This section loois back to some gourd breaking centributions to pubic health, reprodxing then in their original fome and adding a commentary on their sighilicance from a medesp disy pecupective. Robyn M Lucas and Artiony L. Mrakichaed retiew the enyinonmert and diceise: association or ciusation by Sir Austin Bradiord th on estaldiching selationshios betiven ineni and conditions of work or lwing. The original paper is reproduced by permission of The Royal Society of Medicine fies linited (impilwwa.ismarg) Association or causation: evaluating links between "environment and disease" Robyn M. Lucas! \& Anthony I MdMichael? Epidemiological studies typically examine associations terween stadiod may not promide mue information about the relation: an expouare variable and a health euscome. In asesulag the ahap brtwesa enpoiate and oescome in the nounce populacion, caual nature of an observed association. the "Bradfond HHll wath respect cither oo the sclatiomihip that the sample actually thought (1). Fint publiched exactry 40 yrans apo, these criteria designs that muimine the egnal to noule rario. and quickly became a mainstay of epidcmiolopical tesbooks tescarch, requite onc to procerl cabbousty in making erusal and data intepptetation (2). Their chedist nafure suitcel the inferchce. Oner meffient stadics have hern done, in diverse sudy af simple, direcr cautation by discipliner characterizad serrings, and adequanty linining mandeats error (an ineriavic by chavic acientific and mathematical training. property of a stochatic aniverse), ypotematic error (beas) and conceptualization of cheir causarion varies by discipline. While ascociarions can remonoubly he assessed. it is soirntifically utisfying to ducidate the many component Note. though. that particular phraie: "eaual nature". causs of an illnces, in pubtic health tcvcurch the more impot- Causution is as intcrpectatice, not as entity it should not be tant emphasis is on the discevery of neceskary or nuffcicnt reifind. The 18ch-centary Scoetinh phinomopher David Hurne causes that afe amenable is ineerveation. Eytm sov over the pointrd our thar canarion in induced fogleally, aot absennd four decudes since Bradford Hill' paper appeared, the range empinically (3). Theneface we can merer hewew absolunely thut of multivariate, multistage and multi-lerel fesearch quotions expouse X caces disease Y. There is ao final gmof of causation: tackled by cpidemiologines has coolved, as have thcir statistical it in mercly an inficrmoe based on an observed conjanction of methods and their engerement in wider-ranging intendisci- rwo variables (mponene and healh iearas) in time and space plinary researh. Within that context it is eftea not appeopeiate. Thut limitaniee of inductive logic applies, of course, to boeh to seck the discrete cause ot cause of a diseave, but rather to experimental and non-caperimental roseatch. ikentify a complex of interretased and often interactine fac- Around the mil-20ich cenrar. the jhi.

1. This section loois back to some gourd breaking centributions to pubic health, reprodxing then in
their original fome and adding a commentary on their sighilicance from a medesp disy
pecupective. Robyn M Lucas and Artiony L. Mrakichaed retiew the enyinonmert and diceise:
association or ciusation by Sir Austin Bradiord th on estaldiching selationshios betiven ineni and
conditions of work or lwing. The original paper is reproduced by permission of The Royal
Society of Medicine fies linited (impilwwa.ismarg) Association or causation: evaluating links
between "environment and disease" Robyn M. Lucas! & Anthony I MdMichael?
Epidemiological studies typically examine associations terween stadiod may not promide mue
information about the relation: an expouare variable and a health euscome. In asesulag the ahap
brtwesa enpoiate and oescome in the nounce populacion, caual nature of an observed association.
the "Bradfond HHll wath respect cither oo the sclatiomihip that the sample actually thought (1).
Fint publiched exactry 40 yrans apo, these criteria designs that muimine the egnal to noule rario.
and quickly became a mainstay of epidcmiolopical tesbooks tescarch, requite onc to procerl
cabbousty in making erusal and data intepptetation (2). Their chedist nafure suitcel the inferchce.
Oner meffient stadics have hern done, in diverse sudy af simple, direcr cautation by discipliner
characterizad serrings, and adequanty linining mandeats error (an ineriavic by chavic acientific
and mathematical training. property of a stochatic aniverse), ypotematic error (beas) and
conceptualization of cheir causarion varies by discipline. While ascociarions can remonoubly he
assessed. it is soirntifically utisfying to ducidate the many component Note. though. that
particular phraie: "eaual nature". causs of an illnces, in pubtic health tcvcurch the more impot-
Causution is as intcrpectatice, not as entity it should not be tant emphasis is on the discevery of
neceskary or nuffcicnt reifind. The 18ch-centary Scoetinh phinomopher David Hurne causes that
afe amenable is ineerveation. Eytm sov over the pointrd our thar canarion in induced fogleally,
aot absennd four decudes since Bradford Hill' paper appeared, the range empinically (3).
Theneface we can merer hewew absolunely thut of multivariate, multistage and multi-lerel
fesearch quotions expouse X caces disease Y. There is ao final gmof of causation: tackled by
cpidemiologines has coolved, as have thcir statistical it in mercly an inficrmoe based on an
observed conjanction of methods and their engerement in wider-ranging intendisci- rwo
variables (mponene and healh iearas) in time and space plinary researh. Within that context it is
eftea not appeopeiate. Thut limitaniee of inductive logic applies, of course, to boeh to seck the
discrete cause ot cause of a diseave, but rather to experimental and non-caperimental roseatch.
ikentify a complex of interretased and often interactine fac- Around the mil-20ich cenrar. the
jhilospher Kurl tors that intluence the riak of discase (1). This compticates the Popper offered a
solumoe to this pookicm of refiance en induc The general contea wishis which beadford Hill
devel. ing caalal hypeeheses, an by acnually peoving causation. While here. Meut
epidemiological teveanh is nos-experimental, being gists have generally saien a pextical data-
busel afpeoch bo the conducted in an inherenely "noiby" eavironment in fres-fiving notion of
cauabine, comfinably embeacing Bradfind Hilfs popalations. For example, the qualify of the
measuremint of criteria of causality In penctal, those secm well saited to the capouse and of
health status it usually las thas in coesolled moaty noe-ceperimental, bien-peonec confounding-
ridy nature clinical trials or laboratory-based srudies (measusement error) of epidemiolagical
reacanch. These mine criteria, of gaidelises. there ate potential confounding kariables that are
statiutically lay particular cnptume upon the ungeraity of the neletionshiph. asociated with the
exponure variable of intercat while alio its sticngth, the presence of a glausibledone-soponse
ralunionpredictive of the health outcone in their own right, and ship, the consinency of finding in
divene anudies, and coherthese covariates must be cuntrolled for the sample of perwans ence

2. with other disceplinary findings and binesedical rheneys. fit Na. 04-616048 Rather than
proposing abolute criteria, Fradfond Hill cusid. the rule of athase and compechensive
measuranent of pessible crod there as aspect of the asuociaboon hetwecn as oxposus and
confounders for a valad measure of axociation. This in often the enose lady inectprtation of is a
caunation". human healh. Badlond Halls ideat about caual iafereace were formu- Cowiowar
Hratfond Hal als felt mote confidence in Lind in the heady early years of the ris of
noscemmunicuble. a caual epplanation for an wneciution if the ame answer had particulur, the
fint definitive controled dlinical triat - of the reials of atudie of the ume phenoesmoe murvury
becaus (5) - and the eatly vudies of ciganete imokies and lung finduding gose-
envimonenrinteration (12) or dhano (11). of noncomanunicable diease included thote that
enesiled consiatency is not a necestary criterian for a causal iaterpets. mipriving chat, agaime that
buckpround, the challenge soened widh a thiad fictor thar a variably presint and warnm ferher sat
so moch that of chucidating and apportioning comples invetigation, nother thas a asn-causal
conclusion. caisality but. more fundamentaly, of inferring simple. rola. Sperphing That criterion
is eften itatend to mean that any quetiona about the univenal applicabiling of his daaic crietria.
Givaies may have moer than ane ease and that ane-to-une Are they useful in a wisening research
agends within which, limited io ipecific groupe with a paricular envininencal ex: for exanpple,
we uy to identify and quancify the effects of more posurt or is peatly incraved in thec proups thea
the case for Geton meluted to aociesconamic satus, the effeca of iathan of ipecificisy at a uafful
sancept in inuly deign, particulerhy inellinctual framenork thupe and direct our nevearch
quention helmet wearen cepericnce a deckewe in all oypes of iejurys or juer Ten yeass afer
Bradfont Hilfs daisic paper. Rodbman by any npe of endomeriasi, ar enly evarian endimetriousit)
pathogencis of dicese, with multiple componet causer or reven a particular generype and in
eatcame in manifest only mufteient oo fecult in disease devdopeneat. Casal infrenece.
Tompondioy. Tempotalify it a neccuary criterion for a then, would fonis more on lurw well the
roults of epidenio. Gausal awociation between ma exponiec and an euncene, shat esabich
cauality - for each criterion there are situbiens in of the outcomel. ify, the seqairemene that the
experuie maspecede the effect. dose-teipense curve can be demonotased Honever, much quan. a
the only necsesary criverion for a cuab reditionhip berween titative relacionihips nuy be difficult
wo demonitrate er may In the following iestion wr briedly nevirw the Bealford itudf eabibiti a
biolegial gradient in relation to the outcoene Hill oriteril and dhet contemporary ase is
epidemiology? (11). In addioion, it li dear that for many envioutimencal epor: asocations he cios
(a 200-fuld increase in mortality from 17), ospoure to ultratidet raliation and diwase (13), and
pared with non-emolen) have more crodence, being lea likely a biologically piasible, Bradford
HAl note that "this it a fea. Reletively wrak anociatiani are cottenos in contempotiry plausble
depends upon the biabegical knowicules of the day", and methodologs, with minimization of
back, cvaluation of prior belicti" (11). Association or causatice evaluating lirks between
"envirenment and diease" Pobyn M. Lucas s Amthony 1. McMichuel. Cakrexre Coberence and
biological plausitaliry ahare for disese was poremy. Ar abour ahe same rime, three of the a
requirement that the case-and-effect inteopoterion of an wedd s prominent ontodos
cpideminingists argoed that it was asiociation should fit with the knewn facts of the natural hiv
nec the tadk of epidemiology co focus on porerty as a cause of toey and biology of the dieaie. Do
the remporal pueiemi of diveace (22). This divergence of vicwa beari on dhe quesion of
exposuse and the known biological efferts of the exponse fit how far ugsticam should the matier
of cauce - and thesefore wish the observed diseaie gantems? For esample, the "lygicne poocntiel
istervention - be pursued. eases cohenes winh treads in developed counariss on both fewer

3. Aboriginals to be aecribured ro eheir high previlence of heileh: chisdhood intecrions and an
increasing incidence of allergic endangering behaviour at the individual keve, induding uabaland
auroimumune divorderi ( 20 ) . anced dicts, cucessive alsobol conamprion, cifarene smeking.
Exprinime. Dopteventive actions taken oe the tusis of a sedentary behaviour, poor hypiene and
dangstour driving? bo it human clinind rrials allaw the manipaluasa of exponures is the anower
(and, in foct, all levels of causatian are televane). a controlied environment anlilke haman
oboervanional epide ir is deir that causal relarionshipr become mone comples, miological sudies
Laborasory animals are berd to simulere leo quantifiable and leos amenable to formal causal
inference a meatired whis, monitered for divase devnlopment and then outcoene (23). acrificed
so namine pathological shanges. The randomind The existence of formal criecria fore catal
inference may humun atudica to allow ctirtatice of the tue asaciatian reciech quectiona, and thiat
deter us fram consideration of betwoes eaposure and vutcome. In practice, however, control the
big pictuec where the deca are ofeen fuecy and reiadual of confoubding and bias may be
achicvod only at the cest of coofounding is likely. Indced. fanding bodies azay prefer bo
representativencis of study powet. awand rescarch grants to inudics with dear delincition of both
Aualge. Hodtord Hilil and other epidemiolopists recog- exponuse and health ouroome and a
mady designn cunducive nized that the nocion of analory can be taken to impractical to caual
inference. extremes and may depend on the imagination of scientists to In conduios,
opidemiological atudirs seck undersand ues anabges. Clear-cat analogies, howrver, may add to
the ing of the linka betwecn envirenment and health, and thas weight of evidetce for otherwise
weak asocianices. Conider provide spper for evidence bused practice. Whether vuch ife sudy of
the astociation of pesive imoking with lung can- linku can be considered causal can only be
ancascd with conficen. Quantification of exposuec and accuraie meavureincnt of donce oace full
combideration has born taken of epidomislogical all confousders muy be difficuls. Howerer, by
anabogy to the nobe - chasce, bus and conficanding. Boeh pruetical and known risk of lung
cancer in acrive smokes, perions exposed ethical censiderarians mean thar caualiry canoot, in
genenl, to second hand sole plassibly have in increased lung cancer be proved in haman stadies.
Ranter, ir mus be induced from ridk mediated by the same biological pathway. demoeseratod
associabens betwech as exposare and a bealh Bradford Hill dixt nea preserite thee iriteris as
rulesthat outenene. Chatactenienics of that asveciation. judged againa mas be fulfilled before an
suocation can be judged as caisul, seme frameuok, then help as to ases whether that aiveiabut a
way of camining if cane and effect in the rewoable toion is er is not caasal. is more datal
eppoaires centres on the difficuley of iecing the reieasch bothons so cnpompas the domaim of
wecial epidemipure aswociation ef expoure and health cffect - free from ologet of popularios-
level relationihips not reducible bo indibias, confounding and interaction with other espenures.
The vidul-kevel sedy, and of the health conscgamecs of complex research situations in which
this can ecour ire limined mainly eovisonmental and social change proctase. The notion of eause
to dinical trial and jerhape latge obscrvational seudee with has boconse mote comples. with moer
health eatcome hiving impecable design and execution. Contempotary environ- maltiple
component cawes. Dintingaishing which of theie are mental epidemiology confrons non-
homogensout hatlith neceuary ar uificient inceatal so preventive afforts. Bradford ase goupiagg
ef riggn of nappons lakely it have multiple he seated as semponcne caises, but the are not
absoluate. At ctiologics. Expontares can be difficule to quanify and even oo winh statistical R
tetim, the critera of eusality must be vicwod dcfine fee socioeconomic status and urban design)
as well as as abds to judgement, not as artaicers of ncality. to link tctiporally and patially to the
divcase catcome (cg. air pollution and climate changet. Acknowledgements How nould Bradfont

4. Hill have drak with some of the We thanki.Aliakir Woodwad. Lniversity of Aucldend, for
helpinuses in contemporary wocial epidrminkg?? To tale what is ful suggestions dueing the
drafting of this paper. pechape an estrene example, in ats Wodd Heath Roport of 19?8 [21), WhO
conduded that the world greacet rik fuctor Competing interests: nooc declared.