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~1o ~r-k T) t-n f--s Nla9az)f7 ~ _ March ~, ) `1'rl- 'C Particle'- n A Unified Theory of Cancer By LEE_ EDSON 1 DR ohal~ a c~utury,a: small,:.ge~e,!~W sistent and intrepid brand of ' . scientists insisted, often at the top of their decibel range, that- can-' cer is caused by- man's tiniest and most mysterioug natural enemy: the virus. Very few scientists ever lis- tened; if they did, they generally objected. How can a virus cause cancer when doctors don't seem to get it from their patients, or from re- search animals, or from tissue cul- tures?, the - skeptics asked. Why do the old folks come down with cancer more frequently than the young? Why are there so many dif- ferent agents--1,000 chemicals alone at last count-capable of bringing about animal cancers in the Iabora- i tory? And why do Japanese males - ~~ and New York Jews suffer more tl>an ottrcr ethnic and cultural groups from cancer of the stomach, while the Chinese on Taiwan -die -nere-ofiten from cancer of the nasopharynx? Such -thorny questions made life difficult for the - virus theory . propo- nents. But in the last few years a " nubf l mer oeading scientists have rec- - ognized that a revolution in thinking may be brewing in their midst. Lab- . oratory findings in molecular biology, biochemistry and immunology have begun to make scientifi d c n sense a i have inspired a new wave of hope U9„''EDSON 'i$ a science writer who , ,nt1Y+n'-contdbutes to The Times ~,~EaIAe.'I - ~ . nnltinliesl.; Meetings~, devoted to tumor-producing viruses -how they. work and behave-are being held with greater frequency than ever before and are drawing ' more distinguished investigators alb , the time. In Bethesda, the National Cancer Institute, which controls the Govern- ment's cancer research budget, has doubled the allotment for virus re- search over, what it was five years ~ ago; in fact, this, year's budget is twice the size of last,year's, despite ~ a general cut in research funding. The President's State of the Union _ j message, wfiich proposed an inspired, " ; Apollo-like effort to end the scourge of cancer, is likely to increase this budget even further. Dr. Frank Rauscher, who heads the institute's virus cancer task force, says that "the era of the seventies is the era of confrontation with the cancer mystery and will reveal more- about the mechanism of cancer than any time since the inception of research." This extraordinary reviva1of inter- est in viruses can be laid in large measure to Dr.,Robert J. Huebner, 57- year-old head of the institute's viral carcinogenesis branch, a recent win- ner of the National Science Medal and one of the nation's leading disease fighters. Huebner, marshal- ing the findings of the last few years, has -formulated a theory. of cancer that not only lays the disease at-the aroyarype til' t di ctsa°• ~ a " ~sm ~ sra~7: ~ : .pa l ti is heaii~~ilisea . ma~ .one,~ilay saon^ ~4 ~ p iStS~aSr~ltAC~J~+~: kAOwil t0~*ml ' Ir~lear that mqpk3nd'•sx'~To.'~ ~door.3 of-:Lliesvirua,``but 'Actually ` a B1~riiE&ba'1VId." ~ . r c e Moreover, his theory diverges from those of other viral researchers on an even more critical point: he -believes that the C particle is not an infectious virus that invades the body ' and generates disease, but a nonin- fectious virus that is a normal part of all living cells-and has somehow gone haywire. The Jekyll-and-Hyde behind diverse cancers in man-the C particle-turns out to be, in Hueb-, ner's opinion, none other than a form of RNA, one of the two main sub-, stances that govern heredity (al- though the particle, as we_ shall see, has a different function in the cell). H UEBNER is an articulate man with the d.omiaant air of one who has fathered nine- children and with an Inspector Javert complex about getting his bug. He loves nothing more than to expound his ideas. "Let's be clear about one thing," he says, "the cancer virus is definitely not the same kind of bug that causes such well-known infections as mea- sles, polio or the common cold. It isn't spread, horizontally, that is, from person to person, or from an animal or a toilet seat. You don't catch it. The C particle, or rather the genetic material it carries, is sorhethirig we all have in our bodies, and transmit vertically to our off- spring, like a gene that.gives you red hair or blue eyes. 'In fact, the can- w ~, _

(Continued from Page 29) ing, chemicals, radiation an ,rus does, the cancer virus is old age are simply triggei programed to issue orders that switch° on the genom to the cell to grow and grow [the collection of - genes tha until it unhappily creates the make up the virus]," he say, :er - virus ~ is itself a group~ of geriesthousand of. these ''"creatures" have ~ ugly cluster of cells known as "So are a host of other ei -one tiny package of ~~etaitaiice ~n caught : arid `~x-ant~etl; in the cancer which invades other vironmental and hereditar inits among the ithhree-quaiters of a electron m%croscope; and so far some Wy structures and may cause factors that make the diffe; 300~ave been tied to disease in'iq.an t''de~." \ences in cancers between or nilliort genes that make up the ~6$ ethnic. group and anothe ew~haped chromosomes in; ~!d animal. In fact, a "good" lrirtis In Huebner's thinking this, the human cell. ~"~on hica ~ • is hard to find. virus - is on hand, ironically, areas: They , re g all contributoi , ? g~ap of The exhibits the 1?ro1erties to serve a good purpose; it is ~causes, not the real root ~tis, . d `~t meari that the ctisY pa~ce'~s.~'ln}erited. What you do in ', of.a #ving system, but spends a gol a growth particle, perhaps one th e tkouble, which lies in tl. eneisdeal tif its time in an inactive ,~te.~A t,Qf cOe original ;growth cam' ~mction of the C pantic i~er,i~~.t~`.jlse specific group of g the- potential tof cancer, 7.1`nlike ather somnolent biole '. =?n~ders of the enrbryonic ~ that Cal~y with tflre. genes in the ho, nes as ~nats;'such as seeds or s ores, ° of life. "T~he Farticle ~h „ y. ~. ~~; the are kriovjm;~ , ViVhnt ,sefs i,them off? That's the key ~t; nlessed with meta4~olic rna- ~~~' wants to go back to the . Gri I know some ~ i6hinery; to grow and reproduce, eaeh': gO°d old times of its world- The hypothesis is a- sweel quesi3; One has to t}i9ng t! about viruses and how, virus must 1herefore tatch onto a -^~o grax' more embryn, some ing one, . and not all memhei legs eyes and other of the scientific communit ~e in living cells." Et~-':1>~ Ydttises ;'; are- microscopic-50,000; aver&ge-Slxed ones I can sit on the Iost, cell, with its builtan chemical •~~' ' ~spe:cralized products, In a way are convinced that HuebiiE factory. Once uiside the host, ihe wants to start again; to has provided - adequate `proo " Vvirus luddenly makes up for its lown ake the brother of the host .!RNA virus particles -,hm . p~ead of ~; in=-and come in a varietyj ficie~cy by taking. advantage. ofL ~~1 Unfortunately, in the . been found iri animal cancer asl9ia some are spheres, oth~rs~ the ieA s chemical apparatus and pes ,~~rtsson of the complex, mature , but they are. not " easy t ~rods; 'sti~tothers come in groups o V usiing it to make replicas of 3tself' .~y structure, there is no identify in the •tumors of mai e basic compos'ition, The parasite subverts the hos~';a {;,longer an, opportunity for Huebner himself. Ilhas n~ wever; as Nobel laureate Wendell reproduces at its expense, .sometlnmes~,, .such simplistic urges, and in- isolated a C particle -from ~arrley .: of ' the University of Cali-' until the cell dies -of -exhaustion: 'The , stead of a new and useful h~an cancer, but ~ other o1 rnia first revealed in the nineteen- new viruses then stream out of the: grovrth, the body grows a servers claim to have seen i ~irties; is the same for all. A virus emasculated cell and invade a~new~ -~~r. The particle, it seems, .~pecia4ly 'in some cases a¢ontains either deoxyribonucleic acid -cell, then another, spreading infection:,, ,has the power to start us off, breast cancer. Observatior Nll,),,mod.ecules or ribonucleic acid' ~~ughou~t the body-unless st,opped' and the power to kill us." from an electron m~icroscof ) molecules, the chemical build-. by the bodys own virus-destr~iy!ing;x are open to some interpret; Og blocks, of all living things, held antibodies or by a drug that prevents ~ N its basics, this approach tion, however, and there iotogether'by a coat of protein. Sirice the vi~us from replicating in the host . t~~•#Acancer isn't altogether new, disagreement as to whethE ~compasition is-virtuatty the same ~?~~1.q - w~:,Huebner will admit. Back the observers truly saw 'wh, ;I ~o~~the gene, it is not surpris- u:.` Tne:~ cancer virus, the Huebner: r~ the nineteen-forties Dr. they pr+afessed-to see. that scientists have come to `:re- . team's. C particle, operates in -a~ : to- 4.acob Furth of Columbia, one Huebner shrugs off the ej viruses as central to the study 411y different •manner. "Ifs been sit- w:of"the pioneers of cancer re- tire argument by saying tha VWficq, indeed as the key to the <"hng quietly in the nucleus of the ilsegih, performed an animal it is not really necessary t t,~~~ent which suggested e11 ll h i i a t e t me, and suddenly it observe the C ~part cle i ret iof Iite. c rthat leukemia potential i.n , not takes command ~iike a fiifth columnist human ~tumors to knaw ths here d any b f ~„ey can e oun w , only in the body but in the air, on who feels the conditions are ripe," `mi~`' was vertically 'trans- it is there. For its existenc mitted from parent to off- ,othe ground and in'plants. According Hueliner explains. "Instead of repro- spring, and in the nineteen- is unFmistakably indicated, I ~to one theory, viruses are really ducing itself, like the infectious vi-. maintains, by the presence c ~,t•~ ~ ewlyf, ~y~~ (Continued on Page 69) ~~es Ludwik Gross of the a"chemical faotprint" knoR l V Watcrerut ~tratiras P~ as an antigen. claimed the then outrageous „idea of a latent cancer gene. - An antigen is any substanc In later years researchers who that inspires the release believed that cancer must antibodies which attack have a genetic connection put particular virus. Most pri 'the'blame for the disease on telns are - good antigens, at 'defective chromosomes, de- the protein coat of an infe, Pective genes and on certain tious virus itself is often tt 'mutations of the genetic mate- ~body's best defense agaui; rial (or some combination of illness. (Dead 'or weakent these factors). viruses are introduced into tt Huebner's contribution, body in vaccines to comb, based on considerable new such - diseases as polio at data, is the conclusion that influenza.) the many different forms of The presence of an antig( cancer are all traceable to a can be detected by vario morbid change in the same biodhemical methods, and virus, the noninfectious C the nineteen - fifties Huebrj particle. He thus came to call discovered one in animal ca his conception the "unitary cers induceci by DNA virusF theory" because it purports to he called it the T (or tump explain the origin of all can- antigen and its discovery it cers, whether they seem to to the understanding of th arise spontaneously or are type of cancer. Several yeg induced by carcinogenic fac- later, he found the antigen. tors in the environment, such the RNA tumor virus, whic as ciaarette smoke. hA „n„,a,,, +,I,o „r f„„ ,. ,

~~ - 'pr of e ~ : `` ` virai 1tN A "It's a little like the devil," Huebner says about the par- tid'e,. "you know it only by iits wlarks. Medicine doesn't altways have laboratory proof of',f11e-*ause of a disease, but wt . can move forward and.,,. :.~ agit...-Vdt~ .the disease without d . , ... M 0l!*~XHELESS, neithet, gyobnel` nor any or nts .coi- leagut$ b" yet performed thec ' " ; ~ #triov'; tt so dar to1he y eeese .x logist's heart since -; the s' ' ys 916f.•;• Robert Koch,*tlle father . ofj bacteriology:. _.:#.hat`,.;;~, uld ' require isolating thei, viMs trar a numan cancer,~y itt~eCtictg ~it into man•, ; ~rid~: "` ob- im&i, ~~nd consistently_ e • ng 7 the same canc r: .a Qbvaiottsly human voluntem;; ' rd_;. ,~ test.would b4:*, r•istielt :~~. ~ In .tfie ;absence of pro0f' ofX ` `, ` s sort', Huebner's critics;~~- .; gue'tliat it may weli be ~ather°' ~, net;ie, anechanisms that •pro=i~ ' cancer in the cell ' ,and'a`: 'not, tfie morbid expressio&-:of ;,:. _' R~TA'',particle he claims is; e'nauee: Some scientists, for , hold firnt to the mu- Otion.,l~otl~esis--first enun- , . r~iated„in,, 1905 and stili, one,, f the_, most durable theories which maintains~ at a=catttonic i'rritation causes :` ~n ttme''~ ~ genetic dhange` that' ~'F';w ` ~ay ^ de't,ransferred from one,'i=;;: I ~eli~ to'its progeny_'l1his means aame genetic information must ; - 'itta~e been added to, or taken .away rrom, the genes already 4here or ~ome other modifica- Vort ut,ust' have occurred, cTe- p'tting a new situation in ts+hioh the cell is dominated . instrut~tions for producing _ ~~~aaannncet:' fIuebne'r says the mutation bypothesi$ is losing support eVen fromi those who believed 3nit for years, He points to Iui fnteresting experiment. in . Wch an investigator replaced the nucleus of a frog's egg with the nucleus taken from t can(er cell in a frog's dis- !ased kidney. The egg was Pertilized. A healthy swim- ming stage larva emerged Iroan the embryo, indicating . ' that t~he cancer . cell had all the necessary genetic info:'- wation to cause the growth ' Of a normal organism. Evi- dently tite cancerous state had bled to take anything away Or add anything to the - nu- 1~us. ally, a persistent. argu- stems from those experts, ma:nly pathologists, who in- sist that cancer is not a single disease but a family of_ diseases. If it's just a si.xgle diSCWsic'--'cdeZ%,sed by oi<v v3c us -.-ZV:xy are there so many crwri'ical_ly L1ifitlrC;nt ty]iP.S of Cia'1cti'.r "L:L. 't713y. C'.o usi[i'.r::nt cixe.ixica'_s act s. sc?:'ically a ;ai.;is;, dai.~a•ent tumors? "°Il)at'S a reasoraJle ques- tion," Htle}):2er r°.j3ii~2;i, "but I thinli t1xL many fac..;:o of cancer have to do with the type oF target cell in which the i irus 'turns cn,' The diversity of ca*xce, s should not dis- suade ot?e front b£lin viii ; in the common cause, e:;l,;;cially at the violecu?a:' level. After all, we all sprzno from one cell, which contained the information _that mada us all different." ""~ 1. .. .k 1.Ti-IrJIIGa Huebner blames . a vertical, noninfec- tious RR7A v:rus for all can cers, work on horizontally infectious . viruses was im- portant to the development of his theory. Back in 1911 Peyton Rous of the Roclsefel- ler Institute grovnd up a tumor from a Piynlonth Rock hen,. dissolved it 'in a salt solution, filtered out the can- cer cells and injected the resultant cell-free "soup" into other chickens. To his intense fascination, they ull developed tumors. Evidently the extract contained so,nsth'in; thz2 could transmit the hi;l1ly malia ant tumoi from one hen to: a nother. Rous's findings, ti7hen firSt • published, xnade little irr.pact. Everyone said it was fine for the birds, but had no relevance to man. V717en studies of can- cers in othzr specfes yielc?ed no virus, the cancer-virus in- fection theory fell into dis- repute - the same kind of ignominy with which estab- lished medicine greeted the microbe theo•ry of disease when it was first proposed. Rous himself, somevrhat dis- couraged, turx?,-ed to other fields of research. Interest- ingly, 55 ye<^z.rs after R ous had of science tooL a second look at this feat and awarded him the Nobel Prize for'Medicine, During that half - century, evidence oz virus-caused can- cer slo°,rly tric'- .e,, i.n. ?",.e big breaJcti;rov2,ix cccur~ed the ninetee3'x-f ifti"s V'i3 -M 1 ' KI1vik Gross, aax Array sz;. ;eon at- tacl:er: to the D_oa:.: Vet- erans r? dnai;,ist_ aiion I-Iospi tal, sho3:ed by a bri.lic;nt series of exp;,`rixx-tents t: at lers.eniia, a cancer of the blood, could be trans:331ttCd in mice --- though only in the newborn. Gross worked with two inbred strains of mice: the ATi:zt strrin, zviticli shows a high incidence of inherited leukemia, and the C3H strain, which does not i1 car the dis- ease naturally. He injected the leu::emi : :zla9d f.om the ARR mice ifato the lovi-Ieulcemia C3H strain and fo:and that the latter developed the diseasL; in fact, the strain developed not only leukemia but a va- riety of oti'tz.~r cancers. Gross was able to iaer.tify the killer virus, wl3ic3, is now knovvn as the murine lea _emia virus. A few yewr , later researchers were ahIa to see it in the electron i:xicroscope and ovei the yeax:s they found s>milax viruses irx other species in• cludin ;- tnou3h this is in dispute-in man. At first, Gross's monu• mental work was treateri r.iti the s Ame • ekeptical disc;air accorded early virus research Denied working space on oni occasion, he had to set tip hi; laboratory in an unused mill tary latrine. ;";evertneiess, hi; findings on onco ;ei3ic virusI, sti*:lulate.d a )<:ve o, research At the ATafional -Institute of I-lealth, for inst?nce, Drs Sar'~~h Steviart and Bern*- Ec:dy tried to duplicate Gross'. experiment and found in th, le°akemic fluid a rsevr viru which produc2d a group o cance>_'s in newborn animah So man y cancers a ppeared 'v fact (23 in all) ti:at the viru was christed ed polyo::z, (many tumors). NIore su1 pr_sing, W_Zen injected int• (Gonti-px:cc3 n,: Pc;;e 76) 6J~~a~~1d:i~:v Q>..ng"'CSaD4a.3 L-4'~~ :: S .i•ar -n i : 6 12 3--3 •v`:':i11 C''2 :+3-_ C':d:.1:! 33 .r'•,3"'.':'.Ole:'.7.`~" cv:aw.l.adaA 3as` ct S';a3 cn'_M.i -n.-.I JCIZO r':w a.' IJ otner . es;ry sucni~ sters ratsa d "~abbits ~ ;l n , , ,j ,: t~, ~ Gny~ sp}ie ca~ particie aiways, n 1 - yielded 'asplay of tumors; The viru.s: the first discove which crosses species`:bound-'I aries, proved- to -be- made of' DNA. HE discovery of the i polyoma virus created a good, deal "of excitement; it meant l r'~ttiat''a single virus might •be:' ' tht i diesesthatj 6*genn asa: many forms. ,,;Ifiuebner ! J y~ett.texed the- search,~,at, this. ,..poitlt, asking himself wliefher.i %e polyoma eould '-Also'Ae; Ld faund in animals in 'tleic" aan~ 4 4 natural st$ ~ ; ~ ~~ a r`'~"tb'ally occurring "Caricel.'a`~:, kr~ 4 ...-,.. . He had belund him Arecord ~ , i tb!' having tracked do'avii"t#!~ ' oelu'sive _ Q fever and t;16ther' , ~,~~terious- diseases: ; ;TQ„* ~d ., ,bhe polyoma viras, -he•?;began: .;hunting =in the places,r~awlter.e; ~pice were most likely~.',io~ gat'her-crowded urban: areas:~ "' In Harlem, he • trapped H'450; mice on t;he top floor of . o tenement and discove'red,~that half of them carried the¢vtrus,', but no virus was found ;n the , :humanbeings who lived:there.~ He also wondered -whether'~ -tbe Harlem mouse's wild country cousin contracted' polyoma. As the owner'. of' =a cattle farm' in .Maryland~ -. where he raises prze ,Angus,•l ..'bulls, he had no tropble.find-' ing natural breeding places ofti mice in his own hay_ : sheds and nearby gran:aries. +Huebner soon found that polyoma wasi as'widespread in the countryl as in the city. . ' Even in his travels Hueb- ner couldn't get away from mice with polyoma. He ~emem- bers axAng a iiekd mouse scurrying out of sight in. the, "vicinity of Disneyland, ` a rather fitting place for a~ mouse. Huebner promptly, G °climbed a small fence, traced 1 s the mouse to its lair and:dater'- determined that it was acarjry- ing the virus. Out of these forays'Huebner ~ discovered an important fact while the polyoma virus is present in a good many • of the wild mice, the animals were singularly free of can- cer. This was also .true_ of other DNA•& viruses,~~such-.,as__ the adenoviruses--found~-in- throat and adenoids':•of man ••and animals, which-' iio not produce cancers in their nat- 'ural hosts. -It seemed that these in- fectious - DNA viruses could produce tumors in newborn laboratory rodents liy, intjec- tion, but d,id not da so` va'hen

a~iou~the"oti'heikgreat class of viruses, the hundred ,orc so RNA's beginning with the chicken virus-athe first C partiele - disoovered by Pey- ton Rous? Here Huebner and ^. his colleagues hit pay dirt; : RNA viruses, mainly C par- :„'ticles, were found in large ; numbers of animals with nat- urally occurring cancer. The scientists found tfhem in cihick- `ea1~s, mice and cats with tumors, though they found not d,.the virus_ itself but _ the spe- *~ cific antigen of the virus. The big question was: Is the virus ~adharmmless resident in the cell or an assassin in disguise? ~ ~ aa :adouid be~~a ^'c~ ` 'factoriri the gene'rality of hti= man cancer." Early last year several in- vestigators created a flurry of excitement when they claimed to have seen a C par- ' tide in human cancer tissue (it looks like a miniature Cohi- _nese- fortune cookie). Hiueb- ner, however, - wasn't sure, though he admits he would feel like-Balboaa sighting the :Pacific if -he could identify the pwticle for certain. "Ac- 'tually," he. says, "it wasn't that important. By this time a lot of lines of evidence from ' laboratories were fusing, • and -I became •convinced that the. l t h i ~A arm ess ruses are no v 0 answer this question but are behind most cancers iuebner had to know more i aiid`aninnal:' a m n y ..,~a'bQut the care and feeding of - particle. In the next few One off the major pieces of ; months he and his team experianental evidence had GG'Let's be clear about one thing.' `VA I c-rJ€ saYs Huebner. 'The cancer virus is definitely not the same kind' of bug that causes such well- known ' known infections as mensles, n°3" :' polio or the common cold.' 919 ;.. rhr,.. Unted down antigens of the IC-: pa~nticle in virtually every vertebrate that could be ,trapped and hauled into the laboratory. The particle proved td be uwzimgly uJaiquiatmu. rlnvestigatars found it in rats, swine, guinea pigs, monkeys, 'ham°sters and, to show the `evolutionary continuity, in Isnakes. Wherever there were "malignant tumors, there was `-evidence of C particles. ~ Cats were discovered to be a particularly good laboratory .subject for the study of C - particles. Huebner and others found that the feline leukemia virus, present in.75 per cent of cats, crosses species bar- riers and grows well in dog, monkey and human tissue. In 4act; this finding led to a rash ~of public worry over catching 8ncer from cats. To avoid panic, Huebner and his aides, Drs. Murray Gardner and Bernard Hanes of the Univer- sity of Southern California; conducted a survey in the Los Angeles area last year and established, happily, "There is no statisticallv significant dif- ~.. been .gathered the previous year when Huebner's asso- ciates, George Todaro and Stuart Aaronson, attempted to prove a closer . connection bKvem the omoeet ©f oid age - especially the so - called "cancer years" (beginning, by most estimates, after 50)- and an increase in the pro- duction of C-type virus.' One of the striking facts of life is that no cell lives for- ever. Every normal cell is. exquisitely timed from birth to live its assigned lifetime and then die. Only cancer cells seem to seek immortality. Todaro and.Aaronson grew emabryonic mouse cells in a test tube until they reached the age that biologists agTee amounts to dotage in tissue culture. What happened was that a 'number of the cells when they passed the grim boundary line of. old age be- came cancerous - at which , point most of them were start- ample, causes the C particle, , ing to make the' ~ antigeii of I r or indeed 'any other oncogenic. ' the C particle. Evidently :.the . virus, to `make the cancer? " assembly of viral -genes must._ , And how does it actually go " ~ ..L.....+. :... ~:_.., c 1.afv.«e he~VP }lpPl'~ in hhP ral{ uebner`sgbv~i4hoVa.nd'Aelse' where have tested cancer',3'1;' "trigger.s" other than old,age.`': TypicalIy, normal animal ceils", ~ with and without active RNA.'" virus have both been subject-, `' ed to radiation, or have been chemically treated with knowg,'. carcinogens. In one such ex=;~-` _ periment, the carcinogen pro-,~; ' duced tumor cedls iri a colony~? ., with RNA virus .relativ,ely0.. quickly and in great nurnber:• A similar assault on the t at u~-4'~ ~.,~ free, celUs didn't transtorrii :. theti into cancer at all, sti'oug-'?; , ly suggesting that the 1rir~;~~ ,. _was the key factor, in; " ca ncer. UEBNER found '- another, sriking thing: he turned „7aP antigens of C particles iit.,,; . ' embryos. Perhaps nature ~n jia~ ~ t built the C particle into, ~at ' cell for-; a od "~ 90 purimse produce the fast growth need4xt ed by the embrio for ms.tur-, ,<< ing. If the particle' is asso-;.-. - ciated with rapid growtli;che : theorized, then tissues that - grow fast and thus hav°`t~e~x; highest turnover of ;ceils should have more antigens, than more slowly growing,tis'. sue. And so it proved to -bB.,F Huebner found for instanceX-; K , . that the fast-growing inside lining- of- the intestinal tract: ;' shows more footprints of thel°:fi= . :. ~ -C particle than other tissues:~',:~: do, and indeed it shows 'even:.' . ~. more antigenn than- can`.,:be;' : found in most tumors. 'IU1is> also true of the inside of;;the uterus and of the ovaries. But some questions re- mained: If the cancer poten- tial is already in the, cell in the form of an RNA visus, how does one account for the transmission of cancer by the; • injection of the Rous sarcoma, virus? Huebner worried over this for some time, but now gives this explanation: "Rous dealt with young,°~: birds, and he forced in 1ar~e,, amounts of the infect?ous ' , virus which contained genetie ; 4~ information to change normal'., cells into cancer cells. We've ` shown that many chickens ' with C particles, unless killed by soane • other means, are likely to get cancer later in _;,' life, so it seems that Rous's.c .: injection of virus simply pro- r vided the disease-causing level more quickly." There were even more intri- cate puzzlers: What for ex-

sms, ; lzave +"sitown'lrow"tlie DNA'~ rKth2`taucleurs 7ays'down1cheini-,' r, .ca1="orders''-which are carried~ . out by the RNA in the :~reverse+e ~ cytoplasm, directing it to What Huebner envisions there have been similar prom- build the living structure ac- is that a substance can be ising findings. A team of cording to genetic .plan. found. which will restore the. scientists from the Cancer In-. At the Salk Institute in La repressor to its original posi- - stitute and the • Pasteur -1n-~' Jolla, Renato Dulbecco has- tion of control in the cell. At stitute in Paris isolated°~ ia'o shown that a DNA virus present he and several teams chemical inhibitor from vari-.;,; •particle can somehow -incor- across the country are trying ous types of mouse and- rat ls porate itself into the genetic thfind the specific natural :r.e- tissue carrying cancer virus. ' blueprint for•a'\cell and cause pressor for the cancer genes They injected the material; it to behave abnormally. What :of the C particle in a number along with cancer-prodqcin16:r happens, according to Dul- of spei C-type virus, into a colony, of:~i: ' becco, is that the viral genes,Jmice and found they' dei i i l d l rea rus sc y, severa v ,:take up positions . along the ' +A en- oped fewer tumors than initse' ~ double helix of the biueprint iven the °~`~ch were t rere , g ~ ordinasults in revers- ~.~... thus changing the genetic in- t3' but not the inhibitor. " formation- passed on to the ing malignancy in tissue cul-,. These and other experi~~~' cell. (The double helix, of • ture, although they are " not ments make Huebner and l~i~''. course, is the DNA - that is working directly with C par- colleagues more optimistic' •known to be present in the ticles. , At Berkeley,. for in- than they have been in alongi.<; cell; the virus particle is~r stance, G. ; S. Martin, in the •time d~ aKVVL44V1 o w ic : the pu c i : r either invades the -cell or is , Wendell Stanley, expe imented - soon be able to cash ,4th ,-also normally present- it 'is f,,? 'w;ith a;i mutant ' of the- Rous promissory note it has -bee not yet clear which.) ,virus and found that he could ' holding for years from sC,i.en- Little was known of how' . turn a cell induced to grow tists working on a caiice~"~ 'the RNA virus subverts the` abnormally by a virus into a-cure," Huebner says, adding?';" healthy celis; until last year,: normal-growing cell - and reflectively: "You know, afew:~,(~ when Dr. Howard Temin of ' back again-by merely alter- years ago that would have~.; ; -ing the temperature of the been enough to contemplatel°~~ the University of Wisconsin cell's environment a few and, independently, Dr: David as a great end in itself, but'" Baltimore of the Massachu- degrees. At Princeton, in what now the skeptics question all setts Tnstitute of Teclinology, ` rnay be- a landmark experi- values, and even ask whet'her = ,came, up with some sbarbling ment, Max Burger and Ken- it would be wise to have a .evidence.. Temin and Baiti- neth Noonan covered certain cancer-free society in view of mofedisc over ed ered that the RNA 'caaner cells with a plant pro- the population explosion. 1tein called -Conconavalin A am old=fashioned enough to of:.tbe virus can also replace fand found• that they suddenly believe that curing a disease ' t3~.i~double helix and, by so: -, gi that kills 250,000 Americans ew like normal cells. "He 9tfbxi ~f information that gu de ~en removed the protein - a year is a great plus for. a11hs~Iornrai cell process. Here, cover and the nancer growth civilization -and that- utopia ttte :~2NA is iz} charge, and, inr» took,_o(~f ~again will not be reached all at once;1. ~~ ' " ;particle investigations - but step by, step.  :' ~ a kind of " man ~ creaxes , ,Cod" ~, C ; , operation; j gives : ordeis to make DNA which, in turn, ,creaites replicas of itseif. How tfai,c. traaaer of WaCUAtio4,goes on to cancer is still- not known, but Teanin's findings do 'indicate that the complex-' ° Jty - of the mechanism is n'at last yielding to research. :;- H L3EBNER is firm iii` bis ' belief that the answer to'.che d'isease ultimately lies? in:" somehow muzzling the viral cancer genes and forcing them to remain "silent" in the cell (until, he says, "the indi- vidual dies of something else"). This is not so fantastic as it sounds. As a result of re- cent work in molecular biology by Nobelists F. Jacob and J. Monod of France, each growth- controlling gene in the cell is now known to be regulated by another gene that sits atop it and represses f urther cell division. after the organ reaches,its inherited shape and size. The tumor occurs when this "policeman" fails