Document KGYnE01JBRkp6ZaYamV7RMvkw

I .. '1 jI I I I W Ii 1354 DECEMBER 23, 1967 B E F O R E O U R TIME MCet i.e., 1.26 lb. (570 9.) per child per week. If the rate of Before Our Time contamination was 1 p.p.m., a meal containing 100 g. of groundnuts would result in a dose of 0.1 mg. which would be 0.0025 mg. per kg. body-weight in a 40 kg. (88 lb.) SOME ASPECTS OF THE FIRST RECORDED child. The lethal dose ( L . D . ~ ~ i)n 50, of ducklings is 0.4 mg. per kg.; to attain this a 40 kg. child would need to eat 16 kg. of nuts, which is unthinkable. However, if the nuts contained 10 p.p.m. it would require little more than 2 weeks for a child to total an L.D.50 duckling dose. From the data presented here on the state of the nuts in relation to afiatoxin content (tables XI, 1x1, and IV) it would seem difficult for a level of contamination of 10 p.p.m. or more to escape unnoticed; many would discard groundnuts if there was an obvious growth of mould. However, at a level of 1 p.p.m. the fungal growth may not be sufficient to make it obvious to casual ".observation (fig. 1). At this concentration the description of the nuts was predominantly '' many with broken testa There is, however, a real danger that the mould may CASE OF MULTIPLE MYELOMA JOHN R. CLAMP .M.B., Ph.D. Brist., F.R.I.C. LECTUREO, UNIVERSITY DEPART.HENT OF MIDICISE, BRISTOL IN an important series of papers published between 1846 and 1850, John-Dalrympie,l Henry Bence Jones,'-' and W i l h m MacIntyre described all the essential feat& of the disease now known as multiple myeloma. These papers covered the clinical aspects of the disease, the properties of Bence'Jones protein, the posmortem h i ings, and the histological appearances, and left no doubt that the authors considered this a hitherto undescribed ".disease " essentially malignant in nature " affecting the '' osseous system grow on the nuts during a damp period followed by an WILLIAM MACINTYRE arrest in growth with a change in climate or storage William h4acIntyre was perhaps the most remarkable conditions. The nuts may then appear relatively free from member of this outstanding trio. He was, at the time he mould, although they may be dirty. This may well have saw the patient in 1845, 53 years of age and physician to been the case in sample 25 which was classified as in a fair the Metropolitan Convalescent Institution and to the condition, but had a high aflatoxin content. With t h i s last Western General Dispensary, St. Marylebone. On Friday, reservation, it is probable that groundnuts could be Oct. 30, 1845, he was called from his rooms at 84 Harley regularly eaten with an aflatoxin content of up to 1 p.p.m. Street, to see a patient who had been under the care of Whilst on the one hand it would take a considerable period Dr. Thomas Watson for several months. From the history of time for an L . D . ~do~ se to be consumed, it should also be and examination, iMacIntyre noted many important pointed out that no sample examined by us was free of clinical features of the disease, including the severe bone A. @us spores. It is difficult to predict the cumulative pains and could later assess the significance of the path- effect at such levels, particularly as the effect of aflatoxin ological fractures. Equally remarkable was the care with is so species-dependent. Insufficient is known about the which he observed the effect of heat on the urine. In view cumulative effects of low doses to reach a conclusion of the history of edema, one of his first acts when he saw regarding the implications to human hepatoma in Uganda the patient had been to carry out this examination. He except to say that if it does play a role it is most likely to thereby noted and later described all the important be intermittent and chronic. The probability of a toxic characteristics of the protein that subsequently and with dose being consumed at one meal is almost negligible, and little justice became known as Bence Jones protein. T h e at 1 p.p.m. it would require something like 6 months to ability of the precipitated protein to redissolve with a rise total such a toxic dose. in temperature of the urine, only to reprecipitate as the An analogy with currenr views on radiation hazards urine cooled, was clearly described. MacIntyre was also may provide some guidance to the situation. T h e maxi- aware of the other property of this protein-namely, its mum accepted safe cumulative dose throughout any given tendency to precipitate at temperatures considerably lower year is approximately lilOOth of a single lethal dose than those of other proteins. Thus, he noticed that the (Adrian Committee 1966). If the analogy is valid, it protein redissolved at the " coagulating point" of might provide a basis for considering the possible harmful albumin, namely, 160-170F (71-77"C)-the inference effects of aflatoxin in foodstuffs. being that the protein had precipitated at a temperame The obvious speed with which the aflatoxin can well below this. accumulate in groundnuts, given the right conditions, the Dr. Watson had evidently not examined the urine nature of cropping, length of storage, humidity, and rain- during the time that the patient had been under his care. fall in areas where the groundnuts are grown, recommends But he appears to have been present during the discovery a more detailed inquiry than was possible here. Further- of this unusual protein or else MacIntyre discussed his more, the report by Coady (1965) on the isolation of perplexing findings with him, since both physicians quite toxin-producing fungi from other food sources in Ethiopia indicates that attention should not be confined to groundnuts. We thank Dr. J. Nabney for supplying us with details of his method for estimation of aflatoxins before publication; the British Empire Cancer Campaign and the East African Medical Research Council for supporting this research; and Dr. Y. ,M. Clayton for assisting us with the identification of the species of fungi. Requests for reprints should be addressed to M. A. C., Nuffield Institute of Comparative Medicine, Zoological Society of London, N.W.l. REFERENCZS Adrian Committee (1966) Radiolcqicd HPurdr KO Patients: Final Report. H.M. Stationery Office. Allcroft, R.. CUn0gh.n. R E. A. (1963) Chem. Id. 50 (London). Rcfermces continued at foot of n u t Golumn 1. Ddrymplc, J . Dublin f. med. Sei. 1846, ii. 85. 2. Bence Jones, H. Lancet, 1847, ii, 88. 1. Bence Jones, H. Proc. R. SOC.1847, 5, 673. 4. Bence Jones, H. Phil. Trans. R . Sac. 1848, p. 55 3. MacIntvre. W. Med. Chit. Trans. 1850, 33, 211. ~~ MR. LOPEZ, DR. CRAWFORD: REFERENCES-conxinued Coady, A. 11965) Eihiop. med. f. 3, 173. Gmnbr, T.J. (1963) AMIW Land., 88, 214. de Iongh, K., Keunig, R. (1963) R ~ c lTrav. c h b . Pays-Ea E&. 82, 587. h n c e t (19621, ii. 494. Sabney, J., Snbirt, B. F. (1965) Anulysr, h d . W, 155. Ncsbitt, B. F.,O'Kelly,J., Sprgemt, K., Shcridm, A. (1%2) NOMI, Lorrd. 195,1062. Rutishauser, I. H. E., Dean, R. F. A., Burg-, H.J. L.(1962) E. Afr. md.7. 39.478. S a c & K.,Sheridan, A., O'Kclly. J.. Cunnghan. R. E. H.(1961) Nanm, Lond. ISZ, 1096. r /D ~ ~ E . U B E R23, 1967 B E F O R E O U R TIME THE LANCET 1355 &ependently sent a specimen of urine to Bence Jones. It myas customary then for the specialist services to be by practising physicians and surgeons, and Bence Jones had already established a reputation as a chemical pathdogist. BENCE JONES - 1 Henry Bence Jones, of 50 Lower Grosvrnor Street, was ,[chis time only 31 years of age and was physician to 51. George's Hospital. He was able to confirm .aacIntyre's findings and then proceeded to examine the &ary protein in some detail. His papers were therefore ;oncerned with the properties, analysis, and significance ,f this protein, whereas the paper by .MacIntyre dealt mainly with the clinical features of the disease. For this reason, Bence Jones became credited with the discovery of [he protein. Further confusion arose over the part played by Dr. Thomas Watson, since Bence Jones quotes the letter from Dr. Watson which accompanied the urine: The rube contains urine of very high specific gravity. When boiled it becomes highly opaque. On the addition ib& Of nitric acid it effervesces, assumes a reddish hue and ' 2 ., k ' becomes quite clear; but as it cools assumes the consistence and appearance which you see. Heat reliquefies it. What is i t ? " Nevertheless, the fact that the urine ,pecimens were sent on Saturday, Nov. 1, 1845-that is, the day after Dr. MacIntyre had been called in for consultation-supports MacIntyre's claim to the dis@very, and this is established by the statements made by Bence Jones in his papers. In the first he writes: " On the last day of October, a peculiar state of urine was discovered, through the carefulness of Dr. MacIntyre ", I and in the second,` " H e [Dr. MacIntyre] being in i artendance on the case with Dr. Watson, had two days previously first observed the peculiar reactions of the 1 urine." DALRY.MPLE .MacIntyre also described the postmortem examination carried out by Mr. Alexander Shaw, surgeon to the I Middlesex Hospital. The significant findings were in the bones, particularly the ribs and sternum, and the cervical, thoracic, and lumbar vertebrse. The affected bones were softened, fragile, and easily cut, with the interior replaced with a soft, `` gelatiniform ", blood-red substance. Some of this material taken from two of the lumbar venebrz and a rib was referred for histological examination to John Dalrymple, surgeon to the Royal Ophthalmic Hospital, Moodelds, and a member of the Microscopical Society. He described the nucleated cells which were present in great numbers and which formed the bulk of this gelatinifeffnmass. These cells were said to vary in size and shape but the majority were round or oval with the smaller cells " o n e and a half to twice larger than the awragc blood cell or blood disc " (red blood-cells). TABLE I-DETAILS OF PATIENT WITH .MULTIPLE .MYELOMA DESCRIBED BY WILLIAM .HAUNTYRT AND HENRY BEN= JONES - -. Name . _ Address . . Age at death Date ufdeath Occupation ._ .. ., .. .. Soci31 detads . . .. .. .. .. .. .. .MacInryrc ' .Mr.MLondon 45 Jan. 1, 1846 Tradesman Married early Numerous offspring " Holiday ~n Scotland '' Bence Jones-* ` No details. London. 45 47 ` Jan. 2, 1846. Tradesman Grocer ` wealthy. DaIrympIe also noted that the larger and more irregular cells frequently contained two and often three nuclei. These descriptions would be consistent with malignant plasma cells with some multinucleated forms. Dalrymple's paper was illustrated by two woodcuts which were credible drawings of these cells. Both Dalrymple and MacIntyre believed that this disorder was principally a malignant disease of bone. They were puzzled because the tumour had not extended outside the bone, and this they explained by the limited duration of life of the nucleated cells and therefore limited production of bulk by the tumour. THE PATIENT The identity of the patient has so far been unknown. It would also be interesting to know the cause of death that appeared on the death certificate of this first recorded case of multiple myeloma. In order to trace this case therefore, the personal details of the patient were taken from the various papers (table I). Unfortunately, the index of deaths for the tirst quarter of 1846 gives only the names in alphabetical order, the district of registration, and the volume and page number of the entry in the Register of Deaths. T h e initial step in the search was therefore to extract from the index the names beginning with M, of ail males who died in the London area. I n the fist quarter of 1846, of the 45,941 males who died in England and Wales, 7259 had names beginning with M, and of these 437 died in the London area, These names were then arranged according to volume and page number to facilitate the search of the Register of Deaths by officers of the General Register Office. The search instructions were to note all names of men aged 4 5 4 6 , or 47 years, who died on Jan. 1 or 2, 1846. T h e expected number of such men can be calculated. Thus, 437 names will represent all deaths from binh onwards, and from the figures in the Annual Report of the Registrar General for that year about 20 of these would be aged 45 to 49 years. Assuming that the death-rate is equal over this age-span, then only about 12 of these men would be aged 45, 46, or 47. These 12 men would have died over the period from Jan. 1 to March 31, and therefore no more than one of these can be expected to have died on Jan. 1 or Jan. 2. When and where died -. First of January ,, I846 at NO. 37 ; Dcvonshirc i Srrcct Name nnd Surname I Thomas Alexander McBun TABLE II-DET.~ILS OF DEATH CERTIFICATE Sex Agc ______- Male 45 Ye- Occupation Cause of dcath Grocer Atrophy from I Albuminurm Certified Signature. description and residence or informant Mary Davidaon present at death No. 22 Dcvonrhue Srreet When regutercd Eighth of January 1846 I ` Signature 1 of Renstnr i j williun I CRebgupvar i I! I: 1356 DECEMBER 23, 1967 R O U N D THE W O R L D - - V E R Y S P E C I A L ARTICLES f The search agreed with this prediction, since only one man was found who fulfilled all the particulars and this person must therefore be the patient seen by Watson, MacIntyre, and Bence Jones (table 11). It is gratifying to find that the death certificate is consistent with the known personal details, including the holiday in Scotland! Not unexpectedly, the details of the patient given in MacIntyre's paper are correct, in contrast to some of the ".details given by Bence Jones. The cause of death is given as " atrophy from albuminuria This was a reasonable diagnosis, since the term albuminuria was used in those days quite non-specifically to mean proteinuria. Alter- ".natively, the cause of death might have been given as `` McBean's disease with MacIntyre's proteinuria I should like to thank the officers of the General Register Office for their kind cooperation. Round the World ~~ U.S.A. The growth of the Citizens League Against the Sonic Boom, based in Cambridge, Massachusetts, has been suiking. Founded only nine months ago (March 9,1967) by nine charter members, it has today over 2000 members from the U.S.A., Canada, the United Kingdom, and Sweden. The director, Dr. W. A. Shurcliff, is a physicist at Harvard University, and the deputy director, Prof. J. T. Edsall, is a biochemist, also at Harvard. The League includes many other eminent professional men- aeronautical and acoustical engineers, biologists, doctom, lawyers, economists, architects, teachers, and musicians. The League takes up no position about military planes and their sonic booms, but vigorously opposes the development of commercial-i.e., civilian-supersonic transport planes (s.s.r.s). Using facts gleaned from deep within Government reporn on sonic-boom tests, and some wrung from the U.S. Federal AviationAdministration (monolithicallyfor thes.s.~.)the League has prepared an impressive array of moderately written fact- sheets, recording firm evidence that sonic booms of intensiry 1 Ib. p a sq. ft. are intolerable-both to people and to prop- ".- a n d concluding that the 2 Ib. per sq. ft. booms predicted for the s.s.r.s would be ``doubly intolerable The League has moved fast. It has collected a library of technical reports and clippings about sonic booms, drafted and published advertisements in many magazines and newspapen, including several half-page advertisements in the Ncco York T i m , and raised more than $20,000 through voluntary contributions. It has created a national committee; it has taken part in many TV and radio programmes; it is in touch with conservation groups in several countries, including the Anti-Concorde Project (give or take an e) in the United \ Kingdom. I The response has been enormous. Before March, 1967, only a few people had spoken out against the boom; noteworthy among these was Bo Lundberg, then director general of the Aeronautical Research Institute of Sweden. Since iMarch, more than 900 newspaper articles and 40 magazine articles against it "--+we been published in the U.S.A.Nearly every major news- paper has carried an article expressing alarm that Governments propose to subsidise the construction of a machine that, while saving a little time for an elite few and perhaps yielding a small profit for aviation, will destroy the peace and quiet of millions of people. The League says that its educational campaign is to be intensified until the Governments are forced to admit that the sonic boom is more than a small defect in the S.S.T. programme, more than a mere annoyance, but is an outrage to civilised living. The League is not satisfied with Government pro- testations that, at the start at least, the S.S.T.~would be operated only over oceans; it is convinced that, once loosed on the world, they will encroach on assured quiet until uninterrupted sleep will become a historical curiosity. Very Speaal Article ._. .-L I 1- " Well ",said the Boatman, " So Ye've Wakened up ~<, .*x.r.?.;; `` Yes ", I said, ``where am I ? " " In a boat ",said he. `` ~." Thanks I don't ", I said, " I rightly know "c,aannsseweetrheadt.thWe Bhoaw-t bar " Do you mean to tell me that you sit -*craft, and by the look of YOU, have been doing so for tim``eT, haantd'sdwonh'attkInosawidw"h,ehree we are replied. ? " 'bpi " D o you perhaps know where we are I asked, with a touch of sarcasm. " No ",he said. "But . . ." I began. ?. "Look, young feller", he answered, "wh= a-sleepin' in the bilges there, 1 thought ye'd a sensible lad wot I could have a sensible talk e&. .I rl like all the rest of 'em, askin' a mort 0' qucstiom knows answers to. I give up askin` questioas hatched, an' I only asked one then." ``What was that ? " per rr, " Same as yew, young man. When the o m a a01' boot, he say to me, ` George ',he say, ` I'm &my give yew this leaky old craft ter be master of, but Q see, I've nothin' else '. ` Where do I steer for ? ' lo cl L give me a queer ole look an' a wink, an' then SQ he, steer afore yer somewhere '. own nose, I could see bor, an' some day happen pcall he wuz a Suffolker, lite me, Y) t wam't no use pesterin' him with talk an' qucstim, I me mouth shut. ` Dew yew keep 'er afloat, an'into & bor ', sez he, ` an' yew'll find yer time well occupied *, m* that he went off, slow-like up the hard, an' I hipr since." ``There seem to be lots of people on board ",I ~ d . " Toomany. The cussedest lot yew ever did see. WhQ ain't fightin'each other an' lightin' fires fit to burn baDprp out of her, they're arguia' about wot none of 'em&% stand. See that lot up in the bo- there ") he said, becoming more communicative, " clever di& if ever any. Always shoutin' back that they can see ligha or lmd Q summat, and tellin' me how to run this ship. If it ain't it's them others to port and starboard-difEercnt c o k and talk, but the same ideas, more or la$. W m 'em emy job better `a I do, and jumpin' about SO'S yew an% 'er on an even keel. All the same, I'd rather 'a= them chis bunch in the starn, moanin' an' gripin' an' sayin' sinkin'-mt but wot we aren't, 'alf the time. But we h`t done it yet ",he finished with a note of triumph. " Where are you from ? " I asked. `` I'm out of Lowestoft ",he said, " an' if ever I get kdq you'll not find me at sea again, once I get this cargo of -1 ashore. Gawd knows wot the owner wants `em for." `` When " More are we bloody supposed questions "to, arrive ? " I he replied. asked. " I've been a' this ole bitch of a boot some thousands of years now, young feller, an' I don't know when we're goin' to get into port, 00 more than when we started." " What do you suppose I should do ? " I asked him, rather diffidently. ``Yew do what yew please, young feller ",he said. " I'VC got to steer this 01' boot till I get callouseson me backside, but yew please yourself. Some write books about the journey, some read 'em, some fight, or preach, or talk politics, or go who*'. *Not many get near an idea of wot the trip's about, an' they`re usually the quiet sort wot 'ear songs in the wind a' *somethin' lovely in a gull's wing." " Perhaps I could do something, as well as listen 00 wind ",I said, but the Boatman was gazing into the &t did not answer. And that is roughly how I came to be a surgeon. .. .j