R ,~, " ,- f l'lii v\ . r vw I 'IT "" 1,-.(,1". ~~...: '~;:" MEDICAL DISPATCHES

".. PATHOLOGICALSCIENCE j '- Stanley Prusiner is being awarded a Nobel Prize for his groundbreaking theory about what causes mad-cow disease. But what if he! wrong?

BY RICHARD RHODES

I N Stockholm later this month, with and RNA. In Prusiner's coinage, the dis- pomp and ceremony, a fifty-five- easeswere caused by a ""--a "pro- year-old American neurologist and teinaceous infectious particle." biochemist named Stanley B. Prusiner Yet the very week the Nobel award will receive the 1997 Nobel Prize in was announced two reports in the distin- Physiology or Medicine. The coveted guished British science journal Nature award-a gold medal, a million dollars, and price- . less scientific prestige-is , usually divided among two Slow down. or three candidates; only > \ - . . . six times in the past. forty ~ 4£~ Luxebiking and walking years has the Medical No- ..~\i . ~ trip~forthe(ulturally bel Assembly of Sweden's ~ ( Jl (unous.Europe and Karolinska Institute seen fit '\' \-: \ ar~undthe World. d . .. =" ,"\ ~\ \ 1-800-678-1147 to awar 1~t? one sC1en~st I, 1I~\:i\)~~ alone. So It IS a sweet VlC- B f . Id tory indeed for Prusiner, utter Ie h . b . .. &R b' w 0 IS erng honore d "J:lor ~ 0 mson h. d. f .,.,... w.,.,..".co ".. IS Iscovery 0 pnon~. ' www.butterfield.com new biological principle of

- ." Prusiner'scontribution to medical science has been sensational. In 1982, he ...... posited a new kind of in- OpposmgP~~ners:esearch are~cten.~ts who potnt

1: t . t .. to tantaltztno- htnts that a VtTUS tS tnvolved iec 10USagen , umque rn 0 nature, to explain the unusual character- offered further clues that a might istics of a group of rare, transmissible be the carner of T.S.E. infection. Despite spongiform encephalopathies(I:S.E.s~ Prusiner's insistence that the puzzle has diseasesthat kill by damaging the brain been solved,the last word has not ~t been with knots of junk and tiny holes. written about the prion's role in causing In the decadethat followed, as he worked such diseases. to prove his theory, a new previously .In fact, by awarding the prize to Pru- unknown T.S.E. emerged in an ~pidemic siner this year the fifty-three Karolinska that panicked millions. Th..<:l285 outb~ scientists who' make up the Medical No- in~ .9f bovine spongiform enceph-::' bel Assembly explicidy took his side in aIOP~S.E.)-. comm~nly kn~-as an ongoing debate-a debate that may m~d:..co~s-=-a~e~~eu 1~ me sla~ have profound consequencesfor future re- ljO~pl~enty-onefer ot nearly two rn:illion anlma1S:-so_fa1=bWIlen -eg:an - mansearch. of RaIf the NobelPettersson, Assembly,-::he deputy clearly chair- un-

~-a-s-wer- pr05aDlV 1ilIe~d bv~t- derstands the stakes,and he has even im- in tainted meat, fears arose 0 a sim ar plied that persistent skepticism .about ~ - ~pid~c rn numan ~ This climate had contributed to the spread of , ~gen~CUss-e-a ~cie~t1ficand pu~- B.S.E. to hu~an bein~s. "?u;ing the ',I ~ lic attention on Prusrners controversial whole of the mneteen-elghttes, he told I theory that the infectiousagent for the Reutersin October,"the prion was very ~ ! T.S.E.s is not a virus or a bacterium but a controversial. Acceptance took a while. ~ . protein devoid of the nucleic acids DNA This could have delayed moves. It was ~ , '-~, ' . 55 . . , ~e a Doliti~ decision"-in :J}~tai~- then, anthropologists had established Q' b

"aboutwhen to take a!;:1;iQD,and by ~n that the mode of infection wasthe Fore v 'l.l U ek 0 he c 0 r""It was too late.". "A;-:-;And ~LUIC Kar 0 li ns ka neu- practlceo. f canru .bali ZIng. ~LUlexr . d ea d r eta - lOll want to ta e It orne Wit h you' . ~ rologist Lars1!;dstrom was dismissive rives.When, beginningin 1985,bovine of skepticswhen he spoke to ilie Times spongiformencephalopathy began deci- "- upon ilie announcement of ilie prize. mating British cattle-it was spreadby "There are still peoplewho don't believe what Gajdusekcalls ilie "high-tech neo- iliat a protein can causeiliese diseases, cannibalism" of feeding cattle protein but we believeit. From our point of view, supplementscooked down from slaugh- thereis no doubt." terhousewaste-scientists invokedGaj- The tone of iliese endorsementsof- dusek'swork among the Fore to warn fends many researchers in 'the field, a skeptical British Government that including the neuropathologist~ B.S.E. might pass to human beings. Manuelidis, a Yale Medical School Prusiner, who studied medicine at ~;6i~~~~§~~~~~;;~~ the University of Pennsylvaniaand has orm ence halo at . turned u spenthis careerin the Universityof Cal- tanta1i~in?:hints of a ~"No doubt?" ifomia system,beg-an working on spongi- s~ecendy, in NeWRaven. "How form encephalopathiesin 1972, after Ask for yourFREE Winter Vacation , couldthere be no doubt?Is thisscience?" one of his patientsdied of a rarehuman Pa~kagesbrochure. Also receive your Aliliou h some of her collea gu es cede TS.E. Creutzfeldt-]akob disease (C.].D.). Winter Getaway Bonus Packag~so Get g. '.. a taste of all the charm and excitement more ground to Prusmer, by her count In the late seventIes, Prusmer focussed of neighbourlyQuebec.

o only four of ilie fourteen major T.S.E.- his researchon infectiousproteins, and F 0 fi t J . or In orma Ion, caII t0 II Iiree researchlabs iliat aCtUallywork on the during the last two decadeshis labor~- 1 800 363-7777 (Askfor operator 249)

y espouse tory-a well-funded one, at the Um- \" ot \" b O infectiousa gent wholeheartedl 151 our .C 51t e: prion ilieory; nine others considerit un- versity of California at San Francisco \V\,'\v.tourisme.gouv.qc.ca/\,1nter.html likely, and one is undecided. School of Medicine-has published a Transmissible spongiform encepha- hundred and eighty paperson T.S.E.s. ~ rid ..,.." - lopathies--cruel, untreatable,and invari- Prusinerstopped talking to journalistsin t,~"_'il no CANADA Quebec-- ablyfatal maladies-incubate silently for 1986,however, after a skepticalmagazine Heed.mo.e C'o..,,... """ ,.::

~ years before finding their way to the storyby the science~porter GaryTaubes. ~ brain, where they eventuallysignal their One of the scientistsTaubes men- ""--' presencewiili ataxia and tremors iliat tioned was Patricia Merz, who studied progresswithin weeksor monilis to de- the sheepform of spongiformencepha- mentia,coma, and deaili. Prusinerand a lopathy,called , with Henry Wis- Zurich colleague,Charles Weissmann, niewski at ilie New York StateInstitute showed iliat infection depends on ilie for BasicResearch in DevelopmentalDis- pn:sencein ilie brain of a protein iliey abilities.In 1978,after four yearsspent called PrP, which all mammals make. teachingherself to use the electronmi- (They did so by knocking out ilie croscope,Merz identified litde whis- in mice iliat makesPrP and ilien trying kers-what she calledscrapie-associated to infect iliem; without PrP, ilie mice fibrils (SAF.)-in magnifiedsamples of didn't get sick.) In the courseof Ulfec- infectedmouse and hamsterbrains. The tion, the normal PrP protein changes fibrils showedup only in diseasedsam-

cumulatesinto a diseased in damagingform iliat knotstypically called ac- pIes, morenever infective in healiliy the samplescontrols, were,and the ---

amyloid plaques.Prusiner later postu- more of iliese fibrils shefound scattered lated a role for a still unidentified "Pro- acrossthe glowing green screenof her tein X" in the deformationof healthyPrP. microscope.Merz and her colleaguesre- Ultimately ilie assaultleads to spongi- ported this discoveryin a German pa- form damage-a stipple of microscopic thologyjournal in 1981.In 1982,Prusi- -- ho~esth~t developsas the brain reacts ner a?nounced that h~ h~d pu:i?ed a (800) 234-1425 to InfeCtiOn. .I protem that tracked With mfectiVlty.A The first human epid~mic of a year later, he reported that the protein WhidbeyIslan~ and Seauk. WA . ~apa VaIlcy 1:' ~L r " SanFrnnC1SCO Mon~rq PenInsula 'T' SE d h k f " d h d .cl . .L. . . occurre among . t e rore... peo- too tile rorm 0 ro" -s. ape part!". es,. SantaYna VaII ey' 0rang" County'.e or IIun' d e,CO pIe of Papua New Gumea begmmng which he named pnon rods. Citmg in ilie nineteen-twenties.They calledilie Merz'swork, Prusinerallowed that it re- . i1ln An Am . di . . . d b bli h d" h th Play Blues Uannomca ,.. ess: encan pe atrl.aan malne to e esta sew e er or not 50 3CDs & bookin beautiful boxed set """'- and virologist named Carleton GaJdu- thesefibrils representan elongatedform FromTem} Portnoy of Muddy ~ sek won the 1976 Nobel in Medicine of the prion rods."According to Merz, Wate~& EricClapton baI1dso for proving that kuru was infectiou.~;by antibodytests later performed by her lab- ~fi.rloof~~f-~~~ www.harpmaster.com Leam from the Master! - - ~6' . n-IE NEW YOI\KEi\, DECEMBB\ I, 1997 '. . " Fifia IIy... " I k T S E . d . I I . oratory demonstrated t hat Prusmer.s ma e .. .-tamte materIa essm-

G 0 LF prion rods and her fibrils were. one and fectious, whereas treatments known to

the same. Prusiner has maintained that damage protein did block or reduce .. her data were "unconvincing and in- . Prusiner and others also The Money Swing conclusive."Nevertheless, the presence searchedinfected brain samplesfor vi- of these fibrils is now an accepted ral nucleic acid and failed to find it. by Ned Vare laboratorytest ofT.S.E. infection;when Yet, as I emphasizedin my recentbook For the first time, the swin mad-cow disease first apP:a.red i.n "Deadly Feasts,".none of .th~e ~e:i- the heart and soul of le En?land, one of the ~ays BntIsh sc~- ments IS conclusIve: reduCIng Inf~CtIV1ty game IS. accura te1 y ana Iyze d entlStsconfirmed that It was a spongI-. by a processthat damages. . protem may d d' .b d form encephalopathywas by findIng prove only that protein IS a gatekeeper an escn e . ro d-s hape d ... In m fiecte d cow Lorc t he ill ness; raC ill .ng to red uce InLeC-. C Yare's revelations will help brains. Si . cant! however Men isn't tivity by a process that damages nucleic you sharpen your game from convincea~atprotein~o~e carries JE.::. acid may simply demonstratethat the tee to green. feCt1"<;-n~!lhinks-th~rotein nucleicacid can be repaired. Lavishly illustrated. ~~a1LtJ2w-fib.~-PI~~~ On the otherhand, the bestevidence 162pages, 7x9 " paperback ever-probablycontain a nucleicacid. for a viral causeof T.SE.s is that tl1ese c_~ ~ diseases-just like flu and cold viiu-s-e:s=- ' T HE great leap that Prusiner has come in aifferehtsttams-;Wh1c1r-reveal madewith prion theory is to de- ffiemselvesmdifferentSigi1sand symp- duce from the associationbetween pro- toms. Such distinctive strain character- ../ tein and T.S.E.s that the protein causes istics "~true"-that is, producethe the disease.He cameto this conclusion sameetiects as they passfrom host to after he and others demonstratedthat liost. On~ the Naturepapers pUbl1SheO applying chemicals and treatments ThlSOctober,for example,from a team Send check or MO for $22 to: known to damagenucleic acid: didn't headedbz Moira Bruce, of the Instirut=- The Golf Press, 22 Wildrose Ave ~ gg; Guilfordcr cx:>437 .-;~ --; - ~~~ If}","" ~ ~C...;,/3;, ,";.o-\!I~~~ ~~

""' ~- ..:::3""---V 1 'i\/f. : Award-

~ew .l.'fJ-@~n I wi.nning ThoMa9azinc for Girlsand Tho'r Oroams : Editedby . i girls 8-14

~:j~':;df~~~e~;;:Or~la~IS! ! $29/year 800-381-4743 l iiw~aISO~ a catalogof 0 i grtatgifts for www.newmon.org : " mag" at' PO BOX Y . I In IV,.. 3587- " ~ int~lIigentgirts

DULUTH.MN 55803 ~ andwom~n!

-

. .

,.. ~icu:a., \~~ - ~ :1l~-oitJ"

~ i "Our life is sort of lik a bad play, but somehow we've managed to get good reviews."

- - ~6' . ll-iE NEW YORK8\, DECEMBffi I, 1997 '.' Finally... d h P .. k T S E . d . I I - oratory demonstrate t at rusmer s ma e .' .-tamte materIa ess m-

G 0 LF prion rods and her fibrils were, one and fectious, whereas treatments known to

the same. Prusiner has maintained that damage protein did block or reduce ... her data were "unconvincing and in- infections. Prusiner and others also The Money Swing conclusive."Nevertheless, thepresence searched infected brain samples for vi- of these fibrils is now an accepted ral nucleic acid and failed to find it. by Ned Vare laboratorytest ofT.S.E. infection; when Yet,as I emphasizedin my recentbook For the first time, the swing, mad-cow diseasefirst app:~red i? "DeadlyFeasts,". none of .th~e ~e:i- the heart and soul of the En?land,one of the ~aysBrItIsh s~- mentsIS conclusIve: reduang Inf~CtIV1ty . t I I d entlSts confirmed that It was a spongt- by a process that damages proteIn may game IS accura e y ana yze . . . d d' .b d form encephalopathywas by findIng prove only that proteIn IS a gatekeeper d h d ... L d L h ill C ill' d . L an escn e . ro -s ape proteIns m Illiecte cow Lor t e ness; ra ng to re uce InLeC- Yare's revelations will help brains.Si . cant! howeverMen isn't tivity by a processthat damagesnucleic you sharpen your game from convinsea~~Erotein~o~_e carrie~in: acid may simply demonstratethat the tee to green. ~n~hethin.ks-th~rotein nucleic acid can be repaired. Lavishly illustrated. ~~~~~~@.~~..Q~~ On the other hand, the bestevidence 162 pages, 7x9 " paperback ever--probably contain a nucleic acid. for a viral causeof T.SE.s is that tIlese c ' diSeases-justlike flu and cold viIus~ , T HE great leap that Prusiner has come in aifferentsttains;""Wh1-c11:-teveai madewith prion theory is to de- ffiemselvestnd~tS'1giiS and syrnp- duce from the associationbetween pro- toms. Such distinctive strain character- ../ tein and T.S.E.s that the protein causes istics"~ true"-that is, producethe- the disease.He cameto this conclusion sameettects as they passfrom host to , after he and others demonstratedthat nost.On~ the Naturepapers pUbl1SheO i applying chemicals and treatments thiSOctober, for example,from a team Send check or MO for $22 to: known to damagenucleic acid: didn't headedbI- Moira Bruce, of the Institut=- The Golf Press, 22 Wild rose Ave gg Guilfordcr (x;437 ,- ~ ., ' - ,;::=;:--'.",.~- ~-, ~ ~""c =c" " " ,..,. ~I\I" ,,~;YL-:;> ~ ~ ""' ~- ~--t- . - 1 'i\/f =Award-

I wi.nning ~ew1I1t Magalint for 1.'fJ-@~nGjrls and Thtlr Ortams : Edited by . ~girls 8-14 ~oe~~pr~po~~n~Ore,~r!~a~lrls!do~les~hflsto!Y~la~, j $29/year 800-381-4743 l j:w~aISOh3\-r- a catalogof ~ grtat gifts for www.newmoon.org : ' mag. at' POBOX Y . I In IV". 3587- , j int~lIigentgiris

DULUTH,MN 55803 ~ andwom~n!

,- -

~ . -~ ~~~ ,\/ - ~ :Ji~.e~

I "Our life is sort oflike a bad play, but somehow we've managed to get good r~s."

- - -- .. , MEDICP,LUUrAI\-nc:.> :J {

for Animal Health in Edinbur h, identi- ~tem. (Some plant diseases,called J/i=- lied the samestrain of bo\rines 0 onn roids,consist ornaIeen tried,so far without success. the Nobel Assemblyin pastyears and is Nevertheless,Prusiner believes that with an old friend of Carleton Gajdusek,is a more researchit's only a matter of time. !pnon proponent."The T.S.E.saren't my There'splenty of nucleic acid in the field," he said recently,"but I was con- brain samplesthat researcherssrudy, but vincedone day yearsago when Carleton picking out viral fragmentsamong all the heldup a blackenedtest rube at a lecture-- cell debris would be like searchingfor blackenedby exposureto hardradiation- a needlein a haystack.If they'regoing to , and explainedthat the scrapieagent was be found, they'll haveto be painstakingly still alive inside. Radiationdamages nu- detectedalmost moleculeby molecule-- cleicacid, of course--that'swhy radiation but hardly anyoneis looking.The lion's canbe dangerous.That isn't the only line shareof researchmoney is now directed of evidence,but it's compelling." Yet towardprions. (Prusiner's lab hasreceived Laura Manuelidisis quick to dismissthe aboutforty million dollarsover the years.) \\'indows On The Weatller... radiation argument, pointing out that \\"illl.\I;L\illlllm.s fllillilic of matchedwcatllcr many are efficient at repairing ra- T HE virus-versus-protein debate would i,!~(J"'IIC'1!S i!:..6'/~" solid u~, ca~. Or \\;tll diation damage to their . be merelyalrious if a fatal epidemic \Xr;Jthcr\I:\X., ollr flllI-flln~lon \\"calhcrpro-

A fi . P .. 995 di ,. 1 d Offi . all h ccssor. r.or a free catalog, t a con erence mans m 1 , sease werent inVO ve. Cl y, a un- COl1!arl !\1axilnuI11,Inc... ~uelidis told T.S.E. researchf;rs that, dred and s' -ei ht thousand British-cat- S.lutr:\'Y 4,30 BantC! BI::,'d., ~ despite. t he pnon. b an dwagon, al most tl eave SiC. k ene d Wl. th B ...S E since. t h e 508.995-2200.\C\V Ikdford MA 0?74.)... . eve .ng about the T.S.E.s oints to a -;:~e ~ ~st i.d~n.tified. i~ 198~~~~d '-- "ow virus so e ecause0 the long the aCtualtoll orobablvexceedsa million. ~n periods),with PrP acting as .S.E.is indeedtransmissi e through ~eper at som-;-stage in tne=or: eatingmeat, ~ne who ateBritishbe~

Msm's~ ~:~e~eoi~~.sms lifee CYcle: e: the fact of infection'infection, in the nineteen-eip:hties mav have been S HOPtIBtAtBQ EOOuringquaJitytora . d h ' . Iif~me of appreaation. e variety 0 strams, an t e agents ~ ~~~~~o~~:d.r~a~:~illose.n 1989, new regulations on HammerTote Other~producIs . th h 1 . ds( h ttl d d til Handcraftedbirdl alsoavailable persIStence roug ong peno w en ca~e reea w~~~posea. yet un tootdlest filled Spirit Lak~ cells nonnally "clear" proteins quickly), this year sheep were allowed to eat the =t::1 ~~~ f together with what Manuelidis called same rendered slaughterhouse waste that IdealGift Spirit~, IA 51360 ~ the "hallmark of an infectiousagent"- seemsto havespread the diseasein cows. ~70 + shWif19 712~f~ ': its transmissionacross species barriers. In theory,therefore, d1e British mayhave ISO&MC ~ tJiebOOO1.net

Prion proponents point out that vi- been exposed to bovine spongifonn en- ~M.ERICAN WRI~ERS hich d . . f ha1 ..L fro d 1__L Dlckrnso,,' Frost. HemIngway ruses, w come wrappe in proteIns 0 cep OpaUlY m mutron an J;ilIIU seven Faulkner' Kerouac. Melville their own, can nonnally be traced through years longer than d1ey were from bee£ Steinbeck.Fitzgerald' Eliot Year,John Collinge, who Whditman . 7WBauinSTS.Poe $.others the antibodies that an immune system Earlier this Hy rostone : 49-S79 generates to attack those foreign proteins, is a member of the British Government's Scupltor FredBlatt but that the T.S.E. aO'ent h~~nt hppn Spongifonn Encephalopathy Advisory 607-547-9459: brochure ! ke ~--thi =-LJ_- C . nfir d B ' hilli ' P.O.Box206 F1yCreekNYl:J:J:J7 , seen to evo s lIIllliInmato res onse. ommittee, co me ruce s c ng i n y, , owever anuelidis re- newevidence that bovinespongifonn en- . tf5J rte "severalinflammato host cephalopathymay indeed have spread J-.e X IJ~n i. reactions"in rats sea; ected with to humansin the fonn of the new vari- ~ odIc :

ffienew variant Creutzfeldt-Takob disease-ant Creutzfeldt-Jakob disease (nvC.J.D.) Pasta of the Month (lob '; at a egun .ng young people in which was also presented in her Oc- Only$19.95 plus shipping - 2 goumletPASTAS, 2 SAUCES : r ~~p~;~~: ,xT llb r th di b B r h firs and recipes,Agreal gift o! a smafl indulgenceforyourseJf. UrC4L ,--, n. vve erore at scovery, to er Nature report. elore t e t hu- http://www.flyingnoodle.com 800-566-0599 in 1983,British researchersAlaIl Dick- man deathsoccurred, in 1995,Collin e inson and G. W. Outram proposedthat had geneticall en .neeredmice to ma e ~ the ThE. agentmi!!:ht be what they 0 y umanPrP andthen had inoculate ~ed a "virino"-a smallpiece of naked :nemwith B,S.E. Now he reportedthat "-' ~~aa-iJi:at wraps itself in a host after sometwo vearsof silent incubation protein, and thus evadesthe immune ~ ey a e n to develo the disease--

- --,- -- ' ~ .. -58'

The Prince of Evergreens.. .

I Fra.grant Fras~~e BUCKET'SGOT A HOLE IN IT ~ FIr Wreath 24"diameter Wealso ship Fra-s:erRr ChristmasTreesl Keep it under your hat the saying went MostNeedle RetentIVe ' ".." ' $3200 when we wore hats. And secrets diss1pate (in this poem the verb means to leave the pate) like body heat. And some secretscan't quit "Iud.. memo shippingI ry fast enough for human good., ShWedan~'e viz., what my friend's wife's kisses tasted like i1 continental U.S. Anmap' aooit CoIcards",~':ePtOO. and why I didn't sleep with her, for all or """"ure . I4XJnrequest. her vernal allure. DId we need to read Adornedwith a in transcript each taped word of Nixon's waterproofred velveteen bow. contempt for us, like preservedglobs of spit? Giftpackaged with your message enclosed. Don't double-click on the Save icon The (a piggy bank?a jumbled attic?) Christma..~ Wreath Shop "' www.cheta.nettxmashop until you'vethought how much a fossil fuel P.o.Box 15514,Asheville, N.C. 28813 has to forget fossil to become fuel, 1 800 455 3046 or how much childhood we plow under. ~- - - - "Tears, idle tears," the poet wrote, but they've F~: 704-277-7552 got. their :work. cut. out for them, the way ." -. . [email protected] a rIver might 1magtnea canyon.

-WIU1AM MATIHEWS (1942-1997)

~ one distinctive sign being that the mice agency'sT.S:E. p:-dvisoryCommittee. beganto walk backward. (StanleyPrusmer 1S also a member.).The - In the light of theseresults, Collinge, only certain way to avoid a food-borne a prion enthusiast,now fearsa "Europe- T.S.E. epidemic in human beings, in wide" epidemicof nvC.J.D.,"with tensof fact, is to ban entirely the feeding of thousandsof cases."Because projecting animal protein to animals.Yet under the the sizeof any epidemicrequires tracking most recent ED. A. idelines animal a trend line over severalyears, however, fee m e United States it will be at least the year 2000 before ~~~ mllirial~~ statisticianscan make reliableestimates. sources~ts ~~ dogs_euthanized Tony Blair's Labour Government by veterinarians and in pounds, ~ moved, in June, soon after its election, carcassesafter the valuable fur is re- to extend to sheepthe controls on feed moved,and large animals such as road- instituted for cattle in 1989, although l

-- ~ . 'MED/Q:,..L DIJ/'AI LHt.) 59 .. " v,hat a 'prion' really is," and then made that is, until a skeptic came along and clear why the virus-versus-protein de- covertly pocketed a crucial piece of appa- bate is important. J;:-lumps of abnormal ratus,an aluminum prism, while the French ~ protein, he pointed out, are also charac- physicist ~ measuringN-ray intensities. t~stt~f atseasessuCh as~~ Since the room was dark, Blondlot didn't "- dl:i~~d~heu~~toid arthritis. Why realizehe'd been sabotagt:d,and went right sho~e prion be ~quely mnsmissi- on announcinghis measurements;d1e skep- bk wnen-orner such amvloids aren't? tic later gleefully reportedd1is to the world. " ese unreso ve issues leave open e Pathological scienceraises deep ques- Eossibility that an undiscovered virus tions about human perception, Langmuir . ht et rove to be ilie true agent of ilie told his audience, and he went on to say ~~~issible spon iform ence Q- charitably; "These are caseswhere there p~~e wrote.. Chesebro thought is no dishonesty involved but where peo- it would be "tragic to stifle the future re- pIe are tricked into false results by a lack searchneeded to idenrify ilie precisenature of understanding about what human be- of the transmissible agent responsible for ings can do to themselvesin d1eway of be- these diseasesor to impede ilie se"!Ich for ing led astray by subjective effects, wish- drugs required to prevent or cure them." ful iliinking or threshold interactions. . .. , Researchis onlybeginni ng on early de- These are iliings d1atattracted a great deal tection and possible treatment of T.S.E.s. of attention. Usually hundreds of papers If the diseaseagent is viral in nature, ilien have been published on them. Sometimes eventually a vaccine might be developed iliey have lasted for fifteen or twenty years that could prevent infection. If the disease and ilien they gradually have died away." agent is, as Prusiner maintains, a malfor- Extracting what his caseshad in com- mation of a normal cellular protein, ilien mon, Langmuir offereda list called"Symp- finding a way to iliwart it is a much more toms of Pailiological Science,"and those difficult challenge, since all mammals are symptoms fit surprisingly \vell with born with PrP .One clear outcome: the current state of prion theory. Most ATALL BOOKSTORES Prusiner's Nobel Prize will enlarge his tellingly, ~atholo.gical case was likely ~ '\?iRing

,.. influence on the future ofT.S.E. research; to_involve :fan~.c...ilie~ri~s con.tr;TY-,to - A member of Penguin Putnam Inc.- if he chooses to encourage a full range ~en~nc~ -a phrase that certainly de- '"-' of studies-including continuing to search scribes ilie notion iliat ilie prion, alone for a virus-iliat work will go forward. among infectious agents,does not contain nucleic acid. Another symptom was iliat P RUSINER'Swork, for all its energy and "~iticisms are met by ad hoc excuses ambitior1, may yet turn out to be ili--o-ugntup onme spur of the moment," an example of what the Nobel-laureate which might well characterize Prusiner's chemist Irving Langmuir once responseto the dilemma of dif- called "pathological science." ferent T.S.E. strains: ilie pos- Langmuir, who died in 1957, tulate that ilie PrP molecule can made a hobby of collecting sen- fold itself in a variety of ways sational scientific "discoveries" that correspond to different E N G LAN D . ERenlaban.13';Com . " . nc nng.1 y m~tions.rustIC to that turned out to be false- forms of the disease. The eff~ 1 R E LAN D simply~.1~ganl not fraudulent but merely self- is barely detectable"also applies' .Cot~ges, manor houses, ' castles. dlddCldfu ' hih . fa hasd ' SCOTLAND e u e. 0 Slon, W c In ct, since no one emon- . London and Dublin Oats. came and went a decade ago, is stratedtl ~~ inf~ W ALE S . . Weeklyor monthly. probably ilie best-known recent the Holy Grail test-Prusiner's example;ifI..angmuir had still been around, theory has yet to cross this threshold. he would certainly have put it in his list. So far, his. eff~ct isn:t detectable ~t all. . p~ ART In a talk hegave In 1953, he offered the A Speclal1rony IS that the Vlrus- ~ Hel alndcd ut . . w a lIe example of ilie French phYSlcst Rene- versus-protein showdown has happened ---' - es. Prosper Blondlot. In 1903, Blondlot an- before. Until Francis Crick and James --~ ' ;J

nounced iliat he had discovered "N rays," Watson proved, in 1953, that nucleic ~.,;.,.r Lake Dept.N784255 q~!d AIle.s. which ed.. b thing 1:1. .d . d .. "'4111J Minneapolis,MN5540,..1858 were SUppos .0 e some liKe aCl was organIze to carry genetic In- p u... [S http://www.rainylakePuzzles.com X rays, except iliat they were given off by formation, the leading candidate for such common objects as human bodies, that crucial role ~'a5protein. Proteins lost -.cELEBRA110NBOWL ~ bricks, and tables, and made them easier out to nucleic acids the last time. Now, Weddings- Anniversaries to see in the dark. Once Blondlot had despite the Nobel Assembly's precipitous pe~:,.~=.;..«. -- reporte d h1S. dIscovery,. ot her sc1entists" express1on. 0 f rolat th,t he book of nature SpecialHandblownanddcl..d.Inscriptions? Yes. looked for N rays and also found iliem- still gives the. double helix better odds. . RushOrders? Absolutely. 8.S' - $129 12.- $239 408-427-35.12 I - -. -~ .