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consent of the Senate. The Chairman of the Board should be elected by the members and should serve for a term of 2 years. The Board should meet not less than once each quarter and its ~-unction should be to advise and assist the lgational Cancer ~kuthority and its Administrator in the development and execution of the program. The Administrator should be an ex-officio member of the Board. The Board should have statu- tory responsibility for the approval of each year's program plan and budget, but the responsibility for administering the program should rest with the Administrator. The Board should have full investigato .ry powers and should be required to report once each year to the Presi- dent and the Congress on the progress of the National Cancer Author- ity in the accomplishment of its mission. This Board should supersede the presently existing ~ational Advisory Cancer Council, and the members of that Council should serve as additional members of the National Cancer Advisory Board for the duration of their present terms. 12. Cancer is an implacable foe and the difficulty of eliminating it as a major disease mus¢ not be underestimated. A top priority commit- m~m# b~" ~he Con~re.~. the President. and the American'peop|e i.~ required if we are to mouut and sustain an assault on cancer of t|m magnitude envisaged by Senate Resolution 876 and the concurrent r~,~h~*~on ~ the Congress. Such a commitment invoh'es a reco~ition not only of the difficulty and complexity o~ cancer but also of the time ,'rod r~.~ources required to attack it effectively. While it is probably unrealistic at this time to talk about the total elimination of cancer within a short period of time or to expect a single vaccine or cure tha~ will eradicate the disease completely, the progress that has been mad, in the past decade ~rovides a stron~ basis for the belief that an accel- erated and intensified ,~ault on cancer at this time will produce ex- traordinary rewards. The Committee is unanimously of the view that an effectiv:e natiomd program for the conquest of" cancer should be promptly ~nitiated and relentlessly pursued. Bl~mS ~vo I~tP~,~r~.XT ~rl~V~ PA.xmr, REPORT S. 4564 (91ST CON'C~.). ; S. 34 (9~n Coxo.) On T)ecember 4. ] 970, Senator Yarborou.~h ~ntroduced a bill. S. 4564, the "Connuest of Cancer Act". which was based on the recommenda- tions o~ the Pane] of Consultants. While no action could be taken on this bill in the few days remaining for the 91~ Congress. a sim~ar bill. S. ,~t. was introduced in the 9~nd Congress (on ,lanuary ~5.1.0,1) by Senato~ Kennedy and Javits. Briefly. S. 34 proposed: • 1. that the. prevention, diagnosis, and cure of cancer be declared of the highest national priority ; -_.. that an independent Cancer Authority be established to con- duct and support research on cancer, and to'collect and disseminate information on cancer to the public and scientific community; 3. that a national plan be submitted to the Con~'ess. thrfiugh the President, ~or the Conquest. o~ Cancer which would inc]nde: measures to be taken in combatting cancer: ~ time table ~or the accomplishment o~ the measm~ : cost estimates for major portions of the plan. T!55770013

.. 4. that an 18 member.,~h~ational Cancer .&dvisory "Board be. • appl~ved by th~ P'r~sident: with'-the conet~:~ence of the S~ute ~o ad~']s9 ~d a~Js~ ~]{e :~dm~st~;atbr of ~he Caner'Authority. With the delivery of ~wo important ~tateme~ts by the President, early in calenddr year ~971~ it'~as immefiiately evident that a broad consensus acro~ Government~and indeed acro~ the 5"ation~had developed on ~g t~ehne~ and [he ~genqy o~ a major national effo~ to ~nquer cancer ~ rapidly ~ p~ble. Gn ganua~ ~5, in his Sta~ af th'6 Union addre~ to the Nation," the President called for a national commitment" to an intensive campaign to find a cure for cancer. He stated that he would ask for an appropriation of an extra $100 millioa to launch such a campai~ and that he would "ask later for whatever additional funds can b~" effectively used." This request and t~s promise were repe~d in th~ special ~essage on a ~'ational Health Strategy which the President seat. to the Congre~ on Febru- ary i8. ~ that message the Presidcn¢ a~so am~ounced that he would establish a Cancer Co~iqu~t Program within the National Institutes of Health but under its own Director, and a nc.w Advisory Committee to advise the President, the Director of the Program and ~ther officials concernin~ their efforts. Ia tiffs ~ealth M~sage~ the President included an bnportant cau- tion against the danger of nnrealistic expectations: Whea~ we began our space program we were fairly co,dent that our goals codd be reached if only we made a great enough effort. ~e challenge was technological; it did not require new theoretical brekkthroughs. Unfortunately, this ~s uot the ca~ in most biomedical research at the preseat time: scientific breakthroughs are s~ill required and they ofted cannot be foreed~no mater how much money and ener~ is expended. ~V~* should not forget this caution, ~kt the same thne, we should recognize that of all our research endeavors: cancer research may now ~ in the l~st position to behest ft'mn a great infusidn of resources. Iu order to get the intensified cancer research campaign underway without delay, the President included in the Second Supplemental .~ppropriation bill a request for an additional $100 million for can- cer research. This bill was pa~ed by Con~ss on 5fav 94. and the Committee undea~tands~ therefore. ~hat the~ ~ditio~al fim~ will be available ~r obligation on ~uly 1,1971. On May 11~ 1971~Smaator Dominick and Senator Gri~ introduced~ on behalf of the A&nini~ration~ S. 1898~ an "Act to Conquer Cancer." Among the key features o~ tMs bill were thee: 1. ~e bill would ~tabfish a Cancer Cure Program ~thin the 3"ational Institutes of Health~ which shalI have as its obj~tive "the conquer of cancer at the earliest ~ible time." 2. Thd p~am would ~ ~dmini~ered b$ a Dir~r who will ~ appoin~y t~ Prudent ~h ~e advice and con~nt of the Senate, and ~11 ~e under the ~mction of the Pr~ident. TI~C

13 • 3. The' D~ecto~'would serve "~mder the direc~i~ bf th~ Secre- ~aD'¢ I~IF, W~ with res~dct ~ su~ ~ctions ~ ~e'Pr~id~nt rosy 4. -The Program wo~d a~t "m ~ordmatlon ~ the o~her pro- grams ~d acti~ti~ o~ the N~tionul ~itut~ of HealthY 5. ~ C~ncer Cure Ad~ory Cootie wo~d be ~bl~hed~ cons~st~g o~ the S~reta~ o~ ~W, ~e ~irman end members o~ the Natienal Ad~o~ C~ncer Councfi~ and Director o~ the Office o~ Science ~d T~hnolo~ (all o~ the pryingas ex officio membe~)~ ~nd not ~ exc~d ten additionul members ~ be po~ted by t~e ~r~dent. Upon ~he introduction o~ ~ proposed le~slation~ the P~ident reaffirmed hi~ commi~t ~ ~ program w~ch would sub~nti~llv increase our effor~ to find cur~ ~or c~ncer. The te~ o~ his ~a~me~t ~ollows: Cancer h~ become one of m~n~d's deadlier ~nd most elusive enemies. The conqu~ of c~ncer ~ ~a of the m~t important effor~ o~ our time. Su~s will ~st the very 1~i~ o~ our ~nation and our resourcef~n~ss. It will require ~ ~gh sen~ o~ purpose und strong sense o~ ~scip~m. In my m~saga to the Congr~s on ~e State o~ the Union on J~nuary ~ 1971~ and ~g~ ~ my special m~age ~ the Congress concerning ~ ~ational Health Str~te~ on Febru- ury 18~ 1971~ I expr~ed my dete~ution to w~ge ~ success- ~1 campaign ~ga~st this dread d~e~e. I c~ed upon Congrem to uppropriute ~n ~d~tion~l $100 raison to such aa effort. ~ ~m ple~ed that in recent d~ys the ~pro- pfiutions Co~itt~s ~ both the Senate and the ~ouse Repr~ent,tives have ~vorably ~awed this requ~t ~nfl I ~m hopeful that the Hous~which vot~ tofl~y~aad the Seuate will both ~ollow the Committee r~end~tions. F~ns ~D HO~ ~0~ C~v~ Across the ~'ation~ there is ~ growh~g consensus that our vast. scientific and technological resourc~ should promptly be marshaled in an unprecedented attack on this devalating d~sease. Th~ consensus springs both ~rom ~ear and ~rom ho~e. Cunce~' is second only to heurt disease in the number of lives ~t takes in this country. And the nutum o~ its rawges makes it our most faured dise~. If the pr~ent incidence cancer were to eont~ue, some 5~ million Americans who are alive tod~y would contract this dise~e someday. This meuns that cancer would strike one out of eve~ ~our individuals in this eount~and two ou~ of eve~" three ~eric~n ~amilies. St wmfld mean that in the next 10 ye~m alone~ ~ million ~medeans would ~e ~rom ~ncer. ~or many o~ i~ victims~ de~th is ~ slow and painf~ proem. ~d for m~ny of their f~milies~ ~a p~soaM ~ragedy is ~mpo~ded by the tin,helM ~plieations o~ a prolonged ~sease. T!55770015

14 At the same time~ however~ there is much reason for hope. New vistas are now opening for further research into the treatment and prevention of cancer~ the result of some re- markable advances which have been made during the past 10 years as we have multiplied many times over our funda- mental knowledge ~n this area. V.irus r~search~ for example, has demonstrated that can~er can b~ proddced in animals by over 110 o~ the nearly 1,000 viruses tha.t ~ci~nce has identified. We have le.a.rned ~hat animal cancers can be induced by over 1,000 chemical substances. Effective measures for preventing cancer have been developed in animals, aud scientists have even demonstrated that human cancers can be prevented by avoiding exposure to certain chemicals. Other advances in- clude new surgical procedures, more effecti~-e radiation ther- ap.v, and techniques for treating cancer with improved combinations of known drugs. All of tl~ese developments have fueled our hopes and pro- v'idcd a broad frontier of possibilities for researchers in the months and ~'ears ahead. This is ~vhv I was able to suggest m my specml health message to the Congress m February" that ~'of all our research endeavors, cancer research may no~r be in the best position to benefit from a great infusion of resources." I~ORE MONEY AND BETTER ORGANIZATION The time has now come for us to put our money where our hopes are. In the first full budget developed by this adminis- tration last year~ an increase of $20 million was provided for cancer programs. For fiscal year 197'2, the administration re- quest for cancer programs is slightly over $332 million--an increase of $100 milhon from the 197"1 fiscal year. If these re- sources are provided b~¢ the Congress, we should be able to finance a new and massive assault on cancer. If it should turn out that we need more money~ however~ I will not hesitate to ask the Congress to provide whatever funds can be effectively utilized. But I would also emphasize this important point: More money alone will not be enough. Money can help set tile stage for faster progress, but in the end it is brainpower alone whmh can lead us to our goals. Tlfis means, of course~ that we need to mobilize the intelligence and imagination of our doc- tors and scientists. And it also means that we must do a better job o~ tapping the Nation:s administrative and organizational skills, which can help remove many roadblocks to success. Our capacities for efficient management were instrumental in our efforts to split the atom and travel to the moon. Now we need to apply those same capacities to the conquest of cancer. This means~ for one thing, that a wide variety of ressarch activities in all parts of the ~ountry, in many areas of society, and in a great number of disciplines must be carefully coordi- nated. There must be as much cross-fertilization as possible between various scientific pursuits. TI55770016

15 In the past, the National Institutes of Health have had con- siderable success in fostering such coordination and coopera- tion and, in the processs they have earned both the respect of the scientific community and the gratitude of thousands who live happier and healthier lives-because of I~IH successes. It is for this reason that I have asked the Congress to establish a Cancer-Cure Program within the National Institutes of Health~ where it can take the fullest advantage of other wide- ranging research. ~t the same time, it is important that this program be iden- tified as one of our highest priorities, and that its potential for relieving human suffering~not be compromised by the famil- iar dangers of bureaucracy and redtape. For this reason. I am asking the Congress to give the Cancer-Cure Program In- dependent budgetary statu~and to make its Director-respon- sible directly to the President. This effort needs the full weight and support of the Presidency to see to it that it moves toward its goals as expeditiously as possible. I am furthea, recommend-. ing that this ~irector be supported by a strong management group ~,hich has as its one goal the cure of cancer, and which can pursue tbatgoal with single-minded tenacity. In additions I am recommending that a new Cancer-Cure Advisory Committee be set up to provide a broad range of advice and assistance for the President and for others who lead the Cancer-Cure Program, particularly as they work to set intelligent priorities for the Nation's efforts in this area. I am pleased to report that the detailed management and administrative mechanisms for carrying out these plans have been discussed in considerable detail within the National Institntes of Health, with experts in the field outside of Government~ and in the Office of the Secretary of the De- part~nent of Health, Education, and Welfare. As these plans are translated into action~ I hope that the Congress will comment on them and .suggest additional ways in which we cau work toward these m.~uficant goals. I would not want to d~scuss the subject o~ cancer researchs however, without offering a word of caution. Many of the experts that we consulted with told us that biomedical re- search is a notoriously unpredictable enterprise. Instant breakthroughs are ~ew and the path of progress is strewn with unexpected obstacles. As we undertake this crusades we must put on the armor o~ patience, ready to persist in our efforts through a waiting period of unknown and possibly anguishing di~ration. Yet :[ feel confident that with such fundi~g as I have pro- posed, with such organizations as we are de~ eloping, with the dedicated efforts of thousands of men and women f~om many disciplines, and with the cooperation of the Congress and the people of the United States~ we can make great strides against this terrible e~mmy, bringing new hope for all Ameri- cans~nd indeed new hope for all the world. Ti55770017

Labor -and Pdblie Weifars Cora~ttee on March 9 .and -10, 1971, and o,1 Jtme "10,1971. Among .the-witnesses :presenting.testimony were l~prs§en~dfives of the Department of Health, Education, and Wel- fare (incl..'_~ding the Secretary, the Director of the National Institutes of Health~'~ndthe Director of the Natinnal Cancer Institute) ; rep- resen'tdtl/~es of the Panel of Consultants on the Conquest of Cancer; representatives of the Association of American Medical Colleges, the .kmerican Cancer Society, the American Heart Association, and the l~edera~ion of American Societies for E~xl~erimental Biology; and severdl prqminent members o~ the scientific community. In a-ddition, the SubCommittee has included in the hearing record written state- ments..submitted by several members of the scientific commmfity and other~ ~vho are interested in cancer research. Hear.iflgs focused on the opportunities for significant progress in cancer r~earch and the need to develop appropriate organizational and ~fidh~g arran~.ments for an accelerated cancer research effort. For tlm.moSt ~art, discussion centered arotmd the question of how to give cari6gr research the necessary prominence and indel~endence (in ~-erms of program management an~I budget presentation) while ~e- raining thg necessary interplay between scientific disciplines hereto- fore mad~ l~oa/ible by the organizational structure o~ the National Institu[esof Health. Members of the scientific community expressed particulai'ly deep concern about the possibility of fragmentation of the l~ation's biomedical research. III. COMMITTEE ¥IEWS There i~ b~6ad agreement that cancer research has advanced to the stags where a substantial increase in resources and effor~ could be very productive. There seems to be a consensus among cancer research- ors that they are within striking distance of achievingthe basis under- standing 0~cancer cells which has eluded the mostbrilliant medical minds i~ the world for all this time. Several significant breakthroughs have occurred recently, and cancer researchers feel they are close to others. While it is true that such breakthroughs are often "serendipitous'~ and cam~ot be forced~ the Committee feels that a substantial lncrea.c.e in resources~ along with increased organizational efficiency~ will shorten the time necessary to achieve them. The Cancer Panel has identified several broad areas which ~ arr,~nt intensified exploration. For example: 1) ElMde~n~ological Research can identify extrinsic influences (such as chemicals~ viruses~ and radiation) that ~nay play substantial roles in determining the frequency of cancer. Different types of cancer are known to occur with varying incidence in different geographic regions and under varying circumstances of social~ economlc~ nutrifional~ and occupational conditions. Epidemiological identification of intrinsic conditions such as genetic prsdispositm~ n, immunological impairment: TI5577001

17 hormonal effects, or metabolic differences may elucidate other factors affecting the incidence of cancer which could be clinically controlled. 9) C,~e, mlcal Ca~inogenesis is a research area of prime importance because of the variety and quantity of new compounds introduced into the biosphere. I~reliminary efficient screening should be used to eliminate or reduce this hazard. The ability to evoke n~oplastio change in isolated tissue in culture should accelerate the r~earch in defining hazardous compounds and the mechanism by which cancer is caused. Further research is needed on : a) The basic cellular and molecular mechanisms of action of carcinogenic chemicals~ viruses, and radiations. There may be several mechanisms (both genetic and epigenetic) for each class of carcinogens. b) The ~inds of i~teractions of viruses~ ~l~emlcals, and radia- tions which result in the production o~ neoplasms in experimental ani~nals and man. c) The proportion o~ tmnors in man induced by viruses~ chem- icals~ radiations, a'nd combinations o~ ~hese agents. d) The prevention of chemically induced cancer in man by the identification and removal of causative chemicals. It is known that ia most circumstances, a compound is transformed to a proximate carcinogen~ which is then directly involved in the carcinogenic process. There appear to be common chemical character- is.tics oi the proximate carcinogens and also common characteristics o~ the cellular metabolites wi~h which they can react. Further research is called ~or on how to interfere chemically with the nmh~bolism which produces the proximate carcinogen or to inactivate it once it is formed. 3 ) l "h'ology. The recog~titioa that a variety of neoplastic diseases i~ domestic and wild animals are due to viruse~ makes ~t appear increas- ingly probably that some types of human neoplasia are ~ue to viruses. Although viruses have been found in human cancers, proof of thei,' etiologi~ relationship is still incomplete. An expanded study of viruses of cancer should include the mechanisms of a) how a virus initiates cancer, b) how a virus may be carried in cells for long periods of time with.ou.t exp.ressing its cancerous potential, c) how a natural defense agamsv viral oncogenesis occurs, d) how a virus can sometimes cause tamers and sometimes other, non-neoplastic diseases, e) how the pt'esence of a virus can be detected bv characteristic and special chemical reactions, and f) how the interactions between viral infection a~ld chemical carci~mgens occur which sometimes can evoke tumors. 4) Tumor Antigens. The cha,'acterization, isolation. ~nd purification of antigens from normal cells and from specific tumo~ cells are impor- tant both to the understanding of differences in cellular chemistry in the neoplastic state and to the development o~ tools for the study of tolerance or rejection of tumom. Some o~ these antige,~s ma.{" be identical with those fonnd in embryonic tissues; and some may be specifically a~sociated with virus infection. 5) ~ellular Immune Mechanisms. ~,Iuch further work is needed on the chemical, biochemical, and antigenic nature of cancer cell mem- branes in comparison with those of normal cells, especially in terms of the role of the membranes in coordinating cell activity with bodily needs. Substantial evidence indicates that some, if not all, tumors ~. Rept. 92-247--.~, Ti55770019

18 have surface antigens different from normal cells. These difference~ allow recognition and possible eradication of the tumor by cells of the lymphoid or reticuloer~dothelial system of the host. This surveillance mechanism is known to be influenced by genetic, hormonal, chemical, and physical factors, and perhaps by many others. The characteristics of production, distribution, and mechanism of action of the effector cells that i~a~icipate in the defense against tumors are of great im- portance. FaiIure of cellular mechanisms to eradicate emerging tumor populations may be the final step before a tumor becomes established and begins to grow and so is worthy ,o,f intensified study. 6) //r~rm~raZ I~{~ is conve5 ed through the a~ncy of one or more of the five immunoglobulins and perhaps by ot~her proteins in the plasma. Humoral effects on tumor cells span the .range from lethal- ity to apparent protection of the cell by interfering with cellular immuhe mechanisms. The inten'e]ation of the immunoglobulins with other proteins, their relation to receptor sites on the cell, and their influence on cellular immune mechanisms, urgently need clarification. 7) ImcnU~Ol~'oph~fla~i~ a~d Irncnuno~h~rapy have both been showu to be effecti~e in experimental animals, and useful immunotherapy has been repor~d in some children with acute leukemia. Specific and nonspecific stimali may enhance immunologic response of the host's own immunocompetent tissue, both in v4vo and in ~itro. Tech- niques of using specific tumor antigen% additional immunocompetent cells, and nonspecifie immunologic stimuli, are worthy of intensified study. The timing of immunotherapy with respect to other procedures needs clarification, but this form of treatment would appear to be most useful after maximal reduction in tumor size by surgery: radia- tion, or chemotherapy. 8) D4a~nosis. Precise and highly sensitive techniques of diagnosis prior to the appearance of clinical symptoms or of large masses of cancerous tissue are of major importance to advances in therapy. It is suspected that many~ if not most, neoplasms secrete materials into the blood which have remote effects on the patient and which are not yet recognizable with tests available. Immunological assay meth- ods have be~n successfully used to quantify tumor products in bio- logical fluids. For example, chorionic gonadotropin indicates the presence of trophoblastic neoplasia and its detection allows diagnosis and appropriate therapy before a tumor mass is recognizable..k carc~no-embryonic antigen appears in the blood of patients with carcinoma of the bowel, and a sarcoma antigen in patients ~'ith sarcomatous tumor growth. Continuing research to seek biochemical and immunolo~cal means of detectifig cancers early deserves ex- pansion. ~iutomated analytic tedhuiques with comparisons of results against computer-banked data for the healthy population and for the same indi~dual at an earlier date would pro',dde a more precise method for early diagnosis. 9) ~be~no~rapy. Several'disseminate¢l human tumors have been cured with drugs a_lone, giving ample testimony to the proposition that selective toxicity does ekist and that a ]~otential for cure is present. Effort must be extended to understand the interactian of drug, host, tumor, oncogenic agent, and host defens~ mer~hanisms in this equ _ation. Research on which drugs to give fo~ which tumors in what combina- tions, and when in the course of the disease (before operation, after Ti55770020

19 operation~ ~ith rad~otherapy~ a~r widespread metast~s~ eta) ar~ areas of great importance. 10) Tumor G~l~nvt~cs. Only a potion o~ tumor ce]~ are in an ac- tNe ~w~ cycl~ at any one t~e, ~d ~e syn~ of c~tical ~ar co~tituents is ~own ~ o~ur dur~g spedfic ph~ of that cycle. A much d~per understan~ng of selective to,city dur~g ~ffe~t ph~ of the cell cycle ~ needed ~ addition to ~ucidaGon o~ the nat- ural death of ceils ~ the t~or, Gm ~raction of ~ ~ th~ t~or w~ch c~n ~:eprodace~ and te~qhes o~ ~g ~Hs w~ch are not ~ the c[itical ph~ o~ synthesis.,Th~e typ~ of in~rma~on are re- q~red particularly for slow gro~ ing spont~eous neopl~ms h~ experi- m~tal animals and h~ man. 1~) ~a~e~. ~mor cel~ lodged at a distance from the capi~ary or beyond the blood brain barEer may enjoy a pharma- colo~c~l sanctua~ where ad~ua~ drug~ncentrations cannot reach them to ~xert ~e~al e~dc~. Experiment~ and clinical r~earch of this p~bl~m ~ r~uired. 12) New D~gs. Chemical synth~ of compo~ or polymers de- si~ed to ~r~re with critical steps in cancer cell bi~is and metabolism are ~portant. The specie targe~ and t~iqu~ o~ se- lect~g the compounds ~or trial must be arriv~ at by che~ and biolog~s~ ~ coordination, and th~e syn~etic programs m~t be carrigd out in close prox~ty to biological ~sting~ ~ ~at rapid back occurs. Empiric sc~en~g of natural produc~ particulaEy pl~t extrac~ and antibio~ ~n~nu~ to pro~de compoun~ o~ major clinical use~e~. Nearly a dozen substanc~ of bot~ical and mic~o- biolo~cal ori~ are now in clinical use and have demonstrated thera- peutic benefi~ against c~c~r. The pro~ams o~ seth for bota~cal and antibiotic dru~ agai~t cancer shoed be extsnd~ together ~th relevant biolo~icaYscreening in close prox~ity. ~Iuch additional search is also ~eded on: (a) Metabolic or en~atic differences between normal and malignant ~l]s~ which might lead to new drug desi~. b) Sopldsticated testing of compo~ds~ partic~arly antibioti~ aga~t various important biosynthetic enzymes. D~ wMch may affect enzymes tmique to oncogenic vir~ hold panic,at promise for neoplasms found to be ~ed by ~ruses. c) Pharmacolo~ and metabolic d]spositio~ o~ ~own ~tive compo~ ~ h~an cancer patient. . d) Developm~t of ~o~-i~bit~g compo~ ~at are ~mm~osuppr~ve. e) S~th~is and structum-ac~d~ an~ys~ o~ series o~ com- ponds ~at inhibit key enzyme, wi~ the ~ o~ ~scowring species or tissue ~ffer~c~ ~ a~iti~ for ~e dru~. f) Attemp~ to lay ~e gro~dwork for ~e development of new classes o~ d~ that would affect proce~es of mali~ancy o~er than ~ow~, such as inv~ion and met~s. g) Elu~dation o~ the m~s~ whereby certain d~ ~ tentiate the lethal effec~ o~ heat on tumor ~l~. h) A~p~ to ~d new and ~ve dru~ ~ pr~u~ a radio- ~zafion o~ ~om. Pred~ T~g o~ D~g~ ~fore h~an u~ is of ma~or value and m~ be e~nded. The op~mal d~e~ ~ute~ schedule and con~tions TI55770021

2O administration ,nay be learned from experimental animals in addition to the toxicities and side effects which may develop. ~hat is more. development of methods by which a drug c~n be tested in the labora-" tory. for its effectiveness on the patient'~s own tumor prior to its clinical use is an area where important advance can be made. Glinical I~vest~gatio~s in chemotherapy provide an essential link in cancer research, since the ultimate goal is prevention and relief of the dise,,~e in man. Cooperative group studies bring earlier results of higher precision and validity because of the positive intellectual input of several investigators in planning the research. 13) Radiotherapy. Use of new radiation sources may allow avoid- ance of the problems of anoxia in tumor tissues and so substantially improve radiotherapeutic results. Another area of gre~t importance is the continued and expanded study of the effects chemotherapeutic agents in combination with radiotherapy whe~ the optimal choice of drug, schedule, dose, and radiation regimen needs wide investigation. 14) Surgical Imp~'ove~ne,nts can be made which should substantially increase cure rates. These involve the early use of surgery as ~, prever~- tion of the development of invasive and m~t~tatic cancer by removing precance3'ous tissues. In addition, the combition of radiation and surgery m the eradication of established neoplasms is subjec~ to major improvement by appropriate design, precise scheduling, and the use of drugs, to take advantage of the small residual tumor populations after the initial ma~or reductions. Organ trausplantation should be de- velo!~ed as an aid to the extension of curative surgery. 15) Fundamental Biologleal S~.~dles are of the ~reatest importance in disclosing illformation about the causes of cancer and strategy for its cure and prevention. Molecular biology can eludicate DN2k muta- tions. A change in Dh'A structure as a random event or as a response to an environmental trauma may lead to cellular death, or, if the injury is compatible with cellular survival, a nmtation. Following such u mutation, a series of descendants lnay ~.ppear whose change ~n the DN2k, if unrepaired, may be heritable and could be the cause of neo- plastic transformation. In t~e coume of normal growth and matura- tion, this change in DNA ~ ould be reflected in the composition of I~NA, wlfich in part provides messages sl3ecifvin~ t3articular orotein syntheses which determine the cha~-acte~ of ~he~c~ll's enzyn~es and thus its whole metabolic machinery. Mutations and derangements in the repression and derepression of genetic material are suscel~tible of study by a wide range of experimental systems. These studies must be pursued in ~reat detail because of their relevance to cancer. Further -~'ork is needea in the area of biochemistry to support both the search for preventive and therapeutic measures: a) Further documeutation of biochemical diversity iu cell com- ponents and in responses to control factors is necessary to depict the true magnitude of the cancer problem and perhaps to sort cut the threads of unity which must exist. b) Examimxtion of'tumo~ in terms of ~ozym~ is particularly important because, if two different enzymes can catalyze the same ~action but possess different three-dimensional structures, they may respond differently to chemotherapeutic agents~ and the ~o formation may suggest new modes o~[ chemot~herapy. Isozyme