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is concerned, the anti-scrum exerts its action cither on the toxin or on the bacterium itself; that is, its action is either antitoxic or anti-bacterial. The properties of these two kinds of scrum may now be considered.
The term " antitoxic " signifies that scrum has the power of neutralizing the action of the toxin, as is shown by mixing them together outside the body and then injecting them into an animal. The antitoxic scrum when injected previously to the toxin also confcrsimmunity (passive) against it; when injected after the toxin it has within certain limits a curative action, though in this case its dose requires to be large. The antitoxic property is developed in a susceptible animal by successive and gradually increasing doses of the toxin. In the earlier experiments on smaller animals the potency of the toxin was modified for the first injections, but in preparing antitoxin for therapeutical purposes the toxin U used in its unaltered condition, the horse being the animal usually employed. The injections arc made subcutancously and afterwards intravenously; and, while the^dose must be gradually increased, care must be taken that this is not done too quickly, otherwise the antitoxic power of the scrum may fall and the health of the animal suffer. The scrum of the animal is tested from .time to time against a known amount of toxin, i.e. is standardized. The unit of antitoxin in Ehrlich's new standard is the amount requisite to antagonize 100 times the minimum lethal dose of a particular toxin to a guinea-pig of 750 grm. weight, the indication that the toxin has been antagonized being th.it a fatal result does not follow within five days after the injection. In the case of diphtheria the antitoxic power of the scrum may reach 800 units per cubic centimetre, or even more. The laws of antitoxin production and action arc not confined to bacterial toxins, but apply also to other vegetable and nni/nal toxins, resembling them in constitution, viz. the vegetable loxalbumoses and the snake-venom group referred lo above.
The production of antitoxin is one of the most striking facts of biological science, and two important questions with regard to it must next be considered, viz. how dors the antitoxin act? and how is it formed within the hody? Theorctically there are two possible modes of action: antitoxin may act by means of the cells of the body, i.e. indirectly or physiologically; or it may act directly on the loxin, i.e. chemically or physically. The second view may now be said to be established, and, though the question cannot be fully discussed here, the chief grounds in support of a direct action may be given, (a) The action of antitoxin on toxin, as tested by neutralization effects, takes place more quickly in concentrated than in weak solutions, and more quickly at a warm (within certain limits) than at a cold temperature, (fc) Antitoxin acts more powerfully when injected along with the loxin than when injected at the same time in another part of the body; if its action were on the tissue-celts one would expect that the site 'of injection would be immaterial. For example, the amount necessary to neutralize five limes the lethal dose being determined, twenty times that amount will neutralize n hundred times the lethal dose. In the case of physiological antagonism of drugs this relationship docs not hold, (r) It ha* been shown by C.J. Martin and Cherry, and by A. A. Kanthack and Cobbclt, that in certain instances the toxin can be made to pass through a gelatine membrane, whereas the antitoxin cannot, its molecules being of larger size,. If, however, toxin be mixed with antitoxin for some time, it can no longer be passed through, presumably because it has become combined with the antitoxin.
Lastly it may be mentioned that when a toxin has some action which can be demonstrated in a test-tube experiment, for example, a dissolving action on red corpuscles, this action may be annulled by previously adding the antitoxin to toxin; in such a case the intervention of the living tissues is excluded. In view of the fact that antitoxin has a direct action on toxin, we may say that theoretically this may take place in one of two ways. It may produce a disintegration of the toxin molecule, or it may combine with it to produce a body whose combining affinities are satisfied. The latter view, first advocated by Wirlkh. hannonfaes with the facts established with regard to lone action and the behaviour of antitoxins, and may now be rrprttcd as established. His view as to the dual composition of Uk toxin molecule has already been mentioned, and it is evident (hat if the haptopboroos or combining group has its affinity atufied by onion with antitoxin, the toxin will no longer combine with' living cells, and will thus be rendered harmless. One other important fact in support of what has been stated is (hat a toxin may have its toxic action diminished, and may still require the same amount of antitoxin as previously for neutralization. This is readily intelligible on the supposition that the (oxophorous group b more labile than the haptophorous. There B. however, s(ill dispute with regard to the exact nature of the union of toxin and antitoxin. Ehrlich's view is that the two wbsiances form a firm combination like a strong acid and a base. He found, however, that if he took the largest amount of toxin which was just neutralised by a given amount of antitoxin, much more than a single dose of (orin had to be added before a single dose was left free. For example, If 100 doses of toxin were ncutrafijcrf by a unit of antitoxin (v. supra) it might be that 125 ifoses would need to be added to the same amount of antitoxin Wore the mixture produced a fatal resuK when it was injected. Tbis result, which is usually known now as the "Ehrlich phenomenon," was explained by him on the supposition that the "toxin " does not represent molecules which are all the same, but contains molecules of different degrees of combining affinity and of toxic action. Accordingly, the most actively toxic molecule* will be neutralized first, and those which are left over, Out is, tmcombined with antitoxin, will have a weaker toxic irtkm. This view has been assailed by Thorvald Madsen and S. A. Arrhenius, who hold that the union of toxin and antitoxin b comparatively loose,and belongs tothcclassofreversibleactions. being comparable in fact with the union of a weak acid and but. If such were the condition there would always be a certain amount both of free toxin and of free antitoxin in the mixture, intl in this case also considerably more than a dose of toxin vould have to be added to a "neutral mixture" before the •mount of free toxin was increased by a dose, that is, before UV mixture became lethal. It may be stated that while in rmiin instances the union of toxin and antitoxin may be reversible, all the facts established cannot be explained on this •imple hypothesis of reversible action. Still another view, tdvocated by Bordet, is that the union of toxin and antitoxin ii rather of physical than of strictly chemical nature, and repre(cats an interaction of colloidal substances, a sort of molecular deposition by which the smaller toxin molecule becomes entangled in the larger molecule of antitoxin. Sufficient has been »id to show that the subject is one of great intricacy, and no limple statement with regard to it is as yet possible. We are probably safe in saying, however, that the molecules of a toxin Me not identical but vary in the degree of their combining trinities, and also in their toxic action, and that, while in some cues the combination of anti-substances has been shown to be reversible, we are far from being able to say that this is a general law.
The origin of antitoxin Is of course merely a part of the general question regarding the production of anti-substances in general, as these all combine in the same way with their homologons substances and have the same character of specificity. As, however, most of the work has been done with regard to antitoxin production we may Consider here the theoretical aspect of the subject There are three chief possibilities: (a) that the antitoxin is a modification of the toxin; CO that it is a substance normally present, but produced in excess under stimulation of the toxin; (<•) that it i> »n entirely new product. The first of these, which would TMply a process of a very remarkable nature, is disproved by ''•ii is observed after bleeding an animal whose blood contains intiloxin. In such a case it has been shown that, without the introduction of fresh toxin, new antitoxin appears, and therefore n<B( be produced by the living tissues. The second theory is 'be mote probable a priori, and if established removes the "I 4
necessity for the third. It is strongly supported by Ehrlich, who, in his so-called "side-chain " (Seilentrlle) theory, explains antitoxin production as an instance of regeneration after loss. Living protoplasm, or in other words a biogen molecule, is regarded as'consisting of a central atom group (Lcistungskern), related to which are numerous secondary atom groups or sidechains, with unsatisfied chemical affinities. The side-chains constitute the means by which other molecules are added to the living molecule, e.g. in the process of nutrition. It is by means of such side-chains that toxin molecules are attached to the protoplasm, so that the living molecules are brought under the action of the toxophorous groups of the toxins. In antitoxin production this combination takes place, though not in sufficient amount to produce serious toxic symptoms. It is further supposed • that the combination being of somewhat firm character, the side-chains thus combined are lost for the purposes of the cell and are therefore thrown off. By the introduction of fresh toxin the process is repeated and the regeneration of side-chains is increased. Ultimately the regeneration becomes an over-regeneration and free side-chains produced in excess are set free and appear in the blood as antitoxin molecules. In other words the substances, which when forming part of the cells fix the toxin to the cells, constitute antitoxin molecules when free in the serum. This theory, though not yet established, certainly affords the most satisfactory explanation at present available. In support of it there is the remarkable fact, discovered by A. Wassennann and Takaki in the case of tetanus, that there do exist in the nervous system molecules with combining affinity for the tetanus toxin. If; for example, the brain and spinal cord removed from an animal be bruised and brought into contact with tetanus toxin, a certain amount of the toxicity disappears, as shown by injecting the mixture into another animal. Further, these molecules in the nervous system present the same susceptibility to heat and other physical agencies as does tetanus antitoxin. There is therefore strong evidence that antitoxin molecules do exist as part of the living substance of nerve cells. It has, moreover, been found that the serum of various animals has a certain amount of antitoxic action, and thus the basis for antitoxin production, according to Ehrlich's theory, is afforded. The theory also supplies the explanation of the power which an animal possesses of producing various antitoxins, since this depends ultimately upon susceptibility to toxic action. The explanation is thus carried back to the complicated constitution of biogen molecules in various living cells of the body. It may be added that in the case of all the other kinds of anti-substances, which are produced by a corresponding reaction, we have examples of the existence of traces of them in the blood scrum under normal conditions. We arc, accordingly, justified in definitely concluding that their appearance in large amount in the blood, as the result of active immunization, represents an increased production of molecules which are already present in the body, either in a free condition in its fluids or as constituent elements of its cells.
In preparing anti-bacterial sera the lines of procedure correspond to those followed in the case of antitoxins, but the bacteria themselves in the living or dead condition or their maceration products are always used in the injections. ~
Sometimes dead bacteria, living virulent bacteria, and living aupervirulent bacteria, are used in succession, the object being to arrive ultimately at a high dosage, though the details vary in different instances. The serum of an animal thus actively immunized has powerful protective properties towards another animal, the amount necessary for protection being sometimes almost inconceivably small. As a rule it has no action on the corresponding toxin; i.e. is not antitoxic. In addition to the protective action, such a serum may possess activities which can be demonstrated outside the body. Of these the most important are (a) bacteriolytic or lysogcnic action, (6) agglutinative action, and («) opsonic action.
The first of these, lysogenic or bacteriolytic action, consists in
the production of a change in the corresponding bacterium whereby it becomes granular, swells up and ultimately may undergo dissolution. Pfeiffcr was the first to show iiviiA/'*0" 'Da^ 'bi5 occurred when the bacterium was injected juiiao. into the peritoneal cavity of the animal immunized against it, and also when a little of the scrum of such an animal was injected with the bacterium into the peritoneum of a fresh, i.e. non-immunized animal. Metcbnikoff and Bordet subsequently devised means by which a similar change could be produced in vitro, and analysed the conditions necessary for its occurrence. It has been completely established that in this phenomenon of lysogencsis there are two substances concerned, one specially developed or developed in excess, and the other present in normal scrum. The former (Immunkorpcr of Ehrlicb, substance scnsibilisatrice of Bordet) is the more stable, resisting a temperature of 60° C., and though giving the specific character to the reaction cannot act alone. The latter is fcrmcntr like and much more labile than the former, being readily destroyed at 60° C. It may be added that the protective power is not lost by exposure to the temperature mentioned, this apparently depending upon a specific anti-substance. Furthermore, lysogenic action is not confined to the case of bacteria but obtains also with other organized structures, e.g. red corpuscles (Bordet, Ehrlich and Morgcnroth), leucocytes and spermatozoa (Metchnikoff). That is to say, if an animal be treated with injections of these bodies, its scrum acquires the power of dissolving or of producing some disintcgrative effect in them. The development of the immune body with specific combining affinity thus presents an analogy to antitoxin production, the difference being that in lysogencsis another substance is necessary to complete the process. It can be shown that in many cases when bacteria arc injected the scrum of the treated animal has no bacteriolytic effect, and still an immune body is present, which leads to the fixation of complement; in this case bacteriolysis docs not occur, because the organism is not susceptible to the action of the complement. In all cases the important action is the binding of complement to the bacterium by means of the corresponding immune body; whether or not death of the bacterium occurs, will depend upon its susceptibility to the action of the particular complement, the latter acting like a toxin or digestive ferment. It is to be noted that in the process of immunization complement docs not increase in amount; accordingly the immune scrum comes to contain immune body much in excess of the amount of complement necessary to complete its action. An important point with regard to the therapeutic application of an anti-bacterial serum, is that when the senim is kept in vitro the complement rapidly disappears, and accordingly the complement necessary lot the production of the bactericidal action must be supplied by the blood of the patient treated. This latter complement may not suit the immune body, that is, may not be fixed to the bacterium by means of it, or if the latter event does occur, may fail to bring about the death of the bacteria. These circumstances serve, in part at least, to explain the fact that the success attending the use of anti-bacterial sera has been much inferior to that in the case of antitoxic sera.
Another property which may be possessed by an anti-bacterial scrum is that of agglutination. By this is meant the aggrcgation into clumps of the bacteria uniformly distributed m an indifferent fluid; if the bacterium is motile its movement is arrested during the process. The process is of course observed by means of the microscope, but the clumps soon settle in the fluid and ultimately form a sediment, leaving the upper part clear. This change, visible to the naked eye, is called sedimentation. B. J. A. Charrin and G. E. H. Roger first showed in the case of B. fyocyaneus that when a small quantity of the homologous serum (i.e. the serum of an animal immunized against the bacterium) was added to a fluid culture of this bacillus, growth formed a sediment instead of a uniform turbidity. Grubcr and Durham showed that sedimentation occurred when a small quantity of the homologous scrum was added to an emulsion of the bacterium in a small test-tube, and
found that this obtained in all casts where Philter's lysogenie action could be demonstrated. Shortly afterwards Widal and also Grtinbaum showed that the serum of patients suffering from typhoid fever, even at an early stage of the disease, agglutinated the typhoid bacillus—a fact which laid the foundation oi serum diagnosis. A similar phenomenon has been demonstrated in the case of Malta fever, cholera, plague, infection with /'. <,>//. "meat-poisoning " due to Gartner's bacillus, and various other infections. As regards the mode of action of agglutinini, Gruber and Durham considered that it consist* in a change in the envelopes of the bacteria, by which they swell up and become adhesive. The view has various (acts in its support, but F. Kruse and C. Nicolle have found that if a bacterial culture be filtered germ-free, an agglutinating scrum still produces some change in it, so that particles suspended in it become gathered into clumps. E. Duclaux, for this reason, considers that agglutinins arc coagulative ferments.
The phenomenon of agglutination depends essentially on the union of molecules in the bacteria—the agglutinogens—with the corresponding agglutinins, hut another essential is the presence of a certain amount of salts in the fluid, as it can be shown that when agglutinated masses of bacteria are washed salt-free the clumps become resolved. The fact that agglutinins appear in the body at an early stage in a disease has been taken by some observers as indicating that they have nothing to do with immunity, their development being spoken of as a reaction of infection. This conclusion is not justified, as we must suppose that the process of immunization begins to be developed at an early period in the disease, that it gradually increases, aod ultimately results in cure. It should also be slated that agglutinins arc used up in the process of agglutination, apparently combining with some element of the bacterial structure. In view of all the facts it must be admitted that the agglutinins and immune bodies are the result of corresponding reactive processes, and are probably related to one another. The development of all antagonistic substances which confer the special character on antimicrobic sera, as well as antitoxins, may be expressed as the formation of bodies with specific combining affinity for the organic substance introduced into the system—• toxin, bacterium, red corpuscle, &c., as the case may be. The bacterium, being a complex organic substance, may thus give rise to more than one antagonistic or combining substance.
By opsonic action is meant the effect which a scrum has on bacteria in making them more susceptible to phagocytosis by the white corpuscles of the blood (?.».). Such an effect may be demonstrated outside the body by making a j suitable mixture of (a) a suspension of the particular bacterium, (6) the scrum to be tested, and (c) leucocytes of a normal animal or person. The mixture is placed in a thin capillary tube and incubated at 37° C. for half an hour; a film preparation is then made from it on a glass slide, stained by a suitable method and then examined microscopically. The number of bacteria contained within a number of, say fifty, leucocytes can be counted and the average taken. In estimating the opsonic power of the scrum in cases of disease a control with normal serum is made at the tame time and under precisely the same conditions. The average number of bacteria contained within leucocytes in the case tested, divided by the number given, by the normal serum, is called the pkagpcylit index. Wright and Douglas showed that under these conditions phagocytosis might occur when a small quantity of normal scrum was present, whereas it was absent when normal salt solution was substituted for the serum; the latter thus contained substances which made the organisms susceptible to the action of the phagocytosis. They further showed that this substance acted by combining with the organisms and apparently producing some alteration in them; on the other band it had no direct action on the leucocytes. This opsonin of normal scrum is very labile, beingrapidly destroyed at 55° C.; that is, a serum boated at this temperature has practically no greater effect in aiding phagocytosis than normal salt solution has. Various observers had previously found that the serum of an animal unmunucd againsi i particular bacterium had a special action in bringing about phagocytosis of that organism, and it had been found that this property was retained when the serum was heated at 55° C. It U now generally admitted that at least two distinct classes of substances are concerned in -ypsonic action, that thermostable immune opsonins are. develop cd as a result of active immunization and these possess the specific properties of anti-substances in general, that is, act only on the corresponding bacterium. On the contrary the labile opsonins of normal serum have a comparatively general action on different organisms. It is quite evident that the specific immune-opsonins may play a very important put in-the phenomena of immunity, as by their means (he organisms are taken up more actively by the phagocytic ceils, and thereafter may undergo rapid disintegration.
The opsoriic action of the scrum has been employed by Sir A. Wright and his co-workers to control the treatment of bacterial infections by vaccines; that is, by injections of varying amounts of a dead culture of the corresponding bacterium. The object m such treatment is to raise the opsonic index of the serum, this being taken as an indication of increased immunity. The effect of the injection of a small quantity of vaccine is usually to produce an increase in the opsonic index within a few days. If then an additional quantity of vaccine be injected there occurs a fill in the opsonic index (negative phase) which, however, i> followed later by a rise to a higher level than before. If the amounts of vaccine used and the times of the injection arc suitably chosen, there may thus be produced by a series of steps a rise of the opsonic index to a high level. One of the chief objects m registering the opsonic power in such discs is to avoid the introduction of additional vaccine when the opsonic index is low, that is, during the negative phase, as if this were done a further diminution of the opsonic action might result. The principle in such treatment by means of vaccines is to stimulate toe general production of anti-substances throughout the body, so that these may be carried to the sites of bacterial growth, and aid the destruction of the organisms by means of the cells of the tissues. A large number of favourable results obtained by such treatment controlled by the observation of the opsonic index have already been published, but it would be unwise at present to offer a decided opinion as to the ultimate value of the method.
Active immunity has thus been shown to be associated with the present? of certain anti-substances in the scram. After these substances have disappeared, however, as they always do in the course of time, the animal still possesses immunity tat a varying period. This apparently depends upon some alteration in the cells of the body, but Its exact nature is not known.
The destruction of bacteria by direct cellular agency both in natural and acquired immunity must not be overlooked. The behaviour of certain cells, especially leucocytes, in infective conditions led Mctchntkoff to place great importance on phagocytosis. In this process there are two factors concerned, viz. the ingestion of bacteria by the cells, and the subsequent intracellular digestion. If either of these is wanting or interfered with, phagocytosis will necessarily fail a* a means of defence. As regards the former, leucocytes arc guided chiefly by chemiotaxis, i.t. by sensitiveness to chemical substances in their surroundings—a property which U not peculiar to them but is possessed by various unicellular organisms, including motile bacteria. When the cell moves from a less to a greater degree of concentration, »'.«. towards the focus of production, the chemiotaxis is termed positive; when the converse obtains, negative. This apparently purposive movement has been pointed out by M. Verwom to depend upon stimulation to contraction or the reverse. Metchnikoff showed that in iBimals immune to a given organism phagocytosis is.present, whereas in susceptible animals it is deficient or absent. He also showed that the development of artificial immunity is Miended by the appearance of phagocytosis; also, when an a«U-»erurn fa Injected into an animal, the phagocytes which hrnwrly wen indifferent might move towards and destroy the la the lighi ol all the tacts, however, especially those
with regard to anti-bacterial sera, the presence of phagocytosis cannot be regarded as the essence of immunity, but rather the evidence of its existence. The increased ingestion of bacteria in active immunity would seem to depend upon the presence of immune opsonins in the scrum. These, as already explained, are true anti-substances. Thus the apparent increased activity of the leucocytes is due to a preliminary effect of the opsonins on the bacteria. We have no distinct proof that there occurs in active immunity any education of the phagocytes, in Metchnikoff's sense, that is, any increase of the inherent ingestive or digestive activity of these cells. There is some evidence that in certain cases anti-substances may act upon the leucocytes, and to these the name of "stimulins" has been given. We cannot, however, say that these play an important part in immunity, and even if it were so, the essential factor would be the development of the substances which act in this way. While in immunity there probably occurs no marked change in the leucocytes themselves, it must be admitted that the increased destruction of bacteria by these cells is of the highest importance. This, as already pointed out, depends upon the increase of opsonins, though it is also to be noted that in many infective conditions there is another factor present, namely a leucocytosis, that is, an increase of the leucocytes in the blood, and the defensive powers of the body are thereby increased. Evidence has been brought forward within recent years that the leucocytes may constitute an important source of the antagonistic substances which appear in the serum. Much of such evidence possesses considerable weight, and seeing that these cells possess active digestive powers it is by no means improbable that substances with corresponding properties may be set free by them. To ascribe such powers to them exclusively is, however, not justifiable. Probably the lining endothelium of the blood-vessels as well as other tissues of the body participate in the production of anti-substances.
The subject of artificial immunity has occupied a large proportion of bacteriological literature within recent years, and our endeavour has been mainly to indicate the general laws which are in process of evolution. When the ^0,1^*facts of natural immunity are examined, we find that no single explanation is possible. Natural immunity against toxins must be taken into account, and, if Ehrlich's view with regard to toxic action be correct, this may depend upon either the absence of chemical affinity of the living molecules of the tissues for the toxic molecule, or upon inscnsitivcncss to the action of the toxophorous group. It has been shown with regard to the former, for example, that the nervous system of the fowl, which possesses immunity against tetanus toxin, has little combining affinity for it. The non-sensitiveness of a cell to a toxic body when brought into immediate relationship cannot, however, be explained further than by saying that the disintcgrativc changes which underlie symptoms of poisoning are not brought about. Then as regards natural powers of destroying bacteria, phagocytosis aided by chemiotaxis plays a part, and it can be understood that an animal whose phagocytes are attracted by a particular bacterium will have an advantage over one in which this action is absent. Variations in chemiotaxis towards different organisms probably depend in natural conditions, as well as in active immunity, upon the opsonic content of the scrum. Whether bacteria will be destroyed or not after they have been ingested by the leucocytes will depend upon the digestive powers of. the latter, and these probably vary in different species of animals. The blood serum has a direct bactericidal action on certain bacteria, as tested outside the body, and this also varies in different animals. Observations made on this property with respect to the anthrax bacillus at first gave the hope that it might explain variations in natural immunity. Thus the scrum of the white rat, which is immune to anthrax, kills the bacillus; whereas the serum of the guinea-pig, which is susceptible, has no such effect. Further observations, however, showed that this docs not hold as a general law. The serum of the susceptible rabbit, for example, is bactericidal to this organism, whilst the scrum of the immune dog is not. In the case of the latter animal the senna contains an opsonin which leads to phagocytosis of the bacillus, and the latter is then destroyed by the leucocytes. It is quite evident that bactericidal action as tested in vitro outside the body docs not correspond to the degree of immunity possessed by the animal under natural conditions. We may say, however, that there arc several factors concerned in natural immunity, of which the most important may be said to be the three following, viz, variations in the bactericidal action of the serum in ritOj variations in the chemiotactic or opsonic properties of the serum in :•;.•", and variations in the digestive properties of the leucocytes of the particular animal. It is thus evident that the explanation of natural immunity in any given instance may be a matter of difficulty and much complexity.
Authorities.—Bacteriological literature has become so extensive that it is impossible to give here references to original articles, even the more important. A number of these, giving an account of classical researches, were translated from French and German, and published by the New Sydenham Society under the title Aft'eroparasites in Dissase: Selected Essays, in 1886. The following list contains some of the more important books published within recent years. Abbott, Principles of Bacteriology^ (7th cd., London, 1905); Crookshank, Bacteriology and Infective Diseases (with bibliography, 4th cd., London, 1896); Duchux, Traitc de microbwloeic (Pans. 1899-1900); Eyre, Bacteriological Technique (Philadelphia and London, 1902); Fliiggc, Die Jtfikroorganismen (3rd ed., Leipzig, 1896); Fischer, Vorlesungen uber Baklericn (2nd cd., Jena, 1902); Giinther, Einfukrung in das Studium dcr Bokteriologte (6th ea., Leipzig, 1906); Hewlett, Manual of Bacteriology (2nd ed., London, 1902); Hucppc, Principles of Bacteriology (translation, London, 1899); Klein, Micro-organisms and Disease (3rd ed., London, 1896); Kolle and Wassermann, Hantlbuck'drr patkt'gencn Mikroorganismen (Jena, 1904) (supplements are still bcinj; published; this is the most important work on the subject); Lofller. Vorlesun^fn uber dig geschichtliche Entmickdun^ der Lehre von der Baciertctt (Leipzig, 1887); M'Farland, Text-book upon tiif Pathogenic Bacteria (5th «L, London, 1906); Muir and Ritchie, Manual of Bacteriology (with bibliography, 4th cd., Edm, and Lond., 1908); Park, Pathogenic Micro-organisms (London, 1906); Sternberjf, Manual of Bacteriology (with full bibliography, 2nd cd.. New York, 1896); Woodhcad, Bacteria and their products (with bibliography, London, 1891). The bacteriology of the infective diseases (with bibliography) is fully given in the System of Medicine, edited by Clifford Allbutt, (2nd ed., London, 1907). For references consult Centralbl. fur Baffler, u. Parasttenk. (Jena); also Index Medicus. The most important works on immunity arc: £hr!ich, Studies in Immunity (English translation, New York, 1906), and Metchnikoff, Immunity in Infective Diseases (English translation, Cambridge, 1905). (R. M.*)
BACTRIA (Bactriana), the ancient name of the country between the range of the Hindu Kush (Paropamisus) and the Oxus (Amu Darya), with the capital Bactra (now Balkh); in the Persian inscriptions Bakhtri. It is a mountainous country with a moderate climate. Water is abundant and the land is very fertile. Bactria was the home of one of the Iranian tribes (see Persia: Ancient History). Modern authors have often used the name in a wider sense, as the designation of the whole eastern part of Iran. As there can be scarcely any doubt that it was in these regions, where the fertile soil of the mountainous country is everywhere surrounded and limited by the Turanian desert, that the prophet Zoroaster preached and gained his first adherents, and that his religion spread from here over the western parts of Iran, the sacred language in which the A vesta, the holy book of ZoroastrianiBm, is written, has often been called " old Bactrian." But there is no reason for this extensive use of the name, and the term " old Bactrian " is, therefore, at present completely abandoned by scholars. Still less foundation exists for the belief, once widely spread, that Bactria was the cradle of the Indo-Europcau race; it was based on the supposition that the nations of Europe had immigrated from Asia, and that the Aryan languages (Indian and Iranian) stood nearest to the original language of the Indo-Europeans, It is now acknowledged by all linguists that this supposition is quite wrong, and that the Aryans probably came .from Europe. The eastern part of Iran seems to have been the region where the Aryans lived as long as they formed one people, and whence they separated into Indians and Iranians.
The Iranian tradition, preserved in the Avesta and in Firdousi's Shahnama, localizes a part of its heroes and myths in the east of Iran, and has transformed the old gods who fight with the great
snake into kings of Iran who fight with the Turanians. Many modern authors have attempted to make history out of these stories, and have created an old Bactrian empire of great extent, the kings of which had won great victories over the Turanians. But this historical aspect of the myth U of late origin: it is nothing but a reflex of the great Iranian empire founded by the Achacmenids and restored by the Sassanids. The only historical fact which we can learn from the Iranian tradition is that the contrast and the feud between the peasants of Iran and the nomads of Turan was as great in old times as it is now: it is indeed based upon the natural geographical conditions, and is therefore eternal. But a great Bactrian empire certainly never existed; the Bactrians and their neighbours were in old times ruled by petty local kings, one of whom was Vishtospa, the protector of Zoroaster. Ctcsias in his history of the Assyrian empire (Diodor. Sic. ii. 6 fif.) narrates a war waged by N inus and Scmiram, against the king of Bactria (whom some later authors, e.g. Justin i. i, call Zoroaster). But the whole Assyrian history of Ctcsias is nothing but a fantastic fiction; from the Assyrian inscriptions we know that the Assyrians never entered the eastern parts of Iran.
Whether Bactria formed part of the Median empire, we do nol know; but it was subjugated by Cyrus and from ihtn formed one of the satrapies of the Persian empire. When Alexander had defeated Darius III., his murderer Kin the satrap of BactiU, tried to organize a national resistance in the east. But Bactria was conquered by Alexander without much difficulty; it was only farther in the north, beyond the Oxus, in Sogdiana, that be met with strong resistance. Baclria became a province of the Macedonian empire, and soon came under the rule of Sclcucus, king of Asia (see Seleuo.d Dynasty and Hellenism). The Macedonians (and especially Sclcucus I. and his son Anliochusl.) foundcdagrcat many Greek towns in eastern Iran, and the Greek language became for some time dominant :h- r . The many difficulties against which the Sclcucid kings had to fight and the attacks of I'tolemy II..gave to Diotlolus,satrap of Bactria, the opportunity of making himself independent (nbout 255 B.c.) and of conquering Sogdiana. lie was the founder of the GraecoBactrian kingdom. Diodolus and his successors wore able to maintain themselves against the attacks of the Selcucids; and when Antiochus 111., " the Great," had been defeated by the Romans (190 B.c.}, the Bactrian king Euthydcrmis and his son Demetrius crossed the Hindu Kush and began the conquest of eastern Iran and the Indus valley. Forashort timcthcy wielded great power; a great Greek empire seemed to have arisen far in the East. But this empire wns torn by Internal dissensions and continual usurpations. When Demetrius advanced far into India one of his generals, Eucratidcs, made Jiimsdf king of Bactria, and soon in every province there arose new usurpers, who proclaimed themselves kings and fought one against the other. Most of them we know only by their coins, a great many of which are found in Afghanistan and 1 ndia. By these wars the dominant position of the Greeks was undermined even more quickly than would otherwise have been the cose. Aflcr Demetrius and Eucratidcs, the kings abandoned the Attic standard of coinage and introduced a native standard; at the same Lime the native language came into use by the tide of the Greek. On the coins struck in India, the well-known Indian alphabet (called Brahmi by the Indians, the older form of the Dcvanagari) is used; on the coins struck in Afghanistan and in the Punjab the Kharoshllii alphabet, which is derived directly from the Aramaic and was in common use in the western parts of India, as is shown by one of the inscriptions of Asoka and by the recent discovery of many fragments of Indian manuscripts, written in Kharoslithi, in eastern Turkestan (formerly this alphabet has been called Arianic or Bactrian Pali; the true name is derived (rum Indian sources).
The weakness of the Graeco-BacIrian kingdoms was shown by their sudden and complete overthrow. In the west the Ar&actd empire had risen, and Mithradatcs I. and Phraalcs II. began to conquer some of their western districts, especially Areta (Herat). But in the north d acw race appeared, Mongolian tribes, called