X-Rays) Are Available

Home , Isotopes of sodium

CHAPTER I1 MEDICAL APPLICATIONS OF NEUTRON RAYS AND ARTIFICIAL RADIOACTIVITY JOIINH. LAWRENCE Recent advances in nuclear physics have inatle pssil)le practical applications to medical investigation and thcrapy. Soine of the most iniprtnnt factors in bringing abut these advances are the discovery of artificial radioactivity by Joliot and Curie, the production of heavy hydrogen Iiy Urey and his associates, atid the develoliment of the cyclotron by E. 0.Lawrerice anti his collagucs. As J rcsu!! ci the contributions of these and other investigators, artificial radioactivity in practically all of the eleinents and the neutron ray (a penetrating forin of radiation siniilar to x-rays) are available. These products of the nuclear physicist are finding widespread usefulness in the sciences of physics, cheniistry, biology, bacteriology and botany (Hevesy). It is not the purpose of this article to discuss the inany applications of artifiasl radioactivity but rather to summarize briefly some of the medical studies which have been carried out.

NEUTRON RAYS When beams of neutron rays adequate for biological and medical study were developed, interest was immediately centered on their possible effects on neoplastic i tissue. Furthermore, it was hoped that this new form of penetrating radiation would prove of value in unravelling the problems concerned with the interaction of radiation and niattcr. The neutron, discovered by Chadwid, is an electrically neutral particle of matter having the approximite weight of the hydrogen nucleus (proton). Although neutron rays are similar to x-rays and the pima rays of radium in that they can plictrate deeply into tissue, thcy differ from x-rays and ganinu rays in their method of tlcstroyiiig tissue. Wlwii x-rays (and gamma rays) are absorbed in tissue, secondary electrons are emitted which produce tissue ionization, chemical change and '# biolog.ical effect. When neutrons, on the other hand, we directed into hydrogen or into material rich in hydrogen, such as tiuue, a totally different type of ionization rdts (Fig. I). Thc neutrons collide with the nuclei of light atoms such as hydro- p .ad form rccoil particles (protons) which produce a much'morc dense ioniza- tbn the tissues than do electrons resulting from x- and gamma-irradiation. The ooacentratcd ionization following neutron irradiation has led physicists to klievc that neutron rays would be even more destructive to tiuue than x-rays. The de- 13

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DOCUMENT SOURCE Lawrtncr Buktlay Laborrlafy Archlvec wd RwdaOHice

Notos Found By - ~Ifl~~'II .-, IOalra . . 3004813 I,- .- 14 NEUTRON RAYS AKD l~ADIO~\C~l\'l'l'\~

velopment of thc cyclotron, which produces intense beanis of ncutrons, nintlc it possible to test this and other theories. In the cyclotron, high sl)cctl tlcuterons (nuclei of heavy hydrogen) produced by multiple circular accelcrntioii in thc sirong magnetic field are directed against a target of beryllium. This operation protluccs an intense-bam of neutrons. The cqdtion Bei+ Ha- BLo+ ,NI shows that

FIG I.-Ionixntion produced in a Wilson cloud chamber filled with a mixture of air, hydrogen and water vapor after bombardment with neutron rays and gamnla rays from the cyclotron. The thin tracks of ions were prduced by secondary electrons lilxrated by the gamma rays, while the thick and very dense tracks were produced by the recoil prototu resulting from collisions of neutrons with the Iiydrofi.cn atomic nuclei. This pic- ture demonstrates the more Iodized and intense ionization produced in tissues by neutrons when compared with x-rays or gamma rays. (From Lawrence, Handbook of Phy&d Tltrrcr)y, 1939. Courtesy American Medical Aslociation, Chicago.)

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.. . 3004814 NEUTRON RAYS 15 beryllium captures the deuteron to form boron and a neutron. The tungsten tnrgct and the kani of elcctrons in the production of x-rays are analogous to the beryllium target arid the heam of ~leuteroiisin the production of neutrons. During the last lotir years, several sets of cxlxrinients have IK’CII r:irrictl out in this and other Ialiorntories to test the biologic effects of ncutrons. In thc first studies (Lawrence and Lawrence) rats wcre irradiated over the wlicilc IN HI^ with varying doses of x-rays and neutrons. and thc iiitcnvc bicrlogic cffcct rrl iicutrriii radiation, as evidenced Iiy the production of nlarked leukopnias, was tleiiionst,r;itctl. Furthcniiorc. as was predicted, neutrons wcre more destructivc Ixr unit Iri ionization than x-rays. These results, confirmed by the studies of Zirklc ahd Arlrcr- sold, indicated that iicutron rays might selectively destroy some biologic inarcrials to a greater dcgrec than others. The apparent differential effect of neutron irradiation on two different biologic materials, i.c., rats and whcat seedlings, suggcstetl tlw problem of comparing the relative effecta of neutron rays antl x-rays on norni;il and neoplastic tissue. A first approach to this question was made by comparing the lethal effects of neutrons and x-rays on nomial mice antl on sarconia 180 of mice, irradiated iir cifro. The results demonstrated the lethal cffccts of ncutrons on neoplastic tissue antl indicated that neutrons were more sclcdively tlestructivc of this tumor than werc x-rays. Subsequait studies Iiy Zirkle. /\elmsold aud Demp- iter cstaMishccl hcyoncl doubt that diffcrent biologic inatcrials vary in tlicir rclativc sensitivity to neutrons :is conipred with x-rays. These rcsults were confir~nctlaid .I extended by Zirkle and Lanipe. At the satne time the two foriiis of radiatim wcrc cmprdon anotlicr tunior in mice, a inaiiiiiiary carcinoma, and the results again indeed a favoralde differential effect for neutrons. In Table I are suriinlariz.ed the data concerning the rclativc cffects of nciiirws and x-rays on different materials. The figures on fern spores. drosophila antl wheat , reedliqr are those of Zirkle and his co-workers. In a comparison of low voltage

TABLE I COU?AMTIVEErrrcrr 01 %LAYS AND NsunoNs ON VARIOUSORGANISUS

X-Rays Neutrons I X-Ray- N cutroli I-- I Ratio Drosophila ego (9%hatching) ...... I& rm Whut dlingr (p%normal growth) 1,000 5.5s Nord mice (Letlul cfieet) ...... Boo 4.3s Munnvry carcinoma (In vilro 9% taku) J,&w 20.0 Fern sporu (9%inhibition) ...... sa.ooo ago

- .. . - . ._. . 16 XEUTRON RAYS AND RADIOACTI\'IT\' and high voltagc x-rays the ratios are the same for all olijccts. I)ut here thc ratios vary from oliject to oliject. Thus, for the first time, the physician lias a Ixiictrating form of radiation which behaves differently froin any kiiown tliiality oi s-rays iii its biologic effect. Oiily future work can tell wlicthcr tlic iiciitwii Iay wil! !ic rub tively more destructive clinically on one or inore kinds of neoplasms niicl wlicthcr it will be a valual~lenid in the tlicrapy of ileoplastic tlisciisc. Thc pitiiiccriiig work of AcIxruJd in colliiiiating a Ixnni ol fast iicutroiis ntlcquatc [or tlii~riqK-iltic~tcsts ! has made it possible to investigate these prolileiiis. Patients with atl\mcctl carciiionra are now trcatccl rcgularly and inforniation is gaiiietl rcgartlitig cffccts of iicutron rays on tumors and on the skin (Stone, Aclxrsoltl and Lawreiicc). Careful and extensive Incteriological aid pathological studies on a larxc ii~iiiilicr of mice irratliatcd over the whole body with varying closcs of iicutrons have shown that neutroiis pritllcl x-rays in their qualitative effects on tissues (I .awrciicc and Tennant). The hciimtolmietic and Ipphoid structurcs and tlic iiiiicosa of tlic siiiall intestine arc tlie tissues most sciisitive to irradiation. It is tlicreforc iiiipcra- tive that those working with neutrons be protected froni uncluc cx~x~surcas arc those working with x-rays. In the case of x-rays the tulx is ciiclosctl in a Icad- lined room, but the source of ncutrons iiiust Ix surrouiiclcd with walls oI watcr, one of the most efficient and practical absorbers of neutrons. Necitroiis. unlike x-rays, pass through lead or steel. For the present the daily tolcrniice tlnsc has been arbitrarily establishd as one-tenth that of x-rays (as iiicasurcd liy a sinall .I bdcelitcwalled thimlilc inniution chamber). Whether daily tloacs of this iiisgiii- I tude over a long period of time would result in damage is not known. I The recent interesting investigations of Kruger relating to tlie problciii of tlic direct effects of iieutron rays on neoplastic tisue are based ulnn thc fact htwl\cii slow neutrons strike boron they are captured by thc boron nuclcus, with thc ciiiis- sion of two heavy ionizing partides-a helium nucleus (alpha particle) and a lithium nucleus. These two heavy particlea travel approxiiiintcly tlic clianictcr of 3 cell and produce ionization even denser than that followiiig tlircct fast ticiitron bombardment. One might expect great destruction from this tlcnsc. localizctl ionim- tion, which approximates an explosion within the cell. 111 fact. Krugcr lias shown that when tuiiior cells bathed in nontoxic coiicentntimis of Imic acid siilutioii arc hbarded with slow neutrons, they can be killed with doscs of iicntriiiis that arc only a fraction of those necessary to kill than directly. Tlicse results introtlure thc possibility that neoplastic tissue may k infiltrated with colloidal I~iroiiniicl tlicii the region irratliatal with siiull do= of slow neutroiis-dosw which arc 1i;iriiilcss to normal tissue when given directly.

ARTIFICIAL YADIOACTIVITY Radium and other naturally occurring radioactive substances are iinlmrtaiit in nietlical therapy bcuux of the ionizing radiations emitted Iiy thciii. Tlicsc rays (alpha, beta and ganinia) have the property of Ixnetratiiig tissue ill a grratcr or lesser degree and, by producing ionization within tlie tissues, of caubiiig hiologic

300ir81b ARTIFICIAL RADIOACTII'ITY 17 ,.. , _. . . .. \. 1 . .. changes. The sensitivity of neoplastic tissue to these changes innkes thcnc rntliii- active elements valuable in therapy. The radiations eiiiittecl froiii ilicsc clciiiriit .i may be detected by physical instruments such as the elcctroscop niitl tlic Gcipr

counter. Lost radium is traced in this manner. Similarly, ratliuiii atliiiiiiistcrcd 111 animals may be detcctcd within the tissues. At autqxy the cxact ~irii~~iriirriiiii 'h vwiour tiarucr iiiay Ix tlcterniiiiecl physically eitlwr by couiitiiig ~Iicr:idi:iLiiiiis emitted wit)- the use of a Geiger counter or by measuring thc ionization pr(wliicc(l hy tlie ratliatioti in an elrctmscnyx. This fact. together with tlr kiinwleilcy rlint nile of the decomposition products of radium, radium D. is an isotope of Icail. wnlilr~l llevesy to study thc fate aiid tlistriliution of lcatl in plants. Iris work siig~c.rcil :I powerful iiictliml of invcstigation. but unfortunatcly it was liinirctl to ItsIInwiiiq the metalmlism of the naturally nccorriiig radioactive sulistaiiccs, wliiclt ;ire [cw and relatively uninilmrtaiit io biologic systcmr. The advent of artificial railicncrivily changed this state of affairs so that now the physicists can make almost any cleiiiciit radioactive. Cheniiwlly, the radioactive "isotopes" cantiot LK distinguished froiii rlicir ii1.u- tive relatives because they have the same nuclear charge. The radiations wliicli tlic! emit rally make them tagged or labelled atoms. The nuclei of all atnnis arc cniii- posed of various combinations of protons and neutrons tlLit are ratlicr iiitiiiurci! bnund together. The proton has a charge of one and a weight of oiic 3iicl IS tlic .. nucleus of the hydrogen atom. The neutron has no charge but has the miie \veiglit as the proton. A proton is designated thus: lH1,the lower figure dcnoring clurge and the upper figure weight. Consequently, P neutron is written ,\ ilciircrwi. which is the nucleus of heavy. hydrogen, consists of a proton aiid a ncuiron Inwiiul tqcther and is written ,Ha. Protoiis and neutrons are the "building block*" ,' atonis and the number of protons or the charge of the nuclcus dcteniiiwr ilic element. Thus, helium has two protons and two neutrons, and so on Up ~IICii~ii,~ table. When neutrons are added or subtracted, the chemical nature of the LIOOI tloes not change so long as the charge remains the sine. The different wciglir (J( the resulting combination, however, iiukes it an isotope. Some isotopes arc ui~~ul~le and emit radiations in the process of kcoiiiing stable. We are conccrnctl lrcw wtl~ these radioactive isotopes. Whcn deuterons or alpha particles (helium iiiKlri ). which are combinations of protons and neutrons, are flung at atoms at high qds. one nr niore neutrons or protons may be captured resulting in a ncw atolii l,r ~II isotope of the saiiie elcnicnt, which may bc radioactivc. In this way, practically mi\ element can Lx made radioactive in the cyclotron. As noted previously, rdiuiii air1 its relatives and derivatives give off one or inore of the following: alplu InrticIc* (which are heliutii nuclei), beta rays (electrons). and ganinm rays, all o( uliicli are ionizing radiations and produce biologic effects supposedly secondary to ioiiim tion within the tissues. Artificially induced radio-elenients give off similar part iclcs. but, unlike radium, they retain their activity for relatively short leiigihs of iiiiw. i.c., hours or days instead of years. Figure z will perhaps convey to Ihc rcmlcr ' sonic conception of the reactions taking place when elements are made rauiwctive and of what happens to them when they decay. In the of radiosodium pro- I case

-- 3004811 18 N EUTKON RAYS A N D 11A DI OACTI \’IT j- duced by honilxtrtling sotliuni with high spwl drutcrons (a tlcukrnii ran hc thought of as a proton and a neutron tightly hoiiiitl), 11ic ncutroii is capturcd by the nucleus whilc the proton is emitted. Thc capturctl ticiitroii chnngrs ~odiiiiii23 to sodium 24. This unstable isotope givcs off a high slrctl elcctron ai~lI)cconics mnagnesium, which cmits D gamma ray of grat cncrEy. Tlic Ixta and gamma rays emitted from ratlio.wliiim arc ninrc powerful thnii thc ratlintions frrni milium. Radiophosphorus is similarly formal by capture ot the Iieiitron of thc tlcutcroii. Thc phosphorus formed in this way emits Ixta nays oiily and beconies sulfur. Gamnla rays are not emitted.

L RADIO.SODIUM lR0OWD BV DEUTERON BOYOAROMEN1 ,H’ + ,,Nan -+ ,,Nc + ,HI + en^#

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W FIG. Z.-RCACTIONS TAKINGPLACC WHEN RADIO-~ODIUMAND H~o~r~Prrosriro~ua ARE MADCIN TSIC CYCLOTRON. TIIFSCELEMENTS ARE BoMnAnnEn IVITII Hlcl1 SPEEn DEUTERONS. (From Lawrence, In : Handbook of fhysicd Tlrcrapy, 1939. Courtesy Aiiiericnn Medical Association. Chicago.)

The physicist can write similar equations for most of the other radioactive elements. It should again ix emphasized that these radioactive isotops do not differ chemically. nor do physiologic systenis differentiate thcni froin tlicir iiractivc relatives. Actually, the emitted radiations tag thcse vlcnicnts and cnnldc the investigator to identify then1 specifically and follow thcni through lhc Ixxly. Hc cy^ administer a definite amount of an element and then can tleteriiiinc its nbsorp- rion, distribution and excretion. Table I1 shows P partially coinplctc list of the artificial radio-elcmentr, many of which are important in physiology and iiictlicinc.

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3004878 ARTIFICIAL RADIOACTIVITY 19 . The radiations emitted and the “half-lives” are given. At the half-life period the ,__...... ,’ .. . .activity is one-half of the original. At the end of a second perid equivalent to the half-life, the activity is .onefourth the original; at the cntl of another similar period, one-eighth. and so on. Depending on the original activity, tlic radioactive elements can IK clctcctctl over a priocl equivalent to iiiany half-livcs hy nicans oi an electroscope, an electrometer or a Geiger counter. The nunilxr plncctl after tlw last letter of cadi elwwit is tlic ntoinic wciglit of that I’crrticiilar rlcnicnt. Thin. tlicrc are sotliuin 24 ani1 mliuin 23. Imth isotqxr of the naturally nccurriiig iiinctirc ” sodium 23. 11, aliuni a a neutron has ken added. whilc in socliaiii zz a iiciitrrm has been lost, resulting in wistalilc ntlimctive atonis. Howcvrr. roclitinr 22: 23 niitl z.+ have the same charge on the nucleus. i.c.. II : hence chaiiically all three arc alike. antl they cnn he tliffcrentiated only by physical means. As one scans the list. iiii- niediate questions ark. \Vhat happens to iron when given I)y niowli or iiijcctctl ? Is it conipietely al~snrhcd?Is it rapidly excreted? Is it taken up slowly or rapidly hy the Imne inarrow and red cells? What arc the tinie antl quantity rclationsliilw of ingested or injected iodine to the thyroid and pituitary glands? How rapidly arc phosphorus ancl calciiiin cxchnnR4 in bone and tecth, nntl are these sluK:fiisli or dynamic tissues? Ih patients with aiieniia. Curlling’s tlisensc. Atltlison’s tliscasc. parathyroid disease, thyroid clisease. etc.. differ from normal inclivitlunls in hantlling of a single dose of iron, scwliuin. potassium, phosphorus. calcicini. ioclinc. etc. ? Do the various elcnients rcmnin in the Idy a few days or a few months and what are the individual ntw of nietaholism of the various elements in different tissues 1 -‘ . Finally, do these new radioac&ive siilistances have therapeutic Imssihilitics? Since soma (for exainple. phosphorus in hone and iodine ill thyroid) contain ’ tiuuu nhtivdy high conceiitrations of certain elements, is it p0ssil)lc to clcstroy selcc- h lively tissues of neophans inMtrating specific tissues hy giving large doses (con- . trasted to small tracer doses) of the radioactive isotopes? ’ Tahle I1 includes niany isotopes that arc of obvious mcrlical ititcrest. First. there are radioactivc forms of hydrogen, carl~n,nitrogen and oxygen. Except for radio-hydrogen, which has only recently lxen discovered, the other three elcincnts have such very short periods of activity that their use as traccrs is difficult. Scwr- theleu, active carbon and hydrngen are being successfully used in liiologic work. Urey ancl his assnciatcs of Coluiiil>iaUniversity are niaking nonratlicnctive isotopes of these elements, which also are tagged atoms because their weights, differing from the usual form. can be differentiated by wciglit and specific gravity detcriiii- nations. Sodium has ken rather extensively used in physiological and medical studies by Hamilton. His studies and olsn thosc of Mullins have shown that, since small tracer doses of radio-elements have no pliysiologid or biological effect. the results obtained by this tracer method are reliable. Hamilton is using the radioactive forms of sodium, chlorine. potassium, bromine and iodine in his studies on normal subjects and on patients suffering from Gush- ing’s disease, Addison’s disease and various forms of thyroid disease. When labelled .. sodium chloride is taken in solution by mouth, the Geiger counter licld in the siih- jcct’s hand registers the surprising finding that within two minutes soiiie of the

3004819 ..

20 - Atomic Numkr Radioactive Element Radiation

~~ I...... nctp r*lp c1;1y 6...... Piiriirnii ~iulgniiiiiiii m.6 iiiiimtea I...... Pwitron and gamma 10.5 iiiiiiiiiea a...... Pmitrm aid Barnma 1.1 iiiiinitcr 9...... Priritrcni iiul gamma III iiiiiiiitcs It...... Pivaitrnii mul Kaminm 3 yciirs Rcta aiid gaiiinia i4.X Iioiir'i io...... I3cta and gamma io.a iiiiiiiitrs 13...... net. II iiiiiiiitcs 14...... nets lifl iiiiiiiitcs 15...... Reta 14.3 II~S 16...... Dan Rx rhys 17...... Pnuitroti and gamma 33 iniiiutu 19...... Bcta aiul gamma ra.4 Iinurs a...... ncta end gamma I&, day5 13...... Beta and gamma 16 rl;lyr 15...... Beta and camnu 310 (lays *...... Dcta and gamma J? rlayr 17...... Poritron aid gamma 70 days a...... Positron and gamma J(, hniirs m...... Bcta and positron 12.8 liiiurs jo...... Bcta and gamma 13.R hours js...... Bela aid positron 35.. 17 days .... Beta and gamma 34 hours u...... Beta md gamma y...... 8.a days ! .. , Beta id gunnu IJ clays *...... &ta 86 minutes 78...... Beta -: 3.3 clay 4 .' . m...... net. 3.3 rlaps Lb...... Baa and ganuna 43 lllilrlltcs e...... Rcta 83. f Iiriurr ..... Beta 5 days I

scwliuni attiniu Iwc rcnclictl thc fingcrs. Hc has ahtlcvrlolrtl in illis way n coil- veiiicnt nxthcd of cletennining circulation tinie in nor~iinlsihjects aiitl in paticntr suffering from circulatory diseases. In conjunction with Solcy. hc ]ins tlcrnoll- stratnl the concentration of ingested iodine by thc thyroid gland. Ily placing the Geiger cnunter on the neck against the thyroid, the iodine content can IIC mcasured from day to day and characteristic and diffcrcnt cttrvcs for variolls forlns of thyroid disorders hn be obtained. Similar stdies are lxing carried out Ily Ilertr. Roberts, Means and Evans. Finally, after subtotal thyroidectoniy, sections of the removed glaiwls are placed on a film in order to obtain a photograph of the distribution of iodine in the gland so that it may be correlated wit11 the anatolnical structures. Interesting experiments with the use of radiosodium and rarliopotassium

... - ...... - ...... ,. .. 3004880 ARTIFICIAL RADIOACTI\.YTY 21 .- have been carrictl out by Antlcrson and Josepli, who havc clearly tlciiionstratctl the relative inability of adrenalectomized rats to excrete potassium ant1 tlicir trntl- ency to lose sodium. Radioactive phosphorus has ken the most extcnsively risctl radio-isotopc. It has: a relatively long half-life (14.3 days) and can be made in large quaiititics in tlic cyclotron. It is used both as a tracer and as a therapeutic agciit. \\’it11 its aid, tlic ...- ~ plwnpiitdipid ioctnlwJim of aiiiiiiul iuiiiori is Iwiirp r~utliril (Joiirs rt 01,). It I1n4 Ixen fotind that tunior tissue tlocv not have n characteristic tylr of mcialwiliwi. there Ixing no uniformity ainong four different ttimors. i.c.. iiianiinarv carciiion1:t, Iyiiipliain, ly~iipliosarct~~iiaand sarcoma 1%. The ccll tylr (lws nibt tlctcriiiiiic tlic

levcl of tlic phospliolipiill activity of any one tumor. Thc pliospliolipi~ltcirnl lvrr I II ttimors lrars a grcntrr rcscml~lanceto that of tlic more active tissues srirli as livcr. kidney antl intcstine, than to that of tlie less active tisstrs. sricli as iiirisclc :uiil

Iirain. The discovery of Mevcsy and his associates that the solid pnrtions oi tccili , actively exchange Ihoslhorus lias lxcn confirmctl by several otlicr invcstiK:ntor.;. In studies on rachitic rats, Colin and Creenlxrg havc shown that vitaniiii I) raiws the inorganic phosphorus uptake in Inone. When radiophosphorus in sufficient activities in the form of sotliuril plinsp1i:itr is injected into mice suffering from leukemia. tlicre is a sclcctivc (Icliiihi[ioii OC oliosphorus in the tissues chicfly involvnl in this tliscasc. naiiicly. lww niitl Iriiir niarrow. lynipli notlc. liver antl splecn. Since the lrta rays pcnrtratc tissucx icss than P centimeter, thcsc results suggested a method of giving selcctivc !cmlizctl irrnclintion for the treatment of this disuse. Numerous patients suRcriiig frtmi leukemia have been trcatcd during tlie past two ycars. Whcn ratliol,lioslilinriis is given by mouth. alisorption is ncarly complete, and excretion is slow so that tlic ptient can be given continuous, low grade, selective irradiation over a perid ai several days. In mscs of chronic leukemia, it is possildc to prwlucc remissions (with diminution in the white count and decrease in the size of the splccn) siinilar to those following x-irradiation. The dangers of internal ratliurn therapy arc avoided because these artificially radioactive isotopes have short periods of activity and are excreted in a short time. This form of tlierapy does not havc tlic tlisatl- vantage of “x-ray rmctions.” antl the results indicate that it will provc to Ijc :I valuable adjunct in tllc treatment of leiikcniia. Sonic intcrcsting cxlxriiiirnts 1111 radiosulfur by Tarver and Schmidt confirm the prolnliility that the aiiiinal (Irxaiiisiii can convert methionine to cystine. The tissues of rats which hat1 lrcn fctl iiictliitl- nine synthesized froiii radiosulfur were extracted for cystiiie. The prcsciice Ili radiosulfur in the cstractctl cystine indicatnl the conversion. As a final example, the work of Whipplc and his associates with radioactive iron is of interest. Their investigations in noriir;ll and anemic dogs show that tlic norni:d animal absorbs iron very poorly while tlie ancniic animal al)sorl)s niuch iiiorc iroii. according to the needs of its body. The blood plasma was dearly the nicans of .. transport of iron from th: gastro-intestinal tract to its point of molilizatinn for fabrication into hemoglobin, and the speed of absorption and transler of iron to the red cells was spectacular. Further studies showed that “the body controls its

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300488 1 a2 ’ NEUTRON RAYS AND RADIOACTIVITY iron stores by absorption or lack of it. rather than by its capacity to cliniiiiatc it.” They conclude that “the dog excretes iron with difficulty and in siiiall unouim by means of the biliary and gastro-intestinal tracts.”

REFERENCES AEBERSOLD. P. C. The Production of a Beam of Fast Neutrons, Pliysiol. Rev.. 1939. 56 :714-27. ANDFASON.E.. and Joswsr, M. Urinary Excretion of Radiazctire Sodium and Potas- sium in Atlrenalectomird Rats with and without Salt, Proc. Sw. Espcr. Ciol. .!i Md., 1939. 40 :347-50. CAADIVICK,J, I’orsiblc Existence of a Neutron, Nature, 1932, r29:.312. COHN,W. E., and GREZNB~C,D. M. Studies in Mineral Jletnboliriii ivi111 llie Aitl of Artificial Radioactive Isotopes, 11, Tlie Influence of Vitamin D on tlic Pliosphorus Metabolisni ol Rachitic Rats. J. Diol. Cliciii., 1939, 130:2:625-34. HAIIN.P. F., BALE,W. F.. HETTIC, R. A.. KAMEN,hl. D.,ad )vHIPPLL G. 11. I~~Io- active Iron and its Excretion in Urine, Bile, and Feces, J. Expcr. 51.. io.?% 70: 5 :443-451. HAHN,P. F., BALE,W. F.. LA\VPCNCE,E. O., and WiiIprLy., G. H. Radin~i\eIron and its hlctalmlism in Anemia. J. Exper. M., 1939, 69:739-53. HAMILTON,J. G. The Rates of Alnorption of Radio-snlium in Nreininl Humin SUII- jects, Proc. Nat. Acad. Sc., 1937, 23:9:52r-,7. .. - The Rates of Absorption of the Rmliaqctive Isotopes of Sodium. Poti*$iiim. Clilorine, Bromine, and Iodine in Normal Human Subjects, Am. J. PIiyriol. 19,$3. . 1y:3:667-78. HAMILTON,J. G., and ALLES,G. A. The Physiological Action of N;itural ;IINIArtificial Radioactivity, Am. J. Pliysid., 1939, 125 :3:1-4 HAMILTON,J. G.. and Sarv, M. H. Studies in Iodine AIetalalisni by tile Lx of a Sew . Radioactive Isotop of Iodine, Am. J. Pliysiol., 1939, 127:3:557-72. HAMILTON.J. G.. and STONE,R. S. Excretion of Radio-socliunr Follorvi~i~Intravenous At1niinistr;itioii in Man. Proc. Soc. Expct. Biol. & AM.. 1937. 35:595.5@ HIRTZ, S., ROIIERTS.A,, MEANS, J. H., and EVANS, R. P. Rntlionctivc Imliiu 3s an Indicator in Thyroid Physiology, Am. J. Pliysiol., IWO. I&:.\. 565.53) Hcvesv, G. Absorption and Translocation of Lead by Plants: A Comribution 10 !lie Applicatioii of the Mctlincl of Ratlifnctive Iiiclicators ill the Invc\tirltirur nf IIK Changc of Substance of Plants, Biocliem. J., 1923, 17:4.39. - Tlie Application of Isotopic Indicators in Bio1ogic;ll Research. 151zvt1~-1h~ia. 5 :138-157, 1938. Hcvesv, G., HOLST,J. J., and KRWH,A. Investigations on the Exc11.111cr(ti I’hw pliorus in Teeth Using Radiaictivc Phosphorus as Indicator, Lk.t KcI I )an& Vick. Selakab. Biol. Meddal., 1937, VIII:13. JOLIOT, F., and CURIE.I. Artificial Production of a New Kind OI R.-uiio ticiik*it $2- ture, 19.34, 133 :201. JONES,H. B., CHAIKOFF,I. L. and LAWRENCE,J. H. Radioaetivc I’liurplloru* a3 an

Indicator of Phospholipid Metabolirm. VI. The Pliospliolipid hlctdui~rm‘ji Sm- plastic Tissues (Mammary Carcinoma, Lymphoma, Lymphosarcoma. Sxcmm I&), J. Bioi. Chem., 1939, 1~8:~.

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REFERENCES 23

KRUGRR,P. C. Sonic Iliological Effects of Nuclear Disintcgr;ition Prrxliict* oii Kcoplaz- tic Tissu- Proc. Nat. Acad. Sc., 1940, A:181-192. LAWNSNCE.b. 0. l’lie Uiologic:il Actioii of Neutron Hiiys. Hatliol.. 19.37, ~g:.\i3-22. LAWRENCE,J. tl. Artificial Radioactivity and Neutron Rays in Biolopy snd .\lctliciiic. Handbook I’liys. Therapy, Am. AI. Ass., 1939. LAWWENCE.J. €I., AEIIFAS~I.~.P. C.. and LAWRENCE.E. 0. Coiiipirati\*e IXfccts of X-rays and Ncutroiis on Noriiiiil aiid Tumor Tissuc. Proc. Nat. Acad. SC.. 1936, za:543-557. - The Coiiiparativc Effects of Neutrons ;ind X-rays on Normal and Nco~ilastic Tissue, Occas. Piili. A.A.A.S.. 1937, 4:ar5rg. LAWRENCE,E O., atid Coorssv, D. On tlie Apparatus for the hfultiple Acceleration of Light Ions to High Spceecl~.Pliysiol. Rev., 1936, SO:II~I-~O. LAWRENCE,J. H., mid LAWRENCE,E. 0. The Biological Action of Ncutron Rays. Proc. Nat. Acatl. Sc., 1936, 22:12+133, LAWRENCE,J. H., and Scorr. K. C. Comparative hIctalmlisiii of Pliorpliorus ill Nor- mal and Lymplioiiiatous Animals, Proc. Soc. Expr. Biol. & hlctl., 1939. )0:6%-96. LAWRFNCE,J. H., Scorr, K. G.. and Tunz~,L. W. Studies on Leukemia with the Aid of Radicxictive Fliospliorus, New International Clinics, V. 111. Series a, 1939. pp. 35-58. J. B. Lippincott Co. LAWRENCIS,J. H. Nuclear Physics and Therapy: Preliminary Rcprt on a New Method for the Treatment of Leukemia and Polycythemia, Radiology, IWO.35:jr-60. LAWRENCE,J. H., and TENNANT,R. The Compnrative Effects of Neutrons a~idS-rays on the Wliolc Body, J. Exper. AI.. 1937, 66:667-88. .. LAWIWCC, J. H., TUTTLE,L. W., Scorr, K. G., and CONROR,C. L. Strrtliec nn Neo- plums with the Aid of Radioactive lliosptiorus, J. Clin. Invest., IWO, 19:267-271. MULLIXS.L. J. Effect of Radiation from Radioactive Sodium on Penetration of Ions into Nitella, J. Cell. & Comp. Phyriol., 1939, 14:s. Sronr, R. S., LAWRENCE,J. W., and AERERSOLD.P. C. A Preliminary Report on the UK of Fast Neutrons in the Treatment of hlalignant Disease. Radiology, 1910, 35 :jaa-j27. TAIM. H.,and SCIIMIOT,C. L. A. The Conversion of Methionine to Cystine: Experi- ments with Radioactive Sulfur, J. Biol. Cheni., 1939, 130:~:67-80. UREV,H. C., BRIcK\\WNIE. F. G., and hfunrw, G. M. A Hydrogen Isotope of Xfass a, Phys. Rev.. 1932, 39:164. ZXRKLE,R. E, aiid Aansasou, P. C. Relative Effectiveness of X-rays aiid Fast Neu- trona in Retarding Growth, Proc. Nat. Acad. Sc., 1936, u:134-138. ZIRXLC,R. E., AEDERSOLD,P. C., and DLMPS~,E R. The Relative Biological Effec- tiveness of Fast Neutrons and X-rays upon Different Organisms, Ani. J. Cancer, 1937, 29:556-56*. ZXRXWR. E, and LAMPE,I. Differences in the Relative Action of Neutrons and Roentgen Rap in Closely Related Tissues, Am. J. Roentgenol., 1938, 39 :613-627.

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