"That in none of the animal fluids perfect fibrin pre-exists as such; but that both the blood, as also the lymph and lymphatic fluid, contain a substance nearly allied to it-that of the former more, that of the latter less so; which substances, by the contact of oxygen, become sooner or later transformed into real fibrin, and then coagulate." (p. 133.)

With regard to the origin of this fibrin-producing material (Virchow's fibrinogenous substance), he considers it to be a product of the metamorphosis of tissue, and especially those structures which are more intimately connected with the lymphatic system (lymphatic glands, spleen, and particularly the connecting tissue). In these structures, and not in the blood itself, the fibrinogenous substance is formed. From thence it passes as well into the exudations as also into the lymph, being so to say washed out by the fluids transuding from the blood. According as, sooner or later, it comes in contact with oxygen or fluids rich in oxygen, it is sooner or later transformed into coagulable fibrin, the coagulation of which may take place within the tissue itself, within exudations, within lymph or blood vessels. This however is a morbid process, for in health the fibrinogenous substance immediately undergoes another change, and is further decomposed. (p. 137.) It will be seen from this passage, that Virchow places the origin of fibrin not in the blood, but in the tissues themselves, a view which is not proved, but which at all events appears to simplify the mechanism of fibrinous exudations. Thus, the tissue in the state of irritation need not attract the fibrin from the blood in the capillaries, analogous to the secreting cells of some glands, nor need we suppose the coats of the capillaries to become more permeable by the irritation. In the normal state of things the fibrin-producing substance formed in the tissues would be absorbed by the lymphvessels; but in some inflammatory conditions the surplus of fibrin, thus formed, would become accumulated within the tissues, or transude beyond their surface. The lymph, the blood, the exuded fluids, would in such cases become richer in the fibrinogenous material, and the fibrinous crasis (Hyperinosis) would be considered as well a product of inflammation as the exudation itself.

The third section is occupied by the author's essays on Colourless Blood-Corpuscles and Leukemia. He published his first case on white blood in November, 1845.* Tumours of the spleen, cedema of the extremities, cough, diarrhoea, epistaxis, furunculous and pustulous eruptions, and predominance of the white blood-globules, were the principal symptoms. Already at that time Virchow made some remarks which show that he understood his case, and did not confound it with pyæmia, as Bennett, Rokitansky, and other observers had done. He quotes another case published a short time before in Vienna as pyæmia,† and vindicates it as one of leukæmia.

The essay On White Blood and Tumours of the Spleent was written after the author had read Bennett's publication. The circumstance that the latter considers the change in the blood of a pyæmic nature,

* Froriep's Neue Notizen, No. 780. Nov. 1845.

† Zeitsch. der k. k. Gesell. der Aerzte zu Wien, vol. ii. p. 488. 1845.

+ Med. Zeitung, Nos. 34-36. Aug. and Sept. 1846.

The

leads Virchow to the discussion on the subject of pyæmia. latter maintains that there does not exist a distinct difference between the colourless globules of the blood and the pus-globules. He attributes the confusion on the subject of pus in the blood to the erroneous assumption that the so-called lymph-globules of the blood are identical with those of the lymph, and derived as such from the chyle; to the imperfect knowledge of the different stages of development of the white blood-globules; to the neglect of the influence of the media on the appearance of the globules; finally, to the assumption of a certain normal pus (pus bonum et laudabile), which has served as a measure for all other cellular elements, again without paying attention to the different phases of the pus-globule itselt.

"There are cells," the author says, "which are characterized by the existence of several nuclei. These cells are most frequently met with in pus, hence they have been called pus-corpuscles. But they exist also in the lymph and in the blood; they are found among the epithelial cells of serous membranes, in the younger layers of the epidermis, &c. It was therefore wrong to call them pus-corpuscles. . . . . The pus-cell is formed in the exudationplasma, as the chyle-cells; and probably also the colourless blood-cells are found in the chyle- and blood-plasma. The law of development is the same for the pus-cell and the colourless blood-cell; both are relatively embryonic cells, which differ in so far as the former may become developed into connecting tissue (Binde-substanz), the latter into red blood-globules. If, therefore, we find eells with several nuclei in the blood, we must consider them as the foundation for new tissue elements of the blood, no matter whether they are in conditions favourable for further development, or whether they have become obnoxious to the laws of retrogressive metamorphosis, before having reached their normal state of development. There is no cause for calling them pus-globules, but we may designate them colourless blood-globules, as the red globules form their highest development." (pp. 167, 168.)

It is well known that, several years after the publication of this essay, Lebert and Sedillot have again adduced various points by which pus and colourless blood-globules are to be distinguished. Thus they maintain that the former are larger (1 to 5 millimetre) than the latter (o to 1 millimetre); that the former are more yellowish, the latter white; the former spheroidal, the latter slightly lenticular; that the surface of the former is granular, mulberry-like, of the latter more smooth; that the former possess nuclei (of 3 to millimetre) with a cup-shaped impression, the latter very small nuclei ( to millimetre), almost like nucleoli, or fat granules. Although we admit the correctness of the majority of these points, when we compare the usual white blood-globules with the well-developed genuine pus-globules, yet we constantly meet with pus-globules that have all the characters just ascribed to the white blood-globules, and vice versa. If we further take into consideration, that both kinds of globules exhibit in the same individual important changes, according to their stage of development; that pus-globules, when mixed with blood (i.e., a more concentrated fluid), undergo, according to the laws of exosmosis and endosmosis, very marked alterations in shape (by becoming smaller, smoother, &c.), we cannot hesitate to assert that,

* De l'Infection Purulente ou Pyoémie. 1849.

with rare exceptions, the presence of pus in the blood must remain unproved, and especially so in the cases of white blood where no source for the purulent infection could be found.

Virchow therefore denied the pyæmic nature of the cases published in Edinburgh, and "vindicated for the colourless blood-globules a place in pathology."

În another article,* nine cases of pus-like blood, observed by Bichat, Velpeau, Oppolzer, and others, are examined, and the probability of their having been cases of white blood explained. Among the circumstances which appear to lead to an increased number of white globules, we find particularly mentioned-a, loss of blood (Nasse,t Remak, Henle§); b, chronic exhausting diseases (Gulliver's pusglobules); c, serious acute diseases, especially typhus, pneumonia, puerperal fever (Nasse). To the viscosity of these globules, already mentioned by Nasse and others, their motion along the walls of the capillaries is ascribed, as well as the fact that in retardation of the circulation they stagnate sooner than the red globules-a circumstance which has led to the idea of a new formation (E. H. Weber, Rokitansky). Piorry's mistake (Hæmatitis) regarding the explanation of a buffy coat, granular and uneven on its lower surface, which is sometimes seen in such conditions, is corrected. In the paragraph on the relation of the spleen to white blood, the author ascribes the function of sanguification, not to the spleen alone, but also to the lymphatic glands, thymus and thyroid, and liver (E. H. Weber and Kölliker). The splenic bodies are considered as closed capsules with a very minute ramification of vessels on their surface; their arrangement is compared with that of the placenta, where diffusion takes place between two fluids, separated from each other only by a permeable membrane. Similar may be the process in the conglobate glands. If the fluid passing from the glands into the blood exerts an influence on the transformation of the colourless into red globules, it is evident that morbid affections of these glands must be of the greatest importance for the development of the blood.

In a new chapter, Die Leukämie, the author alludes to the history of the development of our knowledge on this subject, and especially to the contested point of priority between Bennett and himself. Every impartial observer will admit that our thanks are due to both authors. Bennett has done much by the excellent cases he has published, and by the observations attached to them, as also by drawing the attention of others to this affection; but we cannot deny that to Virchow belongs the particular merit of having been the first who understood its real nature. Bichat, Velpeau, Oppolzer, and others, had published cases which, in all probability, belong to the same category; but they had not perceived their true bearing; nobody will therefore attribute to them the priority. Such was also the case with Bennett before Virchow's publication had appeared, although his observations had

Med. Zeitung. Jan. 3 & 4, 1847.

+ Untersuchungen zur Physiol. und Pathol. 1839.

Med. Zeit. der Vereins f. Heilkunde in Preussen, No. 27. 1841. § Zeit. f. rat. Med. 1844.

already been much more accurate and valuable than those of his predecessors. We should scarcely have entered into this question of priority did we not consider it justice to do so, as we find, in an excellent handbook of pathological anatomy touching on the subject of Leucocythemia, Virchow's name altogether omitted.

In reference to the name, Virchow is not inclined to sacrifice his “Leukæmia” to Bennett's "Leucocythemia:" he is of opinion that it would be more proper to apply the expression "Leucocythemia," or rather "Polyleucocythemia," to those states in which the white globules are physiologically (digestion, pregnancy) or pathologically (most inflammatory and typhous affections) increased, but only for a limited period; this polyleucocythemia exhibiting as great a difference from real leukæmia as chlorosis from the anæmia of carcinomatous patients. Leukæmia does not merely signify a state characterized by an increased number of white globules, but "an altered development of the tissue of the blood in its dependence on certain organs." There is, in reality, a less perfect colouration of the blood. Several observers (Uhle, Griesinger,t De Pury,+ among the latest) have made the observation, that the quantity of colourless globules is in some parts of the body much larger than in others; as in the splenic vein, which may be explained by a greater destruction of red globules within the tissue of the spleen, or also by increased formation of colourless globules in that organ. The accumulation of white elements in the vena cava and right side of the heart is attributed to the posthumous movements of the vessels during and after death, and to the inosculation of the thoracic duct, whose movements do not cease for several hours after death. The large proportion of white globules in the small vessels of the brain, as first pointed out by Bennett, has been repeatedly confirmed by Virchow; and we had the opportunity of observing it ourselves in two cases, as well in the brain as also in the lungs, the liver, and the kidneys.

The circumstances that, in some patients, the affection of the lymphatic glands prevails over that of the spleen, and vice versa, that in the former cases the elements of the lymphatic glands (viz., "innumerable round granulated nuclei, generally provided with nucleoli, of the size of the usual nuclei of the lymphatic glands, here and there also cells consisting of such a nucleus surrounded by a membrane rather closely attached to it") predominate in the blood; in the latter those corresponding to the elements of the spleen ;-these circumstances lead Virchow to establish two varieties of leukæmia, the lymphæmia and splenæmia. In a case observed by ourselves, where the lymphatic glands were enormously diseased, while the spleen was almost normal, we met certainly with many of the above-described lymphatic elements in the blood, but with still more of the larger white globules which are attributed to the splenic variety. Scherer's qualitative analysis of the blood, in a case of the splenic variety, has exhibited, besides lactic, acetic, and formic acid, gelatin, a peculiar organic body, and 0.4-0.6 per cent. of hypoxanthin. The presence of the latter substance is of

* Archiv f. Path. Anat., vol. v. 39-xx.

f Ibid.

Ibid., vol. viii. 2

peculiar interest, as it will be remembered that it has been discovered by the same chemist in the pulp of the spleen.

With respect to the disease of the blood-forming organs, it is described as a hyperplasia of their constituent elements, first of the glandular cells, then also of the connecting tissue. As the results of Virchow's researches on this head do not materially differ from those of Bennett and other observers, we will not enter on them in this place; we must, however, allude to a very remarkable circumstance with which our author met in several cases of the lymphatic variety.

The slightly enlarged liver contained numerous small whitish granules, generally of the size of a normal lobule of the liver, which exhibited under the microscope nuclear and cellular elements quite like those of the lymphatic glands. This infiltration of nuclear masses appeared to be in connexion with the portal vein. In one of these cases a similar alteration was witnessed in the kidneys. None of the other observers has discovered these formations, and we have ourselves looked for them in vain in the two cases that fell under our observation. We particularly recommend this interesting subject to further attention, as Virchow interprets it as a new formation of glandular tissue, analogous to the hypertrophy of the lymphatic glands, where the glandular tissue is likewise found transgressing the pre-existing boundaries of the glands. He considers this as the product of a lymphatic diathesis-i.e., a progressive inclination of the organs to the formation of lymphatic elements.

Virchow's view concerning the nature of leukæmia is, that it must be considered as a disease sui generis. With him, we expect further elucidation from more extended clinical observations: "Several times,” he says, "the thought struck me, whether acute inflammatory processes may not lay the foundation of the disturbance." (p. 209.) The same idea, we should think, must have forced itself upon the mind of other observers too. The inflammatory character was very striking in the case to which we have alluded as having fallen under our own observation; the following are its main features: the patient was a man, twenty-nine years of age, tall and muscular, belonging to a family not quite free from scrofulous affections; healthy himself in his youth; never affected with ague; formerly an officer in the Polish army; he had endured privation during the last years before the commencement of the disease. This manifested itself, soon after having been wetted through on a cold winter day, by acute pain in the left axillary region, followed by considerable swelling, which increased within three weeks to the size of a fist. The pain then abated, the tumour seemed likewise to decrease, until four weeks later, when, while travelling, he contracted a cold, again suffered severely for a fortnight, and observed a rapid increase of the swelling. Then another remission during about three weeks, followed by a third exacerbation, which was accompanied by a considerable degree of pyrexia and an elevation of the temperature (more than 2° Fahr.) of the left axillary region over the right. A small quantity of blood drawn at that time exhibited, in a thin cylindrical glass, a layer of white globules above that