Chapter 6.5

Biosafety-An Environmental Impact Assessment Tool-And the Role of the Convention on Biological Diversity

Anatole F. Krattiger €t William H. Lesser Cortsriltnnt/5t'nior ProgranutteAdt iser & V isiting PrLtJtssor Ir t t t' r rto t i otral Ac ntlt nt q of tI *' Ent,i rotn rcn t 72.77 Con cl rcs. C ut t't,a,Sioi Izer I and.

Abstract This paper provrdes a description of biosafety, revien's current biosafety regulations and implementation issues,discusses particular needs and priorities in developing countries pertinerrtto the clevelopmentand implenrentationof biosafety regulatory mechanisms,and ideniifies poterrtialroles of the Corrverrtionon BiologicalDiversity in furthering the adoption and applicationof appropriatc'biosafetv regulations world-wide. "Biosafetv" is a term to de.scribepolicies and procedures to ensure the envirr-rnmentally safe applicatiorrof moderrr bit>technololiv,and can be regarded as an environmental impact assessment(EIA) tool. It is argued that geuetically modified organisms have three types of environmental impact: direct (biological,ecological and evolutionary impacts,or "biosafety" Tterst\; indirect (consequencesof the deployment of a new technology); and secondary (sociologicalancl socio-economic).Nothing conceptual needs to be added to biosafetv regulationsregarding biodiversity protection,it is argr-red,and care must be taken to separate direct biosafetv issuesfrom irrdirect ones, and particularly from socio-economicconcerns. Effective analvsis of the latter two categoriescan only be systematically made following initial field trials. Lrrtial empli.lsrsshould be placedon rrationalcapacity building for the implementation of biosafet'r'regulations, r'vithout prejudice to anv subsequent international protocol. The biosafetvaspects related to "transfer,harrdlirrg and use" (Article 19.3of the Conver-rtion)are three separateisslrt's, and care nlLlstbe takerrto approach them irr a scientificallysound and practicall1' ef f ectiyt- m alllllel'.

1. Introduction The Conr.'entior.ron BiologicalDiversitv (hereafterthe Convention) text is quite clearly dominated bt' issuesof conservatiouarrd sustainableuse of biodiversity. Lessobvious is the atterrtiorrdirecteci irr Article 16 to biotechnology. There, biotechnology, among other technologies,is seen as serving trvo roles: .rs a support tcrconservation, and as a means of WidertingPersptclit,t's on BioJirüsity sustainablyusing geneticresources. Irr either instance,the potential existsfor the importation into, or developmerrt u'ithirr, a country of a non-indigenous living organisms, including organisms with geneticmaterial from other species.Improperly controlled, such organisms have a potential for environmental damage by competing rvith indigenous life forms, hybridising n'ith them, or corrsumirrgor infecting them. Such a loss of speciesand habitat diversity potentially has most severeconsequences in the biodiversitv-rich regions,including centresof origin, lvhich are a particular focusof the Conventiorr.

Besides these implied relationships among biosafety, technology transfer and biodiversity, trvcrspecific articles irr the Corrvention address biosafety specifically: Article 8(g) statesthat Partiesto the Corl'errtion should establishbiosafety regulatorv procedures, and Article 19.3requests the Partiesto considerthe need for, and modalities of, a protocol in the field of the safe transfer,handling and use of genetically modified organisms (CMOs). Note that other articlesof the Corrventionmay also be irrterpretedas relevant to biosafety, namely Articles 6(b),7(c), B(h), 14.1(a),14.1(c), 11.1(d), 17.1 and 18.3.Potential specific interpretationsof thesearticles have been dealt with elservhere(UNEP, 1993a;IUCN, 1993) and are rrot further discussedhere.

Procedures for determining the environmental safety of CMOs, including their safe handling in transit, are knou'n commoulv as biosafetv. This is all a lengthy approach to saying that the Conveution is inherentlv irrvolved in biosafety as an important aspect of environmental impact assessment.One of the tasks placed before the Intergovernmental Committee on the Convention,n'hich met in Cenevaon 11-15October 1993,was determining how that requirement could be addressed,and in particular what framen'ork the response should take-whether mandated universally as a protocol or as a recommendation in one form or another (UNEP, 1993b).

Currently, most industrialised countries have biosafety regulations in place, and these include most, but not all, nations of the Organisatiorr for Economic Co-operation and Development (OECD; for an overvielv see Maloney, 1994).The overwhelming majority of developing countries,horvever, do rrot have regulatory or monitoring procedures in place, mainly becauseof a lack of financialsupport and enforcementsvstems, and often inadequate institutional capacitv.Notable exceptionsare Irrdia,Mexico arrd the Philippines, which have establishedregulations arrd incorporated them in natiorrallaws. Others, such as Argentina and Cuba, have regulationsin place which are not incorporatedinto laws but establishedby ministerial decrees.Finally, Bolivia, Brazil, Chile, China, Colombia, Costa Rica, Cuba, Indonesia,Malavsia, Thailand, and Zimbabwe eitherhave ad ftoccommittees, or are in a more or lessadvanced stageof draftirrg regulations.But, due to the above-mentionedconstraints, the processis generallyslorv, and hencethere is substantiallymore to be done in this regard. Itt any case,these nd ftoccomnrittees are gerrerallyset up to review field trial applicationsfor trarrsgenicplarrts-an importarlt function corrsideringthat in Latin America and the Caribbean alorre 32 field trials have been conducted since December 7992.In developing courrtriesirr general,the number has exceedecl65 field trials. Irr industrialisedcountries, well over 1000field trials have beencondr.rcted.

Noter.r'orthvis that all of thesead loc committeesin deveLrping countries only work on plarrt biosafett', and essentraliyrlrthirrg has been dorre so far about micro-organisms and other species.It is onlv a matter of time, however, before micro-organismsare tested in the field. The Cerrtro Irrternacionalde Agricultura Tropical (CIAT) in Colombia, one of the Celrtres of the CorrsultativeGroup orr interrrational Agricultural Research(CGIAR), has alreadv submitted a field trial application for Rltizobirrnrto the Colombian authorities. Colombia is currently drafting a biodiversity law that also containsa sectionon biosafety.

354 A.F. Krattiger€+ W.H. Lesser

Several non-governmental organisations(NGOs) and bilateral and multilateral agencies are currentlv providing assrstancein developing appropriate regulationsand technical expertrsefor implementirrg biosafetyrules. Most of theseagencies have particular sectoralor resir-nalfoci and irlclude: o the Australian Centre for IrrternationalAgricultural Research(ACIAR); . the Arrimal ancl Health IrrspectionService (APHIS) of the Departmentof Agriculture (L'SDA) oi the LISA; o tl.reBiotec[11plogy Advisory Commissiorr(BAC) oi the Stockholm ErrvironmentInstitute (SEI); . the Footl and Agriculture c)rganizatiouof the unitecl Nations (FAO); . the Inter-Anrericaulnstitr.rte for Co-oPeratiorrorr Agriculture (llCA); . the Intermecljate BiotechrrologyService (lBS) of the InternatiorralService for National Agricultr-rralResearch (ISNAR); . the InternatiorralService for the Acquisition of Agri-BiotechApplications (ISAAA); o tl-reRockefeller Fourdatiorr; . the Urrited Nations IrrdustrialDevelopment Organisation (UNIDO), more sPecificallythe International Centre for Geuetic Engineering and Biotechnology(ICCEB); . the United StatesAgencv for InternationalDevelopment (USAID); . Michigan StateUrriversitr'; and . the World Health Organisation(WHO). The objectiyeof this paper is to evaluatethe role of the Convention in the perspectiveof these orrgoing activities. This is clonen,hile recognising that, despite the critical importance of biosafety, it effects biodiversity conserr,atiorronly irrrlirectly.The causality is through the enhanced flow of biotechnology applications, and the implications they may have on the environment in general and biodiversity specificalli'' Hence' Convention resourcesdirected to biosafetyregulations should reflectthis relativeimportance'

2. Environmental Impact of Genetically Modified Organisms

2.L Biosafety and Envirpnmental IrnpactAssessment Environmental impact assessment(EIA) rvas first adopted in the USA in the early 1970s. when it becamecLear that certailtprojects were having an undesirableand unforeseenimPact ou the environmerrt. Several thousand EIA studies ha"'e since beerrcarried out, and most couutriesnow have some form of EIA regulation,as do many multilateralagencies (e.g. ADB, 1gg8;oECD, 1991;world Bank, 1991).EIA is defirredas "a processdesigned to ensure that potetttially sigtrificant environmental impacts are satisfactorily assessedand taken intcr account in the planning, design, authorisatiou and implementation of all relevant types of actir'1]" (Lee, 1989). Thus the process irrvolvesan arralysisof existing environmental conditions arrd arr assessmelltof the significalltimpacts of the proposedaction upon them. "Biosafety" is a term that has been defined as "the policies arrd procedures adopted ttr erlsLrrethe environmentallv sirfeapplication of modern biotechnology" (Persle.vet aI.,1992). Also, as the name implies, biosafetirconcerns the safety of biological material in the environment, alrd hence biosafety regulatiorrs are focused on the direct biological consequencesof introducirrg GMOs into the euvirotrment.In essence,"biosafetr"' addresses three qr-restions:

355 W itler tin g Pe r s1tect i t eso tt Biod ii, er s i t v r What is the nature of the organism to be released? o What is the errvironmentn'here it is to be released? o What is the likelv speciesinteractiorr?

These three aspects can also be regarded as pertaining to direct ertvironmental consequencesof releasingGN,IOs. Errvirolrnrental inrpacts of GMOs, ht w'ever,are more glrmplexand can be cleiinedas beir-tgof one of tlrreetvpes: o direct (biological,t'cological, evolutionarr', i.c. the scopeof biosafetl'); . indirect (consequencesof the cleplot.mentof a nerv technologv);and . secondary (socicrlogicaland s()cio-ecr)uonric,related to the development of a nen' tc-chnologv).

It should be stressedthat these three categoriesare purely descriptiveand are not appropriate for inclusion in a generalbiosafety regulatorv framework. The follon'ing section considers these three impacts rvith illustratiorrs from food cnrps, becauseplarrt biosafety regulationsare relativelv ivell developed arrd prolr.-rblymost relevar-Ltto developing cctuntries irr the short term. L:rboratorr'l.rocedureshave beerrir-r place silrce the earlv i9ti0s,and the researchand scielrtificcommur-ritv has establisher.larr excellent track record.

22 Direct Effects (Biological, Ecological and Evolutionary) Direct effects of a Lriologicalnature resulting from the deplovn-rer-rtrn the errvironment of GMOs can be classified ir.rtofive key types of c()ncernsthat could give raise to an adverse effect (hazard): a) the creation of rrelv rveeds; b) gene transfer betrt'een species in the natural environment tl'rroughhybridisation and introgression(i.e. the potential ior, and implications of, such transfer), c) biological vector efiects (the vector mav have undesirableproperties arrd lead to a potential for disease); d) disruptive e.ffectson ecosysterns(due to the introduced trait to favour evolution of neu' pestsor diseaseaqents or effectson ecosystenrprocesses)-an examplen'ould Lrechanges in nitrogen lei,el in the soil througl'rthe addition of N2 fixing systemsto plants;anc-l e) harm to non-target species(rre'gative effects of the introduced trait to other species,such as beneficialirrsects that feed ou such plarrts,arrd worker safetv).

The five items above are the main subject of biosafetv regulatiorrsas u,e knon' them todat', and the first tu'o are those that are relativelv more important in developing countries compared to industri.rlisedcountrics. This is becnusenore crop relativesare found in the Srruth.

The creation of ner.r'w'eeds can occur either n'hen an introduced plar'rtbecomes establishedn'ithin or bevorrd the field where grorvrr,or lvhen a GMO outcrosseswith wild 'fhe relativesor n'ith other specieswhere it is gron'u. latter is the risk, from an ecologicaland el'olutiouarv stanclptrirrt,of alien geueticinformation "rnoving" tlrrtrughpollinatiorr (or cross- breeding irr the c.rseof arrimals),hylrridis.rtiorr, and introgressiorl into n,ild relatives and natural ecosvstems.This is also called the "corrdr-riteffect" (Colrvell,1989). it is important to rrotethat CMOs themselvescanrl()t "nrove" into u'ild relatir.'es-Lruttheir novel genescan. It is.rlso rmportant to distiuguish betweerrhvlrritlisation and hybridisation followed bv introgressiorr.!Vhilt'hvbridisation bet'"r,eerrsLrecie's is a common ()ccllrrer.lce,introgression is rttrt.

356 A.F. Krattiger& W.H.Lesser

Genetic nraterial ma1' thus get inserted into a crop relative, which may then become a rveed,something of partictrlarconcern u'ith regard to rice (Clegget al., 7993).Many rveedsare closelv related to a crop arrd hybridise freely with them; examples include amaranth,barley, Brassicaspecies, oat, potato, quirr<-ra,sorghum, and tomaio. However, the combined eventsof hvbridisation arrd of geuetic introgressiorrbetn'een related speciesoccurs infrequently in the r.r'ild,n'here. such ht Lrridsmav still remain as distinct speciesover long periodsof time. Less likelv than genetic condtrit effectsis the prossibilitl'that the introduction (i.e. introsression)of rren,characters r.r,ould lead to an exparrsionof the species'ecological range arrd clisplacerratural habitats, or the GMO would itself invade natural ecosystems(Colu,ell, 198u, 1991).A gene for dror,r{ht resistarlcecould increase a plant's fitness and, as a consequence,displace relatetl species n'ith Iesstr.rlerance. Although there is no scientific evidence for tl-recorrsequerlces of this occurring, atterrtiorrmust be paid to it, particularly in areaswhere crop relativesexist. Harm to norl-targL'tspecies can be largelv avoided through the deplol,rnentof geneswith highlY specificactiorl. Experierrce u'ith clevelopmentir-r resistance to chemical pesticideshas provided insights into hon,geues act, sonrethingrrow being applied to inseci resistance thror-rghBncillus tlrttrincitrtsis (c'.g. Arrdren,s et a\.,1987;Tabashnik et aI.,7991).Successful use of this techniquec(-u1 prolong the useful life of some gerreticresources (e.g. resistance genes). and mininriseexp()sure to lrorl-targctorganisnrs. The main problem in assessingthe likelihc.ndof outcrossingald its possibleeffect on the errvironment and biodiversity is limited data availability. This applies particularly to countries with rich but often trnknown biological resources, including centres of origin. Existirrgregulatiorrs exist preciselv to study these "direct" aspectsof environmental impact (see sectior.r3 below). We believe that attention to these direct aspectsare most needed irr biosafety regulations in developing countries, rvhere crop relatives exist and where the potential for condr-riteffect is greatest.

2.3 Indirect Effects (Larger Environmental Consequences) Irrdirect effectsorr Lriodiversitvdue to the deployment of CMOs in the environment involve, frlr our purposeshere, the L.roaclerenvironmental consequences of substitution.These include the potential for: . a reducedtreed for chemicalinputs; . a reduced pressureorr natural habitatsby alleviating the pressurefor conversionof wild larrdsand pasturesthrough irrcreasedproductivitv; and . speediug up reclamatiorr of damaged and/or destroyed habitats (e.9. through reforestation). The reduced rleed for chemical inputs leads to more sustainableagro-forestry practices. Chemical inputs, such as toxic converrtional pesticides, other toxins and fertilisers, have negative effectsor-t natural ecr)systelrsand biodiversitv, particularly when used in large quantities over lorrg periods of time. With the global cr:rstof pesticidesexceeding US$23,000 million annually, the implicaticrts of substituting a portion with genetically engineered resistarrceis signiflcant. The abirrticstresses are.rlso inrport.rrrt,arrd over a third of all area unclercultivation world-n'ide is affected bv drought, folkrw,edby salinitv, mineral toxicitv and mineral deficiencies.Today, as the demarrd for food increasesin developing countries,the traditional ecologicallimits of crops are beirrqchallerrgec-i, and transgeniccrops are likely to addresssuch limits in the lonc ternr.

357 W id enin g Per sptg6li7,g5 o n Bi ttdit,er sity

Typically, existing regulationsfocr-rs on the potential risk of introductions without considering the "rret risk effect", the potential risk of irrtroduction of a GMO minus the potential benefit of such irn rntroductron, such as the reduced nc'ed for converrtioltaltoxic pesticides.Such an approaghcloes not consider the real issue,the net environmental impact, and is, in our judgernent,to be avoideclin the future. In sumrnary,irrdirect errviroume'ntal effects of transgeniccrops can be essentiallypositive. These potential effects should, in our judge'ment,be the basis for estimating the net environmental risk effect.Thc'se indirect effectsare not biosafetv ctrnsideratrorrs|cr se,anrl are related to the adoption of new techrrologiesand to rratiorralneeds and priorities.

2.4 Secondary Effects (Sociological and SocioEconomic)

Finally, other effectsof irrtroducing CN,lOsare of a socio-econoniicand sociologicalnature, and are principallv relatedto thc iniplenientatiorlof the nerv techrologies,e.g. on: o labourrequiremerrts; . farm size (mirrimum farm sizeeconrxries); arrd . changesin product pricing. The magnitude of these secondarv colrsequences,n,hether positive or negative, will deperrd on the rate of change in the institutional structure of agriculture, ne\^' divisions of resporlsibilitiesbetween the public and private sectors,and the kinds of technologiesthat are developed and introduced coucurrentlr'. Often these factors afiect groups diiferentiallv, creating an equity issue. The introduction oi biotechrrology, however, does not necessarily affect equity. An example is the developmerrtirr Me'xicoof non-conver-rtionalvirus resistancein potato (James, 1991;Krattiger and James,1992, 199.1). Smaller farnrs,often lacking accessto chemical protection against p()tato Virllses,rvill be aLrleto use virus resistant potato seedlings distributt'd through the rrationalagricultural researchsvstem. Without additional inputs c'rr changesirr agricultural practices,these farmers will be able to benefit from higher yields. The larger farms which previously used chemical corrtrolswilt be able to maintain yields, while reducilrg the use of ct'ruventionaltoxic insecticidesarrd their corresponding load on the ettvirctnmeut.Thus Lrothsnrall and large farms benefrt-one through increased yields, the other thror.rghreduced irrputs.

Imprrrved Rlrizobitunstraius for nitrogerr fixatiou are another example of positive effects acrossfarm size. Casesw'ill neverthelessarise where certairl groups are disadvantaged by rren'plant-basecltechrrologies, e'specirlly w'herr their efiicient use and effective application requires cc)r1rplex ne\\' nianagemerrt ;rpp roaches.

It has been argued tlrat an arlalysisof socio-economicand sociologicaleffects be included irr biosafetv regr.rlationsto be corrdrrctedbefore field trials are undertaken (e.g. UNEP, 1993a).Front our perspcctive,evaltration is difficult if rrot in'rpossiblebefore field trials have been colrductedto provide some acttraldata on u,hich to base the analysis.lnitial field trials are often structr-rredtrl deterr-uinehqw plalts l,ill furrction a1d behave under llatural couditiotrsas op-rposedto laboratorvor greenhouseconditions. Many organisms behave differently, artd herlce fieJd testing CN'lOs in differerrt environments is a prerequisite for sttrdvins Potentialsocir)-ecr)n(')mic effects. Field trials of GMOs vield the baselineinformation to unciertake sr'rcio-econonricand sociological studies, and biosafety regulations are the means to conduct fie'ldtrials irr the safestpossible way. Without the results from field trials, socio-ecottonticstudies u'ould be purelv theoretical,and of little practicalvalue.

358 A.F.Krattigtr & W.H.Lessrr

A comparisorlwith EIA irr geueralcan be used to clarify this point. Mudge (1993)argues that socio-ecorromicand political consideratior.rsare policy decisions,and that these issues should be analysed at the policv level. This distinction also applies to biosafety and the deplovmerrt of GMOs, where the polio' level arrd projectlevel analysisshould be separated. This r.vould not preclude a countrv from evaluating socio-economiceffects; only it l,r'ould simplv be dorreoutside, but complementarvto, the formal biosafetl'regulatory framework. It is corrch-rdedthat socio-ecorromiceffects, both positive and negative,are likely to occur if biotechnologvapplications are irrtroclucedin a giverrcountry. But countriesare not isolated, and effects would also occur if biotechnologv applications lvere onlv introduced in neighbouring or competingcountries. If the policv decisionhas beerr made that biotechnology applicationsshould be irrtroduced,or at leastbe testedin the field, then biosafety regulatory mechanismsare merely a neans to in'rplementthis policy in the safestpossible \4'ay. lt would be irrappropriateand courrter-productive',in our opinion, to consider thesesecondary socio- economiceifects at the stageof biosafetvregulatiorrs.

3. Structure of Existing Biosafety Regulations Existirrgbiosafetv regulations,for both scierrtificand administrative reasons,incorporate a number of similar approachcsaud practices.Understanding those similaritiesis of value when corrsiderirrgmodificatiorrs and extensionson a broader geographicscale. This section, dran'n irr part from Lesserand Makrney (1993),includes an evaluatiorrof existing regulations in four regards: . basis of regulations, r.r'hetherthev be n'ithin existing statutesor new; . a risk- or technology-basedsystem; . case-bv-casearralysis; and . step-by-stepapproach from field testirrgto commercialisation. Finally, the strengthsand limrtationsof theseapproaches are evaluated.

3.1 New orExistingRegrrlations? The USA, as the first country to implement biosafetyregulations, has had an important role in influencing subsequentregulatiorrs rvorld-wide. Thus an early policy decision, known as the "Co-ordirratedFramen'ork", has been very influential.That decisionstated categorically that biotechnology in itself was not inherently dangerous (EPA, 1984;FDA, i984; OST, 1986); any problernsresulting from the applicatiorrof the technologywould be in the form of existing threats such as plant pests. As a result, it rvas determined that lto ne\\' legislation was required, merelv a reinterpretationand redirectionof existingregulations. That approach led directlv, for example, to APHIS beirrg made responsiblefor evaluatirrgmost biotechnologv applications irr plants.

Manv countries,specifically the Commission of the European Communities for the member states, took the altemative approach of preparing entirely new legislation. The responsibility for administering the rlew statutes may of course be placed u,ithin existing agencies,but the lart'sthemselves are nerv. A consideratiorrof the evolutiorrof enforcementin the USA illustratesthe differilg effects ttf thesetwo approaches.The USA, bv meansof using existirrgregulations and agencies,was, through APHIS, able to begin evalr.ratingapplications for plants very earlv, and it remains toclaythe most erperiencedagerrcv u'orld-rvide. On the other hand, that approach led to

359 Wid eni ng Per s lt e c tiu es on Biodiuer sity

numerous ongoing problems,such as the issueof overlap/duplication of responsibilitieswith the Elrr,ironmental Protection Agencv (EPA) for some life forms such as the expressionof pesticidesby plarrts.Conversely, other life forms are not specifiedand their regulatory status remains unclear,sLlch as for transgenicfish. Moreover, the extensionof the scopeof existing regulationsto this nerv area requires5trnle tortuous definitions.Key among theseis the plant- pest basisof APHIS' responsibilities,hinging on the common practiceof using Aqrobacteriturt tunteftcit'rtsas the vector for introducirlg new geneticmaterial. A. tunrct'aciensis the sourceof the common and problematic crorvn gall disease,even though in the form used in the laboratory as a plant vector it is no longer virulent (Chiltorret al., 1977).On the other hand, APHIS is atr experietice'dagerrcv, w'hich n'ould not necessaril)'have been the choice if nen' regulationswere wri tter,.

For develcping countries, the situation is somervhat different, for fen'have extensive review regulations in place. Anv regulation will likely be a nen, regulation. Few also have technicallytrained agencv staff capableof conductirrgfield evaluations.

Thus, the resporrsiblegroup is Iikelv to be a committee or commission oi individuals employed in different sL'ctors.For thesereasons, developirrg country regulationsare likely ttr consist of nerv lan's. New lalvs are also the onlv eifectivemeans of estabiishinesimilar requlrements acrosscountries.

32 Risk- or Technologl-Based Regulations?

There is widespread support in the scientificcommunity for the view that biotechnologiesdo not in themselvescreate risks. The National Academy of Scierrceof the USA savs that safety assessment"should be based on the rratureof the organism and the environment into which it will be introduced, not on the method by u'hich it n'as modified" (NAS, 1987).This view rvas in esserlcesupported bv the EcolirgicalSocietv of America (Tiedjeet at., 1989),although the study hinged on the procluct/processdebate by stating that becausesome "combinations of propertiescan be achievedorrly bv molecularteclrniques, products of thesetechniques may often be subjectedto greater scrutirrythan the products of traditional techniques".Adopting that reasonablepositiorr requires that biosafety legislation be risk-basedrather than technologv-based.

Under alternatirreterminologl,, this is the choice between process-and product-based legislation.While corrceptuallythe risk- or product-basedapproach is compelling,it does require that risks carLbe iclentified. But biotechnology is a nen'field, so it is difficult to sPecify which products are risky-t-rr more correctly, pose potentially unacceptablerisks- arrd r.t'hichare l1ot.Biotechnology products do not contain altv iltherent risk-s,but they do contaill a ttttt.tlberof uucertairrties,so poterrtialrisks provides a convenient basis for regulatirrns.

Considered more broadly, a'rrisk-based system rvor-rld have to considerthe products of all technologies,irrclr"rding plant breeding. \'Vliile plant breedirrgis generallv regarded as euvironrneutally safe (abbreviatedkr GRAS in the USA), it is rrot possibleto prove this is so in all cases.Hence, a full risk-basedsystem rvould potentiallv be examining many products rvhich are llow esselttiallvexenrpt, and which moreover have an excellentlong-term safetv record.The hvbrid.rpproach suggestedfor the Convention (uNEp, 1993b)of adopting a risk-based svstem but exemptirrg "corrventional" plant breeding and other familiar approachesis only a complex processof targetingbiotechnology products. Thus, for the present,a techrrologv-basedregulatorv svstemseems a11 expedient approach, everr if it is not fully supportablescierrtificallr,.

360 A.f Krattiger& W.H. Lt'ssrt

3.3 Case.by-CaseAppr.oach The case-by-caseapproach is an extension of the preceding discussion of risk- oersls technologv-basedregulatory systems.The case-by-casesystem followed under all existing legislation is based orr the premise that the risk of a particular application cannot be determined theoretically, onlv enlpirically. Thus, even the often-heardposition that single gerretransfornlatiolls are essentiallyharmless cannot be substarrtiatedorr further evaluation (Tiedje et a\.,7989). A scierrtificevaluatiorr m.1y be able to predict when an application is safe in general or or1average, but that information is not useful for any particular case,and hence mav prove to be very problematic.Applving the case-by-caseapproach then involves the testirrg of each arrd everv applicarrt organism. A strict case-bv-caseapproach may, over tinre, be modified rn severalu'ays. First,basecl on extensivepast experierrce,it n.raybe possibleeverrtualll, to exempt classesof products or technologicalapproacl-res irom review. That degreeof experiencehas not been acliievedyet, but mav some day, although APHIS recentlydetermined that tomato varietiescontailing the antisense polygalacturonasegene (the so-called "FLAVRSAVRTM"transgenic tomato developed by CalgerreIrrc.) does not present a plant risk and will therefore no longer be considerecla regulated article (APHIS, 1992).Regulations should retain sufficient flexibility to make such adjustments w,lien appropriate. Second,even while all applicant organisms ma1'be subjectto initial review, the degreeof subsequentevaluatiorr can vary. For example, viral coat proteirr applicatiorrmay pass througl.rthe evaluation stagesrapidly, based on (a) numerous safe prior examples and (b) favourable results from initial trials. But this is more a matter of step-by-stepevaluation.

3.4 Stepby-StepAnalysis Step-Lry'-stepanalysis refers to theprocess of progressionto lesscontrolled and/or larger geographical trials based on acceptable results from prior tests. The trials under this approach progress from initial to (in some cases) full release, unless problems are encountered or the organism proves to be commercially non-viable or is otherwise withdrawn. Although this strategy is an obvious one, two key decisions must be made in each case.These decisions are concerned with how large to make the steps, and how to determine n'hen sufficient testirlg has beerr compleied. The delineation of the size of the steps,or nlore precisely the rate of progressionof the evaluation, must be largely judgement-based. For applications which theory suggestswill not causeproblems, and for which initial trials support the theoreticalprojections, many prudent regulators/scientistswould seriously consider an acceleratedphase of expanded trials, but rvould otherrviseproceed more slowly. The rate of approach would be basedon experience for each ecologicalregiorr. The decision about r.t'herrto termirratetesting is more critical arrd complex. Tlre critical nature comes from the nature of agriculture arrd other related actrvities,which typically involve many small participants over broad geographic areas. Stated succinctly, release means effectively ut.tcorrtrolleduse acrosswide regions. Any problem iderrtified subsequently would be ciifficult if not impossibleto corrtrol.Hence, the safetystandard for releasemust be high. Complexity comesfrom anothersource, the tliffering needsof the severallevels of saiety testrng. At least for the numerous products submitted for testing u'ith the goal of identifying marketable products, the objectivesof the applicant are twofold. Initially, the interest is in determining viability, which requiressome initial resultsoutside the laboratory.But trialsmay

361 WidertirrcPcrsppsIi7t75 ortBiodii,crsitrl

be snrall scale and isolated.Subsequentlv, tlie applicarlt mav require multiple tests to establishperformauce irr field conditiorrs.For maize in the USA, each neu'variety is testedin hundreds of small plots withiu farmers' fields for severalyears prior to commercial release. With multiple companieseach testing multiple varieties,thousarrds of trial sitesare rreeded annuallv. Other applicatiot-tsnrat' rrot require suclr extensiveiesting, but numerous locatiorrs rr'oulclbe the rule rather th.rrrthe exceptiorr. For regulators,the initial,small-scale tests are easilv acconlmodated.At that stagethe emphasis is on safety,n'hich can be achieved through a combination of separation,physical barrier to transference,or sterilitv. Manv svstems,such as thc)seproposed by USDA (but not adoPted)guidelines (53 FR 1131),or those incorporatedinto Philipprirlebiosafety regulatiorrs, specify iour or five levels of isolation based on potential environnrental threats.For APHIS, cotrfinement"r.erifies that the pathogenicpotential contained in the constructionof the orgartism or perfornlauce of the iield test has been renrcrve'd,or rvill be contained" (McCammorr and Medler', 1990).The resultaut difficulty is the abserrceof safety information generated from isolatiorr trials rvhich can be used to structure subsequent,less restrictive trials. That limitatiorr is compoundecl as products approach the commercialisation stage, when the multiple trials rroted above are reqtrired. Isolation for multiple trials is rleither feasiblenor approprrate.Irrrleecl, even the destructiorrof the grain fronr maize trials,assrrnring it coulclbe separated,rvould cost the indtrstrf in the USA millions oi dollars annuallv. The stagesto commercialisationor full releaseare to date the leastspecified arrd the least tested. As of writing, onlv one live genetically engineered organism has been allorved full commercial release(a "NoCall" biopesticide in Ar-rstralia;Kerr, 1989).The FLAVRSAVRTN1 tomato has been grallted APHIS approval in the USA but has yet to be releaseddue to other consideratiolrs,including food safety. APHIS recently, however, proposed a notification systenr (57 FR 53036)under n'hich applicants for subsequent,multiple trials need not seek prior approval but rather need only irLform the Office of Plarrs.The results of this approach will rrot be k-nown for several vears.

4. Discussion and Proposed Strategies under the Convention Biotechnology to date'has establishedan excellent safety record, and biosafety regulations have served an important corrtributing iurrction. The challerrge today is to facilitate the development of biosafety regulations in developing countries to allow for the safe and effective transfer of biotechnology. Access to biotechnology by developing countries is a cerrtral issue for the Corrventiorrand implies appropriate biosafety regulatory mechanisms which, itr turIr, presupposeinstitutional capacitvin regulatorv oversight.These issues warrant partrcularattention Lrythe Couverrti

4.L Harrnonisation of Regrrlations lrrternationalharmonisation of regulatory requirements refers to having equivalent or equal starrdardsthat provide a Lraseon which to establisl-rco-operatiorr. It should not be confused rr'itl-rthe rrecessityof havirrga similar or identical regulatory structure.Identical laws, a strong iortn ttf harmorrisatiotr,rt'ould require.deep changesin lan,s rvhich lr'ouid not be feasiblein coutrtrieswith differirlg juclicialsystenls. Harmonisation-as the term is used here-means compatibility of requirenierrtsand consistencyin reviervs,rather than identical policies, prionties or strategres.

362 A.F.Krattiger ü W.H.Lesser

Harmonisation of biosafetyregulatory mechanisms can be classifiedinto three main tiers, as follorvs: a ) legislative-affecting the rnstitutiorralstructure or organisationwithin a tiovernment that assLrmesresponsibility; f) criterial-for revievr'of rele'aseapprlications affecting the usefulnessof regulations from courrtryto c()Llntrvand the efficacYof the ntechanisnr;and c) informational to be supplied by 2pp1l6ontsaffecting the speed and cost at which differerrtapplications of tl-resame orgarrismmav be submitted in different countries,and the opportunitv ior applicantst() revieh'other appiicationsand to exchangeinformation. The first level of harmonisatiorr would be difficult, if not impc'rssible,to attain. Co- ordinatior.rcan be brolrght about irr different ways, but the underlying principle should be the sliaring of appropriate scientificinfornration anri experienceh,ith the personnel rr,ho have responsibilitv for developing regulations.This lvill further the development of appropriate ()versight strlrctures that are based on scientific prirrciples for evaluation, rather than on political corrsideratirrrrs. Certain internationalharmonisatictrl processes are alreadv underway, and the outcome of a recent workshop demonstratestheir feasibility. The IICA/ISAAA Biosafety Workshop (llCA, 1993)\vas concernedn'ith harnronisationof biosafety regulatory mechanisms in the Southern Cone. In that case,representatives from Argerrtina,Bolivia, Brazil, Chile, Paraguay and Uruguay agreed on one standard protocol and regional organisation pertaining to the information required for field trial applicatior.lsr)f transgeniccrops. Notablv, the decision to createa regiorralcommittee was basedon the rati(rnalethat enhancedaccess to biotechnology applications irr the region would make most effective use of resourcesand personnel. This example illustrates that efforts to harmonise regulations can be very effective, particularly if they take place when regulatir-lnsare being der.eloped.Current regional harmonisationefforts are being carriedout bv OECD for the industrialisedcountries, by IICA for Latin America, and b1' ISAAA for selectedregions, among others. The European Union (formerll' the EuropeanCommunitv) facesformidable obstaclesin harmonisrng policies and proceduresamong its 12 member states,lt'hereas IiCA and ISAAA harmonisation activities are largelycapacity-building endeavours. An alternativeto harmonisatiorrcould bc arr internationallybincling protocol, such as under the Couverrtion (seeArticle 19.314'1-r"r" the Conferenceof the Parties is requested to study the needsfor and possiblemodalities of srrcha protocol).Although a potentially useful irrstrunreut,the possiblelong road that rnight lead to such agreedprotocols rvould do little to iacilitate11-," c1g1'sloprnent of natrorralregulatory nlechanismsand accessto biotechnology,at least iti the medium term. Access to biotechuologies is a cerrtral issue implied irr the Conventiorr, and contributes to a realisation of the paritv in technologv trade implied by ,l9. Articles 15, 16 and ln addition, a universal document or biosafetyprotocol could, in our opinion, result in the leastcommon denominator being accepted,arrd hence make regulations eitherr,rndulv restrictive or practicallyunenforceable. We colrcludethat appropriateharmor.risatirrrr efforts are the nrost effectivemeans for developing strategiesand technicalguidelines for the beneficialadoption of biotechnology A sr-rbsidiarvbodv to the Corrventiorr,or the Secretariatitself, is ideally placed to ass:me the leadershiprole in such harmonisation,tlirough co-ordinatrngarrd strengthenirrp; national and regiorralactivities, and bv rvorkrngcloselv r,r,ith orgarrisatiorrs that hat'e already undertaken sr,rchacti'u'ities (listed irr section1). This activitv inclutles,first arrd foremost,the provision of relevant informatron on current biosafety regulatorv mechanisms and on field trial aoolications.

363 Widening Perspectiueson Biotlittcrsity

4.2 Institutional Capacity Building The prerequisite to furthering effective biosafety mechanisms in developing countries is building institutiorralregulatory capacitl' appropriate for the resourcesof the developing r,r'orld.Anv regulationis only as good as the peoplewho developedand enforceit. Capacity building in this context means the provision of information and experienceto those senior represelltativesfrom science,govenlment arrd specialinterest groups that have been designated by their respectivegovenrmerlts as havirrg responsibilitv for developing and/or implementing regulatory procedures.This can be dorre through small but intensive n'orkshops n'hich enable participarrts to receive hands-orr experience,as is done by the ISAAA BiosafetyInitiative (Krattiger and James,1992). These n'orkshops are supplemented with real applrcationsn'hich allor.vparticipar-rts to l'alk through a decision-making process considering the ratiorraleunderpiruring those decisrons. Another inrportarlt capacitv building consideratiorris whether a country should simultaneouslv develop biosafetv regulationsfor all gror-rpsof CMOs (i.e. plants, animals, iish, micro-orgarrisms,etc.) or begirr n'ith the category of rnost immediate concern and gradually enlarge it. While the first optiou might be desirable,it is probablv impractical for most developing countries due to institutiorralcapacity limitatiorrs. Institutional capacity,in our judgement, is the most important and most urgent acti','ity needed today. The Corrvention-without prejudice for a biosafetyprotocol-\^'ith its network acrosscountries and continents,is ideallv placedto assumea leadirrgrole irr such capacitybuilding efforts,in collaboration n'ith existing programmes.

5. Conclusions Four principal conclusiorrscan be drawn. First, there should be nothing particular and additional about biodiversity added to biosafetyregulations. Biosafetv svstems are intended to protect the entire errvironment,of which biodiversity is a component.While field trials in biodiversitv-rich regiorrswith more closerelatives arrd/or rare speciesmay be more complex to revier.r'arrd conduct for the same level of environmental safety, the complexity is in planning, reviewing and carrying out the trials, not on the regulations themselves.For the Conventiorr,this suggeststhat emphasisshould be placed on implementation of regulatory mechanisms and its human capacity requirements, particularly for those who enforce regulations and revielv applications, rather than on the regulations themselves. Second,u'e believethat care must be taken to separatebiological or environmental issues and socio-economicfactors. The former should be considered in biosafety regulations as done today, the latter in separate,both prior and subsequent,forms. Mixing biosafety and socio- economics n'ithirr the same legislation',vould lead to bad scienceand poor economics and sociology, as rvell as delayirrg all introductior-rs.This is not to say sc'rcio-economicanaiysis should not be corrducted;societies have the right-and indeed obligation-to consider all the implications of a techrrologybefore embracing it. But the analysissliould be particular to a technologv,meanirrg it cannot be irrtrodr.rceduutil the likely outcomesare known after field trial data has been gerrerated. Third, regulatorv steps need to be characterisedfrom irritial,contained trials through to full commercial release.The final stageis the most critical issue for release,as it implies full exposure to the errvironment.Careful considerationof this final stage is required to assure protectionwhile rrotplacing unnecessarvcosts and delaysorr commercialisatiorr.

3& A.F.Krattiger ü W.H.Lesser

Fourth, the fundamental question for ihe Convention is how best to adopt, utilise and harmonise biosafety regulatory mechanismsthat protect biodiversity and the environment rvithout hindering accessto the technologiessought by developing countries.In our judgement, the key aspectsof achievirrgthese goals are: . assisting countries in understandirrg the issues involved, and iderrtifying their own interests; . identifying harmonisation systemsn'hich rvill facilitatethorough and speedv reviews of applications;and . bLrilding human capacity in those responsiblefor implementing any regulatorv svstem. These are all particular activities to be undertaken within individual countries. Our concern is that the negotiation of a protocol will divert attention and resources to the international level, rvhen the real needs are r,ationaland regional.We thereforerecommend that the Parties first emphasise capacity buildirrg activities and somewhat delay considerationof a protocol until couutriesare betterequipped to in'rplementand negotiatea biosafety system or svstems.

Acknowledgements We would like to tlnnk RobertColuell (Uniuersitrlof Cortrrccticttt,USA), Walter laffö (IICA, Costn Rica),Sally McCannnon (APHIS, USil, and GordonMudge (Aspiniuall €t Co, UK for prouiding critical itrforntationand for hel1tfulconrnrcnts on earlieruersiorrs of this nnnuscript.

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