of the soil. But if, on the contrary, it be admitted that malaria is caused by a living organism whose successive generations accumulate in the soil, the interpretation of this fact becomes very simple.

There are, finally, peculiarities in the local charging of the atmosphere with malaria which can be explained only in this manner. If the malarial miasm were composed of gaseous bodies emanating from the soil, or rather of chemical ferments formed beneath the ground and raised into the air by gases or watery vapor, the charging of the atmosphere with the specific poison ought to arrive at its maximum during the hottest part of the day, when the ground is heated the most by the sun's rays, and when the evaporation of water and all chemical actions attain their maximum intensity. But this is very different from what actually occurs. The local charging of the atmosphere is always less strong during the meridian hours than at the beginning and the end of the day, that is to say, after the rising, and especially after the setting, of the sun. Now it is precisely at these hours that the difference between the temperature of the lower layers of the atmosphere and that of the surface of the ground is the greatest, and that the ascending currents of air starting from the ground are the strongest. If malaria consists of solid particles contained in the soil, one may readily understand how their elevation en masse into the atmosphere should take place especially at these two periods of the day.

All these facts, which can be easily verified if the subject of malaria be studied on the spot and without any preconceived notions, explain the tendency which has always been manifested to attribute this specific poisoning of the air to a living organism which is multiplied in the soil; and they also explain the ardor with which hygienists have applied themselves to the production of the scientific proof.

Unfortunately the investigations undertaken for this end have for a long time been fruitless, for the preconceived paludal theory has led investigators to occupy themselves exclusively with the inferior organisms inhabiting marshes. Among these organisms they studied especially the hyphomycetes, which had already acquired so great an importance in dermatology; and their entire attention was concentrated upon the aquatic algae, without even taking the precaution to determine whether the varieties which they thought to be malarial were found in all malarious swamps, or whether they were capable of living within the human organism. It has thus happened that each observer has indicated as the cause of malaria a different variety of alga, whichever he found to be most abundant in the swampy ground that he had to examine. Thus Salisbury has indicated the palmella gemiasma, which is found with us in places perfectly free from malaria, while it is often wanting in malarious marshes in the center of Italy; Balestra, a species of alga which is as yet indeterminate; Bargellini, the palmogloea micrococca; Safford and Bartlett, the hydrogastrum granulatum; and Archer, the chitonoblastus oeruginosus. There is not a single one of these species the parasitic nature of which has been demonstrated; and as regards the two last named varieties, it can be positively denied that they are capable of producing a general infection, for the diameter of their spores and filaments is greater than that of the capillary blood vessels.

It was only in 1879 that Klebs and myself, after having been thoroughly freed, by a long series of preparatory studies, from the unfortunate paludal idea, undertook together some investigations in malarious districts of the most varied character, marshy and not marshy. We employed the system of fractional cultivation, making experiments on animals with the final products thus obtained. We felt ourselves justified in recognizing the malarial ferment in the schizomycete bacillus. The numerous researches made subsequently by us, and by many other observers, in the soil and in the air of several malarious localities, as well as in the blood and in the organs of men and animals specifically infected, have put it henceforth almost beyond doubt that we really have to do with a schizomycete. Very recently, MM. Marchiafava and Celli have succeeded in demonstrating that the germs of this schizomycete attack directly the red blood-globules, and destroy them, causing them to undergo a series of very characteristic changes which admit of easy verification, and which render certain the existence of a malarial infection.

Several observations made recently in Rome tend to demonstrate that the schizomycete of malaria does not always assume the complete bacillary form described by Klebs and myself; but this morphological question possesses no further interest for the hygienist. For him the essential thing is to know that he has to deal with a living ferment which can flourish in soils of very varied composition, and without the presence of which neither marshes nor stagnant pools of water are capable of producing malaria.

We must not think, however, that all earth containing this ferment is capable of poisoning the superjacent atmosphere. Popular experience, certain modern scientific investigation, and the facts which one can often verify when the soil, which was malarious in ancient times and which has since ceased to be so, is turned up to a great depth, all agree in proving that the ground remains inoffensive as long as it is not placed in certain conditions indispensable for the multiplication of this specific ferment. Up to this point the organism lives, so to speak, in an inert state, and may remain so during centuries without losing any of its deleterious power. There is nothing in this fact that ought to surprise us, since we know that the life and the power of evolution belonging to the seeds of plants of a much higher order than these vegetable organisms constituting ferments, may remain latent for centuries, and may then revive at once when these grains are placed in the conditions suitable for their germination.

Among the conditions favorable to the multiplication of the malarial ferment contained in the soil, and to its dispersion through the superjacent atmosphere, there are three which are absolutely essential, and the concurrence of which is indispensable for the production of bad air (malaria). First, a temperature which does not fall below 20°C. (67.5°F.); next, a very moderate degree of permanent humidity of the soil; and finally, the direct action of the oxygen of the air upon the strata of earth which contain the ferment. If a single one of these three conditions be wanting, the development of malaria becomes impossible. This is a point of prime importance in the natural history of malaria, and it gives us the key to most of the methods of sanitary improvement attempted by man.

Let us see first what can be done in this direction without the labor of man. For nature herself makes localities salubrious by suspending for a greater or less time the production of malaria. It is thus that winter brings about in every country a freedom from malaria which is purely thermic, for it is due simply and entirely to a sinking of the temperature below the required minimum. Indeed, if the temperature in winter rises above this minimum, there are often sudden outbreaks of malaria. Sometimes, during very warm and dry summers, the heat extracts all the humidity from the malarious soil, and thus procures for us a freedom from the disease which is purely hydraulic. This may continue for a long time (as happened in the Roman Campagna during the years 1881 and 1882), but may also be completely destroyed by a single shower. Nature also sometimes renders a district healthy in a manner purely atmospheric, by covering a malarious soil with earth which does not contain the malarial ferment, or with a matting formed of earth and the roots of grasses growing closely together in a natural meadow.

In the attempts of purification by suspending the malarial action, which have been devised by man, the same thing has been done; that is to say, it has been sought, to eliminate at least one of the three conditions essential to the development of the specific ferment contained in the infected soil. Naturally, they have not thought of bringing about a thermic purification, such as nature produces in winter, because of the impossibility of moderating the action of the sun; but they have tried from all time to procure hydraulic or atmospheric purifications, and sometimes to combine these together in a very happy way.

The hydraulic systems are very numerous, for the problem which is presented, namely, that of depriving the ground of its humidity during the hot season, necessitates different solutions according to the nature and the bearing of the soil. Sometimes this is done by digging open or closing ditches intended to draw away large bodies of water. At other limes a system of drainage is established, by means of which the water is drawn out of the earth and its level is depressed, so that the upper malarious strata, exposed to the direct action of the air, are deprived of moisture during the hot season. This system of drainage is not a modern invention; the Italian monks understood it as well as, and even better than, we do. In deep and loose soils they used sometimes, just as we do now, porous clay pipes; but when the subsoil was formed of compact and nearly impermeable matters, they employed a system of drainage, the extent and grandeur of which astonishes us. It is that of drainage by cavities, applied by the Etruscans, Latins, and Volsci to all the Roman hills formed of volcanic tufa, the tradition of which I have found still preserved in some countries of the Abruzzi.

We may sometimes establish a double drainage, from below and from above; that is to say, to drain the subsoil, and at the same time increase the evaporation of water from the surface of the ground. It is well known that clearing off the forests of malarious countries has often proved an excellent means of making lands salubrious which were before too damp; for, by removing every obstacle to the direct action of the sun's rays upon the ground, we cause an increase of evaporation from its surface, and may thus be enabled to exhaust the superficial strata completely of their water during the hot season. In very moist lands, which lend themselves readily to deep drainage, the combination of the latter with a clearing of the surface has, in almost every quarter of the globe, rendered possible a very widespread and sometimes a quite lasting freedom from malaria. But, although a nearly universal experience proclaims this fact, there is a school which, following in the footsteps of Lancisi, maintains the contrary opinion, that it is necessary to preserve the forests in malarious districts, and even to increase their extent, since the trees filter the infected atmosphere and arrest the malaria in their foliage. This strange theory was formulated by Lancisi in 1714, on the occasion of the proposed clearing of a forest belonging to the Caetani family, and lying between the Pontine Marshes and the district of Cistema. Lancisi was completely imbued with the paludal notion, and consequently believed that the very severe malaria of Cistema was brought by the winds from the coast marshes, instead of being produced in the soil surrounding the district, which was then covered by this forest. He believed then that the forest acted as a protective rampart, and he prevented its being cut down. But toward the middle of the present century the Caetani had the woods cleared off from the entire belt of land surrounding Cistema. Twenty years later I was able to show that Cistema had gained greatly in salubrity. I published my observation in 1879, and, naturally, was taken to task rather sharply in the name of the sacred tradition. Happily these recriminations led our Minister of Agriculture to have the question studied by a special commission. This commission, after a conscientious examination extending over three years of all the malarious localities in the province of Rome, has just published its report,[[2]] the conclusions of which are entirely in accord with the facts of universal experience. They were not able to verify a single fact in support of Lancisi's theory, while they found many of the same nature as that of Cistema, and which have resulted in overturning the theory entirely.

It has also been thought possible to practice drainage from above by means of plantations of certain trees which would draw considerable moisture from the earth, a method which might really be serviceable in some malarious districts. But in accordance with the idea that malaria is a product of paludal decomposition, the trees selected have almost always been the eucalyptus. It has been maintained that trees of so rapid a growth ought to drain the soil very actively, and also that the aroma of their foliage ought to destroy the miasmatic emanations. I have hitherto been unable to verify a single instance of the destruction of malaria by eucalyptus plantations, but I do not consider myself justified in denying the facts which have been stated by others. There is nothing to oppose the admission that these plantations, when properly made, may sometimes have been of great utility. I maintain frankly, however, that they have not always been so, and that it is necessary to guard against the exaggerations into which some have allowed themselves to fall in recent times. Such exaggerations might have been avoided if, instead of talking about these plantations on the basis of a theoretical assumption, the results only had been studied in places where the eucalyptus abounds. It would then have been known that even in the southern hemisphere, the original home of the eucalyptus, there are eucalyptus forests which are very malarious. This fact has been demonstrated by Mr. Liversige, professor in the University of Sydney, Australia. Among us also, although everybody was convinced by the statements of the press that the locality of the Tre Fontaine, near Rome, had been freed from malaria by means of the eucalyptus, people were disagreeably surprised by an outbreak of very grave fever occurring throughout the whole of this colony in 1882, a year in which all the rest of the Roman Campagna enjoyed an exceptional salubrity. If, alongside of these hygienic uncertainties, we place the agricultural uncertainties, we must conclude that it is necessary to contend strongly against this fanatical prejudice in favor of the eucalyptus tree. These plants are, in fact, very capricious in their growth. In full vegetation during the winter in our climate, they are often killed instantly by a sharp winter frost, by damp cold, by the frosts of spring, or by other causes which the botanists have not yet been able to determine. At other times, if the winters are very mild, these plants grow too rapidly in height, and then are broken short off by moderately strong winds. It should further be mentioned that these plantations are sometimes very expensive. In fact, if the earth contains too much water, it must be drained under penalty of seeing the roots of the eucalyptus rot. Then again, if the subsoil is compact, it is necessary to dig deep trenches in order to give room to the long roots of these trees, and often indeed these trenches must also be drained, as is done for olive trees. The conclusion evidently is that it is better to confine ourselves to hydraulic methods of promoting the health fulness of a locality, the immediate effects of which are less uncertain. And then, when the local conditions are such as to make it desirable to try the effects of plants possessed of strongly absorbing powers, it is better to choose them from among the flora of our own hemisphere. This is more sure, and will cost less.

Simple hydraulic methods of purification, even the most perfect, do not, however, produce permanent hygienic effects, since the moisture necessary for the multiplication of the malaria in the soil is so slight that these effects may be compromised by anything whatever that is capable of restoring a moderate degree of humidity to the ground during the hot season. It has often been thought that a suspension of malarial production would be better assured by suppressing at the same time the humidity of the soil and the direct action of the oxygen of the air upon the superficial strata of earth which contain the ferment. This has been successfully accomplished by the system of overlaying (comblées). This consists in covering the infected soil by thick layers of uninfected earth, carried there either by the muddy waters of rivers or by the hand of man. At the same time the steady drainage of the surface and underground water is provided for. Last year I advised our Minister of War to undertake in another form a hydraulico-atmospheric purification of the district of the Janiculum surrounding the Salviati Palace on the Via della Longara, by draining the soil carefully and covering with a layer of very close turf all the parts of the surface which could not be macadamized. It would seem as if this system had been rather successful, since there has not been this year a single case of fever in the personnel of the new military college, established in the Salviati Palace; while in the Corsimi Palace, which is situated on the same side of the Via della Longara, but which looks out upon that part of the Janiculum which is still uncovered, there have been some fatal cases of fever.

Furthermore, we have had in Rome, during the past few years, some very evident proofs of the efficacy of atmospheric methods of purification. I will confine myself to the relation here only of the most striking instance, one which has been furnished us in the building up of new quarters of the city. There was much discussion at first as to whether the improvements should be undertaken in the parts where they now are or in the valley of the Tiber, for the uncovered lands of the Esquiline and of the Quirinal were malarious, and, as nearly everybody then thought that the malaria of Rome was carried into the city from the coast marshes, it was supposed that this state of things was irremediable. We opposed to this view the fact of the salubrity of the Viminal, which is situated between the Esquiline and the Quirinal, and which ought to be as unhealthy as the two other hills were the malaria of the latter imported into the city instead of being indigenous. Believing it to be indigenous, we hoped that by shielding the surface of these hills from the direct action of the air (by building houses and paving the streets), the malaria would cease to be produced there. That is precisely what has happened, for the new quarters are very healthy. But the malaria is only held in abeyance, and is not definitely overcome; for if an extensive excavation is made in these hills, and the contact of the air with the malarious soil is thus re-established, during a hot and damp season, the production of malaria commences anew. A complete atmospheric purification is nevertheless the most stable of all the methods of obtaining a suspension of malarial production, but unfortunately its realization is very limited, for it is restricted to inhabited localities and to sodded surfaces.

The ideal method of insuring freedom from malaria should be to obtain a permanent immunity, that is, to be able to modify the composition of the infected soil in such a way as to make it sterile as regards malaria, without taking from it the power of furnishing products useful for the social economy. But all the elements indispensable for obtaining such a result fail us utterly just here. We do not yet know what ought to be, in general terms, the composition of a soil incapable of producing malaria, yet retaining those properties which are suitable for vegetation. When we shall have arrived at this first stage, there will still be a long road to travel; and the most difficult part will be to discover a practical means of imparting this salutary composition to all the numerous varieties of malarious soils.

Scientifically, then, in the present state of our knowledge we are unable to affirm anything on this point. Practically, we are not much further advanced. It is very probable that the combination of hydraulic purification with a forced cultivation of the soil has sometimes determined changes in its composition by which it has been rendered sterile as regards malaria. If that has happened, it has happened by chance, and we are unable to reproduce the result at will; for we have not all the data which might enable us to understand how it has come about. Most of the purifications obtained in ancient times, by means of forced cultivation, continued during centuries, have not been definite at all, but the production of malaria has been simply suspended. Hardly was the regular cultivation of the fields interrupted than the production of malaria recommenced. Among the numerous examples that I might cite in this connection, I will limit myself to that of the Roman Campagna. This seemed to have been made permanently healthy under the Antonii, but after the fall of the empire it began again to produce malaria, as if the forced cultivation through so many centuries had never been.

One might, strictly speaking, be content with such a result, and boldly undertake forced cultivation of all malarious districts, without stopping to ascertain whether the freedom from malaria so obtained would be definite, or whether the production of the poison were only suspended. Unfortunately, one is never sure of arriving at such a result, and no one can say, à priori, whether the forced cultivation of a given malarious tract will render it healthful. It must always be remembered that the first effect of forced cultivation, which requires an overturning of the soil by means of the plow, the spade, and the pick, is an unfortunate one, from a hygienic point of view, whenever we have to deal with a malarious country. Experience has shown, especially in Italy and America, that this overturning of the soil almost invariably increases the local production of malaria. And this can be readily understood, since the plowing and the digging in a soil containing the specific ferment increase the extent of surface of the ground in immediate contact with the atmosphere. This first mischievous effect is often gradually weakened by the continued cultivation, and may end by disappearing. At other times, on the contrary, it persists obstinately, and one is often forced in desperation to the resolve to level the ground again and to varnish it, so to speak, with a thick sowing of grass, if he wishes to suspend or weaken the malarial production.

However, when the local conditions will permit, it is well to try whether, by means of forced cultivation of the soil, it may not be possible to increase the efficacy of the hydraulic method of procuring immunity from malaria, or of the hydraulico-atmospheric method of "overlaying." The moment that it is known that this cultivation has frequently been advantageous, there comes forward a crowd of social reasons which induce us to attempt it, even though we be persuaded that we are about to engage in a game of chance. But to dare to attempt it is not all that is necessary; we need also the possibility of so doing, and just here we find ourselves in a vicious circle from which it is not easy to emerge. Forced cultivation cannot be accomplished without the presence of agriculturists in the region during the entire year; and the agriculturists cannot remain in the region during the fever season, for they run thereby too great a risk. For the solution of this question there is but one means: try to increase the power of resistance of the human organism to the attacks of the malaria. It is to a search after the means of accomplishing this result that I have devoted myself during the past few years.

There is nothing to hope for, as regards malaria, in acclimation. Individual acclimation is, and always has been, impossible. The malarial infection is not one of those a first attack of which confers immunity from other attacks. It is, on the contrary, a progressive infection, the duration of which is indeterminate, and which is of such a nature that a single attack may suffice to ruin the constitution for life. Collective or racial acclimation certainly existed in the past, at a time when specific remedies for pernicious malaria were unknown; and even later, when the employment of these remedies was very limited. The acclimation was due to a natural selection made by the malaria upon successive generations, from which it took away, almost without opposition, all those who possessed but a feeble individual power of resistance to the specific poison, while it spared those who possessed this power of resistance in an extraordinary degree. The first were, according to the Grecian myth, the human victims destined to appease the monster or demon who opposed the violation of the territory over which he had up to that time exercised an absolute sovereignty. The second became the founders of the race, and through them, from generation to generation, the collective power of resistance to the malaria was progressively increased. In our own days a like selection may take place among barbarous races, as it does among the cattle and the horses in a malarious region, but it has become an impossibility among civilized nations. By means of the specific remedies which we possess, the use of which is now so general, the lives of a large number of individuals whose resisting powers are very feeble are preserved; and these individuals beget others whose power of resistance to the action of the specific poison is still more feeble. This results after a number of generations in the physical degradation of that part of the human race which inhabits malarious countries.

We cannot, therefore, in the future, count upon the assistance of external natural forces to increase the power of resistance of human society against the assaults of malaria. Such an object can be obtained only by artificial means. It has been sought to attain this end by the daily administration of the salts of quinine, of the salicylates, and of the tincture of eucalyptus, each and every one tried in turn. But the salts of quinine are dear, exercise a prompt, though very transient anti-malarial action, and, when administered for a long time, disturb rather seriously the functions of the digestive and nervous systems. The salicylates, when well prepared, are rather dear, and there is as yet no proof that they possess prophylactic powers against malaria. The alcoholic tincture of eucalyptus is useful in malarious regions (as are all the alcoholics, beginning with wine) in quickening the circulation of the blood; may it, perhaps, also act as a preservative against light attacks of malaria? Possibly. But it is very certain that it possesses no efficacy in places where malaria is severe. It will suffice to prove this to recall the two epidemics of fever which afflicted the colony of the Tre Fontaine, near Rome, in 1880 and 1882. Everybody was attacked, and there were several cases of pernicious fever, although a good preparation of eucalyptus is manufactured in the place and is distributed largely to the colonists during the dangerous season of the year.