No. 3793.

MAY 9, 1896

The Arris and Bale LecturesON THE

PHYSIOLOGICAL FACTORS INVOLVED INTHE CAUSATION OF DROPSY.

Delivered before the Royal College of Surgeons of England onFeb. 17th, 19th, and 21st, 1896,

BY ERNEST H. STARLING,M.D. LOND., M.R.C P.,

JOINT LECTURER ON PHYSIOLOGY AT GUY’S HOSPITAL.

LECTURE I.

THE PRODUCTION OF LYMPH.

MR. PRESIDENT AND GENTLEMEN,-The term dropsy isused to denote the condition in which there is an abnormalaccumulation ’ef lymph in the connective tissue spaces,including -the serous cavities of the body. Under normalcircumstances these spaces contain lymph, but the amountpresent neverexceeds a certain limit. Under no physiologicalconditions cen we speak of the spaces as distended withi&uid. Now, the lymph in these spaces is derived from theblood plasma erc:s.lating in the capillaries. From these in

all states of activity the lymph is transuded, but as fast as ittends to accumulate in the spaces it is removed by anabsorbent apparatus represented chiefly by the lymphatics.As I shall show ’in my second lecture, the lymphatics areaided in this work of absorption, under probably certaindefined conditions, by the blood capillaries themselves. Inhealth, therefore, the two processes of lymph-productionand absorption are exactly proportional. Dropsy dependson a loss of balance between these two processes-on anexcess of lymph-production over lymph-absorption. Ascientific investigation of the causation of dropsy will there-fore involve, in the first place, an examination of the factorswhich determine the extent of these two processes and, sofar as is possible, of the manner in which these processes arecarried out. In the second place, we must inquire how it isthat, under-the clinical conditions in which we know dropsyto occur, there is wn upset of the balance of these two pro-cesses in favour of lymph production. My first lecture,then, will deal with the first of the two processes-i.e.,’Lymph-Production.

In studying the factors which regulate the production ofRymph we must have criteria by which we may judgeof the amount of lymph produced. To this end severalmethods are open to us. The most simple method, and onewhich was the earliest to be used, is the production ofoedema. As a rule, as I shall explain later, we may lookupon the production of oedema as due to increased

lymph-production. Far more delicate, however, than thismethod is the observation of the lymph-flow from a cannulaplaced in a lymphatic trunk, which drains the part underinvestigation. Most delicate of all, but subject, perhaps,o most fallacies, is the ingenious method devised by Royand used by Lazarus-Barlow, in which the specific gravity ofthe tissues is determined. The second of these methods isthe one by which most work has been done and which Ihave used almost exclusively in my own investiga’iors. It is I,- evident that the only constant source of a lymph-flow must I,be the bloodvessels, and our first object must be to see how Itt1le amount and composition of the lymph formed in any Igiven part may be changed by experimental alterations of !,the pressure and chemical composition of the blood flowing ,,through the capillaries of that part as well as by changes intiie walls of the capillaries themselves. In dealing with thefunctions of any part of the body we can often obtain hints ’,,1’3 to the manner of its working from a study of its structure,and I would like, therefore, in the first place to draw your ’iattention to some poirits in the structure of blood capillaries.’These have long been known to consist of tubes whose walls z,are formed of a simple layer of flattened, nucleated endo-thelial cells, which are united together by a small amount of- cement sabctance, as it is called, the lines of junction Ibetween the ceils staining deeply with nitrate of silver. IA Russian observer, Kolossow. has added somewhat to Ithis simple account. According to this observer each

endothelial cell consists of two parts, a hyaline " ground-plate,’’ which immediately borders the lumen of the capillary,and outside this a protoplasmic granular part in which isembedded the nucleus. The ground-plates of the adjoiningcells come in intimate contact with one another, but are inno way continuous,*so that there is a linear cleft between theadjacent portions of every two cells. The protoplasmic por-tions of the cells, on the other hand, are continuous with oneanother by means of processes. If the capillary be stretchedin any way the ground-plates, which are inelastic, are

separated from one another, so that the clefts between themare increased in size. Hence we see in nitrate of silverspecimens made under these conditions that the lines ofreduced silver are much broader than in normal capillaries.Outside the capillary one finds in most instances an ill-developed adventitia which is continuous with the surround-ing connective tissues. The picture thus afforded of a

capillary must suggest at once that it will not be, so tospeak, water-tight, but will permit of filtration between thecells, and if this were the case we would have to look uponthe lymph, which is separating from the plasma circulatingthrough the capillaries, as a filtrate. The fact that the lymphfrom most parts of the body contains less proteid than theblood pla-ma is no argument against this hypothesis. If wefilter serum through porous filter paper the filtrate will havethe same composition as the original serum. If, however,we take a more closely-meshed filter, such as a porous claycell or an animal membrane, we shall find that the filtrate isconsiderably poorer in proteid than the original serum, thebig proteid molecule being apparently unable to go throughthe smaller pores of such a filter. Now this hypothesis,that the lymph is to be looked upon as a filtrateunder pressure from the plasma, has been the guidingidea in the most important works on lymph - forma-tion which have appeared during this century. Thoughwe find it more or less distinctly in the works of the olderwriters-Hales, Hewson, and others-it is to Ludwig and hispupils that we owe its most systematic examination. Accord-ing to this hypothesis, the amount of lymph produced in anygiven part must be proportional to the difference between thepressure in the capillaries and the pressure in the extra-vascular spaces. In most of Ludwig’s earlier experimentson the subject this condition was found to hold good. On

leading defibrinated blood through a limb the lymph-pro-duction in the limb was found proportional to the pressureat which the blood was led through it. In the testis

ligature of the pampiniform plexus was found to increaselargely the lymph production in this organ. In the arm andin the leg extensive ligature of the veins led to an increasedflow of lymph. In all these cases, therefore, an increasedflow of lymph was obtained by increasing the capillarypressure of the part. Ludwig found it more difficult toprove any constant alteration of lymph production incidenton vaso-motor changes, although Rogowicz, working later inHeidenhain’s laboratory, found that vaso-dilatation did givea certain definite increase in lymph-production, and alsoshowed clearly that the vaso dilatation of the tongue pro-duced by excitation of the lingual nerve was followed by anincreased lymph-production in the tongue, which might attimes amount to an actual unilateral cedema of this organ.

In dealing with the laws affecting lymph-production one ishampered by the fact that in the limbs of an animal at restthere is under normal conditions no lymph flow at all, sothat when we wish to study the effects of our various

procedures on the lymph-production in the limb we have

artificially to bring about a lymph-flow by kneading andmassaging the limb. Now this fact introduces at once an’

arbitrary element into the experiment, and Heidenhain

suggested, therefore, that the best place to investigatethe truth of the filtration hypothesis would be on the lymph-flow from the thoracic duct. This writer, therefore, carriedout a long series of researches on the various conditions inwhich the lymph-flow from the thoracic duct might beincreased or diminished, and came to the conclusion that theresults of his experiments were irreconcilable with thefiltration doctrine, and that we must assume that the cellsforming the walls of the capillaries take an active part in1) mph-formation-i.e., that lymph must be looked upon as asecretion rather than as a transudation. A renewed examina-tion of Heidenhain’s experiments, combined, however, witha more thorough investigation of their conditions, has shownme that, so far from overthrowing the filtration hypothesis,they furnish the strongest arguments which have yet beettadduced in it’s favour.

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In dealing with the lymph-flow from the thoracic duct itis essential to know from what parts of the body this lymphis derived, especially since, as is well known, the lymphatics.from all parts of the body, with the exception of the rightupper extremity and right side of the neck, converge to pourtheir contents into this duct. In placing a cannula in theduct in order to collect and measure the lymph the ductsfrom the left side of the neck and left upper extremity areligatured. From the hind limbs we know that in an animalat rest on the table there is no lymph-flow at all. Hence thesources of the lymph are confined to the trunk. We can,moreover, exclude the thorax and its contents, since ligatureof the thoracic duct just above the diaphragm absolutelystops the lymph flow. Therefore, when dealing with thelymph-flow from the thoracic duct we deal only withthe lymph coming from the abdominal viscera. As Ishall show presently, the abdominal viscera, so far as

their lymph is concerned, may be divided into two groups:(1) the viscera drained by the portal vein, and (2) the liver.

In testing the filtration hypothesis on the lymph-flow wehave to investigate whether the flow is always proportionalto the difference between the intra- and extra-capillarypressures. We may regard the extra-capillary pressure asnot varying to any large extent, so that we have to see whateffect is produced on the lymph by variations in the intia-capillary pressure in the intestines and the liver. The

simplest experiments on the subject are those in which somelarge vessel is obstructed. Speaking generally, we may saythat obstruction of a large vein raises the pressure in thecapillaries immediately behind it, whereas obstruction of anartery will diminish the pressure immediately in front of it.If, for instance, we ligature the portal vein the arterial

pressure is very little affected, while the pressure in the veinbehind the ligature rises enormously. In consequence ofthis there is a large rise of pressure in the capillaries of theintestines and spleen, so that the spleen swells and theintestines become black from venous congestion and

haemorrhages are produced into their mucous membrane.The effect of this ligature on the lymph-flow from thethoracic duct is to increase it four or five times. The lymphalso becomes blcody and its total solids are diminished.The diminution in solids is due solely to a diminution inproteids, the salts remaining the same as before, so that wehave here an increased capillary pressure, causing an increasedtransudation of lymph containing a diminished percentageof proteid-a result which is also obtained when proteids arefiltered with pressure through dead animal membranes. The

presence of red blood corpuscles in the lymph is not a

necessary consequence of a rise of pressure in the portalvein. If a less excessive rise of pressure be produced byligaturing the vein, not at its entry into the liver, but justbelow the pancreatic duodenal vein, thus leaving a

circuitous route for the blood to the liver through theanastomoses of this branch, an increased flow oflymph is produced, containing less proteids than normallymph, but which may be quite free from blood corpuscles.A still more striking effect is produced by obstructing the

vena cava just above the diaphragm. The lymph is increasedfrom ten to twenty-fold, and it is found that the lymphobtained after the obstruction is free from red blood

corpuscles and is more concentrated than normal lymph.What is the cause of this increased lymph-flow and why is itmore concentrated ? To answer these questions we mustfind out, firstly, the source of the lymph, and, secondly, thecondition of the capillary pressure in the organ or organsfrom which the lymph is derived. We can determine thesource of the lymph by a process of exclusion. Ligation ofthe kidney vessels and lymphatics has no effect on the usualconsequences of obstructing the inferior vena cava. On theother hand, if we ligature the lymphatics in the portalfissure which carry off the liver lymph we find that a subse-quent obstruction has no effect on the lymph-flow, or, indeed,may slightly diminish it. We must conclude then thatthe increased flow of lymph is more concentrated thanintestinal lymph. In order to answer the second question asto this increased production of lymph in the liver we mustinvestigate the changes in the circulation produced by theobstruction. On obstructing the inferior vena cava andrecording the blood pressure in the chief vessels of theabdomen we notice that the pressure in the aorta dropsalmost at once to a third of its previous height, whereas thereis a very considerable rise of pressure both in the portal veinand inferior cava. It is probable that the effect of the riseof portal’ pressure on the intestinal capillaries is more than

counterbalanced by the severe fall in arterial pressure, soL that there is a fall of pressure in the intestinal capil-; laries. This conclusion is borne out by the fact that if the.j abdomen be open the obstruction of the inferior vena cava

is seen to be at once followed by a blanching of theintestines ; on the other hand, the effect of the simultaneousrise of pressures in the portal vein and vena cava must be toraise the pressure in the capillaries of the liver to three orfour times the normal amount. We have, then, as the-results of this experiment, no rise of pressure in the portalarea and no increase of lymph-flow from the portal area, &

large rise of pressure in the hepatic capillaries, and a verylarge increase of lymph-flow from the liver.The only other experiment of this nature which I need

describe is one in which the thoracic aorta is obstructed.The results of this obstruction on the lymph-flow are some-what variable. In most cases the lymph is diminishedto one-half or one-third its previous amount; in a few casesthe lymph is unaltered in quantity or even slightly increased.In all experiments the amount of proteids in the lymph isincreased. Now if we investigate the state of the circulationunder these conditions we find that obstruction of the-thoracic aorta causes an enormous fall of pressure in theaorta below the obstruction and a corresponding fall in the-portal vein, whereas the pressure in the inferior vena cavais unaltered or in some cases even slightly increased. Wemust conclude, therefore, that in the intestinal capillariesthe pressure has fallen considerably below its normal limits,.while in the hepatic capillaries the pressure is very littlealtered or may even be somewhat increased. Hence the onlyregion of the body below the point of obstruction where thecapillary pressure is not much diminished is the liver. Nowwe find that the liver is also the sole source of the lymph ob-tained under these circumstances. If the hepatic lymphaticsbe ligatured and the thoracic aorta be then obstructed, th&flow of lymph from the thoracic duct is absolutely stopped.In these three cases, therefore, the lymph production in thaorgans of the abdomen is found to be absolutely proportionalto the changes of the capillary pressures in these organs.In another set of experiments we find that a marked increasein the lymph-flow is produced by a general rise of capillarypressure in all the organs of the abdomen. Such a generalrise of capillary pressure may be produced by the injectionof large quantities of normal saline fluid into the circulation,giving rise to a condition of hydraemic plethora. Under suchcircumstances the lymph may be increased from 50 to 100’times in amount, and may in some cases run from the cannula.in the duct in a steady stream. Now, in bydr2emic plethora).there are two changes in the circulation which might.possibly be responsible for the increased production oflymph : firstly, the change in the composition of the blood,and, secondly, the increased pressure in the capillaries othe abdominal viscera. We can decide which of these two-factors is responsible for the increased lymph-flow by a verysimple experiment. Previously to injecting 300 c.c. ofnormal saline we bleed the dog to 300 c.c,, so that after theinjection the total amount of circulating fluid is the same asat the beginning of the experiment. In this way we entirelyavoid any rise of capillary pressure, while we have dilutedthe blood to an even greater extent than in the experimentsin which hydrasmic plethora was produced. The effect ofsuch a simple hydnemia is to increase the lymph-flow from3 c.c. in 10 minutes to 4 or 6 c.c. in 10 minutes, whereas ifhydrsemic plethora were produced the lymph would be in-creased from 3 c.c. to 30, 50, or 100 c.c. in 10 minutes. Itis evident, therefore, that in the production of this increasedlymph-flow the all important factor is the rise of capillarypressure.Exactly the same interpretation holds good for the action

of a certain class of bodies which were grouped together byHeidenhain in the second class of lymphagogues. These-include bodies such as salt, sugar, potassium, iodide, &c.The injection of a strong solution of dextrose (30 grms. in30 c. c. water) into the veins of an animal causes a considerableincrease in the lymph-flow from the thoracic duct. Thelymph at the same time becomes more watery than at thecommencement of the experiment. Heidenhain ascribes thiseffect to a specific excitation of the secretory activities of theendothelial cells. The effect, however, can be explained in much more simple fashion. All these solutions have anosmotic pressure which is considerably higher than that of,normal blood plasma. A solution of dextrose that should beisotonic with the blood plasma would contain from 5 to 6 percent. of this body. When we inject a solution ,containipg

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from 50 to 75 per cent. of dextrose it will attract fluid fromthe tissues until its percentage is reduced to 5 or 6 per cent.,that is to say, 45 c.c. of fluid containing 30 grms. of dextrosewill attract water from the tissues until its total volume isincreased to 500 c.c. Of course, this estimate is merely arough approximation at the truth, since before the sugar hashad time to attract all this fluid a considerable amount of itwill already have left the vessels by diffusion. As a matterof fact, however, we find that injection of a strong solutionof dextrose is followed in a few minutes by a considerabledilution of the blood, caused by an increase in its volume.In some experiments of von Brasol the volume of the circu-lating blood was thus increased to twice or three times itsprevious amount; and these observations have been fully con-firmed in a series of careful experiments made by J. B.Leathes. As we should expect, this increase in the volumeof the circulating blood is attended by a large rise ofcapillary pressures in the abdominal viscera, and we havehere again to decide whether it is this rise of capillarypressure or the change in the chemical composition of theblood that determines the increased lymph - flow. Thisquestion can be solved by using the same method thatwe adopted when dealing with the production of theincreased lymph-flow in hydrsemic plethora. We can

entirely obviate the rise of capillary pressure if we bleedfirst to 300 c.c. and then inject a concentrated solutioncontaining 18 grms. of dextrose. In this case the fluidthat is dragged by the sugar from the tissues into the blood-vessels only just suffices to make up for the previous loss of ’,blood. No hydrasmic plethora is produced ; there is no rise ’,of capillary pressure, and there is no increase in lymph-flow,although an abnormally large amount of dextrose is presentan the circulation. We must conclude, therefore, that theincreased flow of lymph caused by injection of the second- class of lymphagogues is entirely due to the rise of capillarypressure thereby induced, and is in no wise conditioned by astimulation of the secretory activities of the endothelial- cells.

There is one point in the effects of the injection of these’bodies which has been looked upon as a strong argument forthe secretory hypothesis, and which I must therefore mentionshortly here. If we analyse the lymph and the blood at.different periods after the injection we find that the amountof sugar in the blood steadily diminishes, while the sugar inthe lymph first rises to a maximum and then diminishesparallel with that in the blood plasma. At a given periodafter the injection it is found that the lymph contains moreugar than does the blood plasma, and this fact was held topoint to an undoubted secretory activity of the endothelial’cells in the production of lymph. This conclusion, however,is by no means justified. The lymph flowing at any givenmoment from the thoracic duct does not represent the tran-tsudation from the blood at that moment, but is derived fromthe lymph that has been formed some time previously. Ifwe had a solution of sugar in gradually diminishing strengthlowing into a lymphatic trunk of the leg it is evident thatthis fluid would mix with the lymph in the other lymphatics,through which it flowed on its way to the thoracic- duct. Later, the solution of sugar would have dis-

placed practically all the lymph from these channels.and would flow through the thoracic duct almost un-

diluted. It would take, however, some considerabletime to flow from the leg to the thoracic duct, so

’that the outflow from the duct would represent not the fluidwhich was being injected into the leg at that moment, butthe stronger solution which had been flowing in some time,previously. If one compared, therefore, the percentageof sugar in the fluid flowing from the duct and in the fluidflowing into the leg lymphatic at different times after thebeginning of the injection we should obtain a curve exactlysimilar to those obtained by Heidenhain after the injectionof sugar into the circulation, and looked upon by him asundeniable evidence of secretory activity.The dependence of lymph-formation on capillary pressure

ds not, however, the only important relationship brought tolight by these experiments. The amount and composition ofthe transudation through a membrane depend not only onthe pressure at which the transudation is effected but alsoon the nature of the membrane. According to the per-meability of the membrane, so the amount and compositionin proteids of the transuding fluid will vary. You willdoubtless already have noticed that after obstruction ofthe inferior vena cava the pressure in the intestinal- 4:api11aries, although it probably sinks below -its normalheig.ht, is yet as high as that in the hepatic capillaries.

Nevertheless, we get a very small amount of transudationthrough the intestinal capillaries and a very large amountthrough the hepatic capillaries. It is evident, then, that thepermeability of the liver capillaries must be very much moremarked than that of the intestinal capillaries. In the sameway we may compare the permeability of the intestinalcapillaries with those of the limb capillaries. Normally fromthe limb there is no flow of lymph at all, whereas a probablyequal pressure in the intestinal capillaries suffices to giverise to a steady flow of lymph. If we ligature all theveins of the leg a lymph - flow may be set up, butsuch a flow is incomparably smaller than that producedon ligature of the portal vein. We can, therefore, arrangethe capillaries of the body in a descending order of permea-bility, the liver capillaries being the most permeable andthe limb capillaries the least permeable. I have alreadymentioned how, on filtering solutions of proteids throughvarious membranes, the percentage of proteids in thefiltrate increases with the permeability of the membrane.As we have seen, exactly the same thing holds good for thecapillaries in the body. The lymph in the limbs, the filtratethrough the impermeable limb capillaries contains only from2 to 3 per cent. proteids. That from the intestines containsfrom 4 to 6 per cent. proteids, while that from the

permeable capillaries of the liver contains from 6 to 8per cent. proteids-in fact, almost as much as the blood-plasma itself. It is conceivable that we might alter theamount of lymph produced in any organ by changing, notthe intracapillary pressure, but the filtering membrane-i.e.,the endothelial wall of the capillaries. Such a change canbe brought about in the body by various means. A wholegroup of bodies has been described by Heidenhain as hisfirst class of lymphagogues. These substances, which aremostly of the nature of albumoses, can be extracted fromvarious of the lower animals and include leech extract,mussel extract, crayfish extract, and commercial peptone.On injecting a small amount of any of these extracts into thebloodvessels of an animal the lymph from the thoracic ductis much increased in quantity and becomes more concen-trated. Now all these bodies are poisons ; they alter theblood, diminishing its coagulability, and when given insufficiently large doses cause a great fall of blood pressure inconsequence of paralysis of the heart and vessels. I haveshown that the changes in the circulation produced by thesebodies are insufficient to account for the increased lymph-flow, but that the increased flow is due to an alteration ofthe capillary walls in the abdominal organs, especially in theliver. The hepatic capillaries become even more permeablethan before, so that a pressure within them which is littleabove normal is sufficient to cause a great increase of trans-udation through them.Another substance which seems to act directly on the

capillary wall is curare. This body, however, differs fromthe class of lymphagogues just mentioned in the fact that itschief action is on the vessels of the limbs. The effect ofcurare in increasing the lymph-production in the limbs wasnoticed long ago by Paschutin working in Ludwig’s labora-tory. Its direct action on the endothelial wall of the

capillaries can be easily demonstrated in the living frog’sweb. It may be seen that after the injection of curare thecapillary walls become apparently more sticky, so that thecapillaries become filled with a number of leucocytes adher-ing to their walls. A still more potent method of alteringthe permeability of the limb capillaries is to plunge the limbinto water at 56° C. for some minutes. If a cannula hasbeen previously placed in one of the main lymphatics of theleg it will be noticed that, in a very short time afterthis scalding, lymph begins to drop spontaneously fromthe cannula. The lymph which is thus produced ismuch richer in proteids than is lymph from a normal leg.The amount of lymph flowing from the leg can now bevaried within wide limits by altering the pressure in thecapillaries either by ligature of the vein or artery, injectionof salt solution, or production of vaso-motor paralysis. Bythis scalding, in fact, we may reduce the limb capillaries tothe condition of liver capillaries.

In conclusion, from this study of the conditions of lymph-production in the various parts of the body we must con-clude that the endothelial cells of the vessels take no activepart in the production, their vital activities being confinedto the maintenance of their integrity as a filtering membranewith properties differing according to the part of the bodyin which they happen to be situated. The amount and com-

position. of the lymph transuded in any part are determinedsolely by two factors : (1) the permeability of the vessel waU

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and (2) the intracapillary blood pressure. The more per-meable the capillary the greater is the amount of lymphtransurled under any given pressure, the greater is its con-ceotratirtn in prnteids. and the more easily is the amount oflymph altered by plight changes of pressure.

The Hunterian Oration:REFLECTIONS ON JOHN HUNTER AS APHYSICIAN AND ON HIS RELATION TO

THE MEDICAL SOCIETIES OF THELAST CENTURY.

Delivered before the Hunterian, Society on Feb. 13th, 1896,

BY G. NEWTON PITT, M D. CANTAB.,F.R.C.P. LOND.,

SENIOR ASSISTANT PHYSICIAN. LECTURER ON PATHOLOGY, AND DEMON-STRATOR OF MORBID ANATOMY AT GUY’S HOSPITAL, ETC.

{THE first part of the Oration dealt with the life ofHunter and his experience as a physician, which was shown,to have been by no means inconsiderable. Dr. Newton Pittthen continued as follows. 1

Until the latter quarter of last century, as Mr. Quain pointedout, there was no medical education in London. Surgeonsand apothecaries were suppo-ed to be able to pick upa sufficient smattering of their work by attending the

hospital for a few months, and physicians were educatedelsewhere. Some half-dozen each year took the degreeof M.D. at the Universities of Oxford or Cambridge,and these alone could become Fellows of the College ofPhysicians of London, while a much greater number pro-ceeded to medical degrees either abroad or at Edinburgh.Owing to the genius and energy of the elder Monro and

others, the education at Edinburgh was far ahead of anythingin London, and we naturally find that medical societies andperiodicals flourished there before they became establishedin the south.

Before knowledge can be classified and accurate con-clusions drawn, 16 is necessary that a large amount ofmaterial should be collected from many sources Theformation of medical societies and the publication of transac-tions and periodicals form a feature in the medical historyof the last century, contrasting strongly with that of theseventeenth century. Previously to this the Memoirs of theRoyal Academy of Sciences in Paris and the Philo-

sophical Transactions of the Royal Society of London werealmost the only publications in which English medical caseswere reported. Many English physicians had graduated atParis, and the Philosophical Transactions contain, up to theend of the century, over 1000 medical papers. A large- number of medical men have received the honour of the

Fellowship of the Society, and not the least distinguishedof these wAs John Hunter, who contributed numerous

papers, for the most part dealing with questions of naturalhistory.Edinburgh medical Societies -The School of Physics was

initiated in 1720 on the lines of the University of Leyden,and in 1783 there were 400 students of medicine. TheMedic2l 8Jticty was founded in 1’131, the records reachback as fa,r as 1737 and the members received t charter in1778. This society collected and published five volumes ofmedical essays and observations between the years 1733 and1744. Cullen, Hunter. Oliver Goldsmith, Fothergill andRichard and William Budd were among the members. The

Society met every Saturday evening during the wintersessions when papers were read. The publications werelargely contributed by the first Monro-i.e, John-whosemarvellous energy and ability contributed so essentii,lly tothe success of the school. He contributed papers on thenutrition of foetuses, on the diseases of arteries, on thelacrymal canal, on white swelling, on hernia, on the obstruc-tion of ureters by stones, on ulcers, on procidentia uteri, onthe preparation of bodies for dissection, on the anatomy of

the lower jaw and of the duodenum, on chalybeate waters,and on new instruments, a range of original work unequalledat that time in this country. ]&yacute;fedical and Philosophical Cona--vieniaries by a society of physicians in Edinburgh wereedited by Dr. Andrew Duncan and 20 volumes were issuedbetween 1773 and 1799. They were continued as the Annalsof Medicine till 1804. The publication consisted of reviewsof books, original medical observations, and medical news.They form the most valuable contemporary record o.fimedical activity of London quite as much as of Edinburgh.The Philo.<ophical r5’nciety published three volumes underthe title Essays and Observations, Physical and Literarybetween 1754 and 1771. The 31sc1llopian !:3ocicty was insti-tuted in 1774, and consisted of five physicians and tensurgeons, who met and supped together once a month. TheH.’dnbvrylz Ht7rveian BO()l.d1/ was founded in 1752 and the

Ali1"rlldhi.an Socitty in 1785. The Royal Physical Societyof Edinb1l7’gh was founded in 1771, incorporated in 1788,and merged with the Chirurgico-Medical Society in 1796.The Royal Society nf Rdi.nb/11’gh dates from 1783 ; theHi.beruirr,n Merlir’rz Edinburgh, from 1791.The only medical society in england outside London was

the Medical Society of Colchester, instituted in 1774.An examination of the history of the societies which were

started in London shows that eioch society owed its origin to.the energy of one or two men, and in many instances the

society faded away at their death. Until the latter part ofthe century there was no education for students in Londonbeyond that given by a few private lecturers. As late evenas 1783 we learn from the Medical Register that the follow-ing was the complete list of lecturers in London. Anatomy.’Mr. W. Cruickshank, at the Hunterian Museum in GreatWindmill-street ; Dr. R. Maclau’rin, a.t his house in Mark-lane ; Mr. Blizard, at the London Hospital; Mr. John Sheldon,at his house in Great Queen-street; and Mr. Henry Cline, at;St. Thomas’s Hospital, who bad also been appointed Pro-fessor of Anatomy to the Corporation of Surgeons in 1781.Surgery Mr. Percival Pott, F.R S., at St. Bartholomew’sHo-pital ; Mr. John Hunter. F.R.S., in the Haymarket; anc)Mr. J. O. Justamond, F.R.S., in Macclesfield-street, Soho.Physic : Dr. Fordyce, at his house in Essex-street and atSt. Thomas’s Hospital : Dr. Saunders, at Guy’s Hospital; ardHr. Maddocks, at the London Hospital. Most of thelectures, it will be seen, were not delivered at the hospitals,but at the lecturers’ houses, where several of them had largeschools ; and from Mr. Rivington we learn that the school ofthe London Hospital first offered a complete course of ednca-tion in 1785 and commenced to give clinical lectures in 1793.From the minutes of the Corporation of Surgeons we learnthat their Professor of Anatomy gave a yearly course of sixlectures on the muscles and of six on the viscera, theproposal that he should also give three on the bones havingbeen rescinded.The following appear to be the chief of those to whom the-

new medical societies were due :-William and John Hunter,John Sheldon, Dr. Foart Simmons, Dr. Saunders, Dr.

Fothergill, and Dr. Lettsom. The societies may be dividedinto two classes, those started by practitioners for thepurpose of publishing cases and those started by teachersas a means of keeping in touch with students and juniorpractitioners and of teaching them how to report anddiscuss cases. In most instances the posession of a

library, from which the members could borrow books, wasconsidered a very essential and important feature. In thestudent societies, at any rate, the money was raised byinnumerable fines rather than by fixed subscriptions.The Fellows of the Royal College of Physicians used to

meet from time to time to discuss medical questions and theyissued six volumes of Medical Transactions between theyears 1772 and 1820.The societies associated with William Hunter were the

two medical societies of 1753 and 1764. They were bothsmall ; the former consisted of physicians and the latter oflicentiates. The first society published at intervals thevolumes of medical observations and inquiries, and nothingmore was heard of the societies after Dr. Hunter’s death.

The Medical Society (1).-The first medical society in Londonwas founded in 1752 by some hospital physicians who met.together for their mutual improvement in the practice oftheir profession once a fortnight on Monday evenings at theMitre Tavern, Fleet-street. After some time they decidedto form themselves into a society for collecting and publishing" Medical Observations and Inquiries," six volumes of whichwere issued between the years 1757 and 1784, the first papor-