The fanciful views of the humoralists as to the etiology of gout exercised almost undisputed sway up to the latter half of the eighteenth century. At that time the great Scottish physician, Cullen, took up arms against a doctrine which appeared to him unjustifiable in conception and baneful in practice. He inclined to the solidists rather than to the humoralists, claiming that gout was the outcome of a peculiar bodily conformation, and more especially of an affection of the nervous system. While he categorically denied that any materia peccans was the cause of gout, he yet admitted that in prolonged cases a peculiar matter appeared in gouty patients. But, in view of latter day revelations, Cullen, with singular prescience, maintained that the said matter was the effect and not the cause of gout.
Albeit, notwithstanding the almost universal deference accorded to Cullen, his theory, promulgated in 1874, though previously adumbrated by Stahl and afterwards reinforced by Henle, secured but few adherents. The source of this was not far to seek. For ever since the discovery of uric acid by Scheele in 1776, and its detection in tophi by Wollaston, an increasing body of opinion inclined to the view, that in some obscure way the life history of gout was bound up with that of uric acid.
Still, despite able advocacy in this country by Sir Henry Holland, Wollaston, and others, not to mention Continental authorities, such as Cruveilhier, it was felt that scientific proof of the truth of their contention was still lacking. But not for long were they left in doubt. For, in 1848, Sir Alfred Garrod’s momentous and epoch-making discovery of the presence of uric acid in the blood of the victims of gout allayed all doubts, and seemed then and for long after an all-sufficient explanation of the protean manifestations of the disease.
This distinguished physician enunciated his views in a series of propositions which embodied the result of his researches and incidentally laid the foundations of the uric acid theory.
This great physician held that, in true gout, uric acid in the form of urate of soda was, both prior to and during an attack, invariably present in the blood in abnormal quantities, and was moreover essential to its production; but with this reservation, that occasionally for a short time uric acid might be present in the circulating fluid without exciting inflammatory symptoms. This comparably with what obtains in lead poisoning, and on this account therefore he did not claim that the mere presence of uric acid therein would explain the occurrence of the gouty paroxysm.
He further averred that gouty inflammation is always accompanied by a deposition of urate of soda, crystalline and interstitial, in the inflamed part. Also that “the deposited urate of soda may be looked upon as the cause and not the effect of the gouty inflammation. Moreover, that the said inflammation tends to destruction of the urate of soda not only in the blood of the inflamed part, but also in the system generally.”
In addition, Garrod postulated implication of the kidneys, probably in the early, and certainly in the chronic stages of gout; and that the renal affection, though possibly only functional at first, subsequently became organic, with alterations in the urinary secretions.
As to the anomalous symptoms met with in gouty subjects, and alike those premonitory of a paroxysm, he ascribed them to the impure state of the blood, and due principally to the presence therein of urate of soda. Of causes predisposing to gout, if we except those attaching to individual peculiarities, they are either such as will lead to increased formation of uric acid or to retention of the same in the blood.
On the other hand, the determining causes of a gouty fit are those which induce a less alkaline condition of the blood, or which greatly augment for the time the formation of uric acid or such as temporarily check the eliminating powers of the kidneys. Lastly, his final axiom was that—in no disease but true gout is there a deposition of uric acid.
No tribute to Garrod’s masterly achievement could err on the side of generosity. A truly scientific physician, he built on the rock of sound clinical and pathological observations. For measured restraint, he stands out in pleasing contrast to those who, lacking his clinical acumen and sound judgment, brought not grist to the mill, but vain imaginings based on Garrod’s hard-won facts. His researches in truth constitute a landmark in the history of the pathology of gout, with their substitution of facts for pure hypotheses. True, though it was that, for half a century before, there was a growing suspicion that lithic (uric) acid was the malign factor in the induction of gout, still it was not till Garrod’s discovery of uric acid in the blood and tissues of the “gouty,” that any definite step towards the elucidation of the problem presented by gout was attained.
One aspect of Garrod’s theory that much exercised the minds of his contemporaries was that for him uric acid was the alpha and omega of the disease, and as Ewart remarks, “If we are not over-anxious as to the stability of this mid-air foundation, everything is evolved smoothly from it on the lines of the theory.” Fortunately, however, for the progress of the art of medicine, men were over-anxious as to the why and wherefore of that accumulation of uric acid in the blood which Garrod held to be a necessary antecedent of gout. He himself, as we know, attributed it to a functional renal defect which may be inherited or acquired. To others, however, this assumption of renal inadequacy was not wholly satisfying, hence the origin of the many widely differing hypotheses from time to time advanced as to the pathogeny of the disorder.
Broadly speaking, the various conceptions proffered as to the causation of gout fall into one or other of the following categories. The primary alteration in gout is variously assumed to be:—
(1) In the blood or tissues, the so-called histogenous theories.
(2) In the bodily structures, either inborn or induced.
(3) In hepatic inadequacy.
(4) In hyperpyræmia.
(5) In the nervous system.
In his classic work, “On Urine” (1860), Parkes expressed his scepticism as to the valency of Garrod’s assumption of a primary renal inadequacy. In shrewd forecast of latter day views he was of opinion that both uric and phosphoric acids existed in some untoward combination in the blood or organs, and that this same impeded its excretion. As he says, “If this be the case, the deficient elimination is, as it were, only a consequence of more important antecedent aberrations in metamorphosis of which impeded excretion is a natural sequence. What these are, however, is quite unknown; but an unnatural formation of uric acid, either from food or tissues, may possibly be part of them.”
In 1866 Barclay lodged another objection to Garrod’s hypothesis, viz., that the baneful influence of uric acid was exercised passively and physically. Not only did he regard it as “far too mechanical,” but he also strongly dissented from his axiom that gouty inflammation was invariably attended by uratic deposits. Thus he asks, “Must we of necessity find urate of soda in the stomach and the bronchi before we can admit gouty gastritis, or gouty bronchitis?” Seemingly he believed in the existence of these two clinical entities, and inasmuch as urate of soda had not been detected in situ in these disorders, he felt justified in denying that “true gouty inflammation is always associated with, or caused by, the deposit.” Moreover, this conclusion, he considered, derived colour from the fact that, “though the deposit and the inflammation were associated together in the joints, the urate of soda was seen in other parts without any evidence of its exciting inflammation there.”
His own view was that the primary change lay in the blood corpuscles, this being induced by the serial ingress of “gout producing elements” into the blood stream. As to the retention of uric acid, he deemed it not the cause, but merely a symptom, a consequence of gout. Thus he says, “The good living and the stimulants do not simply cause an excess of uric acid to form, but they end by causing some more permanent change, and probably one affecting the blood globules, which reacts on the kidney, putting a stop to the excretion of uric acid, and causing its retention in the serum, where, passing in the round of the circulation, it is very apt to become deposited as urate of soda.” Moreover, his observations of the effect of colchicum in checking a gouty paroxysm, seem to indicate, “that there is a disease to which the name ‘gout’ is applied, distinct from the excess of uric acid in the blood serum which attends its progress.”
The imaginative insight of Barclay is very remarkable. If we substitute the white for the red corpuscles we see how closely his views accord with those prevalent at the present time, when so important a rôle in the genesis of gout is attributed to the leucocytes. Moreover, as Ewart observed, the views of Barclay and Parkes approximate in principle to those afterwards propounded by Ord and Ebstein, that the bodily tissues “take an active share in determining the deposition of uric acid.”
It is, however, but fair to note that, long prior (1854) to Barclay, Gairdner held that “the disappearance of urea and uric acid in the urine and their accumulation in the blood” was but symptomatic and not causative of gout, coupling with it the suggestion that there was some antecedent nerve influence at work.
Laycock, too, it may be noted, considered Garrod’s theory inadequate, adding that “Gout is characterised not by urates in the blood but by the genesis of uric acid in the tissues, and its action thereon, and is especially characterised by peculiar changes in the innervation of the individual.”
In 1872 Ord took up the novel standpoint that there was an inborn tendency in the fibroid tissues of gouty subjects to undergo a special type of degeneration, which same might be inherited or acquired. Also that this innate peculiarity was attended by excessive formation of urate of soda in these tissues, and which subsequently gaining entry therefrom into the blood, was deposited promiscuously in the body with a predilection for relatively non-vascular structures, viz., cartilages.
As to the local inflammations typical of gout, Ord’s attitude was somewhat ambiguous. Thus he maintains, “The local inflammations do not necessarily depend upon the deposit of urate and the deposit is not a consequence of inflammation; at the same time, it is probable that excess of urate in the blood produces irritation of tissues.” Neither did he believe that the local inflammatory reactions were of necessity in every instance specific, viz., due invariably to mechanical irritation by uratic deposits, but that they might be initiated by injuries, exposure to cold, etc. Lastly, as to the migration of the disorder from place to place, he believed that for its explanation direct or reflex nervous agencies had to be invoked, for he held the opinion that the local gouty “degeneration and inflammation tend to infect the rest of the system through the blood, and to set up similar actions elsewhere through reflex nervous influence.”
We see, therefore, that for Ord gout, as Ewart observes, was “a mode of decay” or a “disease of degenerations.” “The local tissue degeneracies supply a basis for the uratic deposits and the general degenerative changes multiply the sites exposed to an infiltration from the contaminated blood; whilst reflex mechanisms step in as additional determining agents.”[4]
Reminiscent of Ord’s view is the hypothesis associated with the name of Ebstein. As the outcome of experimental study he arrived at the conclusion that the primary factor in the causation of gout was a disturbance of tissue nutrition culminating in death or necrosis of the damaged textures. The initial nutritional derangement was ascribed by him to the irritant effect of soluble neutral sodium urate. This necrotising agent, following the development of “free acid” during the process of necrosis, was transmuted into the acid urate. Subsequently this same was deposited in crystalline form in the necrosed area. He held these areas of necrosis quite as typical of gout as the uratic deposits, and postulated their combinations to be necessary for the production of a true gouty focus, claiming that he had detected such foci in cartilage, tendons, kidneys, and connective tissue.
Experimentally, Ebstein endeavoured to induce a gouty condition in fowls by ligaturing both ureters, thus thrusting upon the circulation the dammed-up uratic secretion. In other instances he administered to the same animals subcutaneous injections of neutral chromate of potassium, attributing to this substance the power of inhibiting the excretion of uric acid viâ the kidneys through its action on the renal parenchyma. Subsequently, after death he noted the incidence of uratic deposits in joints, muscles, tendon sheaths, and liver, the same being more copious in those animals subjected to chromate injections.
His conclusions were: (1) That necrosing and necrotic processes are developed in various organs as a result of some irritant. (2) That uratic deposits occur in the necrosed area resembling those met with in gouty subjects. (3) That an inflammatory reaction with small cell infiltration ensues in the vicinity of such necrotic areas.
But, in regard to these experimental investigations, they are obviously incomparable to the morbid processes that presumably occur in gout in man. Moreover, as shrewdly pointed out by Levison, experimental ligation of both ureters would certainly engender uræmia rather than anything approximating to gout.
Again, his experiments with urates and uric acid, by which he claims to have demonstrated their action as chemical irritants capable of inducing necroses in tissues, have proved fallacious. This, for the very cogent reasons pointed out by Luff, which run as follows: “Not only is there no proof that the neutral sodium urate upon which he depends for the starting of the gouty changes, ever exists in the human body, but, on the other hand, very strong evidence to show that it never can exist in the human body.”... “The neutral sodium urate is an extremely caustic and unstable compound, and is decomposed in the presence of carbonates, so that it is impossible for it to exist in the blood. The first factor upon which Ebstein relied for his theory for the causation of gout therefore disappears.”
Again, Ebstein’s fundamental proposition that in gout uric acid was produced in many tissues not normally concerned in its production, was ruled out by Horbaczewski’s establishing the fact that in health uric acid is a by-product of the metabolism of almost all tissues. Lastly, the strong toxic properties accredited by him to solutions of the urates was disproved by Pfeiffer’s experiments. This observer showed that urates, in such degrees of concentration as may exist in the human body, are incapable, when injected into the tissues, of inducing necrosis.
In summarising the doctrines of Ord and Ebstein, it may be observed that if the latter’s contentions have been disproved, Ord’s claim that the tissues of gouty subjects exhibit a specific tendency to degeneration has also as yet not been substantiated. Albeit, we must not forget that in 1883 Ralfe subscribed to Ord’s views as to the tendency to textural degenerations in gouty subjects, either through heredity or acquirement. For this observer, however, the basal factor in the production of the disease was a diminished alkalinity of the blood, due to a surcharging of it with acid and acid salts. Disagreeing with Garrod’s assumption that deficient renal elimination was the prime cause of the retention of uric acid, he was of opinion that “the first step in the process lies in the failure of the tissues to reduce the acid, as it occurs in health.”... “In the large glands or where the current of the circulation is free, the uric acid is carried into the blood and gradually reduced to urea; in tissues outside the current of the circulation, the insoluble uric acid is not so readily carried off, and so on the slightest disturbance is deposited, as is the case in cartilages of the joint, the ear, etc.” As to the determining cause of the gouty attack, he invokes the agency of the nervous system to explain its incidence, for he held it probable that the primitive failure of the tissues to reduce uric acid eventually led to derangement of some special nerve centre, which disturbance occasioned the gouty outbreak, with resultant “accumulation of uric acid in the blood and deposition of urate of soda in the tissues.”
In 1895 Berkart propounded a mode of genesis which may be regarded as a variant of Ord’s theory. The severity of the symptoms of acute gout were such as he deemed incompatible with their production as a result of simple mechanical irritation by crystals of biurate of soda. Uric acid, he held, must be afforded a humbler rôle than that of a proximate cause. It was, for him, but an epi-phenomenon, the accompaniment of a panarthritis, the origin of which was as follows:—
While not postulating the identity of rheumatoid arthritis in gout, he yet held that both disorders originated in some obscure form of atrophy of the bone substance, and that the degenerative change also overtook the cartilages and fibrous tissues of the joints. Subsequently, there ensued a necrosis in the tissues in and around the joint. The degeneration and subsequent necrosis, he held, were the outcome of a profound “vice of nutrition.” The pain, inflammatory reaction, œdema, and cuticular desquamation were the direct result, he thought, of the necrosis. The excess of uric acid in the blood he referred to leucocytosis, and in part to disintegration of the tissues.
That some obscure connection obtained between gout and hepatic disorder has been for long an axiom in high favour, with both clinicians and pathologists. This hypothesis found its chief exponents in Murchison and subsequently Latham, and to discussion of their individual views we now proceed. The first named authority held gout to be either merely a result or a variety of what he termed lithæmia. In other words, gout was the outcome of a depraved condition of the blood, due to faulty digestion and functional disturbance of the liver.
Now the conditions that lead to functional derangement of the liver are in the main such as favour the development of gout. Nevertheless, such hepatic disturbances do not inevitably culminate in outbreaks of gout, at any rate of classical type; but, unquestionably, such may eventuate in symptoms currently recognised as distinctive of incomplete gout, e.g., headache, palpitation, cramps, dizziness, sleeplessness, etc. Moreover, if the faulty habits leading to such hepatic derangement be persisted in, they are but too likely to induce outbreaks of frank gout. “Articular gout,” said Murchison, “is so to speak a local accident which, though sometimes determined by an injury, yet may occur at any time in persons in whom the normal process by which albuminous matter becomes disintegrated in the liver into urea is persistently deranged.” Following such hepatic disturbance, the secretion of bile decreased with resultant abnormal metabolism of proteins, and in this way was produced an accumulation of uric acid. This, moreover, according to Murchison, was, especially in the later stages of gout, reinforced by the concurrence of renal inadequacy, which he also postulated as a factor in the production of the disorder.
The tendency to lithæmia Murchison held to be hereditary, and in this was supported by Goodhart, who, discussing its occurrence in young children, was strongly of the opinion that it was due not to dietetic irregularities but to a “constitutional tendency on the part of the individual”; a conclusion, as he thought, strongly supported by the fact that it is more commonly met with in the children or descendants of the “gouty.”
But we have to recollect, as Duckworth observes, that lithæmia, “even when persistent and not due to accidental causes, is not by itself gout.” Moreover, gout is not the only morbid condition in which urates are in excess in the blood, for such obtains, e.g., in leukæmia, pneumonia, anæmia, Bright’s disease, etc. Also, underlying Murchison’s theory is the further unwarrantable assumption, viz., that the “gouty” diathesis is identical with the “uric acid” diathesis.
Now, as we hope to show later, whatever be the proximate cause of gout it is at any rate not uric acid. The fact, too, that higher degrees of lithæmia are to be met with in conditions, not even remotely connected with gout, renders it impossible to accept the view that the excess of urates in the blood is responsible for all the varied symptoms accredited by Murchison and his followers to lithæmia. For the same reason, it is difficult to uphold the hypothesis that “the tendency to lithæmia in early life may be an early expression of the ‘gouty’ diathesis.”
In short, excess of uric acid in the blood or lithæmia is not pathognomonic of gout, much less of “potential” gout. But further discussion of this assumed relationship of lithæmia to gout may well be postponed until, in the light of recent blood analyses, we come to consider more narrowly the contention at one time widely held, that lithæmia is an irregular manifestation of gout.
If we are compelled to adopt a more judicial attitude in regard to lithæmia, what of the similar assumptions as to the relationship of lithuria or lithiasis to gout? Now lithuria, like lithæmia, was and probably still is by some held to be an inherited “gouty” proclivity. Sufferers in youth from lithiasis were deemed likely to develop gout in later years. Not only was lithiasis observed to precede but also to be a concomitant or sequel to gout. Nevertheless, although uric acid, gravel and calculi, sometimes arise in those of “gouty” diathesis, these instances are but isolated, so rare indeed as to entitle them to be regarded as mere coincidences. Moreover, when we recall the fact that the formation of calculi takes place in the urinary passages, i.e., outside the economy, it renders even more improbable the hypothesis that the two morbid phenomena are diverse expressions of the “gouty” diathesis.
As a matter of fact, the large bulk of “gouty” subjects are immune from gravel. Conversely, only a negligible percentage of the victims of gravel develop gout. The geographical distribution of the two disorders is wholly distinct one from the other. The Indian native is a martyr to stone, but notably exempt from gout. Coming nearer home, we find stone relatively common in Scotland, but gout rare. Plowright’s researches, too, revealed no correspondence between the incidence of gout and the prevalence of stone in the several counties of England. In some counties in which the mortality from gout was high that from stone was low, and Norfolk, the one most prolific of stone in England, enjoys comparative immunity from gout.
Reverting now to Latham’s views as to the hepatic origin of gout, we find them very similar to those formulated by Murchison. He held that the defective transmutation of glycocine into urea was responsible for the occurrence of uric acid in the urine. These chemical irregularities were attributed by him to functional disturbance or partial suspension of the normal hepatic metabolism. This, again, was referred back by him to some obscure change in the central system, viz., that part of the medulla oblongata from which the vagus takes origin.
Excess of carbonaceous materials in the blood was considered by Hare to be an essential, though by no means the sole factor in the genesis of gout. This same “hyperpyræmia,” as he terms it, was also, he believed, responsible for migraine, asthma, epilepsy, and other paroxysmal neuroses. For the alternation of attacks of acute articular gout with paroxysms of migraine, asthma, and epilepsy, seemed to him to indicate a kindred origin. The same inference, also, he deemed might be drawn from the well-ascertained fact that the temporary or even permanent cessation of long standing asthma, migraine, and epilepsy, might exactly coincide with the onset of acute gout.
These alternations and substitutions seem to suggest that the preceding alterations in metabolism are similar in nature, finding expression indifferently in gout, asthma, epilepsy, etc. Carbon foods, he considered, are much more likely to accumulate in the blood than the nitrogenous. Ingestion of the latter is swiftly reflected in increased elimination of nitrogenous excreta. On the other hand, following the intake of carbonaceous foodstuffs, no such rapid and proportionate increase in the excretion of carbonic acid ensues. In other words, the capacity of the organism to deal with or katabolise in response to the absorption of excess of carbon foods, is strictly limited. Muscular exercise and exposure to cold, factors which but slightly influence protein katabolism, are largely responsible for adequate carbon katabolism. Accordingly, given deficient exercise, excess of carbonaceous food and a warm temperature, an accumulation of the carbon content of the blood is favoured.
Hare considered that present day habits of warm clothing, warm rooms combined with excessive intake of starch and sugar, are precisely the favourable conditions for producing a state of hyperpyræmia. Increased fat formation would of course tend to diminish such a tendency to carbon accumulation, but this capacity in many subjects is conspicuously lacking, and may already have attained its limit.
Hare contended also that excessive intake of starch and sugar by inducing a state of “glycogenic distension” of the liver, might through compression of the intra-hepatic portal capillaries, lead to congestion of the retro-hepatic portal venous system, and sequentially of the gastric and intestinal mucosa. Through consequent inhibition of digestion and absorption, a condition of hyperpyræmia is induced. This, under varying conditions, may eventuate in acute gout, the coincident pyrexia of which is curative of the underlying hyperpyræmic state, and of all those hyperpyræmic manifestations (irregular or suppressed gout) which so often are the harbingers of an on-coming articular outbreak.
It may be noted en passant that the influence of the nervous system was frequently invoked directly or indirectly in many of the theories already discussed. Stahl, it will be recalled, was the pioneer in this direction, and later Cullen and Henle propounded the view that “the origin of the affection was probably to be found in the central nervous system.” Gairdner, too, by implication, as also Laycock, postulated a neural origin for at any rate some of, the phenomena of gout.
But it was reserved for Edward Liveing (1873) explicitly to advocate the nervous origin of the disease, his reflections on the paroxysmal nature of the attacks, its tendency to periodicity leading him to suspect its kinship with other neuroses.
Those inclining towards the neural conception were later strengthened in their convictions by Charcot’s momentous identification of the nervous origin of certain arthropathies. Accordingly, in 1880, we find Sir Dyce Duckworth advocating the view that gout was “a primary neurosis,” “a functional disorder of a definite tract of the nervous system.”
The gouty neurosis, Duckworth contended, may “be acquired, intensified, and transmitted; also that it may be modified variously and commingled with other neuroses; that it may suffer metamorphic transformations, or be altogether repressed.” Arguing by analogy, Duckworth saw in the paroxysmal attacks, the tendency to periodicity and alternation in the manifestations, evidence of an alliance between gout and the various neuroses.
He further postulated that “this diathetic neurosis determined a disorder of nutrition and led to the perverted relations of uric acid and sodium salts in the economy.” He also held that the localisation of attacks, and the determination of urate of soda to the affected part was also due, in all probability to nervous influence. And the temporary renal incapacity for excretion of uric acid was also attributed by him to the same nerve inhibition.
We see, therefore, from the above, that Duckworth was well justified in describing his view as a combine of the humoral and neural hypotheses. His pathological differentiation between primary or inherited gout and secondary or acquired gout is as follows: In the primary type “the toxæmia is dependent on the gouty neurosis ... and is therefore a secondary manifestation.”
In secondary or acquired gout, “the toxæmia is directly induced by such habits as overload the digestive and excretory organs, and consequently prevents complete secondary disposal of nutritional elements of food; that if, together with such toxæmia, distinctly depressing and exhausting agencies, affecting the nervous system, come into operation, the special neurotic manifestations of the gouty diathesis will occur, and be impressed more or less deeply upon the individual and his offspring.” It is generally conceded that Duckworth’s theory as to the genesis of gout is pre-eminently catholic in conception, because, as Ewart rightly remarks, “it represents the most complete theory published in this country on the general pathology of gout,” and because “the able advocacy of its propounder has given it the support of arguments derived from pathological analogy and from clinical influence which will demand careful examination and searching criticism before they can be either disproved or adopted.”
Albeit, it must be frankly admitted that Duckworth’s perception of gout as a tropho-neurosis of central nervous origin has never gained wide acceptance; this no doubt largely because it was insusceptible of proof. In an endeavour to remove this reproach. Sir Willoughby Wade promulgated the view that the causal change in gout was partly in the central nervous system, partly in the peripheral nerves of the inflamed limb. In other words, he regarded gouty arthritis as the outcome of a local neuritis, this latter being set up in the first instance by the faulty blood state, viz., uricæmia. On the other hand, the central nerve centres might occasion or aggravate the general gouty tendency through their influence over “recognised seats of metabolic activity.” Also the same might, through the medium of the vaso-motor nerves, determine the incidence of local attacks. It will be seen that Wade’s theory is but a variant of that propounded by Duckworth, viz., neuro-humoral.
It will be recalled that as far back as 1889 Duckworth displayed disquietude as to the adequacy of the purely chemical or purely physical view of the pathogeny of gout, as sufficing for an explanation of all its varied phenomena. Thus he writes: “It is incumbent, I believe, to invoke not only a chemical and physical basis for gouty disease, but to include also, in a comprehensive view, the marked determining influence of the nervous factor in the problem.”
Whether we agree or not with Duckworth’s view of gout “as a diathetic neurosis, due to a central neurotic taint, and originating from prolonged toxæmia,” it does, I think, mark the dawn of a reaction from the uric acid theory of its causation. Still, this latter conception continued to dominate the field until seriously called in question by the results of Magnus Levy’s researches. His revelations were, in truth, almost revolutionary, and doubts now accumulated as to the propriety of the terms “uric acid diathesis,” “uric acid intoxications,” “lithæmia,” etc., so long credited as being responsible for not only nearly all the minor ailments flesh is heir to, but especially those relating to joints and muscles, all alike attributable to the presence of excess of uric acid or urates in the blood.
To hasten the process of disillusionment there came from the side of the physiologists the announcement, almost unanimous, that uric acid, though in minimal amounts, is a normal constituent of the blood, organs, and tissues. Thoroughly purged now of their obsession as to the pathological potency of uric acid, there awoke a spirit of inquiring scepticism. On all sides it was felt that the whole problem must be looked at afresh, untrammelled by previous conceptions, no matter how high the sanction. How else, indeed, could the chaff be winnowed from the grain, the illusions born of inaccurate observations be replaced by the substantial form of truth?
Still, it would be ungracious to withhold our due meed of admiration for the masterly manner in which the views of the earlier physicians as to the causation of gout were elaborated, the shrewd and often prophetic inferences, well buttressed by arguments based on clinical and pathological analogies; these the more wonderful when we recall the meagreness of the positive material at their disposal, and that little, alas! how often ambiguous!
In light of latter day views, too, we may well admire the swiftness with which the inadequacy of Garrod’s theory to explain all the protean phenomena of gout was realised. Like Duckworth, they rightly apprehended gout to be “something beyond the resultant effects of aberrant relations of uric acid; that it consists in something more than a perversion of animal chemistry; that it is not to be explained as a mere outcome of gastric or hepatic distemper; and that it is not the appanage only of the middle-aged or elderly high liver, and intemperate drinker, because, as is well known, it affects also sometimes in early life the high thinker and the laborious bread-winner.”
That the uric acid theory should more than any other have found ready acceptance, is not so much to be wondered at. The one solitary pathological fact that emerged out of the mist of hypotheses was that established by Garrod, viz., the excess of uric acid in the blood. It survived and still survives the corroding test of time. Surely such must be the fons et origo mali, and how obtrusive the uratic deposits, so ready to hand, objective affirmations of the truth of their contention.
This apparent simplicity how delusive! yet not wholly unprofitable. For if in these latter days our knowledge of the life-history of uric acid and purin bodies in the organism has evolved from “a state of chaos and guesswork to one of system and scientific accuracy,” the seeds thereof were sown by these hardy pioneers, their, to us crude, researches in the dark regions of bio-chemistry.
Here it would appear opportune to outline our plan of procedure in approaching this abstruse subject—gout. In the coming chapter we shall attempt to define and classify the various types of the disorder before passing on to discuss its etiology and morbid anatomy.
Now all will agree that the more recent revelations of chemical physiology and chemical pathology have an intimate bearing on the problem to be considered. We shall therefore, before proceeding to the more purely clinical aspects of the disease, deal with the modern conceptions of protein and purin metabolism, more especially the latter. Subsequently our scrutiny will be narrowed to consideration of the chemical structure of uric acid, its solubility, sources, mode of formation and destruction. In possession of these facts the relationship of uric acid to gout will be dealt with, in regard to respectively uric acid excretion, uricæmia, and uratosis.
The inadequacy of the uric acid theory of the causation of gout will then be discussed and the possible intrusion of an infective element in its genesis advocated. This accomplished, we shall proceed to the section dealing with the clinical aspects of the disorder, its regular and so-called irregular manifestations. Thence we shall proceed to the diagnosis of gout, while the terminal chapter will be devoted to that all-important subject—the prophylaxis and treatment of the affection.