The Brookhaven Medical Program: Its Present Needs for Future Healthy Development

Page 1

The Bookhaven Ieciiccll Program: Its present needs for future healthy developrnent, The medical program a t Brookhaven during the four years it has been operative has developed two main lines of endeavor which utilize toa very high degree the special facilities available at the Laboratory, The first of these general programs has been the evaluation of neutron capture the:rapy from the realm of calculation to that of clinical trial. This procedure utilizes the nuclear reactor for a neutron source. Neutron capture therapy has been shcwn t o be feasible for experimental treatment of glioblastoma multi fo me, obvious deduction t8hatneutron capture therapy can in principle be appliec? t o therapeusis of malignancies other thm those of the brain, notably those of the lung where again no adequate therapy is available. development of neutron capture therapy clinically is dependent upon developmc.nt of knotdedge simultaneously along several lines. Data now available lead to the First is the further exploration o f neutron effects on the intact animal with specific regard tothe organ slrztems o f primary interest. This problem requires experiment dst n dies for dosimetric data of neutron at tenu at i or in tissue equivalent phantoms, animals of various sizes with special measuring devices and data to be obtained on patients at the time of actual treatment, and further development of special measuring devices suitable' for this specific study. firth er, it requires increasingly accurate analysis of the energy spectrum used s o that sy cia l biological features of various energies may be profitably_emplnyed7-. -----1- t Second, it requires further study of the 1of the probably most useful of the capture e

Page 2

and uranium. These three elements all have large thermal neutron cross section captures, all emit alpha particles as a result of such capture, and in lithium and boron the radioactive isotope decay is practically instantaneous so there is no residual hazardous product t o be concerned 'IlxLrd, it requires much greater development of the field of kinetics of dist rib i it ion of EL soluble material in various body areas. This study must be done on a variety of disease conditions in order that specific distortions of body components lending themselves peculiarly well to such studies may be obse:rved. The kinetics observed are o f primary physiological in tg rest in many respects and are by no Tneans of interest only inthe capt in e therapy study. They are, however, demanded for further developnent of t h e neutron capture therapy problem. Fourth, it requires much more specific knowledge of the effects of high dose rates of radiation applied to a small volume of the body, and in particular further knowledge of the response of body tissues to such studying the effects of very high dose rates. Conversely, capture the r spy provides one of the best means of It nay be ps ren the tin ally poi?ted out that such studies are by no means limited to it lts ct ani7121s, but lend themselves well to isolated biochemizal, physiological and ~ i cro biological ~systems. All these approaches are being developed a t R-ookhaven. obtain & in all categories will be of interest to clinical investigators and biologists in many other fields, but the priinary prograx can be cer ried out It thus can be seen that capture therapy orly by scientists having contivuous access to a suitable reactor.

Page 3

The secoqd li.ne of endeavor which i s developing a t Brookhaven isthe exploration of the usefuln.ess in clinical rnedicine of short lived radioactive isotopes, i.e., those having a radiological half - life of six hours o r less. It i s evident that ii react,or is necessary to the developinent of such a proof a t least partial avoidance of certain radio logie s1 hazards inherent in iso tones with longer half - lives. They also give promise of usefulness in loc cli zed radiation to naturally circmscribed body vol mes many of which have therapeutic promise. Short lived radioac-Live isotopes applied to therapeutics give promise One of the outstanding features of Fhort lived radioisotopes applied to biological systerm is again ahi ch c’qse rate. Brookhaven on the usefulness of chlorine38 in the control of fluid accumulat ions in body cz vi ties due t o malignancy. half-life and the k:inetics of its distribution following inJection into a h3dy cavity such as the peritoneal cavity are such that about 90 percent of the energy of radiz - tion is delivered to the cavity and only about 10 percent ex apes to deliver total body radiation. t o those observed with colloidal go13 have been obtained. whereby these fluid accumulations are diminished are unknown and it is the endeavor a t Brookhaven, by study of the kip.etics of body constituents such as sodium, chloride and water acmss the membranes before and after radia - tion,to gain some insight into the control liv g factors. that better understanding of the effects of such localized radiation as well as physiological methods of enhancing the loc c liz ation are toa very large extent dependent upon further knowledge of many of the same factors concerned in neutron capture therapy, i.e.,kinetics of distribution,local to ler s rce, dose rate effects, energy spectrum of radiation. St c dies are under way a t Results in fluid co c tro l simi kr

Page 4

The free interplay of stimulation of these two programs between the vario-7s members ofthe Xedical Department as well as between departments a t Brookhaven, as for exar*ple, Reactor Operations, 1nstranen.tation and Health Physics, Chemistry, and Physics, leads to a very healthy state of scieme in the iQ st it uti on and one which is characteristic only of Rrookhamn by virtue of ready access to5reactor for medical scientists interested in such a progam. The medical prograp st Brookhaven has developed by gradual evolution. Able clinics1 and medical investigators have been furnished with adequate professional facilities and as the result of constant contact with physicists, chemists, reactor engineers and allied sc lent is ts, have develo?ed naturally the foregoing program; although it should be stateci there was an initial prograv of this gerieral type conceived accord i rg to a broad plm. ?ach step in the development of the Ted ical program a t bookhaven, whether growth of physictd plrrlt o r growth of yrogram, has been the result of fruition of earlier endeavor. This has led to the gradual occupancy of numbers of buildings previoysly part of the pre - existing am.y hospital at Cam, Uptop, as the projects demanded. There has beer, as little forced growth as possible,, modification of ex-istinp building strictures. Physical plant growth has alwzys entailed miniuum The purely accidental chznce location of the F'edical Deprtment in the old army hospit-1- has permitted this growth t o occur within adjacent buildings.h

Page 5

D.e program of t h e Brookhaven National Laboratory Nedical Department can be succinctly stated as follows: 1. To a tilia e thermal, epithermal and fast neutrons for studying their biological effects and t o determine their app lica bi - lit y to medical therapy and diagnosis, 2. To study the biological effects of administered radioactive isotopes and t o determine their usefulness i n medical dl.agnosis and therapy. 3. To explore the biological effects and possible medical application of very high energy p,article radiation. 4. To carry out fundm-ental studies in biochemistry, physiology, medical physics, pathology and micrcbiology which a r e necessary t o develop Neutron radiation effects are being studied from two viewpoints: first, the biological effects of neutrons of different energies; and second, the usefulness of thermal neutron caFture as a practical medical radiation therapy for cancer. For my medic:al use of neutrons a conplete understanding of their biological effects is required. biological systems and specific chemical effects. using the classical techniques of ned ical science. informative studies are being developed using labelled compounds t o thrcw light on specific effects which may be en comte red in the synthesis and utilization of proteins and lipids,inthe responses o f inunune rnechanisns This i s being obtained by study of animals, Observations are mede In addition, more

Page 6

of intact animals and inthe changes in rates and fl nal distribution of body water and i t s sol!ltes. body of knowledge whic'h deals in det3i.l- crith precisely formulated conditions upon the assumption that wcrk i n this general field will continue a t In th ls way there cm be developed an orderly The development of this specific body of knovledge rests universities and that our major effort cm be devoted tothe nroblems more specifically re k todt c our program. To determine the prs ct icd it y of neutron capture therapy, much additional effort is necessary. The energy of the neutron particle is of the greatest importance Z.TIvarious energy ranges may each have different biological uses, To develop capture therapy it becme evident atthe outset thit it would be necessary t:, embark u;)oa a ph srm co logical and tox5cological study of the elements used for capt were actions since existing information i s inadequate and the phnmacology and toxicology as modified bj the neutron exposure must be clearly understood. of distribution of elements used for capture reactions is another program which it i s necessary t o develop ina specific context. biological indices of rad is tion and radiation effects is essential to The development of progress in this field. Yfch of the i.nformation which will be developed for the neutron capture program will also be of great value in predicting the behavior of radioisotopes higher to untried. While on a pirrely logical basis it might seem desirable to develop the basic knowledge :Zrst, it must be ernphssized that the ultirnate responsibi lit y of a medica:l research program i s a]-leviation of disease. que ntl y while fundamental resesrches are in y ogress, knowledge i n all

Page 7

stages of development i s being apFlied to palliation and control of disease manifestations. To a pain wracked cancerous individual, surcease from pain i s a major accomplishment and should not be withheld merely because the cancer itself w.nnot be brought under complete control at any To carry out the above prciTam the Ik d ical Department has been Theseorganized division ally according to six scientific disciplines. are respectively : ?h;lsld?gy, Microbiology, Biochemistry, Pathology, Medical Physics and Clinical Vedicine. whose scientific staff i s drawn from clinically trained men in the other five divisions, each division represents a team of scientists skilled in basic Drocedures and in their clinical application to s sec if ic medical in clinical applications. With the exceztton ofthe%s pital, Thereby i s @ned immediate reflection of scientific a dvm ces Attention xlust be called to the organization of a division of medicine there is great need of physicians qualified in radiological physics together with physicists who have had experience with physicians and medical Columbia and the Dormer Laboratory where such people can be trained adequately even further in this field. today, one a physician and ore a physicist, who can provide the nucleus of in stm ents laid fr0.n medical physics on the part Df t'ne other divisions. Tn a research prograx devoted to application of atomic energy t o medicine In the application of the atomic energy program t o There are very few centers such a s Dr. Fail la ' s department a t The use of the reactor in our program has required us t o develop iJe are fortunate in having tvo men on the staff The .service requirements are large for professional ad

Page 8

a medical physics division will inev?t,o’nly exist thol-i.;h it mynot be so effec:.s must be carried dowg to or gar levels, cell lev cls and cell cor st it - The tra jr lng and experiences required are much difTerent from Ttis antici:-ated this will become a recognized field of to train 9h;:sicians a ii di fid to i row rt to qthers thc especial r quire The staff reqvirements heretn outl.ine:i art’ in. funda.lcy.te1 apeerrtent with the proDosa1-- siibrtitted ir: t h e general laborstcry plan of 3ecember 1052. In this plar the staff require-ients were estibated a t 37. In they e sent organnegcessary YdditiQEs tothe staff reqiJired iy the developlent of the reactor staff me-tbcrs woluld be OP, t h e c7TtiTuinp staff and 24 on t h e rot,?.tin< staff. n ical staff and other staff requiren-bents are the s me 4s noted inthe qeneral Twelve assistants wou.ld be nec ess iry for clerical ar,d other d ii in is tr st ive assip-Gents. To operate a 48 bed hospltF-1- atot21 staff is rzquired of 66 social- servj-ce and pe.tient welfare, to yet her with 25 other persons t o pro-

Page 9

The present staff of the de psr tn ent numbers 23, plus two add it i ow7l men on 11-ili-targl eeve and three a3cj it ional ‘nen to whom as o f today t o 3F scientists.in a.,:tlve rc+-lcrwit ing wo gra a is being patto loss o f !!?en ever the nast year t o thc doctor draft. policy of the department, i n so fsr r?,c’ it car, be done, tq fill sen’or pos ii l cns by prow ti or.after >rr)?er 9 ?cPss-!!w-t and sen m ning of the scientists in the twc. lower ranks, coir,:.sre2 t o 16 todzy. All partial comit ment s noted above are ir! th ehir her ranks.

Page 10

On the 17,Lsis 0:; experienct.: sained in operating this tjT? of hospital over the past four ye us the present hospit3.1 organization has been developed which provides four ca'?cer services and two non-cancer services. Fo-2.r ofthe five cancer services presently cox ern the treatment of Tet s static csacer o f the t kr roid,brain ccncer, metastatic cancer lodging inthe bony structures, may be made lLn neiitron capture them?;? for cancer ofthe luqg, which will cons t it w tea fifth cancer service in the hosyi.ta1. The two n?+csqcer services presently cbncern them elves w_th 1) mr dic v3s cul ard ls ease and ditions, ;:re ofiem ? 1J til it y 'n e lucid a tiny the b3havior of a variety or" elements in other aspects of Brookhaver,'s wed icd Tirograr",. It i s enance wi+.h the growth and development of the fields of kq.3wledge there in concerned. :I hospital. of not less than 4€! beds and cot w.s ~ e than 54 beds i s required adequx t ely to carry out this prog rw of research and aevelqpmnt. The llepzrtnent, woild be eb leto carry out th ts progr above numbers of staff' rne-ribers only because it i s ar? i cte gral pr?rt o f ?trockh:xvep %t ional LSi.borstox-y and became uch scientific coll n borst ion, aid and assistance CY! be obtained as i s do^^ at prey mt fro ' .the other scientific an2 serlr.i.ef? departpents of the Labcrr.tory. ";?..e in terre la tim shi ys between the vzricus …