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Kidney International, Vol. 37 (1990), pp. 1019—1025 HISTORICAL ARCHIVES CARL W. GOTFSCHALK, EDITOR

Henry Bence Jones (1813—1873): On the influence of diet on composition Including a previously unpublished treatise on the subject and a bibliography of his writings LEON G. FINE

Division of Nephrology, Department of Medicine, Center for the Health Sciences, UCLA School of Medicine, Los Angeles, California, USA

Eponyms have done much to perpetuate the fame and fortunepating in chemical analyses of biological tissues and fluids. of . In the case of ', the applica-Indeed, the contribution of Jones to the chemical analyses of tion of his name to the unique protein appearing in the urine of"vegetable fibrine, vegetable albumen and vegetable casein" patients with multiple myeloma persists in the vocabulary ofwas duly noted in the appendix to Liebig's famous book on modern medicine but largely obscures the reality of the man andAnimal or Organic Chemistry in its Application to his contributions. In fact, other than contributing a singlePhysiology and Pathology [62]. publication on the subject [151 in which he erroneously con- Upon returning to , Jones developed an impressive cluded that the protein was an of albumin, Jones dis-reputation as an animal chemist, being called upon to give played no particular interest in the disease. Rather, he was anumerous lectures on the subject. In 1846 he was elected and chemist with perhaps the widest ranging knowl-Fellow of the Royal Society. While he was regarded by Flo- edge of chemical pathology in England during the mid-nine-rence Nightingale as the best "chemical doctor" in London teenth century and counted such eminent persons as T.H.[59], his clinical talents were not equally appreciated. Sir Huxley, , and MichaelClifford Abbot, in eulogizing his contributions to biochemistry Faraday amongst his friends and patients [571. confesses: "Clinical teacher he was not, he did not pretend to The life and contributions of Henry Bence Jones (Fig. 1) havebe. For this reason and because of his scandalous unpunctuality been reviewed elsewhere by Coley [581andRosenfeld [59] andthere was no competition for his clerkship" [60]. the reader is referred to these articles for details of his career. Suffice it to say that he obtained his clinical training at St. Henry Bence Jones's overview of the "Chemical Circulation" George's Hospital in London from 1837—1839, first as an apprentice to the and then as a "perpetual pupil," The purpose of this article is to focus upon principle contri- that is, a full-time medical student. After taking ill with rheu-bution of Henry Bence Jones to the literature of animal chem- matic fever he decided upon further training in Chemistry andistry, namely his body of work on the influence of diet on urine composition. It is relatively easy to trace the evolution of his spent a year at University College as a private pupil of Profes- sor Thomas Graham and George Fownes. Fownes, who wasideas by focussing upon his own reviews of topics over an Graham's assistant had studied with Justus Liebig (1803—1873)extended period. Fortunately, he wrote three books, which at Giessen in Germany and was able to convey to Jones thewere essentially compilations of lectures on animal chemistry, around the beginning, middle and end of his career. The first, in techniques of organic analysis which were emanating from1842, was titled, On Gravel Calculus and Gout: Chiefly an Liebig's laboratory. Being persuaded of the important impact that animal chemistry was to have on the practice of medicine,Application of Professor Liebig's Physiology to the Prevention and Cure of These Diseases [3]. Jones had returned to England Jones completed his medical education in 1841 and immediately left for Giessen for a period of study under Liebig. from Giessen and used the book to disperse knowledge of The atmosphere in Liebig's laboratory must have been elec-Liebig's ideas across the channel, claiming little originality of tric at the time, with students from all over the world partici-thought for himself. His second book, "On animal chemistry in its application to stomach and renal diseases" [19] was pub- lished in 1850 after he had contributed significantly to the 'Despite the fact that the name Bence-Jones was hyphenated in an literature with original investigations. His final book, published autobiography published by his youngest son nearly 50 years after his in 1867, entitled "Lectures on Some of the Applications of death (57), all publications during his lifetime lack the hyphen and are Chemistry and to Pathology and Therapeutics" [50], catalogued in contemporary bibliographies under "Jones." HBJ'sencompasses his extensive experience of animal chemistry and mother's family name was Bence. its application to specific disease states. In it he attempts to © 1990 by the International Society of Nephrology define such conditions as diabetes, gout, fatty deposition in the

1019 1020 Fine: Bence Jones on urine composition

"creator of vital or nervous force and we are beginning to regard it as a converter of latent into active force." Since the force latent in the elements of food was measurable as heat generated and a mechanical equivalent could be derived, quan- titative "energetics" was beginning to surface in physiology. The above considerations are of importance in interpreting his writings on the effects of diet on urine composition. Urine composition as a reflection of food intake and tissue breakdown: The essential contribution of Henry Bence Jones Jones's view of the chemical circulation, which appears in his work on animal chemistry of 1850 [19], is shown in Figure 3. On the one hand food which is absorbed through the gastrointesti- nal tract is incorporated into the "system," that is, into the tissues. Substances present in excess pass into the urine to- gether with waste substances produced by the organs of the body. The concept of "excess" nutrients passing into the urine was seen by Jones as an escape mechanism, although he was unable to understand the means by which the "excess" is determined and was unwilling to invoke the term "unvitalized portion" to describe this. Stated in his own words: "Food makes blood, blood makes muscle; this, when used, returns in a different form into the blood again and passes out by the breath and urine. This is the first and most healthy systemic or larger circle" (referring to the left side of Fig. 3). "The second, less healthy relation is caused by excess food or diminished wants of the system (referring to the right side of Fig. 3). The excess passes into the blood from the stomach and passes out by the breath and urine. I consider that we do not know why or how the excess of food is thrown off by the kidneys, but it is not the less certain to me that the food as well as the changes in the Fig. 1.Portraitphotograph of Henry Bence Jones (From the Library, Wellcome Institute for the History of Medicine; reproduced withbody affect the urine." permission). These statements, viewed in retrospect were of great impor- tance in introducing the concept of "metabolic balance" to the minds of physicians. However, they contain a subtle, but important, difference from our modern concept of balance. liver and Bright's disease in terms of specific disorders ofRather than regarding renal excretion, as we now do, as the physiological chemistry. means of maintaining the constancy of the internal milieu in the The most obvious conclusion arising from these works is thatface of a widely varying pattern of food intake, Jones consid- Jones clung with fervor to the doctrines of his teacher inered the passage of the constituents of food directly into the Giessen. Liebig's overview of the interconversion of biologicalurine without being assimilated into the structure of the organs, molecules, which were tabulated by Jones (Fig. 2) in 1842 [3]as being a "less healthy" state of affairs. was patently incorrect. For instance, was depicted as He further considered the urine to contain its constituents in arising from uric acid and his proposal for preventing thedirect relation to the action of on the tissues. Thus, formation of uric acid stones was to increase the rate ofduring muscular activity the urine will contain increased oxidation of uric acid to the more soluble urea by increasing theamounts of oxygen and sulphur; increased "nervous" activity supply of oxygen. This could be achieved by providing vigorousleads to an excess of compounds containing oxygen and phos- exercise and limiting the intake of non-nitrogenous foods,phorous, that is, phosphoric acid and alkalies. Although these which were thought to inhibit such oxidation. The uric acidconclusions were not correct in all of their details, they pro- "diathesis" he thus viewed as a resistance of the tissues to thevided a very important stimulus for physicians to begin to look action of oxygen. This emphasis on oxygen availability, dietto the chemistry of the urine for insights into the pathophysiol- and exercise punctuates many of his subsequent papers and wasogy of disease. The following examples demonstrate Jones's a direct extension of Liebig's ideas. By 1850 these views hadtalent at designing the simple but decisive experiments which not changed substantially. He considered non-nitrogenous sub-allowed him to arrive at the general conclusion that urine stances to be substrates upon which air and oxygen acted tocomposition reflects dietary intake in a wide variety of circum- form heat, water and carbonic acid, and that one of the mainstances. functions of oxygen is to generate body heat. No substantial deviation from these notions occurred toward Variations in the acidity of the urine in health [10, 11, 16] the end of Jones's career but they are couched in the pseudo- Jones analyzed gastric juice and found it to be highly acid and scientific jargon of the times [501. The human machine is ato contain water, salts, non-nitrogenous organic substances and Fine: Bence Jones on urine composition 1021 ALBUMEN OR FIBRIN.

I (Irateof Ammonia. Sulphur.____ Choleic Acid. Phosphate Phosphonis. I otLune. Urea. Carbonic Sulphuric PhosphoricCarbonic Carbonate of Acid. Acid. Acid. Acid. Ammonia.Fig. 2. The metabolic fate of albumen or Carbonate of SulpKte. Phosphate. fibrin as summarized by Henry Bence Jones Ammonia. [3].

diuretic to increase the quantity of the urine and hence to lower the concentration of its constituents.

BLOOD Excretion of alkaline and earthy phosphates [10, 11, 26] Jones detected salts of phosphoric acid in the urine in the form of the earthy phosphates containing either lime (calcium) or magnesia (magnesium) or in the form of alkaline phosphates containing soda (). He showed that the increased alka- FOOD URINE linity of the urine caused only the earthy phosphates to precip- 3. Henry Bence Jones's concept of theA "chemical circulation" in Fig. itate. From these observations he was able to dispel the health (left) and disease (right) [19]. then-current concept of a "phosphatic" or "earthy diathesis" by demonstrating that the precipitation of phosphates in the urine was a consequence of nothing other than the alkalescence albuminous or nitrogenous substances. The nature of the acidof the urine. Despite a lengthy search for diseases associated had yet to be determined but he reasoned that if acid is "setwith an increased amount of phosphate in the urine, he was free" from the blood, it must be separated from alkalies, that is,unable to find any other than acute inflammation of the brain "if one equivalent of is set free in theand delirium tremens [13]. In these latter conditions, when food stomach, one equivalent of soda must be set free in the blood.could be taken, the quantity of phosphates was normal but The greater the quantity of acid in the stomach the greater thewhen no food was ingested the quantity of phosphates in the quantity of alkali in the blood and the more alkaline must theurine was remarkably diminished. This is probably the earliest serum become." He demonstrated that the quantity of acid indescription of the ability of the kidney to conserve phosphorus the stomach rises when food is taken and falls as it empties. Induring a period of very low phosphorous intake. a reciprocal fashion, he noted that the acidity of the urine ebbed and flowed in a diurnal fashion; it was lowest (that is, most On the presence of sulphates in the urine [23, 26] alkaline) after meals, and attained its maximum acidity prior to the subsequent meal (Fig. 4). This description of the "alkaline What seems to be a perfectly obviously finding today bore tide" following meals not only represents an innovative exper-reporting by Jones in 1849, namely, that increased intake of iment in human physiology but was used by Jones to demon-food or sulphur in the form of medicines or sulphate of strate that a random measurement of urine acidity could not bemagnesia led to a marked increase in urinary sulphate excre- used as an indication of whether a patient required acid ortion. Furthermore, he was able to show that excessive muscular alkaline medicines, the acidity varying as it does with digestion.action which would occur in delirium tremens, acute chorea and He went on to demonstrate that animal foods caused a greateracute inflammation caused an increase in urine sulphate excre- outpouring of gastric acid than vegetable foods and that thetion, consistent with the notion that it was entering the blood alkaline tide is, consequently, more pronounced in meat eaters.following the breakdown of muscle. Excretion of uric acid (lithic acid) in the urine [7, 16] Effects of medicines on the acidity of the urine [53] Jones found that the quantity of urate of ammonia in the urine Jones found that ingestion of caustic potash (KOH) made the is also influenced to a minor extent by food intake and that theurine constantly alkaline but did not inhibit the variations in increase which follows a meal is independent of the nature ofurine acidity related to meals. In contrast, tartaric acid rendered the food. More importantly, he showed that acid urine morethe urine acid and, likewise, did not obscure diurnal changes in readily forms a deposit of urate than does alkalineacidity. Tartrate of potash was found to be the most effective urine. This important observation destroyed yet another dogmaalkalinizing agent. To compare the effects of fixed and volatile which prevailed at the time, that is, that the mere presence of aalkalies he compared the effects of tartrate of ammonia and precipitate of amorphous sediments in the urine indicates ancarbonate of ammonia on urine acidity and showed that neither excess production of uric acid. On the basis of his observations,of these compounds reduced the acidity of the urine. he suggested the use of alkalis to prevent or dissolve uric acid Whereas physicians had been examining urine for centuries crystals in the urine and the elimination of acids from the diet.in order to pronounce on the nature of diseases, Jones's He argued that precipitation of urate of ammonia is bestessential contribution was to show that an appreciation of prevented by increasing fluid intake or by administration of anormal physiology is critical to an understanding of changes in 1022 Fine:Bence Jones on urine composition

8REAKFAT HOUR DINNER HOUR BREAKFAST

Fig. 4. Diurinal variation of the acidity! alkalinity of urine and gastric Contents as measured by Henry Bence Jones [19]. urine composition. The fact that a variety of dietary manipula-urine and the bile together contain the component parts of the tions elicited major changes in the urine composition had achanged organs. major effect on the evolution of the concept of metabolic Sugar and amylon vanish like the fatt does by hunger. They balance. have served, likewise, for supporting the process of respiration and they hinder the quick changing of the existing organs. By A previously unpublished treatise on the urine composition of offering an oxydable material in some other new form to the carnivores and herbivores2 increasing action of the oxygen. They at least make it not to be The following section is taken from a manuscript written bya necessary condition of life as in carnivorous animals. In Henry Bence Jones and retains the spelling and sentenceTiedemann's and Gmelin's experiments, geese which were fed construction used by him: with albumen (where also foods free from nitrogen were alto- "Food which does not contain nitrogen, viz. fatt, sugar,gether excluded) died straight away by starvation. This is a amylon, beer, gum, wine, brandy, serve for supporting theproof that, in grass- and corn-feeding beasts, a resolution (that process of respiration for the production of animal heat. No partis, degradation—Author) of existing organs either does not or constituent of the animal body which partakes of life is free occur or ensues in a much smaller degree than in carnivorous from nitrogen. This is just the reverse of plants where all the sap contains nitrogenous material dissolved, but where it exists inanimals. no part of any organ except in the cells of the seed which The composition of the urine also shews this. The urine of perform a function similar to animals. carnivorous animals continually contains sulphuric acid and The fatt is in the animal body fluid, it is without form and canphosphoric acids combined with potash, soda or ammonia. We have no proper life. It can not be applied to the production ofknow exactly whence these two acids come. The fibrine and the any organ because the food containing nitrogen, in and of itself,albumin both contain sulphur and phosphorous. In the resolu- already contains all the constituents of the organs, with respecttion of their composition the sulphur is changed into sulphuric to their elements, in such a manner that nothing from without oracid by the taking up of oxygen and the phosphorous into from within is necessary to be added for the reproduction of thisphosphoric acid. Both pass out of the body united to bases. In organism. the urine of grass feeding animals these two acids are wanting or Amylon, sugar, beer and wine and ale, food not containingthey are observable therein only in very small quantity. If the nitrogen, are like fatt. They cannot be applied in the process ofresolution (that is, degradation—Author) of the muscular fibres nutrition to form structures. The experiments of Magendie onof the membranous and albuminous organs ensued just as the nourishing power of sugar and starch shewed sufficientlyquickly in the vegetable eaters as in flesh eaters, the urine must that animals solely supported on these, died exactly as bycontain the same principles. But here we find no phosphoric starvation. By hunger, the fatt just disappears. It does not passacid and in place of uric acid we find benzoic and hippuric acid in the excrements. It disappears in the form of carbonic acidand carbonate of soda. If also the metamorphosis of the existing and water. Hybernating animals are, before their torpidity,organs in these beasts proceeded in a similar way to what it loaded and covered with fatt. When they awake where, exceptdoes in flesh eating ones, so must we again find sulphur and the lungs, no other essential organ is in activity all the fatt ofphosphorous as sulphuric and phosphoric acids in the urine; but their body has disappeared. It has manifestly served for respi-both are wanting. Indeed it has been observed in many ill with ration for the production of animal heat during the long contin-urine flux that the urine contains hippuric acid. The same uance of its sleep. But, therefore, no nourishing of the bodyobservation has been made in children. In the organisms of the takes place. No part of the organism has increased in mass.carnivorous animal, that substance (that is, hippuric acid— They have, on the contrary, without compensation, suffered aAuthor) is produced from the substance of their organs which is metamorphosis. A secretion of bile and urine has taken placeapplied to the breathing process. And, if it is allowed that in without the evacuation besides of solid excrements. But theequal times a grass eating and carnivorous animal absorb equal quantities of oxygen, so must the nourishment of the grass feeder contain materials which are capable of changing them- 2SeeAppendix. selves into gall or a contribution which supplies its place, just Fine: Bence Jones on urine composition 1023

because their organs change themselves less rapidly and be-exertion in the horse signify the same as the inspiration of a cause their own bodies supply this in much smaller quantities.larger quantity of oxygen for when the activity of the organs of In certain diseases, as may be proved, the nourishment freerespiration is heightened, there is a quicker absorption of from nitrogen does not suffer this change which is indispensablyoxygen. One hence sees how, in other beasts, as in man, by necessary for respiration. In diabetes the amylon becomes nomeans of more oxygen the uric acid completely disappears further changed than into sugar and this sugar becomes re-when they take exercise but is present when they rest; exactly moved from the body without undergoing any change. It isin a similar way to what happens in the change of hippuric acid probable that in this disease there is a disturbance in theinto benzoic acid. In fact, if to hippuric acid 6 atoms of oxygen function of the liver which, after all, appears to be appointed forare added, it divides into carbonic acid, ammonia and benzoic the production of bile. It is probable that in this disease thisacid." organ plays a great part. The composition of this substance (that is, glucose—Author) is of much importance for the nourishment Henry Bence Jones's place among the early clinical chemists free from nitrogen both in men and in animals who are con- The rapid development of chemistry in the early nineteenth scious thereof. Sugar, gum, pectin contain hydrogen and oxy-century and the application of chemical principles to the study gen in the same proportions as in water. They may be consid-of living organisms gave rise to the development of analytical ered as compounds of and water and it is thus, by theirtechniques for studying biological tissues and fluids. Among the reception into the body, (that is, by means of the food free ofpioneers in the field were Antoine Francois Fourcroy (1755— nitrogen) that a certain quantity of carbon is introduced which1809) in France, Jöus Jakob Berzelius (1779—1848) in Sweden is not wanted for increasing the mass (that is, for the reproduc-and Justus Liebig (1803—1873) in Germany. In England the tion of their organs). This carbon disappears from the body asearliest clinical applications of chemistry were studied by carbonic acid. The urine of the horse contains one twenty-ninthAlexander Marcet (1770—1822) and (1785—1850). of the carbon of the food. The excrement contains only 1/3 butBased upon the work of these early investigators, the field of this 1/3 consists of undigested woody fiber. medical chemistry gradually entered the consciousness of the The process of nutrition in young animals (carnivorous) ismedical profession in England, led by the efforts of George different from the full grown condition. The milk of the carniv-Owen Rees (1813—1889) and (1814—1854) both of orous animals contains milk sugar even as the milk of other.Guy's Hospital, and Henry Bence Jones of St. George's Hos- This last contains carbon and water. It seems to make thepital. Both Rees and Bird carried on the tradition at Guy's Hospi- change of the existing organs in youth less quick. The meta-tal, analyzing biological material for the purpose of medical morphosis of the organs of the grass-eating animals assumes thediagnosis, a practice which had been established by Richard following form: if we add to five atoms of albumin of fibrin theBright (1789—1856) who developed the first medical wards elements of 22 atoms of water and four atoms of oxygen, whichdirected solely to the study of patients with renal diseases. is supplied, as we supposed, by respiration, we have all theWhereas Rees's work included studies on a wide variety of elements of excretion and secretion. biological materials, Bird directed a large part of his time to a 5 atoms of protein C240 H370 N70 055 study of urinary calculi with extensive use of the microscope to elucidate the nature of urinary deposits. Bird stood out as a Add 22 atoms of water H44 022 critical thinker and was not ready to accept Liebig's theories as and 4 atoms of oxygen 04 readily as his colleagues, and criticized Liebig' s approach of regrouping atoms to substitute the conversion of one substance we have C240H1N70081 This is equal to: to another [61]. Indeed he challenged Liebig's idea that uric 6 atoms of hippuric acid acid is converted to urea by pointing out that in anemia, the C108H66 N12030 ratio of uric acid to urea was decreased whereas in fevers it was 9 atoms of urea C18 H72 N36018 increased, the exact opposite of Liebig's contentions. 8 equivalents of ammonia H40 N16 and 3 atoms of choleic acid It is a pity that Henry Bence Jones did not share Golding C114H18N6033 Bird's critical stance towards Liebig's ideas, since he was the only true experimentalist among the early clinical chemists. C240 H1 N70 081 Whereas others were satisfied with straightforward chemical In the metamorphosis of the organs of the carnivorous animal,analysis in health and disease to arrive at presumptions about 5 atoms of gall arise from 5 atoms of their organs. From themechanism of disease, Jones was more of a physiologist and above it follows that only three atoms of gall arise from thechemist than a physician. He was among the earliest doctors to change in the organs of the grass feeder. One carbon which iselucidate human physiology by direct experimentation and his absent exists in the benzoic and hippuric acids which, in thepainstaking daily documentation of the data attests to his urine of carnivorous animals, are wanting. This substance,vigorous scientific training. Indeed, it is ironic that in the which is necessary for respiration is replaced by sugar, amylon,instance in which Jones conducted nothing more than an etc. and generally by the nourishment which does not containorganic analysis of a urine constituent from a patient with nitrogen. From the urine of horses we get in a wonderfulmultiple myeloma to discover the "Bence Jones protein," his manner, today hippuric acid, tomorrow benzoic acid, withoutplace in the annals of medical history was attained. In fact, his the state of health of the horse altering. If the beast rests andreal contribution was to demonstrate that urine composition in does no work, the urine contains hippuric acid; to the contrary,health and disease is not necessarily determined by a fixed by exertion and exercise benzoic acid is formed. But work and"diathesis" or a given disease state but by dietary factors which 1024 Fine:Bence Jones on urine composition lead to variations in excretion on an hourly or daily basis.their tissues. He considered that differences in the composition Where dietary patterns are fundamentally different on a long-of the urine must have derived from differences in the meta- term basis (as he discusses in the present treatise on herbivoresmorphosis of the tissues rather than from differences in diet per and carnivores), differences in urine composition can be antic-se. Liebig held the identical view. For instance in discussing the ipated. Although his explanations for such observations do notexistence of phosphoric and sulphuric acids in the urine of always hold up in the of present knowledge, his contribu-carnivores Liebig states: "We know perfectly the source of the tions in introducing "physiological thinking" to clinical medi-two latter acids. All the tissues with the exception of cellular cine was substantial. tissue and membrane contain phosphoric acid and sulphur, which latter element is converted into sulphuric acid by the Acknowledgment oxygen of the arterial blood—It is plain that they are derived from the metamorphosed tissues" [62]. Jones himself adhered The manuscript by Henry Bence Jones is reproduced with the permission of Mark Bence-Jones, a direct descendent of Henry Bence to this concept as late as 1850 and considered metabolites of Jones. food appearing directly in the urine, without prior assimilation into the structure of tissues, as being an abnormal circum- Reprint requests to Leon G. Fine, M.D., Division of Nephrology, stance. His later work must have altered this view, for in each Department of Medicine, Center for the Health Sciences, UCLAcase in which he examined the effects of a dietary change he School of Medicine, Los Angeles, Calkfornia 90024, USA. was able to show a change in urine composition within a relatively short period. It thus appears likely that the manu- Appendix. Details of the presently published manuscript script was written at an early stage of his scientific life. The manuscript written in the handwriting of Henry Bence Jones was recently found among his unpublished notes and Bibliography of Henry Bence Jones letters which were sold at auction. They are currently in the 1.JONES HB:On the presence of sulphur in cystic oxide, and an possession of the author. The section herein is part of a account of a cystic oxide calculus. Med Chir Soc Trans XXIII: four-page manuscript and is headed "#5." It is preceded by a 192—198, 1840 single paragraph (not included herein) which deals with uric 2. JONES HB: Zusammensetzung der stickstoffhaltigen Nahrungsmit- acid in the urine. It is followed by sections #6 and #7 (also not tel des Pflanzenreichs, des Albumins des Gehirns und des Eigelbs. Liebig, Anna! XL:65—69, 1841 included herein) which deal with the formation and breakdown 3. JONES HB: On gravel, calculus, and gout; chiefly and application of "fatt" and the fate of carbon in the food, respectively. of Professor Liebig's Physiology to the prevention and cure of A perusal of Liebig's book on Animal Chemistry [62] reveals these diseases. London, Taylor & Walton, 1842, pp. xii, 142, -16, 8 that most of the thoughts expressed by Jones in this manuscript 4. JONES HB: Remarks on the calculi in St. George's Hospital. Med Chir Soc Trans XXVI:100—lll, 1843 may be found in Liebig's writings, including some of the 5. JONES HB: On the sugar in diabetic blood. Med Chir Soc Trans specific examples used to explain the concepts. This being the XXVI:212—215, 1843 case, it is not unreasonable to assume that this may have been 6.JONESHB: On the decomposition of Salts of Ammonia at ordinary part of a series of lectures which Bence Jones gave shortly after temperatures. Phil Mag XXVI:234—237, 1845 his return from Giessen, possibly those which he delivered at 7. JONESHB:On the state in which the uric acid exists in the urine. Med Chir Soc Trans XXVII:l02—l18, 1844 the Middlesex Hospital in 1843. Could this manuscript simply 8. JONES HB: On the presence of oxalate of lime in the urine. Med contain the notes which he took from Liebig's lectures? This Chir Soc Trans XXVII: 146—161, 1844 appears to be unlikely for a number of reasons; the text is not 9. JONES HB: Microscopical pathology. On the deposits in albumin- written in a cursory or abbreviated form, and it is not clear that urious urine. Lond Med Gaz 1:270—272, 1845 10. JONES HB: Contributions to the chemistry of the urine: On the Liebig actually gave a course of lectures in Giessen since Bence variations in the alkaline and earthy phosphates in the healthy state, Jones does not mention such an activity in his autobiography and on the alkalescence of the urine from fixed alkalies. Phil Trans [57]. He does indicate, however, that he "took daily lessons Royal Soc London 335—350, 1845 from one of the professors in the University of Giessen in the11. JONES HB: Contributions to the chemistry of the urine: Part II. On early morning before the laboratory work began, and mentions the variations in the alkaline and earthy phosphates in disease. Phil Trans Royal Soc London 449—460, 1846 that he copied a paper, drawn up in English by one of his fellow12. JONES HB: Ueber das verschiedene Mengenverhaltniss der durch pupils, which contained some of Liebig's ideas on animal die Nieren auszuscheidenden Phosphoraure im Säuferwahnsinn physiology. However, the section which discusses diabetes und in der GehirmentzUndung. Lond Med Gaz 1847 mellitus appears to be one which a physician would include in13. JONES HB: Some instances of the contrast between Delirium tremens and inflammation of the brain, as regards the quantity of his lectures to medical students and is likely to be the work of phosphoric acid excreted by the kidneys. Med Chir Soc Trans Jones. Liebig was not a physician and did not discuss individual XXX:21—38, 1847 disease states in his book other than to provide an overview14. JONES HB: Papers on chemical Pathology; prefaced by the Gulsto- chapter entitled "Theory of disease" [62]. For the above nian Lectures, read at the Royal College of Physicians, 1846. reasons it seems likely that this manuscript was part of a lecture Lancet ii:32—35, 60—64, 88—92, 1847 15. JONES HB: On a new substance occurring in the urine of a patient series which Bence Jones had compiled himself. with "mollities ossium." Phil Trans Royal Soc London 55—62, 1848 It is also evident that it must have been written at an early16. JONES HB: Contributions to the chemistry of the urine: Paper III. stage in his career, prior to his experiments on the effects of diet Part 1. On the variations of the acidity of the urine in the state of on urine composition described above. It emerges that he health. Part 2. On the simultaneous variations of the amount of Uric Acid, and the acidity of the urine in the state of health, and on the considered the differences in urine composition between herbi- influence of sulphuric acid, sulphur and suiphates, on the amount of vores and carnivores not to be due to differences in their dietary sulphates in the urine. Phil Trans Royal Soc London 235—261, 1849 intakes but to differences in the intrinsic rate of breakdown of17. JONES HB: Appendix to a paper on the variations of the acidity of Fine: Bence Jones on urine composition 1025

the urine in a state of health. Phil Trans Royal Soc London 262—270, 40. JONES HB: On the simultaneous variations of Hippuric and Uric 1849 Acids in healthy Urine. Chem Soc J XV:80—88, 1862 18. JONES HB: On a case of albuminous and fatty urine. Med Chir Soc 41. JONES HB: On the composition of the amorphous deposit of Urates Trans XXXIII:313—342, 1850 in healthy Urine. Chem Soc J XV:201—213, 1862 19. JONES HB: On animal chemistry in its application to stomach and 42. JONES HB: On the production of Diabetes artificially in animals by renal diseases,London,J. Churchill, 1850, PP. 139. Serialized in the external use of cold. Roy Soc Proc XIII:537—540, 1864 Lancet i:69,l37,197,259,323, 1850, and ii:37,102,l63,225,287,349, 43. JONES HB: On the rapidity of the passage of crystalloid substances 375,1850 into the vascular and non-vascular textures of the body. Roy Soc 20. JONES HB: Extrait d'une lettre sur les modifications qu'éprouvent Proc XIV:63—64, 1865 les sels ammoniacaux en traversant l'économie animale. Paris,44. JONES HB: On the rate of passage of crystalloids into and out of the Comptes Rendus XXXI:898, 1851; Liebig, Annal LXXVIII:251— vascular and non-vascular textures of the body. Roy Soc Proc 252, 1851 XIV:220—223, 400—424, 1865 21. JONES HB: On Truth in Medicine. London, G.J. Palmer, 1850 45. JONES HB: Address to the Chemical Section of the British Associ- 22. JONES HB: Contributions to the chemistry of the urine: Paper IV. ation for the Advancement of Science. Brit Assoc Rep XXXVI: On the so-called chylous urine. Phil Trans Royal Soc London 28—33, 1866 6510—6600, 1850 46. JONES HB: On the chemical action of medicines. Brit Assoc Rep 23. JONES HB: Contributions to the chemistry of the urine: Paper III. XXXVI:38—40, 1866 Part 4. On the variations of the Sulphates and Phosphates in47. JONES HB: On the existence of the textures of animals of a Disease. Phil Trans Royal Soc London 661—668, 1850 fluorescent substance closely resembling quinine. Roy Inst Proc 24. JONES HB: Second appendix to a paper on the variations of the IV:564—572, 1866 acidity of the urine in the state of health. Phil Trans Royal Soc48. JONES HB: On the chemical circulation in the body. Roy Inst Proc London 669:676, 1850 IV:449—460, 1866 25. JONES HB: On the saliva and pancreatic juice. Med Times 2(n.s.): 49. JONES HB, DUPRE A: On a fluorescent substance resembling 579—582, 1851 quinine, in animals; and on the rate of passage of quinine into the 26. JONES HB: On the variations of the sulphates and phosphates vascular and non-vascular textures of the body. Roy Soc Proc exreted in acute Chrorea, Delirium Tremens, and Inflammation of XV:73—93, 1867 the Brain. Med Chir Soc Trans XXXIV:277—3 14, 1851 50. JONES HB: Lectures on some of the applications of chemistry and 27. JONES HB: Lectures on respiration and secretion given at the Royal mechanics to pathology and therapeutics. London, J. Churchill & Institution to the members of the pupils of St. George's Hospital. Sons, 1867, pp. 314 Med Times Gaz (newseries) 2:307,363,417,471,525,579,1851; Med 51. JONES HB: On the solubility of Xanthine (Uric oxide) in dilute Times (new series) 3:1,57,113,167,219,269,371,425,477,607,1851. hydrochloric acid. Chem Soc J VI:211—212, 1868 MedTimes Gaz4:5,101,309, 1852 52. JONES HB: Croonian lectures on matter and force. Given at the 28. JONES HB: Clinical Lecture given at St. Georges Hospital. Med Royal College of Physicians in 1868. viii.London,J. Churchill & Times Gaz (New series) 4:457—460, 1852 Sons, 1868, pp. 223 29. JONES HB: Sequel to a case of albuminous and fatty urine, 53.JONESHB: On the variations of the acidity of the urine that occurr published in the Transactions for 1850, with some account of two when vegetable and mineral acids are used. St George's Hosp Rep other cases of so-called chylous urine. Med Chir Soc Trans IV: 1869 XXXVI:79—98, 1853 54.JONESHB: Biography of . Proc Roy Soc Lond 30. JONES HB: On intermitting Diabetes, and on the Diabetes of Old XVII: l—68, 1869 Age. Med Chir Soc Trans XXXVI:403—432, 1853 55.JONESHB: The Life and Letters of Faraday. (2 vols.), London, 31. JONES HB: On the intensity and quantity of electric currents. Phil Longmans, Green & Co., 1870 Mag V:363—367, 1853 56. JONES HB: The Royal Institution: Its Founder and its Just Profes- 32. JONESHB:On the dissolution of Urinary Calculi in dilute saline sors. London, Longmans, Green & Co., 1871 fluids, at the temperature of the body, by the aid of electricity. Phil 57.JONESHB: Bence-Jones, H. An Autobiography with Elucidations TransRoyal Soc London 201—216, 1853; .Journde Pharm XXIV: at Later Dates. Edited by A.B. Bence-Jones, London, Gusha & 379—381, 1853; Paris, Soc Biol Mn V:9—1l, 1853 (Compt. Rend) Sons, 1929 33. JONES HB: On the acidity, sweetness, and strength of wine, beer, and spirits. Roy Soc Proc VI:378—380, 1853; Phil Mag VII: 143—145, Additional references 1854; Roy Inst Proc 1:381—393, 1851—54 34. JONES HB: Report on the accommodation in St. Pancreas Work- 58.COLEYNG: Henry Bence-Jones, M.D., F.R.S. (1813—1873). Notes house. London, G.E. Eyre & W. Spottiswoode, 1856 andRecords, Royal Society of London 28:31—56, 1973 35. JONES HB: On ventilation, and the means of determining its59. ROSENFELD L: Henry Bence-Jones (1813—1873): The best "chem- amount. Roy Inst Proc 11:236—245, 1854 ical doctor" in London. Clin Chem 33:1687—1692, 1987 36. JONES HB, DIcKINsON WH: Recherches sur l'effet produit sur Ia 60. ABBUTT C: St. George's Hospital Medical School. Address by Sir circulation par l'application prolongée d'eau froide aIasurface du Clifford Abbut. Lancet ii:781—785, 1922 corps de l'homme. Journ de Physiol 1:72—89, 1858 61. COLEY NG: The collateral sciences in the work of Golding Bird 37. JONES HB: On Sugar in the Urine. Chem Soc J XIV:22—42, 1862 (1814—1854). MedHist13:363—376, 1969 38. JONES HB: On the occurence of deposits of crystallized Phosphate 62. LIEBIG J: Animal chemistry or organic chemistry in its application of Lime in human Urine. Chem Soc J XV:8, 1862 to physiology and pathology. Edited from the author's manuscript 39. JoNES HB: On a deposit of crystallized Xanthin in human Urine. by William Gregory with additional notes and corrections by Dr. Chem Soc J XV:78—80, 1862 Gregory and others by John Webster, Cambridge, 1842