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The next millennium and epidemiology:

searching for information

Pró ximo milê nio e e p id e mio lo g ia:

e m b usc a d a info rmaç ão

1 Departam en to de Ep id em iologia e M étod os Qu an titativos em Saú d e. Escola N acion al d e Saú d e Pú blica, Fu n d ação Osw ald o Cru z . Ru a Leop old o Bu lh ões 1480, sala 828, Rio d e Jan eiro, RJ 21041-210, Brasil. castiel@m an gu in h os.en sp. fiocru z .br

Lu is David Castiel 1

Abst ract On th e eve of th e n ew m illen n iu m , it h as becom e ‘n atu ral’ to ad m it th e em ergen ce of t en d en cies t o p erform eva lu a t ion s a n d in ven t ories of t h e p a st a n d a t t em p t s t o foreca st fu t u re scen arios. W h ile recogn izin g th e en su in g u n certain ties, th e cu rren t p ap er tak es th is p oin t of view a s t h e p oin t of d ep a rt u re for p rop osin g a d iscu ssion on t h e fu t u re d irect ion s a n d p rosp ect s of ep id em iology. Based on th e p ertin en t an alyses p erform ed by th e Su ssers (fath er an d son ), I ap -p roach an d d iscu ss th e sco-p e an d lim its of n ew as-p ects assu m ed by th e field , es-p ecially to th e ex-ten t th at it h as in clu d ed tech n iqu es an d in stru m en ts from bioin form atics an d m olecu lar biolo-gy. In th e latter areas (am on gst m an y oth ers), th e n otion of in form ation h as gain ed en orm ou s im p ortan ce. I th en p roceed to an alyz e th e con cep tu al origin s an d sh ifts in th is n otion , in ad d i-tion to p ossible rep ercu ssion s an d effects on th e field of biological scien ces in gen eral an d th eir research p ractices in p articu lar.

Key words Ep id em iology; Molecu lar Biology; In form ation

Resumo Dian te d a exp ectativa d e u m n ovo m ilên io, torn a-se “n atu ral”ad m itir o su rgim en to d e in clin ações p ara p roced erem -se a avaliações e balan ços d o p assad o e a ten tativas d e p rever-se cen ários fu tu ros. Este texto p arte d este p on to d e vista – recon h ecen d o su as in certezas – p ara p ro-p or u m a d iscu ssão d os ru m os e ro-p ersro-p ect iv as d a ero-p id em iologia. A ro-p art ir d as an álises n est a d i-reção p elos Su ssers (p ai e filh o), são abord ad as e d iscu tid as o alcan ce e os lim ites d e n ovos asp ec-t os a ssu m id os p ela d iscip lin a , esp ecia lm en ec-t e, a o in clu ir ec-t écn ica s e in sec-t ru m en ec-t os d a bioin for-m ática e d a biologia for-m olecu lar. N estas áreas (en tre for-m u itas ou tras), é n otável o fato d a n oção d e in form ação p ossu ir en orm e im p ortân cia. São, en tão, an alisad as origen s e d eslocam en tos con -ceitu ais d esta n oção e p ossíveis rep ercu ssões e efeitos n o cam p o d as ciên cias biológicas, em geral, e d e su as p ráticas d e p esqu isa, em p articu lar.

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“We learn to bu ild discou rses on reality th at are h igh ly abstract, bu t w h ich w e k n ow h ow to rec-ogn iz e as tru e or false. It is a gen eraliz ation , a fan tastic extrap olation of ou r im m ed iate exp e-rien ce w ith error or lie. In fact, th is is a con crete, u n iqu e exp erien ce by w h ich w e learn sim u lta-n eou sly alta-n d colta-n cu rrelta-n tly a u lta-n iqu e th ilta-n g alta-n d a d iscou rse on th is th in g th at is d ifferen t from w h at w e learn ed abou t it.”

Hen ri Atlan

Introduction: turn-of-the-century, inventories and forecasts

It is kn own th at “en d s of p eriod s” exercise cu ri-o u s effects ri-o n h u m a n b ein gs. Th ey m a y b e weeken d s (h ere, sp ecifica lly, th ere is a n o bvi-ou s, stron g lin k to leisu re, by op p osition to so-ca lled “wo rkd a ys”), en d s o f th e m o n th (p a y-ch ecks a n d b ills...), en d s o f th e yea r, d eca d es, q u in q u ecen ten n ia ls (a fa scin a tio n with n u m b ers en d in g in fives a n d zero s), tu rn s o f cen -tu ries, an d so on ... Wh en su ch p eriod s en d , we join in acts of celeb ration , join t rem em b ran ce (com em m oration ), weddin gs, birth days, qu in -q u ecen ten n ia ls, cen ten n ia ls (o f b irth s a n d d eath s of b oth p erson s an d h u m an creation s)... An “en d of p eriod” is obviou sly an arb itrary, con ven tion al tem p oral category (hum an grou p s cu ltu rally d efin e th e ways b y wh ich th ey m ark th e p a ssa ge of tim e) crea ted by th ese p ecu lia r b ein gs th a t p ro d u ce th in gs wh ich recu rsively a ffect th em in wh a t is o ften a n u n p red icta b le way.

In th e face of p resu m ed “ch ron ological ter-m in ation s”, th ere eter-m erges th e task of p rod u c-in g eva lu a tio n s, c-in ven to ries, a n d va lu e ju d g-m en ts. To wh at en d s? In very sig-m p lified terg-m s, several can b e id en tified :

a ) m o re exp licit en d s: to m o n ito r a n d o b jectively id en tify trajectories an d p rocesses u n -d er wa y over th e co u rse o f a given p erio -d o f tim e;

b ) less exp licit en d s: to (re)d escrib e for ou r-selves (b y red escrib in g to o u rr-selves) “wh a t h ap p en ed” in term s of ord ered n arratives, fu ll of sym b olic com p on en ts, seekin g m ean in gs in th e “su b jective” h a p p en in gs th a t a cco m p a n y th e even ts of ch ron ological tim e.

Th ere a p p ea rs to b e a p a rticu la r n eed to p rep a re fo r th e vicissitu d es o f th e “fa te” th a t “awaits u s”... We n eed p eriod ic stru ctu res to allow fo r th e o rd ered n a rra tives o f o u r (re)d e -scrip tion s of ou rselves an d ou r su rrou n d in gs.

A brief com m en t is in order on our m etaphor-ical con stru ction s with regard to th e n otion of p a ssin g o f tim e. In th is sen se, th e p a ssin g o f

ch ro n o lo gica l tim e is u su a lly seen a s a m ove-m en t, allowin g for two cases:

1) tim e as th e m ovem en t of ob jects in con -tin u ou s, lin ear fash ion , with th e fu tu re m ovin g in ou r d irection an d th e p ast b ein g left b eh in d . 2) tim e as m ovem en t across a lan d scap e. In th is ca se, tim e ca n a lso b e seen a s “sto p p ed ”, wh ile we a re th e o n es th a t m ove th ro u gh it (e.g., “we a re gettin g to th e en d o f th e yea r, o r close to Ch ristm as”). In a word , th e m etap h ori-ca l stru ctu re p resen ts “tim e” p a ssin g u s fro m fron t to b ack, wh eth er we are stan d in g still an d “it” is m ovin g toward s u s or we are m ovin g to-wards it, wh ile “it” rem ain s static. Th at is, som e-th in g or som eon e m u st be m ovin g... Th ere is n o o th er wa y, sin ce a s th e p o et o n ce sa id , “Tim e n ever stop s.”

Acco rd in g to La ko ff (1992), su ch d escrip -tio n s o f tim e in term s o f m ovem en t, o b jects, a n d p la ces h a ve a b io lo gica l b a sis, sin ce o u r sigh t sp ecifica lly d etects th ese p h en o m en a , wh ile we h a ve n o sp ecific sen sors for th e p a s-sage of tim e. In ord er to p erceive tim e, we m u st u se referen ces ob tain ed from ou r availab le vi-su al sen sors. Yet we are u n aware of th is in ou r d aily lives. In fact, th is d oes n ot even m atter in solvin g everyd ay p rob lem s (an d it m ay b e m ore co n ven ien t to ign o re it). As La ko ff & Jo h n so n say:

(...) All th is d etailed an d con sisten t

m etap h orical stru ctu re is p art of ou r d aily lit-eral lan gu age for tim e, so fam iliar th at w e n or-m ally d o n ot realiz e th at it is a or-m etap h orical con stru ction” (Lakoff & Joh n son , 1980:82).

Rega rd less o f th e m eta p h o rica l co n figu ra -tion of tim e th at com es in to p lay, th is p relim i-n a ry com m ei-n t req u ires id ei-n tifyii-n g th e “top ogra p h ica l” p e rsp e ctive a d o p te d by th is co m -m en ta tor, situ a ted a s I a -m b elow th e Eq u a tor, with all th e p ossib le sin sth is m ay en tail, esp e-cially th e geograp h ical an d sociocu ltu ral gap s (with u n avoid ab le b iases an d p reju d ices) vis-à-vis th e p la yers in th e An glo -Sa xo n scen a rio, wh ere m ost ep id em iological work an d fu tu ris-tic sp ecu la tion is p rod u ced . I refer to th is lin e of work b ecau se of its u n d en iab le in flu en ce on th e field of ep id em iology world wid e. Soon er or later we feel th e rep ercu ssion s of wh at h ap p en s in ep id em iology ab ove th e Equ ator.

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ou tlin e for ep id em iology “in th e n ext m illen n i-u m”. In oth er word s, m y goal is to call atten tion to th e d escrip tion of fu tu re scen arios (even ad -m ittin g th e d eclin e o f fu tu ro lo gy, a d iscip lin e in vo gu e in th e 1970s) in o rd er to o rien t wh a t cou ld (or sh ou ld ) b e “th e b est” (in sofar as p os-sib le) p ro sp ects fo r Su b -Eq u a to ria l ep id em i-ology.

Wh ile th ere is a n u n d erlyin g “eva lu a tive fu ror” in th is exercise, ju stified by th e sp irit of exp ecta tio n su rro u n d in g th is p erio d o f “n ew tim es”, o n th e o th er h a n d it is n ecessa r y to a d o p t a certa in d egree o f co m p la cen cy b a sed on th e obviou s reason s for th e fallib ility of an y cu rren t fo reca st: in a d d itio n to th e u su a l “o b -ser va tio n b ia ses”, th ere is a lso a grea t la ck o f p recisio n resu ltin g fro m th e in sta b ility a n d ra p id p a ce o f to d a y’s tech n o scien tific a n d so-ciocu ltu ral ch an ges.

Ou tsid e th e walls of acad em e, astrologers, “wizards”, “p rop hets”, “soothsayers”, an d various crystal-ball “exp erts” are in great dem an d. Esp e-cia lly (et p ou r cau se?) a t a m o m en t wh en th e n atu ral scien ces in gen eral h ave b egu n to view m ost of th e system s su rrou n d in g u s as com p lex an d d yn am ic, th u s h igh ligh tin g th eir stoch astic ch aracter an d resu ltin g u n p red ictab ility (in d e-term in istic e-term s). Worse yet, som e research ers a t “sta te-o f-th e-a rt” resea rch cen ters, like th e San ta Fé In stitu te in th e Un ited States, h ave b e-gu n to d ou b t th e p ossib ility of reach in g a u n i-fied th eory for com p lex system s. Accord in g to th em , o n th e o n e h a n d th ere m a y b e excesses an d d istortion s in th e so-called “scien tific jou r-n a lism” with rega rd to su ch id ea s a s er-n tro p y, ch an ce, ch aos, an d in form ation , am on gst oth -ers. On th e o th er, th e p ro b lem s sta rt with th e la ck o f p recisio n in th e co n cep t o f “co m p lexi-ty”. More th an 31 d efin ition s for th is term h ave a p p ea red a lrea d y, to th e p o in t wh ere th e id ea h a s lo st its m ea n in g, a n d a t lea st o n e a u th o r h a s b em o a n ed th a t we a re m ovin g fro m co m -p lexity to -p er-p lexity (Ho rga n , 1995). Wh eth er su ch issu es a re p ertin en t o r n o t, in ever yd a y term s th ey u n d erm in e b elief in th e red eem in g a b ility of scien ce to m itiga te h u m a n su fferin g an d resp on d to th e an xiety id en tified ab ove in th e (re)d escrip tion s of b oth ou rselves an d wh at is go in g o n a ro u n d u s, in th e fa ce o f th e u n -cea sin g p rolifera tion , m u ltip licity, a n d sim u l-tan eity of even ts...

Befo re m ovin g o n I sh o u ld to u ch o n two p o in ts. First, th e “n ext m illen n iu m”, o r ra th er its “sp irit”, is alread y am on gst u s... In fact, it h as b een said th at th e fu tu re b egan som e tim e ago. Exam p les ab ou n d in oth er field s of kn owled ge, in secto rs o f (b io )tech n o lo gica l p ro d u ctio n , an d in th e “fu tu ram ic” ch aracteristics assu m ed

by sociocu ltu ral p ractices in con tem p orary so-cieties, alon g th e lin es p reviou sly h in ted at by th e gen re kn own as “scien ce fiction”.

Predicting the future:

a jigsaw puzzle without all the pieces

Wh en we were kid s, we u sed to h ave fu n p lay-in g with ka leid o sco p es, wh ich wo u ld a ssu m e va rio u s a b stra ct sh a p es, with sym m etrica l p la n es [k ali- co m es fro m th e Greek k állos, o r “beautiful” (h en ce calligrap h y) (Ferreira, 1986)]. Th e d esign s ch a n ged th eir a p p ea ra n ce b a sed o n th e m ech a n ica l m ovem en t o f th e o b ject, m ain tain in g th e sam e elem en ts, th rou gh a p lay o n m irro rs. We co u ld co n tro l th e sp eed o f th e ch a n ges a n d even ca refu lly sto p th e toy a n d sh ow th e resu ltin g d esign s to ou r frien d s.

Alon g th e lin es of th is p layfu l m etap h or, th e n ew “ka leid o sco p es” a re b u ilt with electro n ic m icrocircu its lin ked to screen s (LCDs or trad i-tio n a l vid eo s o r kin esco p es) a n d / o r in ter n et n etworks, with exten sively m u ltip lied elem en ts th a t sh ift cin em a tica lly, wh ereb y th e im a ges can b e an im ated , in scrip t form , an d an th rop om orp h ic, allowin g for con trol (or socalled “in -tera ctivity”) with o b jectives, p h a ses, o r (fo r th o se wh o so d esire) h ea vy d o ses o f co m p etitio n a n d sco rin g (vid eo ga m es) o r even “h u -m a n o id ” d e-m a n d s (see Tam agotch i, th e egg-watch , an d equ ivalen ts).

Alth ou gh it m ay b e a tru ism , it is im p ortan t to stress th at ou r ob servation s are a p roced u re th at seeks to d em arcate som e in telligib ility in a h yp ercom p lex, in tertwin ed , an d sim u ltan eou s p ictu re. Very well, in th ese tim es m arked by th e p ro life ra tio n o f “n e w ka le id o sco p e s”, m ixin g th e p layfu l an d figu rative sen ses (th e rap id an d ch an gin g su ccession of im p ression s an d sen sa-tion s), ou r goal is to ascrib e p ossib le m ean in gs to th e n ew “figu res” th at are sh own to u s, view-in g th em view-in itially as m ysteries, like an oth er toy, th e p u zzle, wh ich a lso ser ves to d esign a te a n “en igm a” o r “p erp lexity”. Th e p o in t is th a t we feel n ot on ly d eligh t with th e im ages p rod u ced b y th e n eo ka leid o sco p es. We a re b o th o b -sessed an d b ewild ered by su ch d azzlin g virtu al aesth etics.

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th e p u zzle. Mea n wh ile, o th er p ieces a re co n -sta n tly b ein g a d d ed th a t p rovid e m u ltip le, co m p lex “co n figu ra tio n s”, d ep en d in g o n th e ob server’s p oin t of view. Th u s, m ore th an ever b efore, faced with th e u n p red ictab ility of con tem p o ra n eity, p red ictin g th e fu tu re h a s in -crea sin gly b eco m e a n exercise in p rovid in g a fea sib le ord er for th e p resen t. Su ch p red ictive exercises sh ou ld b e viewed in th is ligh t.

Describing the “epidemiological situation”

Petersen & Lu p to n (1996) p ro d u ced a critica l text with b rillia n t a rgu m en ts o n th e resu lts o f co n trib u tio n s b y risk-fa cto r ep id em io lo gy in co n stitu tin g th e “n ew p u b lic h ea lth” a n d its corresp on d in g “n ew m orality”. Wh ile a rh etoric of regu lation is d evelop ed th rou gh th e risk d iscou rse, it is n ow th e “irration ality” of in d ivid u -a ls -a d o p tin g h -a rm fu l lifestyles th -a t m u ch b e a p p ro a ch ed th ro u gh th e ra tio n a lizin g ligh t o f ep id em iology. Th e au th ors em p h asize th e cen tral role of statistical an d ep idem iological quan -tification in th e con struction of ep idem iological “truths”. In reality, such “facts” are p resen ted un -der th e gu ise of th e n eu trality an d objectivity of scien tific kn owled ge, with ou t revealin g th e so-cially defin ed con tin gen cies by wh ich ep idem i-ological con stru ction s are bu ilt an d in terp reted. Fu rth erm ore, in th e p u b lic com m u n ication of fin d in gs, th e in d eterm in ation an d corresp on d -in g m a rg-in o f erro r -in h eren t to o p era t-in g th e statistical/ ep idem iological device when referred to the in dividual are n ot usually exp lain ed clear-ly, an d wh en th ey are, th ere is n o certain ty as to th e d egree o r relia b ility o f u n d ersta n d in g b y th e la y p u b lic receivin g su ch in fo rm a tio n . As d iscu ssed p reviou sly (Castiel, 1998), in d ivid u -als gen erally lack statistical literacy train in g al-lowin g th em to access kn owled ge to h an d le th e im p lication s of p rob ab ilistic reason in g.

Is it still p ossib le to sp eak of Ep id em iology in th e sin gu la r a n d with a ca p ita l “E”? Th a t is, th ere is stron g evid en ce th at d ifferen t ep id em i-ologies h ave taken sh ap e wh ose adjectives h ave b ecom e “last n am es” [in Portu gu ese an d oth er la n gu a ges in wh ich a d jectives fo llow n o u n s – Tra n sla to r’s n o te], co n n o tin g d ifferen t cla n s an d sp arkin g feu d s an d d isp u tes for h egem on y to ach ieve cap ital-letter, d om in an t statu s. So as n ot to d well too lon g on th is top ic, a su m m ary of th e essen tial d ifferen ces in su ch watersh ed s was su ggested by Pearce (1996) (sligh tly m od i-fied ), a n d d esp ite th e lim ita tio n s in h eren t to su m m arization , it is su fficien tly illu strative (for greater d etail, con su lt th e au th or). On th e on e

h a n d , th ere is “tra d ition a l” ep id em iology (th e au th or u ses th e term in a favorable ligh t) wh ose “m o tiva tio n” is p u b lic h ea lth a n d its id ea ls – p ro m o tio n , p reven tio n , a n d th e co n tro l o f in -ju ries to h ea lth , th ro u gh stru ctu ra l ep istem o-logical strategies with a realist focu s an d p op u-lation stu d ies an d in terven tion s in a h istorical a n d cu ltu ra l co n text, u sin g o b ser va tio n a l re-search tech n iqu es.

On th e o th er h a n d , th ere is “m o d ern” ep i-d em io lo gy, wh o se “m o tiva tio n” is scien tific/ a ca d em ic, with a p red o m in a n tly b io m ed ica l view u sin g red u ction ist ep istem ological strategies of a p ositivist b en t, stu d ies a n d in ter ven -tion s at th e in d ivid u al level (in organ s, tissu es, cells, a n d m o lecu les...), with th e exclu sio n o f exp erim en tal research con texts an d tech n iqu es (wh ose b asic m od el is th e ran d om ized clin ical trial). Th is sch em e, in ad d ition to its p oorly d is-gu ised Man ich eaism , elu d es several issu es. In p rin cip le, it is a t le a st d e b a ta b le to a ffirm a clear d istin ction b etween th e ep istem ological strategies an d ap p roach es of th e variou s water-sh ed s. Fu rth erm o re, a s a n a lyzed b y Ayres (1994), p u b lic h ealth u n d erwen t a d ecisive re-arran gem en t in term s of scien tific n orm ative-n ess iative-n th e Uative-n ited States with W.H. Frost iative-n th e 1940s a n d 50s, in a p ro cess th a t b ega n in th e late 19th cen tu ry. A h ygien ist sh are of th e field wa s in co rp o ra ted b y th e sta te, i.e., p u b lic h ealth p er se. An oth er p art, in th e d iscip lin ary fo rm o f p reven tive m ed icin e, wa s lin ked to m ed ical an d h ealth care activities, with rep er-cu ssion s on th e train in g of h ealth p rofession als a n d th e sh a p in g o f co rresp o n d in g b io lo gica l kn owled ge on th e h u m an d isease p rocess. Ep i-d em io lo gy a s a scien tific a ctivity to o k h o li-d in m ed ical sch ools togeth er with oth er b ioscien -tific co n ten ts in m ed ica l tra in in g. Th a t is, we a re n ow exp erien cin g th e p a roxysm of a sp lit-tin g tren d th a t a p p ea rs to h a ve gen era ted a t lea st two ep id em io lo gies d isp la yin g d iffer en t stru ctu res. On e is “sa n ita ry/ co llective”, in ter-ven tio n ist, lin ked to p o p u la tio n -b a sed p ra ctices, su rveillan ce, d isease con trol, h ealth ed u -cation , etc., in a sen se a su b sid iary of th e oth er, “scien tific/ a ca d em ic”, p rod u cin g evid en ce on th e “n a tu ra l h istory of d isea ses”, in rela tion to wh ich b oth p u b lic h ealth an d m ed icin e are ex-p ected to b ase th eir action s.

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sh ift. Clin ica l m ed icin e su b sta n tia tes itself, an d th e ad jective is p rovid ed by th e ep id em io-logical tech n iqu es wh ich p rod u ce a su ggestive-ly solid b asis – evid en ce!

Ba ra ta (1996) id en tifies th e id eo lo gica l d i-m en sion s ei-m b ed d ed in th is sh ift, with ei-m p h asis o n th e p o sitivist fa cet o f th e tech n o b io -scien ces, th rou gh closely lin ked m yth s: 1) th e u n co n d itio n a l o b jectivity o f scien tific kn owl-ed ge an d its cap acity to d isp lay “tru th s”; 2) th e p ower of th e p rob ab ilistic q u an titative arsen al in th is p ro cess; 3) th e n o tio n o f u n lim ited p ro gress in th e tech n o lo gica l d evelo p m en t o f p rod u cts, tech n iqu es, an d in terven tion s aim ed at p reven tion , d etection , an d treatm en t; an d 4) th e stro n g b elief in th e n eu tra lity o f scien tific en terp rise, wh ose m ain p rem ise is th e d ich otom y b etween su b ject a n d o b ject a n d co n se -q u en tly th e con trol of b oth , op tim izin g ob jec-tivity an d avoid in g th e h azard s of su b jecjec-tivity. Desp ite th e tria ls a n d trib u la tio n s o f th e stru ggles for p restige, th e situ ation som etim es sh ows a p ictu resqu e sid e. A cu riou sly d ram atic an d u n ab ash ed review by Carl M. Sh y (1997) in th e orth od ox Am erican Jou rn al of Ep id em iolo-gyp roceed s literally to a “ju d gm en t” of acad e-m ic/ scien tific ep id ee-m iology. Th e field’s alleged “crim e” was to h ave d evoted itself p rim arily to stu d ies wh ose m ain p ersp ective was to “d iscov-er” risk fa cto rs in th e rela tio n s b etween given exp osu res in grou p s of in d ivid u als an d th eir re-sp ective o u tco m es, a co n ser va tive p ro p o sa l wh ich , a cco rd in g to th e p ro secu tio n witn ess (th e au th or), con stitu ted a “failu re”, sin ce it ex-clu d ed com m u n ity an d ecological d im en sion s an d th eir in terrelation sh ip with socioecon om ic, cu ltu ra l, a n d b eh a vio ra l a sp ects in th e u n -d erstan -d in g of th e in -d ivi-d u al -d isease p rocess.

Th is exp licit critical stan ce by au th ors from th e An glo -Sa xo n ep id em io lo gica l co m m u n ity towa rd s “m o d ern” ep id em io lo gy a n d th e a s-su m p tion of th e lim ita tion s of risk-fa ctor id e-o le-o gy is q u ite recen t. As su ggested in a p revi-ou s stu d y (Castiel, 1998), it m im ics certain as-p ects o f th e so -ca lled La tin Am er ica n so cia l ep id em iology of th e 1970s, of a Marxist strain . Co u ld it b e th a t th e fa ll o f th e Berlin Wa ll in 1989 b rou gh t greater freed om for th e so-called left-win g in tellectu a ls o f th e Un ited Sta tes, to th e p oin t th at th ey can n ow sp eak ou t with ou t fear of a retu rn to witch h u n ts?

Tracing the future of epidemiology

Let u s n ow tu rn to a ren own ed An glo -Sa xo n ep id em io lo gist o rigin a lly fro m So u th Africa , n ow b ased at Colu m b ia Un iversity in New York,

alon g with h is son , i.e., Mervyn an d Ezra Su sser (1996). A stu d y d ivid ed in to two p ap ers (a p re-lim in ary version was p resen ted at th e Con gress of Ep id em iology in Salvad or in 1995) d escrib es p a st ep id em io lo gica l era s a n d p ro p o ses a fu -tu re p ic-tu re: th at of h ealth statistics, b ased on th e m ia sm a p a ra d igm , in th e first h a lf o f th e 19th cen tu ry; th a t o f in fectio u s d isea ses, with th e germ th eory, in th e late 19th an d early 20th cen tu ries; a n d th a t o f ch ro n ic/ d egen era tive d isea ses, em p h a sizin g th e exh a u stio n o f th e b lack b ox (risk factor) th eory, d u rin g th e latter h alf of th e 20th cen tu ry.

Ac c o rd in g t o t h e Su s s e r s, t h e fie ld ’s fu -t u re is sh a p ed by “eco-ep id em iology” (wh ose m etap h orical p arad igm is th at of “Ch in ese b ox-es”), ch a ra cterized b y a n eco lo gica l p o in t o f view stu d yin g “rela tio n s with in a n d b etween localized stru ctu res organ ized in a h ierarch y of levels” (Su sser & Su sser, 1996:676); an an alytcal ap p roach in volvin g “[a]n alysis of d eterm i-n ai-n ts ai-n d ou tcom es at d ifferei-n t levels of orga-n iza tio orga-n : with iorga-n a orga-n d a cro ss co orga-n texts (u siorga-n g n ew in form ation system s) an d in d ep th (u sin g n ew b iom ed ical tech n iqu es)” (Su sser & Su sser, 1996:676) (h ere, rea d esp ecia lly reco m b in a n t DNA m an ip u lation tech n iq u es an d m olecu lar m a rkers a n d p ro b es, co n stitu tin g wh a t is a l-rea d y kn own a s “m o lecu la r ep id em io lo gy”). Th e p reven tive a p p ro a ch is b a sed o n “[a p p ly-in g] b oth ly-in form ation an d b iom ed ical tech n ol-ogy to fin d levera ge a t effica ciou s levels, from co n textu a l to m o lecu la r” (Su sser & Su sser, 1996:676).

In o th er wo rd s, th e Su ssers a p p ea r to feel th at a b righ t fu tu re for ep id em iology rests p ri-m arily on th e tran sd iscip lin ary con ju gation of b ioin form atic tech n iq u es with so-called “m ol-ecu lar ep id em iology”.

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Th is p o sitio n p o stu la tes th e in flu en ce o f th e am ou n t of ch itin ou s m ar in e zoop lan kton , like co p ep o d s, tin y cru sta cea n s, elem en ts in th e fo o d ch a in o f fish , a s h o sts fo r th e vib r io. Th e cop ep od p op u lation is a fu n ction of glob al clim a te ch a n ges (like th e El N iñ o p h en o m e -n o-n , wh ich p rovides rai-n , bri-n gs -n u trie-n ts from th e coastal areas, an d h eats th e ocean ), an d its m ove m e n ts a re re la te d to th e m a rin e win d s a n d cu rre n ts. In a d d itio n , m o le cu la r ge n e tic p ro b e s h a ve a lso sh own th a t ce rta in vib rio stra in s a ssu m e a via b le a n d p a th o gen ic sta te , yet refra cto r y to cu ltu rin g in th e la b o ra to r y. On e can thereby detect an d coun t Vibrio ch oler-aein en viron m en tal sam p les an d m easu re th e co rresp o n d in g d egree o f co n ta m in a tio n (Co l-well, 1996).

Th e exp ressio n “b io in fo rm a tics” en co m p a sses m a th em a tica l a n d co m p u ter tech -n iq u es em p loyed i-n th e stu d y o f b io lo gica l p ro b lem s. Su ch tech n iq u es a re u sed in crea s-in gly as p owerfu l tools to stu d y n atu ral system s in variou s b ran ch es of b iology: ecology, gen et-ics, evolu tion , im m u n ology, virology, an d ep i-d em iology (Levin et al., 1997).

Th e field in corp orates n on lin ear an d n on -p a ra m etric m a th em a tica l m eth o d s a n d th e stu d y of gen om ic seq u en ces of p ath ogen s ( Es-ch eriEs-ch iaa n d Listeria), o r so ca lled p h ylo ge -n etic a-n alyses; i-n vestigatio-n of h ost-age-n t co-evolu tion ary in teraction s; gen etic im m u n oep i-d em iology; an i-d m oi-d elin g of im m u n e resp on se p attern s resu ltin g from th e com p lex d yn am ics in vo lvin g p a th o gen s a n d th e im m u n e system with co n tro l stra tegies (Levin et a l., 1997, o p . cit). Man y n ew d ru gs h ave b een d evelop ed u sin g th ese tech n iq u es. Th ere a re p h a rm a co ge -n etic p ro sp ects fo r exp a -n d i-n g th e p ower to id en tify gen om ic ch aracteristics of in d ivid u als, grou p in g th em accord in g to th eir corresp on d -in g gen otyp ical con figu ration s an d p rescrib -in g m ore “p erson alized” an d su p p osed ly m ore ef-fective d ru gs (Coh en , 1997).

In o rd er to sim p lify th e p resen ta tio n , we will classify issu es p ertain in g to th e m ath em at-ical m od elin g of “m olecu larization” asp ects of ep id em iological stu d ies. We h ave d iscu ssed th e p ertin en ce o f th e exp ressio n “m o lecu la r ep i-d em iology” in a p reviou s article (Castiel, 1998), b u t it is wo rth wh ile to refer to its d escrip tive sid e n ow an d th en p roceed to th e d iscu ssion of its b asis in m olecu lar b iology.

First o f a ll, h ow d o es o n e d efin e th e term ? Sim p ly sp eakin g, m olecu lar ep id em iology con -sists of th e u se of b iological m easu res or m ark-ers a t th e m o lecu la r level in ep id em io lo gica l research . In oth er word s, stu d yin g th e relation s b etween exp osu re a n d d isea se in p op u la tion s

th rou gh m eth od ological ap p roach es p rop er to ep id em iology.

Th e n ecessary q u an tification s or m easu re-m en ts are b ased on re-m od ern re-m olecu lar b iologi-cal lab oratory tech n iqu es, aim ed at th e follow-in g: a) d irect d etection of ch an ges follow-in m olecu lar stru ctu res (b o th p a th o gen s a n d in d ivid u a ls su scep tib le to d isea se) a n d b ) in d irect d etec-tio n u sin g im m u n o lo gic tech n iq u es to verify th e existen ce of sp ecific m olecu les from given p rod u cts of gen e activities. Th e term origin at-ed fro m ca n cer ep id em io lo gy stu d ies u sin g m olecu lar b ioch em ical tech n iqu es in th e 1980s (McMich ael, 1995).

It also serves to: 1) d em arcate th e grad ien t o f even ts fro m exp o su re to d isea se – in tern a l d ose, b iologically effective d ose, early b iologcal effect, an d altered fu n ction / stru ctu re, clin ica l p ro gn o stic sign ifiica n ce; 2) id en tify exp o -su res to lower or old er d oses to p re-su m ed n ox-io u s a gen ts; 3) red u ce cla ssifica tox-io n erro rs in exp o su re va ria b les fo r d isea se; 4) in d ica te m ech an ism s; 5) estab lish th e role of exp osu re to given fa cto rs in th e su scep tib ility a n d va ri-a b ility o f in d ivid u ri-a l resp o n se; ri-a n d 6) exp ri-a n d th e verification of risk levels in in d ivid u al an d grou p term s (Sch u lte & Perera, 1993).

Gro u p s o f stu d ies h a ve em erged in th e Un ited States th at h ave b egu n to d iscu ss rela-tive risk/ b en efit issu es in vo lved in th e tra n si-tio n o f p red ictive gen etic tests fro m b a sic re-search to clin ical p ractice. Th e b en efits are evi-den t: screen in g of variou s diseases in n eon ates, m a kin g ea rly in ter ven tio n p o ssib le in m a n y ca ses. Bu t fo r d isea ses like b rea st ca n cer, d e-sp ite th e availab ility of p red ictive gen etic tests, th ere is still n o evid en ce th at p reven tive m ea-su res or op tim u m treatm en t are d evoid of risk or fu lly effective. Th e risks can b e su m m ed u p in th e issu e of “p red ictive u n certain ty” as to th e o ccu rren ce o f fu tu re d isea se vis-à -vis so m e tests. Th is a lso a p p lies to n o n -gen etic tests (Holtzm an et al., 1997). In fact, th is is still on e of th e cru cial p rob lem s in risk as a p rob ab ilis-tic category for exp osed in d ivid u als in clin ical co n texts. Ph ysicia n s (a n d p a tien ts) gen era lly feel alon e at su ch tim es, with n o d ata as to th e valid ity an d u tility of recen tly d evelop ed tests. An d I b elieve th at even wh en th ere is access to su ch d ata, d ecision s h ave n ot b ecom e su b stan -tially safer or gu aran teed .

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a-jor ch an ges over th e cou rse of evolu tion . On th e oth er h an d , oth er gen es are u n d er stron g selec-tive p ressu re. For exam p le: th ose codin g for cell m em b ra n e p ro tein s. Du e to th e co m m o n o rigin of m edically relevan t bacteria, on e can con -struct the resp ective evolution ary trees based on the an alysis of the gen es codin g for the con stan t m acrom olecu les (McDad e & An d erson , 1996).

Se q u e n cin g o f o t h e r gro u p -sp e cific va ri-ab le b acterial gen es is u sed to typ e strain s an d id en tify d ifferen ces b etween su ch b acteria. Alth ou gh it is n ot p ossib le to con stru ct an evolu -tio n a r y tree fo r a ll viru ses, sin ce th ere a re n o co n served m o lecu les a s th ere a re with b a cte-ria, th ere are con served an d variab le gen es al-lowin g for th e id en tification of relation s with in viral grou p s. Th is tech n iq u e is also called p h y-logen etic an alysis (McDad e & An d erson , 1996). Such p rocedures serve to: 1) study outb reaks of d iseases of u n kn own origin (e.g., h an taviru s, a resp ira to r y d isea se with a h igh ca se-fa ta lity rate); 2) d etection an d id en tification of cu ltu re-resistan t b acteria (e.g., Wh ip p le’s d isease, a sys-tem ic d isease in volvin g arth ralgia, ab d om in al p ain , d iarrh ea, m alab sorp tion , an d wastin g); 3) esta b lish m en t o f u n u su a l fo rm s o f d isea se tran sm ission (e.g., AIDS an d HIVp ositive d en -tists); 4) verification of lon g in cu b ation p eriod s in rab ies in fection s (b ites in im m igran ts h avin g occu rred in th eir cou n tries of origin m ore th an six years p reviou sly), 5) p aleom icrob iology (ge-ograp h ical id en tification of th e origin s of retro-viru s stra in s in th e ca se o f H IV a n d H TLV-I) (McDad e & An d erson , 1996).

Even so, it is im p ortan t to h igh ligh t th at in th e cu rren t sta te o f th e m o lecu la r a r ts, o n e n otes th at exp osu res to p resu m ed extern al car-cin ogen ic agen ts lead to th e form ation of DNA m u ta tion s in recep tor tissu es (a d d u cts?). Th is d oes n ot n ecessarily m ean estab lish in g cau sal n exu ses, sin ce th ere are still elem en ts m issin g a t th e in d ivid u a l level to su sta in th e rela tio n -sh ip b etween su ch m o lecu la r a ltera tio n s a n d ca n cer gen esis (McMich a el, 1995). In o th er word s, even with th e vigorou s evid en ce b a ck-in g th e d eterm ck-in an t role of certack-in b iom arkers in ca rcin o gen esis, excep tio n s to a sso cia tio n s viewed as cau sal h ave n ot b een u n con d ition al-ly ru led ou t (Vin eis & Porta, 1996).

Discussing the scope and limitations

Bioinformatics

Th e greatest com p u tation al ch allen ge in h igh ly n on lin ear stoch astic system s is th e rep resen -tation of com p lexity an d th e im p act of con trol

m easu res. Dep en din g on th e p roblem , all scales ca n b e im p o rta n t, fro m th e in d ivid u a l to th e greater m etrop olitan level. Th e cen tral issu e is th e followin g: h ow d oes on e effectively a d ju st a n d ca lib ra te th e n u m b er o f elem en ts in th e m od el to a given con text?

Th e re a re m a n y e p id e m io lo gica l st u d ie s a p p ro a ch in g th e d yn a m ics o f in fe ctio u s d is-e a sis-e s fro m th is-e a b ovis-e -m is-e n tio n is-e d p is-e rsp is-e ctivis-e (see Levin et al, 1997, op. cit). Still, in so-called m ath em atical m od elin g an d com p u ter sim u lation tech n iq u es on e m u st con sid er su ch com p lica tin g fa ctors a s in tera ction s b etween sp a -tia l a n d gen etic h etero gen eity, n o n -lin ea rity, a n d sto ch a sticity. Even grea ter p ro b lem s fo r m o d elin g in ep id em io lo gy a re tra n sm issio n variab ility accord in g to social an d geograp h ical sp ace or th e d iversity an d h eterogen eity of in d ivid u a ls. How a n d a t wh a t level ca n o n e rep resen t sp a tia l va ria tio n s in in trin sica lly n o n -lin ear con tact p rocesses u n d erlyin g tran sm is-sion ? An exam p le is th e h igh ly d yn am ic sp atial a n d tem p o ra l p a ttern s in th e AIDS ep id em ic a n d th e p o ssib ility o f ch a o tic, n o n -lin ea r d y-n a m ics iy-n esta b lish iy-n g co m p lex tra y-n sm issio y-n n etwo rks (with h igh d egrees o f im p recisio n ) (Levin et al, 1997).

An d we sh ou ld rem em b er th at m ath em ati-cal m od els can p rovid e an u n ju stifiab le feelin g of verisim ilitu d e. In reality th ey are im itation s or sim u lation s of reality th at attem p t to rep re-sen t wh ere d yn am ic or com p lex p rocesses an d system s really occu r. Accord in g to p h ilosop h er Naom i Oreskes of Dartm ou th College, q u oted by Horgan (1995:77), “Verification an d valid a-tion of n u m erical m od els of n atu ral system s is im p o ssib le.” At b e st , o n e ca n o b t a in p a r t ia l, a p p roxim a t e kn owle d ge. Th is is d u e m a in ly b e ca u se su ch m o d e ls d e a l wit h “o p e n” sys-tem s. Affirm ation s th an can b e firm ly verified (o r va lid a t e d ) a re o n e s d e a lin g wit h “clo se d ” system s, in wh ich all of th e variab les are taken in t o a cco u n t a n d a m e n a b le t o m o n it o r in g t h ro u gh m a t h e m a t ica l lo gic a n d a lgo r it h m ic ap p roach es.

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fictio n s”. Fu rth erm o re, th ey co n stitu te a n ew m o d a lity fo r p u ttin g fictio n s to th e test. With th e n ew p ersp ective raised by th e d evelop m en t o f (b io )in fo rm a tic tech n iq u es, th e u se o f in creasin gly p owerfu l com p u ter system s as sim -ulation tools has led to the rise of “n ew sop hists” in th e scien tific m ilieu .

Sten gers (1993:153) refers to “resea rch ers wh ose in volvem en t n o lon ger relates to a tru th wh ich lays fiction s to rest, b u t to p ossib ilities, wh a tever th e p h en o m en o n m a y b e, fo r th e m a th em a tica l fictio n th a t rep ro d u ces it”. Th e sa m e a u th o r q u ite p ro p erly ra ises th e eth ica l issu e of sim u lation : to “wh at” d oes an in vesti-ga tio n p erfo rm ed o n virtu a l m o lecu les a n d p o p u la tio n s refer? To wh a t exten t a re su ch stu d ies p erform ed exclu sively on ab straction s, a n d wh a t a re th e rep resen ta tio n a l lin ks to “tru e” elem en ts b elon gin g to th e so-called “re-a l” wo rld . Th erefo re, wh “re-a t kin d o f en u n ci“re-a tes ca n th ey gen era te? Th ey o bvio u sly n o lo n ger con stitu te exp erim en tal or ob servation al fin d -in gs.

In a word , wh at kin d of d ata or fin d in gs are o b ta in ed o r p ro d u ced b y sim u la tio n stu d ies? Th is situ ation ch allen ges th e id ea of tru th as an a rra n gem en t in vo lvin g th e exp la n a tio n a n d “reality”, a n otion d ear to th e n atu ral scien ces. Su ch con tin gen cies wh ere th e n otion of virtu -ality im p oses itself fu rth er su bvert th e organ i-zation an d con sisten cy of scien tific d iscip lin es an d kn owled ge.

Lévy (1995) p rop osed a sch em e to d eal with th is o rd er o f p ro b lem s. Acco rd in g to h im , a n y even t can : 1) b e laten t in its virtu ality an d exist a s su ch a n d 2) m a n ifest itself in its a ctu a lizatio n , a n d th u s o ccu r. In th is sen se, a ctu a liza -tio n wo u ld in ven t a fo rm o f h a p p en in g a s a m od ality of creation (Lévy, 1996). Th e “tem p o-rality of actu aliz ation”, a cco rd in g to Lévy (1996), “is th at of p rocesses. (...) To th e ex ten t th at th ere are as m an y tem p oralities as vital problem s, virtu alization m oves in tim e w ith th e tim es. Virtu aliz ation em erges from tim e to en -rich etern ity. It is th e sou rce of tim es, p rocesses, an d h istories, sin ce it com m an ds actu alization s w ith ou t d eterm in in g th em . Creator p a r excel-len ce, virtu aliz ation in ven ts qu estion s, p roblem s, d evices th at gen erate acts, p rocess lin -eages, an d m ach in es for th e fu tu re”(Lévy, 1996: 139-140).

I d o n ot feel th at Lévy h as solved th e p rob -lem satisfactorily. In m y op in ion a b rief ob ser-vation su ggests th e risk of sem an tic ravelin g: if th e even t “exists” at on e level an d “h ap p en s” at an oth er, wh at d oes it m ean “to exist” after all? Th at is, we fin d ou rselves in th e m id st of on to-lo gica l issu es in a stra n ge co n text wh ere th e

b ord ers b etween wh at is p ossib le, real, virtu al, an d actu al b ecom e fu zzy.

Th e triu m p h a n t to n e em p loyed b y Lévy su ggests a d eification of Virtu ality [wh ereby th e cap ital “V” b ecom es a “logical im p osition” (!?)]. In d eed , alon g th is lin e of reason in g, Itwou ld be a “m an ifestation” of (an d for) virtu ality. Wou ld it th u s b e m a n d a tor y to b elieve th a t virtu a lity p o ssesses th e (o m n i)p o ten ce o f “existin g” in o rd er to b eco m e a n a ct, i.e., “to h a p p en”? Derivin g fro m th is ela b o ra tio n is th e esta b lish -m en t of p rocesses wh ich in elu ctab ly con stitu te sta ges o r p h a ses o f th e h a p p en in g wh ich , we stress, m ay or m ay n ot actu ally h ap p en .

Fro m th e b io lo gica l p o in t o f view, Lévy’s reason in g wou ld b e q u ite ap p licab le to b acteria rep ro d u cin g b y fissip a ro u sn ess a n d o cca -sion ally u n d ergoin g m u tation s from in flu en ces in th e co n text. Bu t a fecu n d a ted h u m a n egg con stitu tes a h ap p en in g of a qu ite d ifferen t or-d er fro m th a t o f a n a or-d u lt o rga n ism . On e ca n even con ceive of th em b ein g d istin ct h ap p en -in gs, a lb eit p o ssess-in g l-in ks to ea ch o th er. A h u m a n egg a p p ea rs n o t to p o ssess a m in d , wh ile a n a d u lt o rga n ism a p p ea rs to p o ssess on e. Here, th e cau tiou s u se of th e verb “to ap -p ear” is d u e to ou r in ten t n ot to d elve in to an i-m ist th eological d iscu ssion s. In d eed , n ote h ow Lévy lead s u s toward s su ch issu es.

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M olecular biology

We tu rn n ow to th e p ertin en ce o f th eo retica l a n d ep istem o lo gica l co n ten ts co n veyed b y m olecu lar b iology an d wh ose lin ks to m olecu-la r ep id em io lo gy (with o r with o u t q u o ta tio n m arks) are obviou s. Th is lead s u n avoid ab ly to a p ro b le m . How d o e s o n e p ro d u ce a b a la n ce d d escrip tion with syn th esis a n d d ep th with ou t com m ittin g im p rop rieties or n eglectin g essen -tia l a sp ects o f th e field , esp ecia lly if th e p o in t o f view o f th e o b server-in terp reter is situ a ted in th e ep id em io lo gica l field ...? Fo r b etter (o r wo rse), a t th is sta ge o f th e ga m e, th e a llu sio n to (m o re) d ifficu lties sh o u ld n o t p reven t u s from con tin u in g ou r exercise. Th e greatest risk is to scare off an y erstwh ile an d u n d erstan d in g read ers on ce an d for all an d p erh ap s to fu el th e fires of ou r critics...

Molecu lar b iology (MB) em erged as a d isci-p lin e th rou gh th e fu sion of ch em istry an d b iology, with th e creation of tech n iqu es with a lan -gu age of th eir own , th e ob ject of wh ich are b io-lo gica l m a cro m o lecu les (Atla n , 1986). Th ere are several exp ression s with a ju xtap osition of asp ects th at are correlates of th e so-called MB field . Two are p articu larly evid en t: b iotech n ol-o gy a n d gen etic en gin eer in g. Tech n ica l vigol-o r a p p ea rs in b o th , ru led b y th e criteria o f p ro -d u ctivity, a p p lica b ility, a n -d effica cy. Th e term “en gin eerin g” even d erives from th e n otion of “en gin es”: skills a n d d evices a llowin g o n e to overcom e op p osin g forces.

In th e tech n o lo gica l field , m o re a n d m o re d o u b le-fa ced p ro d u cts a n d p ro cesses fo r u se by m en are in ven ted by en gin eers wh ose p ow-er a p p ea rs in th e “grea t rivow-er o f tech n iq u e, wh ich in overflowin g is cap ab le of b oth fecu n -d atin g th e a-d jacen t p lain s an -d cau sin g irrem e-d ia b le ero sio n , e-d ra ggin g to p so il a n e-d ca u sin g p o llu tio n , relievin g m en o f th eir b u rd en a n d su b jectin g th em to n ew ob liga tion s, ela b ora tin g a con test th at m an u factu res as m an y ‘wtin -n ers’ as it d oes ou tcasts, d evelop n g com m u -n i-cation s fosterin g im p roved ‘com m u n ion’ even wh ile m u ltip lyin g th e n u m b er of ‘excom m u n i-cates’” (Lesgard s, 1994:11).

Th is sh arp d iagn osis by Lesgard s is accom -p a n ied b y a frigh ten in g sta tem en t. Th e in tel-lectu als wh o p u rp ort to d well on “wh at is goin g on” an d to p rod u ce reflection s con cern in g th e wo rld a ro u n d th em h a ve n ever la gged so fa r b eh in d th e ch a n ges p ro d u ced in th e vo rtex o f th e p reva ilin g tech n o lo gica l tren d , p erh a p s d u e to th e fa ct th a t th e sim u lta n eou sly p rolif-era tive a n d d izzyin g effects h a ve u n iq u ely a l-tered ou r ways of seekin g ord er in th e world by su bvertin g n otion s of tim e an d sp ace, id en tity,

rela tio n s with th e b o d y, th o u gh t, a n d d isea se (Lesgard s, 1994).

Alth o u gh it m a y seem o bvio u s, n o te th a t cu rren t b iotech n ological en gin es req u ire d eep an d u rgen t reflection an d in vestigation . In ou r case, m an ip u lative tech n iqu es u sed on h u m an b ein gs are a p articu larly h ot issu e in relation to Lesga rd ’s to p ics. Bu t wh a t will o u r “b io -p o in t o f view” b e? How d o we co n ceive o f a n d d ea l with life scien ces tod ay? With wh ich an alytical tools? Un d er wh ich ep istem ological p rem ises? Or a re th ese q u estion s n ot releva n t? Th ey a re. Bu t th e “en gin eers” (gen etic an d oth erwise) are p reoccu p ied with m ore “con crete” “th in gs” – to effica cio u sly p ro d u ce n ew (b io )tech n ica l o b -jects a n d m a ke th em a va ila b le a s q u ickly a s p ossib le.

In o th er wo rd s, I b elieve we sh o u ld d o u b t th a t cu rren t co n cep ts a n d in str u m en ts b a sed on gam es to an alyze lan gu age an d sym b ols are co n sisten t en o u gh to “m o n ito r” a n d u n d erstan d wh at is goin g on in th e tech n ob ioscien -tific world . To accom p an y th is m ilieu , I b elieve we m u st d elve in to th e “b iotech n icalities” an d seek in so fa r a s p o ssib le to a cco m p a n y th eir u n cea sin g p ro d u ctio n , even wh ile kn owin g th at we are at a d isad van tage in th is “race”. It is q u ite d ifficu lt to carry ou t attem p ts to d ecod e, tran slate, an d alm ost sim u ltan eou sly reflect on th e m u ltifaceted rep ercu ssion s of th e tech n o-b io scien tific field a n d its p ro lific p ro d u ctio n wh en on e is rem oved from th e p rod u ction cen ters an d / or lacks th e m in im u m tech n ical train -in g (wh a tever th a t level m igh t b e) fo r su ch a n u n d ertakin g.

Va rio u s ed itio n s o f Scien ceexp ressed th e first d o u b ts a s to th e relia b ility o f th e exp eri-m en t th a t p ro d u ced Do lly. Th e o rigin a l p a p er h a d b een p u b lish ed in N atu re. Bo th jo u rn a ls are sou rces of freq u en t con su ltation by h ealth , scien ce, an d tech n ology colu m n s from th e lay p re ss. Two a rticle s in Scien ce cove re d th e fo l-lowin g th em es:

1) Reco gn itio n o f th e p ertin en ce o f Ca rlo Woese’s th eory (two m on th s after h e form u lat-ed it) con cern in g th e existen ce of a d om ain of u n icellu lar livin g b ein gs d ifferen t from all oth -er on e-celled b ein gs.

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so p h istica ted m o lecu la r tech n iq u es. Yet h is stu d y received n o reco gn itio n wh a tso ever wh en it was p u b lish ed in th e Proceedin gs of th e Nation al Acad em y of Scien ces. Woese was con -sid ered an in trovert. He n ever atten d ed th e sci-en tific m eetin gs of th e m icrob iology societies. So m e co n sid ered h im a “n u t”. Th e p o in t wa s th at h is article was ign ored by th e m ore p resti-giou s m icrobiologists of th e tim e (Morell, 1997). Eve n t s like t h is a re h a rd ly u n co m m o n . In th e field of gen etics, th e lack of recogn ition for Men d el’s sem in a l wo rk is in fa m o u s. Gen etics h isto ria n s p o in t o u t th a t h is gro u n d b re a kin g st u d y wa s o r igin a lly p u b lish e d in a m in o r jou rn al.

2) Th e recen t a p p ea ra n ce o f a “n ew” su b d iscip lin e, fu n ctio n a l gen o m ics (FG), a p re -d icta b le fiel-d in lo gica l term s, a lth o u gh still p oorly d efin ed , b u t alread y freq u en tly q u oted in th e sp ecialized d om ain s (Hieter & Bogu ski, 1997). Very well, wh ile th e term “gen o m e” (a n organ ism’s set of gen es an d ch rom osom es) was co in ed over 75 yea rs a go, gen o m ics wa s o n ly crea ted in 1986 to d efin e th e d iscip lin e in ch arge of m ap p in g, sequ en cin g, an d an alyzin g th e gen om e. Gen om ics can n ow b e d ivid ed in -to stru ctu ra l (th e co m p lete, h igh -reso lu tio n tra n scrip tio n o f th e p h ysica l gen etic m a p s o f an organ ism’s DNA) an d fu n ction al (th e ap p li-cation of stru ctu ral kn owled ge to estab lish th e gen es’ fu n ctio n s, b a sed o n sta tistica l a n d b ioin form atic tech n iqu es).

Th e fu n dam en tal strategy (...) is to exp an d th e scope of biological in vestigation from stu dy-in g sdy-in gle gen es or protedy-in s to ‘stu dydy-in g all gen es or p rotein s at on ce’ in a system atic fash ion (...) [m y em p h asis]. Fu n ction al gen om ics p rom ises to rap id ly n arrow th e gap betw een sequ en ce an d fu n ction an d to yield n ew in sigh ts in to th e beh avior of biological system s” (Hieter & Bo -gu ski, 1997, op. cit: 601).

Th e a r ticle q u o te d a b ove d e scr ib e s stu d -ies ra n gin g fro m th e co m p leten ess o f yea st gen om es to gen etic ap p roach es to th e d iagn o-sis, p ro gn o o-sis, a n d trea tm en t o f ca n cer th a t co u ld a lrea d y b e in clu d ed u n d er th is n ew “h ea d in g” (Hieter & Bo gu ski, 1997). Strictly sp ea kin g, will “fu n ctio n a l gen o m ics” tu rn o u t to b e (o r is it a lrea d y) a n im p o rta n t field , a n d will it th u s m erit o u r effo rts to a cco m p a n y its resu lts? FG is alread y b ein g viewed as th e form th e h u m a n gen o m e p ro ject will a ssu m e over th e n ext m illen n iu m , a fter th e d escr ip tive/ stru ctu ral p h ase (Morel, 1997). Wou ld it b e ap -p ro-p riate n ow to con sid er it ju st a -p assin g fad tu rn in g tech n o b io scien ces in to a sp ecta cle? Fo r b etter (o r fo r wo rse?), h ow m u ch o f ea ch (o r b o th ) o f th e a b ove will it tu rn o u t to b e?

Ra re in d eed a re th e situ a tion s th a t a re rea d ily d iscern ib le in d ich o to m o u s ter m s (i.e., like b la ck-a n d -wh ite, wh en th e n o rm is u su a lly sh ad es of gray). As if it were p ossib le, b ased on an an alysis in th e h eat of even ts, to reach con -clu sive ju d gm en ts (of th is m agn itu d e) vis-à-vis th e em ergen ce of a field or d iscovery. In gen era l, it is im p o ssib le to q u ickly p erceive th e in -n o cu o u s-n ess (wh ich ge-n era tes th e q u o ta tio -n m a rks) o f a fin d in g like “co ld fu sio n”, wh ich p roved to b e a flu ke a n d wa s relega ted to th e p a st. At a n y ra te, th ere is stro n g evid en ce fo r th e relevan ce of fu n ction al gen om ics. Bu t will it b e p o ssib le so m e d a y “to stu d y a ll gen es o r p ro tein s a t o n ce” in h u m a n b ein gs a n d m ea -su re th eir effects? Th e m ost sen sib le an swer is in con clu sive: m ayb e...

Su ch exa m p les in d ica te th e grea t d ifficu l-ties on e faces tod ay in keep in g u p -to-d ate an d certain of th e p ertin en ce of fin d in gs p resen ted in th e m ain p u b lication s from on e’s resp ective field , p lu s th eir in tersectio n s (n o t to m en tio n th e cou n tless in tern et sites an d lin ks...). I fear th is m ay b e th e scen ario th at is u n fold in g: th e great p rob ab ility of extrap olatin g ou r cap acity to fo llow a n d u n d ersta n d th e m in u tia e a n d sp in -o ffs o f wh a t is p ro d u ced (to th e p o in t o f sa tu ra tio n ) in o u r a rea s o f in terest. Th ere is a p leth ora of in form ation ...

Bu t let u s b e o p tim ists. So m e issu es a re am en able to sp ecific treatm en t, p rovidin g ways to d eal with given ord ers of p rob lem s. Follow-in g th e lFollow-in e of th Follow-in kFollow-in g of Lesgard s, Sh ep s, an d Tarn ero, an argu m en t worth y of n ote is d evel-o p ed b y Gilb ert Hevel-o ttevel-o is (1994), n evel-o tin g th a t

“w h at ch aracterizes m odern scien ce is th e break w ith sym bolic d iscou rse an d m etalin gu istic sp ecu lative k n ow led ge. N eith er tech n iqu e n or m ath em atics belon gs to th e ord er of lan gu age (...). Gam es are created w h ich are n ot n ew lan -gu age gam es, alth ou gh lan -gu age is n ot totally exclu d ed an d frequ en tly in terven es (...). W ith in th ese gam es (...) th in gs are n ot decided th rou gh con versation , bu t th rou gh calcu lation (in creas-in gly perform ed by com pu ters) an d tech n oph ys-ical exch an ge, w h eth er efficaciou s or n ot (...)”

(Ho tto is, 1994:63). Fro m th is p ersp ective, to stu d y th e co n cep t o f in fo rm a tio n wo u ld a p -p ear fru itfu l.

Seeking information

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follow-in g: evolu tion an d n atu ral selection . Yet as we sh all see, th e n otion of in form ation is p articu -larly im p ortan t an d will b e th e ob ject of ou r at-ten tion .

Sch olars gen erally estab lish in au gu ral m om en ts. With th e eom ergen ce of th e n otion of in -form ation as a qu an tifiab le elem en t, referen ces ten d to con verge on th e classical work of Sh an -n o -n a -n d Wea ver, Th e M ath em atical Th eory of Com m u n ication (1949), in wh ich th e a u th o rs d evelo p a th eo r y o n th e m ea su rem en t o f th e am ou n t of in form ation in a m essage tran sm it-ted by a com m u n ication s p ath way. Th ey create th e n o tio n a n d th e fo r m s o f m a th em a tica l treatm en t of “b in ary d igits” (b its), u n its of b a-sic in form ation for th e fu n ction in g of com p u t-er system s a n d wa ys o f ca lcu la tin g a n d d ett-er- eter-m in in g th e storage cap acity of th ese eleeter-m en ts fo r p ro cessin g a n d tra n sm issio n . In o th er word s, if com p u tin g op erates on sym b ols, b its co n stitu te th e u n its o f th ese sym b o ls (d evo id of m ean in g) allowin g for su ch op eration s. Th is is all qu ite trivial for an y n ovice in tod ay’s com -p u ter arts. Bu t su ch were th e b egin n in gs of cy-b ern etics (n ow referred to as first-ord er cycy-b er-n etics), a d iscip lier-n e wh ose sem ier-n al text b y Nor-b ert Wien er, Cybern etics, was p u b lish ed in 1948 an d wh ich wou ld d eal with “in form ation” an d sh a p e it in to “p ro gra m s”... Neverth eless, h ow d o es th e ca lcu la b le co n cep t o f “in fo rm a tio n” with h igh m ath em atical, statistical, an d cyb er-n etic co er-n teer-n ts exteer-n d to m o lecu la r b io lo gy? Maria M. A. Jorge (1993) an d J-P. Du p u y (1995) trace th is tran sition in sim ilar fash ion . Accord -in g to Jorge, th e “-in tellectu a l -in fra stru ctu re of m o lecu la r b io lo gy” is situ a ted in th e p o stu la -tion of a com p lem en tarin ess b etween p h ysics a n d gen etics a s p o stu la ted b y Niels Bo h r a n d d evelo p ed b y o n e o f h is d iscip les, Ma x Del-b rü ck.

Du rin g th e 1940s, stu d ies b y Delb rü ck’s gro u p co n vin ced h im th a t gen es were m o le -cu les viewed from th e p ersp ective of q u an tu m p h ysics. Bu t th ere a p p ea red to b e a b io lo gica l p rin cip le o f u n ce rta in ty wh ich h a m p e re d a n u n d e rsta n d in g o f th e ge n e tic m in u tia e. Th e two d iscip lin es were d rawn togeth er by th e d is-covery of n ew laws of p h ysics ( Jorge, 1993).

Th e id eas raised by in form ation com m u n i-cation s th eory an d feed b ack regu lation served in itially as a n ew “lan gu age gam e” to ap p roach th e p h en om en a of h ered ity an d gen etics. Th u s em erged su ch con cep ts an d term s as “in form atio n”, “p ro gra m”, “co d e”, “m essa ge”, “tra n sla -tion”, an d “tran scrip tion”.

An oth er p h ysicist, Erwin Sch rödin ger, asked th e q u estio n in 1944 (in th e fo r m o f a b o o k),

W h at is Life?a n d su ggested th a t a n a n swer to

m ech a n ism s o f h ered ity a n d gen etics m igh t co m e fro m p h ysica l la ws (Du p u y, 1995). Fox-Keller (1995) p oin ts ou t th at it was Sch röd in ger wh o p rovid ed th e n o tio n o f ch ro m o so m e a s scrip t/ cod e.

Accord in g to Fox-Keller (1995), th e very ex-p ression “in form ation”, with stron g m etaex-p h ori-ca l co n n o ta tio n s sin ce it wa s exp lo red in th e 1950s by th e d iscoverers of th e DNA d ou b le h e-lix, Wa tso n a n d Crick, co n verged towa rd s th e n o tio n o f in stru ctio n . Bio lo gist a n d scien ce h istorian Fox-Keller an alyzed th e evolu tion of th e co n cep t in th e 20th cen tu r y a n d h ow th e o rigin a l sen se o f th e in fo r m a tio n th eo r y wa s n ot m ain tain ed in th e d escrip tion of th e fu n c-tio n in g o f n u cleic a cid s in p ro tein syn th esis. Fu rth erm o re, th is p ersp ective tu rn ed th e ge -n etic co d e i-n to a “m essa ge” (see m esse-n ger RNA) assu m in g th e form of “ord ers”. Tod ay, th e p red om in an t p oin ts of view see gen es as cau se, m ach in es as organ ism s, an d organ ism s as m es-sages. It is essen tial to b e clear th at all lan gu age is n o t o n ly d escrip tive b u t a lso “p erfo rm a tic”, i.e., so cia lly co n stru cted a n d co n textd ep en -d en t, a n -d m u st th u s b e eva lu a te-d a s to its ef-fectiven ess an d n ot accord in g to tru e/ false cri-teria (Fox-Keller, 1995).

Acco rd in g to Jo rge (1993), o n e ca n th u s classify m olecu lar b iologies in two fu n d am en -tal watersh ed s (with in term ed iate areas): 1) th e “o fficia l” o n e, b a sed o n th e n o tio n o f “o rd er b ased on ord er”, wh ere th e livin g b ein g resu lts from stab le p rocesses of ord ered con stru ction , b y regu la r, u n va r yin g rep etitio n , su ch th a t so o n er o r la ter su ch m ech a n ism s will b e d is-covered (th e h u m an gen om e p roject ap p ears to feed o n th is p ersp ective); 2) th e “o th er” o n e, th e cen tral id ea of wh ich is “ord er b ased on d isord er” (or n oise), wh ere u n p red ictab ility, ran d om n ess, in stab ility, b ifu rcation s, an d im p on -d erab len ess are cru cial to th e gen esis of livin g b ein gs.

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fa ct th a t it ser ves b o th th e m o lecu la r wa ter-sh ed of ord er (n eo-m ech an ism ) an d th at of d iso rd er (n eiso vita lism ). In th e first ca se, th e n iso -tion is lin ked to calcu latin g an d p rocessin g so-called in form ation al u n its (like b its), as ap p lied to th e a b ove-m en tio n ed field o f b io in fo rm a t-ics. If life is in fo rm a tio n – a n d th is is th e h y-p oth esis of “ord ered” m olecu lar b iology – th en livin g b ein gs ca n b e exp la in ed o n th e b a sis o f th eir a lgo rith m ic in fo rm a tio n co n ten t (AIC) (Gell-Ma n n , 1996) [with a lgo rith m b a sed o n th e co n cep t o f th e co m p u ta tio n a l m a ch in e p ro p o sed by Ala n Tu rin g, “given seq u en ces o f logical/ m ath em atical in stru ction s orien ted in a sp ecified d irectio n” (Atla n , 1991: 217), o r m ore sim p ly, as a ru le (or set of ru les, i.e., p ro-gra m ) to ca lcu la te/ com p u te som eth in g (Gell-Man n , 1996)].

From th is p ersp ective, th e com p lexity of b i-o li-o gica l system s ca n th u s b e m ea su ra b le a n d com p u tab le, esp ecially allowin g for m an ip u la-tio n s. Th is is th e p o sila-tio n ta ken b y n eo -Da r-win ist Da n iel Den n ett (1995), wh o co n sid ers evo lu tio n by n a tu ra l selectio n a n a lgo rith m ic p ro ce ss o ccu rrin g in th e m o le cu la r re co rd o f n u cleic acid s. In h is op in ion , “Darwin’s d an ger-ou s id ea” p ertain s to th e fact th at th e “algorith -m ic level is th e level th at best accou n ts for th e sp eed of th e an telop e, th e w in g of th e eagle, th e sh ap e of th e orch id , th e d iversity of th e sp ecies (...)” (Den n ett, 1995:59), even with ou t th e ob lig-ation of p rod u cin g su ch ch aracteristics (an d by exten sion , with ou t th e n eed to reach u s). Neu -ron al fu n ction in g an d th e so-called cyb er n etic system s (a n a lo gica lly ca lled n eu ra l n etwo rks) a lso o b ey a lgo rith m ic a n d th u s in telligib le ru les (i.e., on es th at can b e m od eled ) from th e p o in t o f view o f a co m p u ta tio n a l n eo m ech a -n ism . However, th is “co m p u ta tio -n a l su r veil-lan ce” of h u m an s b ased on th e n otion of “cold , calcu latin g in form ation” was ch allen ged by th e so-called secon d-gen eration cybern etics m ove-m en t ca p ta in ed by Hein z von Foerster (1991). Th is Vien n a-b orn p h ysicist was on e of th e foreru n n ers of th e n otion of in form ation as th e u n -d erlyin g elem en t in self-organ ization by livin g b e in gs, wh o wo rk wit h in fo r m a t io n u sin g re-cu rsive, au ton om ou s, an d self-referred p rocess-es su ch th a t th eir o rga n iza tio n o f th em selvrocess-es an d “reality” occu rs in in fin ite circles, in an as-so cia tio n o f in fo rm a tio n with life a n d kn owl-ed ge. Th is occu rs in h u m an s th rou gh th e sp eci-ficity o f th e h u m a n m in d , a llowin g o n e to b e co n scio u s o f scie n ce it se lf – t o o p e ra t e o n e -self w ith scien ce(th e etym ological root of con -scien ce).

Su ch p rop osition s resu lt in an ap p roach b e-tween cyb ern etics, b iology, on tology, an d ep

is-tem ology (b oth in th e sen se of th e qu estion s as to k n ow in gan d th e p ossib le an swers con cern -in g th e issu e of k n ow ledge). Cyb ern etics looked a t itself a n d p ro p o sed a s its en u n cia tes th e q u estion s as to wh at it m ean s to exist, to kn ow [an d its d erivation s vis-à-vis ob server-su b ject (wh o kn ows?) a n d o b ser ved -o b ject (wh a t is kn own ?)] (von Foerster, 1991). However, on e of th e risks of th is p ersp ective is th at of fallin g in-to a kin d of n eo-vitalism – red u ction of th e b io-logical sp h ere to th e p sych ic/ m en tal, wh ich af-ter a ll p o ssesses p a rticu la r co gn itive p ro p er-t ie s. Su c h p ro p e r er-t ie s o r igin a er-t e fro m e m e rg-in g “com p lexological” m od els, th e “rg-in terest rg-in wh ich”, accord in g to Atlan (1991), “lies in estab-lish in g h ow stru ctu res an d fu n ction s are p ro-du ced th at play th e role of creatin g m ean in gs in th e eyes of an objective observer. From th ere on , su ch m od els are con fu sed w ith th e im m ed iate, u n iqu e ex p erien ce of ou r su bjectivity (...) [We con fu se] th e form of creativity w e p erceive an d d escribe in certain n atu ral p h en om en a w ith th at of ou r ow n spirit” (Atlan , 1991:110). In gen eral, wh en we ap p roach evolu tion ary p h en om en a in m a cro m o lecu les a n d th ereby a p p ly in -fo rm a t io n a l n o t io n s, we a re p ro ce e d in g t o a n a logica l/ m eta p h orica l tra n sp osition s (“n o-m ad iso-m”) of con cep ts froo-m d ifferen t ord ers of organ ization . Th is occu rs wh eth er we affirm ei-th er of ei-th e followin g:

a ) th a t evo lu tio n o ccu rs b y n a tu ra l selection at th e (m olecu lar) level of algorith m ic in -form ation con ten ts.

Th e ab ove b elief fosters th e so-called gen e fetish ists, th ose wh o b elieve in gen om ics as th e co d e-o f-co d es, th e b o o k-o f-b o o ks, th e Ho ly Gra il, a n d th e gen e a s a n exclu sively m a teria l en tity, b earer of a h eavily d eterm in istic cau sal action , a th in g in itself. Fetish es, as th e su b stitu tes th ey are, p rovid e a con creten ess with op -era tio n a l en d s fo r th e gen o m e. Th ey h a ve th e fu n ction of m akin g th in gs ap p ear well d em ar-cated an d con trollab le, som eth in g wh ich is oc-casion ally p ossib le to con ceive of an d ab ove all a llows o n es to o p era te. Bu t u n d er m a n y cir-cu m stan ces th is p rop osition is u n ten able, sin ce

“th e reality an d m ateriality of th e gen om e is si-m u ltan eou sly sesi-m iotic, in stitu tion al, si-m ach in ic, organ ic, an d bioch em ical”(Haraway, 1997: 99) a n d th u s d ep en d s o n th e co n text a n d is d iffi-cu lt to con trol or p red ict, or

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In h u m a n s, to live is m o re th a n to kn ow, wh ich is m ore th an to p rocess in form ation . Yet cu rren tly, “‘Life’, m aterializ ed as in form ation an d sign ified by th e gen e, displaces ‘Natu re’, preem in en tly preem bod ied in an d sign ified by old -fash ion ed organ ism s”(Ha ra wa y, 1997:134). By th e way, Den n ett’s p ecu liar verve (1996) serves to in ad verten tly illu strate th is sh ift qu ite clear-ly. Th e Am erican p h ilosop h er goes to th e p oin t o f ca llin g th e evo lu tio n a ry p ro cess by n a tu ra l selection “Moth er Natu re”. Yet it wou ld ap p ear th at th is den atu red m oth er refu se to n u rse b oth th e m in eral kin gd om (with its q u akes an d vol-can oes) an d m eteorological p h en om en a...

Fin ally, ru n n in g th e risk of su stain in g con -cep tu a l sta n ces wh o se id eo lo gica l sp in -o ffs a n d sociocu ltu ra l rep ercu ssion s a re p rob lem

a tic, to sa y th e lea st, it is essen tia l to d istin -gu ish b etween “in fo rm a tio n” a s co n stitu en t p o ten tia l a n d kn owled ge. Kn owled ge is wh a t actu ally occu rs in th e ord erin g an d in tegration of variou s “(in )form ative” elem en ts. Th e ratio-n a liziratio-n g d iscu rsive p ressu res of ep id em iology (b o th cu rren t a n d fu tu re) a re u n d en ia b le, th ro u gh its scien tific m o d els o f in telligib ility. Bu t rath er th an takin g th em as u n con d ition al, in elu ctab le tru th s, it is essen tial to d istin gu ish (with in su ch p ro p o sa ls fo r kn owled ge) th e p rem ises an d vicissitu d es of th e con stitu tion of th eir elem en ts for ou r kn owled ge an d in terven -tion in h ealth , in ad d i-tion to th eir fu n c-tion s in th e p o ssib le id io syn cra tic in terp reta tio n a n d creation of m ean in gs in th e lives (h owever th ey m ay b e...) of each an d every on e of u s.

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