1524 ] RADWUM AND ITS, THERAPEUTIC EFFECTS. [DEC. 12, 1903.

with a velocity of about 20,CCO miles a second. These rayshave but little penetrative power.The $ rays appear to resemble the cathode rays of a Crookes's

tube ; they are negatively charged, more penetrative tlhan thea rays, and consist of particles of about 1he one-thousandth ofthe miass of a hydrogen atoml. They are powerfully actinic. -

The y rays are the most penetrative of. all,'and evidentlyresemble tlle Roentgen rays from a hard tube.Not content with manufacturing this extraordinary emana-

tion and with emitting three kinds of rays, radium appearsto have a hand in the genesis of the but recently discoveredgas helium, so that we have the antithesis of a gas of ab-solutely negative properties being produced by a substance ofaltogetlier extraordinary properties.AMadame Curie has measured the atomic weight of radium,

which is 225 ; that of thorium is 232 ; it would be placed inMendelejeff's table in the group of the alkaline earths.Attempts have already been made by various observers to

use the wonderful properties of radium in practical mediciine.It has been suggested by Mr. Soddy that consumptive patientsshould inhale the emanation so as to bring the powerful agentinto as close contact as possible with the diseased lung. Afew milligrams of radium bromide might be placed inwater in a suitable inlialer, and the emanation drawn into thelungs with a deep breath; what effect if any this treatmentmight produce is not yet known, but astrongword of warningto patients not to attempt such a remedy without previousmedical sanction may not be out of place. Owing to theproperty the emanation has of imparting radio-activity, theeffect of the inhalation would probably continue for a con-siderable time, for the walls of the air passageo would for thetime become radio-active themsplves.Experiments have been made by Pfeiffer and Friedberger on

the bactericidal action of radium rays; the micro-organism ofcholera, of typhoid fever, and of woolsorters' disease weredestroyed by a three days' exposure to 25 mg. of radiumbromide placed in close proximity. This result is not veryencouraging, still it must be remembered that the Roentgenrays have no bactercidal effect, thouglh their beneficial effectsin certain diseases cannot be doubted.Though tlle micro-organisms of certain diseases are not very

susceptible to radium rays, thl human tissues are. It is un-safe to carry radium about in one's pocket; several cases areon record of an inflamnmation and ulceration of the skin fol-l9wing sucl a proeedure; even the carrying of it in a glasstube from one patient to another may set up an inflammationsimilar to that induced bv an improper use of the Roentgenrays, and any ulcer formed is highly intractable and may lastfor weeks or months.E. S. London tested the effects of the rays onI mice. Red-

dening of the ears and blinking of the eyes appeared on thethird day; general torpor and paralysis followecl, with death,on the fourtlh or fiftlh day; the skin and brain were the partsmost affected. London has also discovered that pelsons whoare almost blincd can perceive light when radium is broughtnear, and that people with perception of light, but not ofform, can detect the shape of objects which are in the neigh-bourhood of the screen. He thinks that there may be in thisa possibility of teachling such blind people to write or draw.Persons who are totally blind are unaffected by radium. Theposition of the radium can, he reports, be detected witlcovered eyes. and even when the box is held behindl the head.I regret I have not been successful in repeating the latter ex-periment, possibly because the fragment of radiumi that Ipossess is too miinute.The chief physiological effects of radium. so far as at

present investigated, can be arranged in three groups:I. Effects on the skin producing inflammations and ulcers.2. Effects on the niervous system producing paralysis and death.3. Luminous effects produced in the partially blind.The radiations of radium have been trie(l in various

diseases, prinCiipally those in which the Roentgen raysand Finseni light have been found useful, and inmany cases dlistinct benefit has resulted. .The effects pro-duced appear to be similar to those produced by the Roentgenrays. At present the prohibitive cost of radium precludesits more frequent trial. Should it become possibleto obtain it in larger quantities, we may speculate on the usesto which it may be put. In practical medicine it would doaway with our bulky and costly .-ray installations; patientswould instead be provided with a fragment of radium sealedin a tube which they would themselves apply as directed tothe affected part. Vadiographs of the teetlh or bony walls ofcavities could be, taken by introducing a fragment of radium

and placing the negative outside. A few grams of radiumwould light up an *-ray screen brilliantly through an inch ormore of lead, and this it would continue to do for perhaps a.thousand years; thus we should have a perpetual source oflight and heat. An objection toits usewould be tlat the leadwould have to be enclosed in running water to prevent it fromfusing; another objection would be that it would be quiteunsafe to go near it unless one were completely clothed inleaden armour, otherwise one would run the risk of havingone's skin destroyed and one's nervous systeml paralysed.Could this slight difficulty be overcome the reign of coal andsmoke would be over; a small receptacle of radium in a housewould both warm it by day and light it with a soft diffusedlight by night; a sufficient block placed in the furnace cham-ber of an Atlantic liner would drive it backwards and for-wards for generations across the ocean.Our knowledge of Nature's seerets is ever advancing, and

for those who wish to join, and there cannot be too many ofthem, in the investigation of suC}1 enthralling subjects asthese new elements, muclh help and encouragement isafforded by this ouir Royal Scottish Society of Arts.

RADIU1 AND ITS THERAPEUTIC EFFECTS.By JOHN MACINTYIE, M.B., F.R.S.E., F.R.M.S., M.I.E.E.,Surgeon for D)iseases of the Nose and Throat, and Consulting Medical

Electrician. (aasgowv Royal In-firimaary; Lecturi-er on Diseasesof the Nose and Throat, Anderson's Collegc

Medical Scllool.

ANY statement made at present about the therapeutic effectsof radium can only apply to the experimental stage of in-quiry. Three questions, at least, maybe asked, however, andthese are: (I) Have the salts of radium any therapeuticvalue ? (2) In what class of diseases are they likely to prove,useful? (3) How do any results yet recorded promise whencompared with those obtained from othler agents. suclh as theFinsen light, .r rays, or high-frequency currents because thephenomena observed, when studying the salts of radium,suggest at once the possibility of therapeutic action similarto that due to the last-nameed forces:> It may at once besaid, from the experiments already published, that. to someextent. they possess tlherapeutic value, andt, for the mostpart, as yet in the same class of cases in whiclh the otherforees have already been tried with success. The third ques-tion is more difficult to answver, for reasonis which will appearin this paper.

It may be as well also to state here that. just as in the caseof all other branches of electro-therapeutics, we have not yetany record of great improvement or cure in any case of seriousmalignant disease situated deeply in the tissues or within thegreat cavities of the body. Any records of results so farobtained have been in the superficial parts or within theaccessible cavities. It has been suggested that small quanti-ties of radium might be introduced into the deep tissues illserious malignant diseases, and left there, but most surgeonsafter studying the properties of radium will meantime becareful in carrying out the suggestion, and take due precau-tion that the active agenit canl be withdrawn agrain if required.Be that as it may no results so far of such a sugestion havebeen fruitful.

Pr operties of ]?adi/fai21.During tVe past six months we have learned much from the

physical laboratory about the properties of radium whichhave a distinct bearing upon surgical work. To begin with,the one important thing wheni experimenting with a newagent is to find out its nature and strengtlh. At first, whenthe radium salts were obtained, many concluded that all thatwas required was what the miiakers termed a chemically puresalt of the element, if elemiieint it be. This is not so, becausethe salts which axe offered to tlle surgeon vary very much inwhalt is to them the most vital thing-namely, radio-activity.Apart altogether from-i its enormous cost, the experimentershave the greatest difficulty in obtaining suitable specimens.A considerable number of medical men and others have sub-mitted samples of brom--ide of radium to me for an opinion,and I am bound to say many of themni were doiibtfully of anytherapeutic value. It would be of the greatest value to theprofession if some standard measurement could be obtained,because once in possession of this fact experimenterscould regulate the dosage by the distance from which theyheld the salt from-l the part, and the tiine during which it wasapplied.Unfortunately no such standard is easily available, and w6e

D- c I2 10. AIMADISTEAETCEFCS xL-~12

lhave to fall back upon the foll'owing: (a) The physiologicaleffects' when applied to the tissues of a normal subjectwhich involve discomfort and risk; (b) the action uponphotographic plates; (c) the fluorescence upon a suitablescreen; (d) the power to dischaxge the electroscope. Someexperimenters like Mr. Soddy have methods of their own bymeans of liquid, but these are complicated. In any caseevery experimenter should not only ask for chemical purityof the salt, but also for some guarantee of radio-activity, andhe will find all sorts of figures mentioned, from 40 units(uranium being the unit) to i.,8oo,ooo units of radio-activity.A further test, of course, may be had when once the surgeonhas obtained results in a case, because he can compare onewith another.The second important question is to be found in the fact

that the emanations are not all of the same kind. Since mylast commutnieation to the BRITISH MEDICAL JOUIRNAL (June6th) we have learned much from the physicists about therays whiclh emanate from radium, owing largely to thebrilliant researches of M. Curie, Professor Rutherford, SirWilliam Ramsay, Mr. Frederick hioddy, and others. In thepaper referred to it was suggested that the physicists dividedthe rays into three kinds, called respectively a, 0, y rays, andit was understood that the a rays are new, whilst the secondset resemble tlle cathode rays, or what Lenard first described,and the third set correspond to .' rays. Some doubt has beenthrown upon the last named, and various workers have ex-pressed different opinions on the subject. Lord Kelvini statesthat the experimenters believe the a rays to be positivelyelectrified bodies larger than those constituting thesecond' set. They are easily stopped by solids, liquids, orgases and they are acted upon by a magnet. The a rays aremuch smaller and are probably atoms of radium or perhapsmolecules of bromide of radium, negatively electrified, easilyinfluenced by the magnet and corresponding possibly to thecorpuscles aiid electrons or the fine particles of matter whichmake up the cathode stream in the Crookes's tube, LordKelvin goes on to say a simple prima-facie view is to regardthe third set as merely vapour of radium. These rays areneutral and are not acted upon by the maglnet. In support ofthis view the Honourable R. G. Strutt comes to the conclusion,as the resiult of experiment, that in some ways the 'y raysbellave differently f-om the Roentgeni rays. Clearly, therefore,it is important that surgeonls should discover which of theserays may be the active agents.Inasmuchi as frequently the salts are applied througlh mica,paper, glass, or aluminium screens it is difficult to conceivehiow these can affect the tissues. This reduces the questionto the other two. While there is some doubt as to the thirdset and will be unitil more is knowni about them, it is naturalto think that tlhe / rays have more to do with the results.This view is further strengthened by the fact that even if the-y rays were proved to be x rays, they are so small in quanititythat, knowingof what we do of the results of the powerful x-raytube, it is (lifflcult to see how they can produce the result. Ifwe accept this view of the question theni the $ rays are pro-bably the powerful agents upon the tissues. In a communi-cation to me Sir Oliver Lodge is inclined to accept this view,of course with all reservation in the present state of ourknowledge. In any case the subject is of importance andfurther experiments are necessary.

WNrhat we do know, however, at present, is that the B raysare more penetrative than the a rays and that the y rays arestill more so. It does not, however, necessarily follow, fromwlhat has beeni said that the a or 'y rays will not be proved tobe of thei'apeutic value. On the contrary, many think theymay be, and Mr. Soddy in the pages of this JOURNAL suggestedinhalations of the a rays in respiratory troubles, and hlis ideawas based upon physical research and their bactericidalproperties.As I have said, from the fact that radium is usually applied

througll screens when treating neoplasms the a rays canscarcely reach them, and, therefore, wlhatever results havebeen obtained in these aflection-s are not the result of theirapplication. It remains to be seen, however, whetler theywill have ani effect wheni applied differently. For this reasonsome experimenters are having salts of radium applied onpaper, like a plaster, but of course in this case the tissues aresubjected to all three emanations. Sir William Rtamsay andMfr. Soddy have shown that the a emllanation is a gas and thatthis contains lhelium. which itself is one of the most inertsubstances known. The spectrum of it is not got at firstfromthe a rays, but it subsequently appears. This lhas led to theview that radium is not ail elemenlt at all, and that it is being

'I

split up into simpler elements. This involves another ques-tion that secondary or more changes are taking place and thatnecessarily forces are liberated. What effect these may haveupon norm-ial or diseased tissues when applied to them cannotbe stated at present. Anotlher important phenomenoln as a re-sult of the emanations is the powver of fluorescence whichthese rays possess and also the most extraordinary thing yetrecorded of radium, namely, its power of constantly giving offheat. The possibilities of all these tllings must be thought ofwhen we are trying to i-eason out the effects of the agent uponidiseased tissues, also tllat they are, wlhen in sufficient quan-tity, destructive to life. At present, how^evcr, notlhing deti-nite can stated.

Resilts.It is exceedingly difficult to obtain defilnite statements as

to cures after the application of radium from alny papers yetpublished. There are many accounts of experiments, butonly a few references to cures, and as I have already said, anysuccess recorded seems to have been in lupus, rodent ulcer,and superficial lesions of the skin or within accessible cavi-ties. A case of malignant disease of the palate and lip wastreated in the clinic of the late Professor Gussenbauer. Thepatient was aged 6i, and had been sepeatedly operated on forwhat is termed cancer of the palate and lip with no benefit.The parts were exposed to the rays of bromide ofradium, and the case, whieh was reported to the VienneseImperial Academy of Science, responded to the treatment,the tumour gradually and completely disappearing. Fromthe same source thp cure of a case of melano-sarcoma wasreported. Drs. Goldberg and London, of St. Petersburg, havepublished a preliminary paper upon thle results of the appli-cation of the Becquerel rays in skin affeetions. The physio-logical effects were first of all studied by applying the raysfrom radium to the skin of normal subjects. Two cases ofrodent ulcer are recorded in thecommnuinication, one a patient,a man aged 58, and who had suffered from the disease for tenyears; and another aged 48, who lhad been ill for eight years.The results in both cases were satisfactory. After mention-ing the advantages of such an agent over other more compli-cated methods, they conclude that undoubtedly in radium wehave a new and energetic therapeutic agent.

(ases of rodent ulcer have also been referred to in the laypapers in tllis counitry, but on application to the surgeons incharge of the departmelnt of the hospital where the patientswere treated, I find notlhing lhas bepn publislhed in the profes-sional journals. Ilnquiry as to what lhas been done abroadwith radlium elicits the samiie evidence of puil-ey experimentalwork. Tlhus one friend of mine, at nmy reluest, describedwhat lie ha(d seen at the Paris lhospitals two moniths ago. Hereports simply a number of nien miiaking- experimiients indifferent affections, who were exceedingly reticent wlheniasked about improvement or cuire, particularly when tllequestion was put with reference to malignant disease. Dr.I)arier, of Paris, has made two commiiulnications to theAcad('mie des Sciences during the last month, and I havealso had reports of much the same kiid(l by a visitor duriingthe autumn to Breslau, where improveement and decidedtherapeutic action wverp seen in smiall lesions or small parts ofthe lesions in skii aftfections. Dr'. Delsaux has been tryingthis agent in lupus of the larynix, anld reports favoutrably uponits use. He quotes the early work of WValkoff an(d Giesel,also that of 1)anlos, an(l also referq rea(ers to the papers ofHallopeau anid Gadaud, Carez, Oudin. IBlandamiour, Tremo-li&-res, l)anysz [and Bohn. Dr. M. A-V. Cleaves reports severalcases treated vitlh radium, anld says : " The fact that radiumemits rays of a greater penetrating, power and of a hliglher-ibration than the cathode rays-that is, the*'y rays, taken inconnexion witlh the change in appearance ant relief obtainedlin tile writer's case of sarcoma and thle cure of the casesreporte(l, stimulates the hope that in radium a therapeuticmeasure of value over anid above thle x rays is atcommand.."In my last comI1munication to the BRITISH rMEDICAL JOUIRNAL

I stated that I ha(l convinced myself, fr omii the application ofthe l ays of bromide of radiu in to small patchles of lupus androdent ulcer, that somle at least, if not all. the rays eoimiingfrom the salts lhad a therapeutic effect. AVith a -iew o)f tryingthe agenit still further I seleeted antlher case. o)ne o)f epi-thelioma of the nose. Thle selection of a ca.se is by no meansan easy matter. It mnust always be rememibe-red that inmalignant disease it is right that the,patient slhould havethe benefit of what sulgical scielice has shi4vwn t{l be the mostspeedy and efficacious way of dealing with the diisease. Takethe case of imialignant disease of the laryn7iix, which is a good

D*p. '12, .1"3.1 RADIUill AND -ITS THERIPEUTIC EFFECTS. I'mm B.[Kmzon ;OVRX&l 1525

1526 ST, B$- I] THE TREATMENT OF CANCER. [DEC 12, 1903.

examiple of what I am stating. After the brilliant resultsrecorded by Sir Felix Seolon at last year's meeting of theLaryngological Section of the British Medical Associationfroii thyrotomy very few surgeons in this country, however-well aequainted they may be with the results obtained fromany of the newer methods, would hesitate to urge his patientto undergo immiiediate operation in the hope of saving themuch miiore serious and dangerous o)peration of laryngectomy.h-lence it comes that miiost of the cases at present selected fortreatmiient by- X rays. radium, or such agents are considerediinoperable, and, thanks to early diagnosis and the numiiber ofmen nowadays skilled in the use of the laryngoscope, these-re few in number. The case which I ani about to recordwvas sent to me for treatmiient, and after carefully explainingimiatters to the patient the selection of the agent was leftto me.One reason for selecting this case was the fact that it was

taking a step fartlher than in applying it in ordinary ulcerat-ing rodent ulcer. The feature of this case was the local in-duration as well as ulceration. I had no (loubt, however, aswas proved afterwards, that by rays the mass could beb)roken down and improved. The diagnosis clinically andmnicroscopically was epithelioma. The patient was a managed 78. Its history was that it began as a wart thirteenyears before. After four or five years increased, but still slowgrowth took place, but one year ago signs appeared of rapid.development. The ulcerated parts indicated the seat of theold wart. The skin was afected externally, and the newgrowtlh extended tlhroughout the whole lengtlh of tlle ala. Itwas irregular in slhape and mor-e prominent anteriorly. Fortlhe most part the skin was unbroken, but there was an ulcerabout -1 in. in diameter on the point of the nose. The diseaseextended to thle septumi and passed inside the vestibule to a

_ - ,'~~~~I

Epitheliorn;iO 10OS': A. vonditi) i bec;o ve treatmient. un iteied Jyrladiumt bromimdo condaitiou it pimetent ufter x-i-ay treatnment.

distance of more than In so that tIme mucous membranewvas involved, particula-rly on the outer wall near to the in-ferior turbinated body. Tle specimen of indium appliedweighed io mg. It was of great radio-activity, and had pro-du1eda distinct-burn oi the normal skin of the body whichlasted for monthis. ailthough it had only been applied for onehiouir and thiroughi a plate of mica. Nevertheless, the factthat it was applied tirst, at a distance to thle patient and theniearer and near-er until it was practically resting on the skin;thlat some of the sittings gra(lually increased in duration wereover forty-five minutes ; aiidi that thiirty-nine applications ofm-dumlbromide failed to prodluce the slightest change as far asITcould detect, it was unfair to submit the patient to furthiertrial, and a: rays were commenced. Aks hiad been anticipated,thie hiard matter very speedily began to break down. An im-pro)vemnent was distinctly seen within a week. The applica-tionof thexrays was given at first daily and then at intervals.I-n all thlirty-seven applications were giv-en and in fiveweeks the treatmenmt was stopped. The progress continue-dsteadily without treatment for one month afterwards, and thepar-ts iniside, andi outside are now niearly well. In the firstphiotograph the lesioni is seca before any treatment was

applied, and the second shows its condition at the presentday.One's first conclusion about the failure of radium to do

anything in this case might be that the a rays are superior tothe emanations of radium; doubtless in this case they were.but the question arises Is it not one of degree? Had Ihad salts of greater radio-activity and a greater quantity ofthem, or had we been able to apply them longer, the resultmiight have been different. The results in rodent ulcer leadone to suppose that this mlight be the case, and this leads meto another point which has often struck me when treatingsuch1 diseases as rodent ulcer and epithelioma with any ofthese new agents, namely, apart fromii the class of disease,the patient's idiosyncrasies, and many other circumstances,there would seem to be a difference in response to treatmentaccording to the state of the lesion at the time the agent isapplied. When the parts are ulcerating or fungating, both ofwhiclh conditions may in a sense be looked upon as the resultsof attemipts on the part of the tissues to cast out disease, oneseems often to get the quickest and afterwards a good result.Of course it has to be reiiembered in this connexion that asa rule the cases one gets for treatment are inoperable, andmost of them are exactly in these conditions. Our experienceof superficial tumours where the skin is unbroken is morelimited so far.

I lhave noticed the effect of the breaking down of the tis-sues in more than one case of epithelioma when being treatedwitlh radium. At present I have a serious case of epitheliomaof the fauces and tongue under treatment. The patient wassent to me as quite inoperable, the lesion )eing far too oldand extensive. A large proliferating mass had a projectingpart the size of a small nut, which was steadily growing, muclhto the inconvenience of the patient in swallowing, and itseems to have been arrested and is now breaking down. Ihave also observed the same thing in another case of epithe-liomnla of the fauces at present ulnder observation.

Ire trying to answer the questions raised at the beginningof this paper, from wlhat I recorded in my previous communi-cation published in the BRITISH MEDICAL JOURNAL in .1 une ofthis year, and all I have since learned, it is exident that thesalts of radium have a therapeutic effect. These results, inmy experience, have been in lu-pus and rodenit ulcer, for thenost part as yet in limited lesions, and where the agent couldbe applied directly to the affected part. The indicationswould point further to its being useful in the same class ofaffections as are at presenit beincr treated witlh the v rays,Finseni light, or hiiglh-frequency currents. Thirdly, that theexperiments, so far, do not justify comparison between thesalt of radium and other agents; and, lastly, tllat what iswan-ted at present is further investigation into the physio-logical and other properties of the different radiuii salts. lnpursuance of this I have tried to get salts of greater radio-activity and in muich larger quantity. buit no matker has been,so far, able to satisfy me upon the tests which I asked for, orto supply me with sufficient quantity.

REFERENCES TO TIHERAPEUTICS.Walkoff, Photographiselhe Runidschoat, October, i9oo. Giesel, (3eselscl,.

T. xXXiii, 'p. 3s96 et NVatfe,forschernlung, Munclien, 1899. Gusseu-banier, case slhown to the Aiennese Iimip. Acad. of Science, 1903.Goldberg and London, St. Pletersb. gnedicin-chirargisclhen Gesselschaft, AprilI7th, i903. Barier, Paris icacludnie de Science. 1903. Deisanix, La PresseOto-Larymnqololique, Belge. No. 8, 1903. Cleaves, Adrlanced Therapeattics,November, I903. Daulos, .innales de Dermlatol. ct SVphiligr., 902, IPP. 156.490. 620, 723. ilallopeau andl (;adanid, ibid., 1902, p. 720. Carez. Annalesde 1'VElectroth6rapie, Jauuary, 1902. Ondin, AnnaUes (le Dermatol. et Syphiligr.,.J]ly -3d, 1902. Blandamour. Thlse del Paris, Novemiiber 26tl, I902.Trnlmol,'-res, Presse M('dicale, Deceacber ,i;th. i902. Danysz, Acad. de.S`ciences, Febluary i6t1, 1903; Presse AUdicale. February 25th1. 1903. Bolin,1clad. des Sciences, May 4tll, 1903; Pres.se M(dicale, May 13111, I903.

ON THE TREATMENT OF CANCER.By LOVELL DRXGE, AI.A., M.D.OxoN.,

Medical Oflicer, II atfield Union Infirmary; Coroner for Herts.

TilE satisfactory results obtained from the treatment ofuterine fibroids by oil of cinnamon led to a specuilation con-cerning the therapeutic blue of the oil and its mo(le ofaction. This speculation dovetailed in, curiously enough,with a stu(ly of the cond tions connected with the formationof blood clot in the veins of pregnant an(a lying-in women.As a result I was led to exhibit the oil in full doses in aninoperable case of canicer of the breast. Certa-in reactionswere then noticed, and a woman whose breast I intended toremove because of the presence of scirrhus growth was inconsequence of these observations placedI under the influence