ORIGINAL PAPER

Precaution or Integrated Responsibility Approachto Nanovaccines in Fish Farming? A Critical Appraisalof the UNESCO Precautionary Principle

Anne Ingeborg Myhr & Bjørn K. Myskja

Received: 14 December 2010 /Accepted: 6 March 2011 /Published online: 5 April 2011# The Author(s) 2011. This article is published with open access at Springerlink.com

Abstract Nanoparticles have multifaceted advan-tages in drug administration as vaccine delivery andhence hold promises for improving protection offarmed fish against diseases caused by pathogens.However, there are concerns that the benefits associ-ated with distribution of nanoparticles may also beaccompanied with risks to the environment andhealth. The complexity of the natural and socialsystems involved implies that the information ac-quired in quantified risk assessments may be inade-quate for evidence-based decisions. One controversialstrategy for dealing with this kind of uncertainty is theprecautionary principle. A few years ago, anUNESCO expert group suggested a new approachfor implementation of the principle. Here we comparethe UNESCO principle with earlier versions andexplore the advantages and disadvantages by employ-ing the UNESCO version to the use of PLGAnanoparticles for delivery of vaccines in aquaculture.Finally, we discuss whether a combined scientific and

ethical analysis that involves the concept of respon-sibility will enable approaches that can provide asupplement to the precautionary principle as basis fordecision-making in areas of scientific uncertainty,such as the application of nanoparticles in thevaccination of farmed fish.

Keywords The precautionary principle . Ethics .

Scientific uncertainty . Nanoparticle . Aquaculture .

Responsibility

Introduction

Biocompatible and biodegradable polymer-based par-ticles may be advantageous for drug delivery pur-poses and medicinal applications. Of these polymers,polylactides (PLA) and poly (−lactide-co-glycolide)(PLGA) have been the most extensively investigatedfor drug delivery [29]. Polymeric nanoparticles haveseveral advantages in vaccine delivery; they canprovide sustained delivery of vaccines, they cansolubilize drugs for intravascular delivery, and theycan improve solubility of vaccine antigens againstenzymatic degradation. PLGA encapsulated DNAencoding antigens are protected against enzymaticdigestion and can therefore be released over extendedperiods of time. Within aquaculture one of the mostimportant constraints for further growth is theprevalence of diseases. This has caused intensivesearch for novel and improved vaccines. One new

Nanoethics (2011) 5:73–86DOI 10.1007/s11569-011-0112-4

A. I. Myhr (*)GenØk—Centre for Biosafety,Forskningsparken, Breivika, NO 9294,Tromsø, Norwaye-mail: anne.i.myhr@uit.no

B. K. MyskjaDepartment of Philosophy,Norwegian University of Science and Technology,NO 7491,Trondheim, Norwaye-mail: bjorn.myskja@ntnu.no

interesting possibility is the use of nanoparticles fordelivery of vaccines, as for example PLGAs. Mostprojects involving the use of PLGAs is still underdevelopment, and has been most extensively studiedfor human and animal use where rodents is used asresearch animal, while only a few studies has beenpublished where fish is the main target [37]. On theother hand, there is at present limited scientificunderstanding of the mechanisms underlying uptakeand persistence of PLGA as nanoparticles afterinjection into an animal [29]. Main areas of uncer-tainty are with regard to the immunological andtoxicological impact, biodistribution and degradabil-ity after injection and whether the polymeric nano-particles can be distributed to the environment. Thepresent lack of scientific understanding of the healthand environmental effects of distribution of nano-particles involves a challenge with regard to riskassessment and management.

PLGAs have at the macrolevel been used inmedical applications and hence provide some under-standing with regard to persistence, distribution andside-effects [1]. When we turn to the use of PLGA fordelivery of vaccines at the nanolevel, new questionsarise. For example whether the reduction of sizeinvolves new uncertainties, if the use on a new targetanimal, fish, may cause novel effects and if theparticles can spread to surrounding environments withunforeseen consequences. All these questions arerelevant with regard to identification of potentialharmful consequences when PLGAs are used invaccines. One controversial strategy for dealing withthis kind of uncertainty in regulation is the precau-tionary principle, which will be the main topic of thesubsequent discussion.

Given that we have different degrees of knowledgeregarding assumptions of harmful consequences, it isreasonable that these possible harms should be dealtwith according to different principles. In cases where wehave sufficient experience to quantify the probabilities,risk assessments is the commonly accepted way tohandle the problems. There are of course differentdegrees of subjectivity regarding the estimates as well asthe value assessments involved, but these are usuallyhandled by a scientifically based discourse. In cases ofuncertainty one can argue for the use of differentprinciples, including a more or less subjectively basedversion of risk assessment, given that the usualexperiential basis for quantifying risk is deficient. An

alternative is the conservative maximin or minimaxprinciple, proposing that one should minimize maxi-mum harm. In the international governance debate,however, the majority has supported different versionsof the precautionary principle.

But it is not obvious that these methods for dealingwith uncertainty are relevant for the issue we are facing,namely how to handle the possible risks in nanotechnol-ogy application such as the use of PLGA particles in fishvaccination. A case can be made that we are primarily ina situation of scientific ignorance regarding nanotech-nology, and that we have no basis for making plausiblehypotheses about causal relationships and mechanismsleading to harm. What we are left with may be mereunfounded speculationswhere one guessmay be as goodas the next, and given that technology applications willlead to harm, they may be of a radically different naturefrom the ones proposed at such early stages. If this is thecase, precaution is not an alternative, as all versions ofthe principle demand some kind of plausible harmscenario as basis for instigating precautionary measures.

This line of argument has some merit in regard tonanotechnology in general. We are in a state ofignorance regarding both the benefits and harms thatmay result from this interdisciplinary research in awide range of technology areas. This problem is not thesame regarding particular technology applications, orat least, not all of them. The case we are discussing isone where we can draw up some plausible harmscenarios based on what we know about the particles inquestion from the use at the macrolevel, as well asknowledge within vaccinology and about farmedsalmon and marine ecology. Although some harmscenarios are beyond precaution due to deficientknowledge, others clearly are not. We will assume thatthe epistemic conditions are on a scale from probableharm scenarios which should be subjected to riskassessment, via plausible harm scenarios calling forsome kind of precautionary or related regulatorymeasures, to more or less speculative scenarios wherepotential harm is a matter of speculation, similar to thehyping of potential nanotechnology benefits. In thislatter case, there is no scientific basis for regulatorymeasures. But there are a number of issues concerningthe use of PLGA nanoparticles in fish vaccines thatshould be classified as a matter of scientific uncertain-ty, and in these cases there are grounds for suggestingsome kind of regulation even in the absence of dataenabling quantified risk assessments.

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The precautionary principle has been accepted bymany national governments as a basis for policy-making, and it has become important both ininternational environmental law and internationaltreaties [5,10,11,38]. Implementation of the precau-tionary principle entails three interrelated proposals:the first one concerns caution in the face ofapplication of new technology, the other emphasizesthe importance of conducting risk associated research,and the third entails that precautionary actions need tobe taken. In this paper our focus is on the firstproposal –the policy decision to trigger the precau-tionary principle. The implementation of the precau-tionary principle in political decisions is and has beena subject of heated scientific and public controversies[17,34]. So-called weak versions are criticized asbeing vacuous. The paradigmatic example is found inthe declaration issued by the Rio Conference onEnvironment and Development:

‘Where there are threats of serious or irrevers-ible damage, lack of full scientific certainty shallnot be used as a reason for postponing cost-effective measures to prevent environmentaldegradation’ [50]

The formulation ‘lack of full scientific certainty’implies that some degree of scientific certainty isrequired. But when there is some certainty, it isusually possible to make fairly good risk assessments,and precaution becomes superfluous. The demand ofcost-effectiveness is also held to undermine thereduced burden of proof required to instigate precau-tionary measures.

Strong versions are argued to be detrimental toscientific and economic development. These ver-sions are held to place unreasonable regulatoryburdens on new technology utilization, reducingreturns from innovation, limit utilization of tech-nology worldwide and providing disincentives forresearch. A typical example is the Wingspreadversion:

‘When an activity raises threats of harm tohuman health or the environment, precautionarymeasures should be taken even if some cause-and-effect relationships are not fully establishedscientifically. In this context, the proponent ofan activity, rather than the public, should bearthe burden of proof.’ [41]

Adding to this criticism of the principle as beingeither too weak or too strong is the number ofcompeting definitions of the precautionary principle,leading to further difficulties for implementation inlegislation and employment in actual cases. In thefollowing we intend to highlight some advantages anddisadvantages with the UNESCO version comparedto other versions of the precautionary principle, usingPLGA particles for delivery of vaccines as a casestudy. We will argue that the UNESCO version of theprecautionary principle evades some of the conse-quences that have been criticized in earlier versions.However, also the UNESCO version has problematicaspects that we will describe. Moreover, we discuss towhat extent a combined scientific and ethical analysisthat involves the concept of responsibility willimprove the basis for decision-making under scientif-ic uncertainty and thereby contribute to a sociallyrobust development and application of nanoparticlesfor delivery of vaccines.

The Precautionary Principle; The Adequacyof Weak and Strong Versions

The precautionary principle is a normative principlefor making practical decisions under conditions ofscientific uncertainty. Gardiner [15] suggests that thefollowing elements are essential to the principle:

& Threat of harm& Uncertainty of impact or causality& Precautionary response

As we can see this raises a host of questions, withregard to how to define harm, how to assess andsystematize uncertainty and when and how to initiatea precautionary response. The actual content of theprecautionary principle and the practical implicationsof its implementation in policy issues are controver-sial [14,35,54]. Several formulations of the principle,ranging from ecocentric to anthropocentric, and fromrisk-adverse to risk-taking positions, have been putforward.

Weak versions of the precautionary principle areoften grounded in narrow utilitarian ethics, andapplications involve risk/cost-benefit analyses. In thiscontext, the principle may be used as an option tomanage risks when they have been identified throughrisk analysis. For example, the Rio Declaration

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employs the weighing of costs and benefits, andsimilar wording has been reproduced in the preambleof the Convention on Biological Diversity and inarticle 3 of the Framework Convention on ClimateChange. Strong versions are active in nature, shift theburden of proof to the proponents of the activity andoblige regulators to take action, for instance byimplementation of risk management procedures [54].

Weak versions of the principle are criticized asvacuous, whereas strong versions are often consideredtoo narrow, focusing on environmental risk withoutconsidering the costs of existing practices to theenvironment or taking into account relevant non-environmental concerns [15,25]. For instance, em-ployment of a weak version of the precautionaryprinciple to PLGA as carriers of vaccines in aquacul-ture would focus on the proposed benefits while thepotential risks to health and the environment wouldbe downplayed due to the present lack of scientificunderstanding. Weiss [52] demonstrates the motiva-tion behind weak approaches when he states, ‘desir-able innovations can be blocked by an excess ofprecaution’. He proposes to prevent this excess byintroducing ‘a new principle of Innovation andAdaptive management, to the effect that precautionaryaction should not unreasonably interfere with aninnovation that promises major benefits until thedangers and benefits of this innovation are wellunderstood’ [52]. Postponing intervention waitingfor evidence of harm, as Weiss suggests, empties theprecautionary principle of content. This demonstratesthat a ‘wait-and-see-strategy’ is opposed to theprecautionary principle, and must rather be regardedas an alternative strategy. Postponing interventionmay in some circumstances be an option dependingon the state of understanding and the possibility forreversibility of the hazards caused by the technology.The wait-and see-strategy as a way to undermine therationale of precaution is a common criticism of weakversions. If the PLGA nanoparticles showed promis-ing results in vaccination, the version would recom-mend use even if there were plausible grounds forsuspecting environmental harm, as long as the basisfor determining the level of harm was insufficient.

On the other hand, a strong precautionary assess-ment of polymeric nanoparticles applications forexample based on the Wingspread statement, wouldtend to emphasize the risks of using them, neglectingdetrimental effects of the existing vaccination practi-

ces, as well as the potentially positive effect of moreeffective vaccines for food production and enhance-ment of animal welfare.

Although there is leveled reasonable critiqueagainst strong and weak versions, the complexchallenges by scientific uncertainties must be dealtwith in some way or another. First, because there isgeneral agreement that we are politically andmorally obliged to avoid foreseeable harm [20].Second, because the present controversy on how todeal with unintended effects due to employment ofnew technology is an issue that we need to resolveon its own account [9]. Furthermore, full certaintyabout potential unintended health and environmentaleffects is unattainable prior to full-scale employmentof the technology. The complexity of animal andenvironmental systems implies that the informationachieved by doing laboratory research and in riskassessment is not adequate for evidence-baseddecisions. Thus, the reasons for introducing theprecautionary principle, namely how to approachand acknowledge lack of scientific understanding inpolitical decisions, is as relevant today as in theearly Nineties.

Implementation of the Precautionary Principle

The implementation of the precautionary principlerequires that there are indications of adverse impacts,and that risk-associated research is initiated. Hence,indications of adverse impacts must be documented ina scientifically acceptable way before a precautionarymeasure can be initiated. What is held to beacceptable evidence for action differs markedly inweak and strong versions of the precautionaryprinciple. For example, Article 15(1) of the CartagenaProtocol on Biosafety states that;

‘Risk assessments undertaken pursuant to thisProtocol shall be carried out in a scientificallysound manner … Such risk assessments shall bebased, at a minimum, on information providedin accordance with Article 8 and other availablescientific evidence in order to identify andevaluate the possible adverse effects of livingmodified organisms on the conservation andsustainable use of biological diversity, takingalso into account risks to human health.’

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Usually what is regarded as scientific evidence isconnected to quantifiability, and scientific soundnessis likewise associated with quantified science. Forinstance, a typical example of a systematized quanti-fied risk approach to genetically modified organismsis the principle of substantial equivalence [27]. Aslong as we are talking about risk, quantified evidencemeans measuring probability of an identified undesir-able effect. By demanding scientific evidence beforeemploying the precautionary principle, the BiosafetyProtocol requires documentation indicating that thegenetically modified organism in question causesharm to health or the environment.

The EC communication on the precautionaryprinciple [10], on the other hand, focuses on thequality of the information. A focus on the quality ofinformation relates to what type of scientific under-standing is known and what there is a lack ofinformation about—without requiring ‘degrees’ or‘levels’ of proof, expressed as quantified probabili-ties. Hence, scientific uncertainty and indications ofharm would be enough for acceptance of employ-ment of the precautionary principle. The firstapproach corresponds to a weak version of theprinciple, whereas the second indicates a strongversion. The weak version demands measurements,which presupposes that we possess the kind ofknowledge that would make precaution superfluous.Accordingly, we would be better off with standardrisk assessments. However, the strong version mayopen up for endless negotiations as to what isuncertain and unknown, as well as what shouldcount as indications of the ‘unknown’. In addition,the strong versions tend to overemphasize thepotential adverse impact of the proposed action ascompared to the situation this action seeks to amendor improve, resulting in a presumption for postpone-ment of technology implementation based on anarguably one-sided risk focus.

Thus, a demand that there need to be availablescientific information to determine whether precau-tionary steps should be taken, fails to evade thecriticism of weak versions of the principle forbeing vacuous. On the other hand, the postpone-ment of scientific assessments in the strongversions combined with the myopic focus onindications of environmental risk, may fail tobalance the risks with benefits or, in other cases,risks of non-action.

The UNESCO Version of the PrecautionaryPrinciple

The recent UNESCO report on the precautionaryprinciple [49] may indicate a promising middleground between the present strong and weak versions.One reason is that it gives a thick description of theissues at stake, incorporating various ethical valuesconcerning intra- and inter-generational equity, envi-ronmental responsibility, sustainable development andstakeholder participation. The UNESCO versionreplaces scientific probability with plausibility, andalso emphasizes that uncertainty is the trigger forapplication of the precautionary principle. Further-more, it defines the limits of the principle by statingthat ‘if a hypothesis posits radically new andunfamiliar mechanisms and processes, it is notplausible’; in which case the principle is not relevant.Moreover, the UNESCO principle involves evaluationof the consequences of both action and inaction in aparticipatory process. Accordingly some of the pitfallsof both weak and strong versions seem to be avoided:

‘When human activities may lead to morallyunacceptable harm that is scientifically plausiblebut uncertain, actions shall be taken to avoid ordiminish that harm.Morally unacceptable harm refers to harm tohumans or the environment that is

– threatening to human life or health, or– serious and effectively irreversible, or– inequitable to present or future generations, or– imposed without adequate consideration of the

human rights of those affected.

The judgment of plausibility should be groundedin scientific analysis. Analysis should be ongoingso that chosen actions are subject to review.Uncertainty may apply to, but need not belimited to, causality or the bounds of thepossible harm.Actions are interventions that are undertakenbefore harm occurs that seek to avoid ordiminish the harm. Actions should be chosenthat are proportional to the seriousness of thepotential harm, with consideration of theirpositive and negative consequences, and withan assessment of the moral implications of bothaction and inaction. The choice of action shouldbe the result of a participatory process.’

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Due to the level of detail, this version gives amore comprehensive account than the ones we havediscussed above. It is specific concerning what kindof harm that is basis for precautionary action, thusevading the critique that the principle is either toovague or too demanding. Unlike weak versions, theUNESCO principle does not demand scientificcertainty or evidence of benefits and harm prior toaction. Unlike strong versions it does not focusonly on the negative potential of the proposedactivity, but requires an assessment of inaction aswell as action. This version involves no shift of theburden of proof, as the Wingspread statement does,and is arguably less problematic concerning tech-nology implementation.

Still, this version may face the charge of beingunclear on key issues, at least if the precautionaryprinciple is intended to be action guiding. This isclearly the case with the phrase ‘morally unacceptableharm’ and its specifications ‘threatening to life orhealth’, ‘serious and irreversible’ and ‘inequitable’.Some guidance is however given in the UNESCOreport by its reference to participatory mechanismsand democratic pluralism and the insistence on theneed for case-based reflective value judgments: ‘Astrength of the precautionary principle being aprinciple is its open-endedness and flexibility, whichcreates a possibility and an incentive for sociallearning.’ (p.51). In the following we will furtherelaborate on these points, bearing in mind that thereport proposes a procedure rather than a recipe fordealing with particular cases of scientific uncertaintyregarding harm, using introduction of PLGA fordelivery of vaccines in aquaculture as our case study.

Threatening to Human Life or Health

The purpose of vaccination is to protect fish againstdisease, with the intention to improve animal welfareand the economy of aquaculture. All fish incommercial aquaculture is meant for human con-sumption, hence this raises the issue of safety forconsumption. To the best of knowledge of theauthors no studies on the implications of eatingPLGA mediated vaccinated fish exists. If, however,someone presented a scientifically plausible scenarioof the PLGA nanoparticles not being fully degradedand having toxic effects, we have a situation similarto the scientific controversy surrounding the uncer-

tainties of the effects on human and animal healthby consumption of genetically modified foods.Although highly contested within science [13,51],there are reasonable scientific arguments for caution,for example based on documented unintended effectsin different kinds of breeding and gene modification,combined with the fact that absence of proof of harmis not equal to proof of absence of harm. But this fallsback on the question of how to decide that anindication of harm is to be considered scientificallyplausible. Only the scientific community can decidethat, and as stated in the UNESCO version ‘Thejudgment of plausibility should be grounded inscientific analysis’. However, as illustrated abovethere are significant disagreements between scientistson matters such as these, depending on their trainingand work context [28]. What is plausible for onescientist is highly unlikely for another, depending ontheir perspective. One could counter this by sayingthat a situation with scientific disagreement anddifferent perspectives on the relevance of the uncer-tainties involved leaves us in a state of ignorance andambiguity and thus beyond the conditions for usingthe UNESCO principle. But then the principle willhave a very restricted validity area compared to mostversions of the precautionary principle, and we arestill left with the problem to determine what can becharacterized as uncertainty and what as ignoranceand ambiguity.

Serious and Effectively Irreversible

In a similar vein, what is to count as serious harm tonature is based on contestable value judgments thatare not self- evident. Mankind has always interactedwith nature and done alterations to the naturalenvironment for better or worse. Since nature can bedescribed as an indefinite number of interconnectedself-adjusting biological systems, ‘harm’ becomescontext-dependent. Destruction of some elements ofan ecosystem, inevitably gives advantages to otherelements, ensuring that harm in most cases issimultaneously a benefit. For instance, farmed salmonwill escape or be released, and the escaped salmonwill compete with wild salmon for food, habitats andspawning grounds. Escaped farmed salmon may alsospread parasites and diseases and through mating withwild salmon change the genetics of the wild salmonpopulation [12].

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Genetic interaction between farmed and wildsalmon population can cause reduced mean fitnessand lower reproductivity. At present we do not knowwhether the PLGA particles and vaccination willaffect salmon reproducibility or survival in wild, butthe possibility cannot be ruled out. Assuming im-proved fitness of farmed salmon, some would say thatthe escape of salmon with subsequent depletion of thewild stock due to interbreeding and competition,represent no harm. We still have wild salmon,although somewhat different from the original variety.Others will consider this to represent serious harmsince a) the genetic interaction will result in reducedgenetic diversity (although this may be contested),and b) the escaped farm salmon will replace the wildrelative, which is problematic for our distinctionsbetween nature and culture, expressed in the valueplaced by most people on the idea of naturalness. Inthis particular sense the escapee is less natural thanthe native salmon.

Clearly we cannot determine what is a seriousinterference with nature, and certainly not what is tocount as serious harm unless we determine whichaspects of nature and its functioning that is to beregarded as worth preserving as it is today. Thus thequestion of serious harm is correlated to conceptionsof how to maintain and preserve nature and biodiver-sity [4]. The vagueness makes specific value baseddiscussions needed which is also argued for in theUNESCO version of the principle. However, anenvironmental change does not necessarily imply anadverse effect as illustrated above with the case ofescapes by farmed salmon. Hence we questionwhether participatory processes can guide the choiceof action in such cases, and that consensus in societyregarding the nature of harm to the environment canbe achieved. Furthermore, such processes may onlyinclude those effects that are valued by the society asnegative as for instance effects on specific species asbutterflies etc. and leave out impacts on ecosystem aswell as abiotic components.

Moreover, even if we agree on some change asclearly harmful, the phrase “irreversible harm” isdifficult to use in an uncontroversial technologyassessment. For instance, the PLGA particles maybe distributed by escape or release of vaccinated fish,and by accidental release of the vaccine. In aquaticenvironments use of PLGAs may be irreversible sincethey can be distributed over vast areas, distances, and

possibly pass physical and physiological barriers.However, as polyesters in nature, these polymersundergo hydrolysis after administration, formingbiologically compatible and metabolizable moieties(lactic acid and glycolic acid) that are eventuallyremoved from the body by the citric acid cycle [2].Since PLGA undergoes such a hydrolysis they willmost probably be degraded short time after adminis-tration and hence involves a low plausibility fordistribution into the environment. On the other hand,these particles are to be distributed at nanolevels thatentail that different biological and physiologicaleffects may occur. For instance, studies have shownthat toxicity of particles increases with the decrease ofparticle size and increase of overall surface area [18].Evaluation of the factors that affect nanomaterialexposure requires measurement of properties asparticle size, shape, surface area, and surface chem-istry with implications for the safety by application.Although the PGLA nanoparticles are biodegradablethey may also have higher reactivity due to theirincreased surface area; hence have a potential tointerfere with natural processes. These problemscould be classified as matters of scientific ignorancerather than uncertainty, and be relegated beyond thescope of precaution. But as these altered propertiesare based on documented research, there is a case foraccording the plausibility by a case-by-case approachbased on previous or analogous use and in relation tothe novelty at the nanolevel, and thus as matters ofuncertainty.

The most prevailing questions that need to beanswered in relation to the environmental and healthimplications of nanomaterials are: What are the fateand transport mechanisms of nanoparticles? Whichexposure routes are relevant? How do nanoparticlesimpact the natural environment including animal andhuman health? Vaccines with PLGA as carrier may bereleased during vaccination and from the vaccines.Although the PLGA is biodegradable, it is at presentnot known if the PLGA used in vaccines may havechanged biodistribution patterns as well as persis-tence. Although encapsulation ensures more directuptake by cells it also entails release of the antigensover extended periods of time. Another issue concernsPLGAs adsorption tendency and degree of aggrega-tion at a macro versus a smaller level that also need tobe investigated. Predatory animals can also spread thePGLA and the vaccines in the environment. Accord-

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ingly, there is a need to initiate experiments with thepurpose to investigate the stability of PGLA particlesin aquatic systems, uptake in aquatic organisms,including marine fish and mammals. But even ifthese acts represent irreversible alterations to theenvironment, it is not obvious that they representharmful alterations. Also after we establish withreasonable certainty the extent to which PGLA basedvaccines have irreversible effects on the environment,we still depend on value judgments to decide whetherthis is harmful.

In this context it is worthwhile to bear in mind theearly days of the debate surrounding geneticallymodified organisms, where several proponents ofgrowing genetically modified plants commerciallypointed out that no escape of transgenes to wildrelatives had been recorded, and it was unlikely that itwould happen on any significant scale. When suchescape was documented some years later, the propo-nents of the genetically modified crops did not seethis as a problem for their conception of this as afruitful technology. Typical arguments are that trans-genes generally give the wild plants small competitiveadvantages and transgene spread should not beconsidered to be more harmful to the environmentthan gene flow from traditional plant breeding crops[31,33]. Despite the fact that this spread is irrevers-ible, many consider this spread to represent accept-able harm. We can also imagine that if thesetransgenic wild plants became ‘superweeds’ [16],threatening both crops and the diversity of ecosys-tems, the same people could merely say that this is nosignificant harm when considering the benefits of thetransgenic crops, the wide array of herbicides we haveto use to control the weed, and how much nature wehave left that will never be affected by these weeds.

Even when there is some case of irreversible and inseveral ways destructive changes due to humanactivity; we still depend on contestable values to givemeaning to concepts such as ‘harm’, because they areboth descriptive and normative. We have to determinetheir normative content to be able to use them asaction guiding, and this can only be done through thediscussion of actual cases, as is clearly the intentionof the UNESCO principle. But in this area theUNESCO version stumbles on similar problems asthe strong versions, such as the Wingspread state-ment. It is not enough to state that plausible threats ofirreversible harm should lead to precautionary meas-

ures, as long as we have no way to ascertain what isto count as ‘harm’. Furthermore, in the UNESCOversion the concept of morally unacceptable harm isinterlinked with serious and effectively irreversiblewhich is problematic. How can these terms be used tochoose the best action in an open and flexible way?The question of what is to count as harm is highlydependent on a scientific analysis, involving both thedisciplines involved in development of the technologyin question as well as they who have competence inecology and biology. Moreover the complexities ofthe technical issues of novel technological productsdo also represent insurmountable obstacles to a well-informed public value discussion. Hence, we willargue that instead of using participatory processes forchoosing actions, a better approach would be toidentify different societal conceptions that can beused in comparison with the present biological andecological understanding [32].

Inequitable to Present or Future Generations

Inequitable distribution certainly is morally wrong,but how is it possible to estimate distribution ofbenefits and harm of future applications of a newtechnology? There is a wide and growing discussionon global justice [39,40,43,45] that demonstratessome of the difficulties in determining what is tocount as an equitable global distribution of goods andburdens among people living today. Solving thisquestion as part of a precautionary approach toparticular technology applications does not seem anyeasier. Of course, in many cases this point will mostlikely be irrelevant, for example when discussingvaccines in fish. But when it is relevant, as is the casewith nanotechnology and biotechnology related issuessuch as patenting, bioprospecting and strategies forfunding of research and development, the issues mustbe solved in an inclusive debate rather than as part ofemploying the precautionary principle to a particulartechnology application. We assume this point isincluded in the UNESCO version of the principlemainly to avoid the charge that the real suffering ofexisting people is sacrificed for potential suffering offuture generations.

The issue of equity in relation to precautionarythinking seems more relevant regarding future gen-erations. But equity concerns reasonable distributionbetween members of the same society, be it a local or

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a global community. We do not have this relationshipwith future generations, and we are unable to sharegoods with them on an equitable scale since we donot know who they are, how many they will be orwhat their interests will be. If we extrapolate fromknown history, we can safely conclude that theseessential facts are impossible to predict. ‘Equity’ isnot a suitable moral concept in this context, since it isconnected to an ethics of reciprocity. Hans Jonas [22]suggests that responsibility is a more basic ethicalprinciple than reciprocity since there can be noreciprocity between future generations and us. ForJonas, the fundamental lesson of technology devel-opment is the power humankind has acquired, that inthe last instance enables us to destroy the possibilityof any future human life on earth (Ibid. 26f.). Thus hesuggests a new categorical imperative to replace theKantian: ‘Act in a way that makes the consequencesof your acts conform with the permanent real humanlife on earth.’ (Ibid. 36)

Another important and new moral challengeaccording to Jonas concerns our shared responsibility,since our acts are collective acts. The moral impera-tive becomes political. Our responsibility for futuregenerations must be at the core of any precautionarythinking, and the UNESCO version commendablyincorporates this. This is, however, not a matter ofequity but of responsibility in the sense employed byJonas. We should leave an earth that gives cominggeneration the opportunity to decide what kind of lifethey want to lead. Environmental responsibilityrelates to human existence, and suggests that theEarth should not be left in a worse state than the statein which we received it.

Perhaps Jonas’ perspective on environmental re-sponsibility implies a precautionary approach; but headds an important caveat. We have a duty to gainknowledge in order to contribute to the good of futuregenerations, which implies the acceptance of uncer-tainty (Ibid. 28), while at the same time encouraginginnovation. A restrictive precautionary policy mayprevent rather than promote the future state of theearth. Rather than a narrow interpretation of theprecautionary principle with emphasis on ‘avoidanceof harm’, the focus in an ethics of a responsibilityapproach is directed to how we should promote agood life also for future generations. In this contextvaccines in general may help to ensure a more stableproduction in aquaculture which is important in both

rich and poor countries but also for posterity.Although we cannot know the preferences of futuregenerations, we can be certain that a stable andsustainable food supply will be as essential for themas it is for us. On the other hand, genetic pollutionmay reduce the possibility of finding and developingalternative sources of food production. It has beenargued that fish farming involving carnivorous spe-cies is not sustainable as it is practiced today [36], andfuture food production may have to develop newways of exploiting marine food resources. If the useof PLGA as carriers of vaccines in fish farmingendangers this opportunity, we have to deem itmorally unacceptable. But we do not need theprecautionary principle to discover that it is wrongto undermine alternative marine sources of foodproduction. Jonas’ ethics of responsibility is moresuitable in that respect.

As illustrated above, this ultimately raises thefollowing questions; for whom may PGLA as carriersfor vaccines be morally unacceptable, and whichmoral theories or principles should be employed? Forinstance, the biotechnology industry advocates ac-ceptable environmental and health impacts of DNAand GM vaccines while others claim there areunacceptable impacts. PGLA has been approved bythe FDA based on their history for use in clinicalapplications [29]. Does the use at a nanolevelrepresent new concerns? Does the distribution to anew organism, fish, represent new questions? Doesthe shift from medical application at a low level tolarge-scale distribution in aquaculture involve newchallenges for control and monitoring? These issuesrequire research by different groups of scientists foridentification of potential impacts. Unless we havesome indications of the answers to these questions,the UNESCO principle’s demand of precautionaryaction against interventions that are ‘inequitable tofuture generations’ will remain mere words. But thereport does provide a promising procedure for how toavoid this charge.

Participatory Case-Based Approach as Solution?

So how does the UNESCO version attempt to avoidthe vagueness trap of precautionary thinking? Theanswer may be found in the final demand of aparticipatory process that shall include all affectedparties. The report claims that ‘moral judgments are

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less subject to plurality and rest on a firmer basisthan the ethical theories one adheres to’ [49] andexpresses a belief in a yet undiscovered universalbasis for ethics, forcefully stated by several previousauthors (see e.g. Jonsen and Toulmin [23]). Thus weare more likely to reach consensus as a result of theprocess. This belief in a tendency towards moralagreement in particulars is basis for expectinggenerally acceptable and more stable results of theparticipatory deliberation.

Participatory processes are in the vogue in presentday technology governance. Engaging the public isusually justified through some kind of stakeholdertheory [42] or deliberative democracy theory [7].Although there are overlapping ideas between thetwo approaches, a deliberative democracy approachis more in keeping with the normative ideals in theUNESCO report. According to this approach, dem-ocratic decision-making is expressive of mutualrespect and of justice. It provides a wider argumen-tative basis for decisions [19] as lay people may haveunique, valuable contributions to complex andcontroversial political issues [7,55]. In Stirling’s[47] analysis of the rationale for public engagement,he highlights in addition the role of public engage-ment in restoration of legitimacy and public trust.The issue of trust has also been argued byMacnaghten et al. [30], who considers that engage-ments represent an extraordinary opportunity to builda robust prospective role for the social sciences inshaping the future of nanotechnology research andinnovation processes.

One crucial problem with participatory processes isthe fact that many people have no wish to spend timeon them, due to their lack of relevant knowledge andlack of interest in entering extensive learning pro-cesses, as is demonstrated in several focus groups andinterviews [21,46,48]. Therefore we should ask why itis important to involve the public in discussions ofissues where they may lack both knowledge and theinclination to participate.

If we assume that a participatory process can givevaluable results, we still have to question theassumption that this process will result in a stablenormative consensus. Participatory processes open upfor a plurality of views and conflicting perspectivesthat create a dilemma concerning how and when toreach a decision, since the aim of any participatoryprocess in relation to the precautionary principle is

generating information for decision-making. TheUNESCO report fails to present evidence for theclaim about particular moral judgments being lesssubject to plurality, and the disagreement on how todeal with the more or less plausible harms fromdistribution of any vaccines to be used in aquaculturehardly supports their case. On the contrary; almosteverybody agrees on the theoretical assumption thatirreversible damage is wrong, but disagrees on theparticulars, and on the strategies for handling suchharm. Thus there is no guarantee that staying withmoral judgments of concrete cases will help usresolve the moral issues involved.

In many cases the reason for disagreement is notmoral, be it theoretical or practical, but one ofplausibility of risks. For instance an analysis of theevolution of policy discourses [8] on nanotechnolo-gies indicated that, while gradually more participantsenter the public debate, the issues of concern havebecome more narrowly defined. After a phase wherenanotechnology emerged on public and policy agen-das, and a subsequent one in which debate about awide range of implications of the possibly radicalpotential of nanotechnologies was expanding, a globalpolicy discourse that focuses primarily on environ-mental, health and safety risks is now gaininggrounds. As Doubleday writes:

‘So rather than addressing questions of howparticular conceptions of health and thehuman body are reproduced by nanotechnolo-gy research programmes, the dominant visionof nanotechnology as a public issue concen-trates on the toxicology of nanoparticles.’(Ibid., p.213)

The disagreement often concerns what futurescenarios that are likely, not the ethics of dealingwith these scenarios. The discussion can also beframed as a psychological one rather than a factual ora moral disagreement: risk-averse versus risk-accepting personalities, although it is reasonable toregard the psychological state to some extent to beinterdependent on beliefs [24]. In short, the assump-tion that disagreement is moral and can be resolvedthrough discussing cases rather than theories andprinciples appears to be misguided. In issues likethese it is even difficult to construct meaningfuldistinctions between empirical facts and value judg-ments. For instance, with PLGA as carriers of

82 Nanoethics (2011) 5:73–86

vaccines there are at present lack of empirical dataand no scientific consensus of the various type ofuncertainty embedded with its use. The problem is theissue regarding identification and interpretation ofrelevant data and approaches for gathering more datarather than how to handle these data in practicalreality.

Even if the UNESCO definition of the precaution-ary principle clearly is more specific and a betterguide for regulation than the paradigmatic weak andstrong versions preceding it, the UNESCO versionstumbles on the assumption about less plurality inmoral judgments. We have no reason to expect thisbecause interpretations of the issues at stake differ, asis exemplified by the continuing debate betweenEurope and the USA, Canada and Argentine on themoral acceptability of the release of geneticallymodified organisms [52].

Responsibility Versus Precaution

The UNESCO version replaces scientific probabilitywith plausibility, and emphasizes proportionality ofaction relevant to ‘the seriousness of the potentialharm, with consideration of their positive and nega-tive consequences, and with an assessment of themoral implications of both action and inaction.’ Inthis way it is neither reducible to a demand for riskassessment nor an unreflexive obstacle to technolog-ical progress due to a myopic risk perspective. Butassuming that the precautionary principle is meant tobe action guiding, the UNESCO principle provides noway to decide what is to count as scientific plausibil-ity in a situation of scientific disagreement. Especiallyin new and controversial areas of research, suchdisagreement is common.

The UNESCO report is right in that the responsi-bility for making a decision on technology applica-tions is and should be political mediated by a wide,open and responsible debate in accordance with theideal of deliberative democracy [7]. The debate mustbe based on best scientific knowledge. We will arguethat this calls for a privileged position for experts(natural and social scientists, as well as ethicists) inaccordance with Aristotle’s theory of practical argu-mentation where accepted opinions (endoxa) includethose of the majority as well as those of the majorityor the most respected of the wise, i.e. the experts [3].

The Aristotelian privileging of expertise does notexpress elitism or disrespect for the rationality of laypeople, but a reasonable assumption about the valueof knowledge and understanding gained from years ofspecialization in theory and practice. As emphasizedabove, lay people have an important role to play inthese debates, since they can represent an outsideview, serving as corrective to myopic tendencies bothwithin the nanotechnology community as well aswithin nanoethics. Moreover it has also been arguedthat lay people may see matters that the expertsdiscount or fail to notice since they are immersed inthe scientific culture with its epistemological andethical assumptions [55].

In the current governance debate, however, thebelief in the value of public participation is toostrong. As we have pointed out, there is evidencethat lay people themselves reject this role. Sincethey present sound arguments for this rejection, inaddition to ‘voting with their feet’, using delibera-tive democracy theory to say that they should getinvolved is a self-defeating exercise. In several ofthe studies, lay people express that they either dotrust experts or that they wish to do so. This can beread as an implicit claim that the experts should betrustworthy, in the sense that they should takeresponsibility for the moral acceptability of whatthey do.

In order to fill that role of taking responsibility inour current project, we need scientific studies of theeffects prior to using the nanoparticle based productscommercially, where scientists determine the uncer-tainties and suggest the range of possible outcomeswhich is subsequently followed up by targetedresearch. However, with regard to nanotechnologythere are reasonable disagreement on the range ofoutcomes and the plausibility of the different out-comes. Hence, even if everybody agrees to the list ofprinciples for delimiting relevant harm, we willdisagree on how to balance different scientificscenarios. For example, the different scientific dis-ciplines that are presently involved in the epistemicdebate employ competing models or analogies forbasic assumptions on how to frame the scope forfurther research as well as with regard to regulativeframeworks. Since the principles and paradigms ofthe different scientific disciplines differ, they have nocommon ground to discuss means for gathering newscientific understanding.

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In this sense the ethics of responsibility is relatedto a precautionary approach that emphasizes thenecessity of initiating risk-associated research [53].Such risk-associated research entails that the scientistsshould identify uncertainty and that they shoulddiscuss the evidence and arguments for the differingassumptions and communicate this disagreement tothe public and political authorities. Potential threatspointed out by respected scientists with relevanteducation and practice, threats that the scientists atthe moment are unable to indicate the likelihood of,should be communicated as part of the studies.Recognizing fallibility is an inherent part of scientificpractice, and scientists should always regard unex-pected damage to be likely when introducing benefi-cial new technology.

But who are the experts that should be involvedin a best scientific practice approach as the one wesuggest here? That depends on what scientificknowledge is relevant for the examination of risksand uncertainties with regard to environmental,health, social and economic effects. Valuableinsights can be drawn from science and technologystudies and the debate on precaution where acentral point has been the integration between newtechnology and modern democratic society, makingthe social and normative essential and internal partsof the technology rather than mere additions andexternal [42]. Regulation of the development and useof nanoparticles as carriers for vaccines is obviouslynot merely a question of nanotechnology andaquaculture. The scientific evaluation group shouldencompass a wide range of experts, includingimmunologists, biologists, marine ecologists, sociol-ogists and ethicists.

The scientists should not restrict themselves toscientific work in a narrow sense. Their research isbased on certain values and will have consequencesfor nature and society. They have a duty toquestion the soundness of these values and toevaluate the consequences should be regarded asgood or acceptable—or they should ensure thatsomebody else does this reflexive examination.Since most scientists lack the background andresources necessary for this kind of ethical analy-sis, their duty to assess the values and implicationsof their research activity would be fulfilled if theirresearch integrates social science and ethics per-

spectives on the relevant science and technology.This should not be regarded as ‘outsourcing’ ofethics, as is often done in ELSA-research. Thescientists have a duty to take part in mutuallearning processes with the humanities researchersthrough discussion of the technology in thissocietal and ethical perspective. Only by thisinterdisciplinary cooperation can the public begiven resources that are valuable for their partici-pation in an open debate of the relevant issues.Hence, our approach can be considered as a returnto a principle of best scientific practice based on anethics of responsibility.

To avoid morally unacceptable consequences forfuture (or even present) inhabitants of the earth, weneed to pay heed to the words of the scientificcommunity and combine it with common senseexpressed in the ethics of responsibility. We have amoral responsibility to anticipate and prevent negativeconsequences irrespective of the degree of humancontribution to the potential harm. This kind ofresponsibility is not fully captured in precautionarythinking where only human activity triggers the moralobligation. Thus the problem lies in the collectivenature of responsibility [22].

There are incentives that seek to promote a broadsense of responsibility [26] such as the EU’s ‘Codeof Conduct for Responsible Nanosciences and Nano-technologies Research’ [6] and voluntary measures.However, we see the concept of responsibility not toonly endorse and stimulate reflective awareness inorder for researchers to be able to communicatesome of the issues at stake to the general public orenable the scientists to reflect on the conditions theyperform their research under, as well as the choicesthey make. It is also about enhancing deliberation onthe course of action of all stages of the developmentprocess that leads to the context of the end user inways that for instance will realize the expresseddeliverables promised to and endorsed by publicbodies. In order to carry out this kind of responsibilityreflection, scientific and technological expertise must besupplemented with ethical expertise. Although one candiscuss to what extent deciding on the good is an area ofexpertise, systematic normative reflection certainly is[44]. Thus, some kind of interdisciplinary expert-basedreflexive work is necessary in order to fulfil thedemands of scientific responsibility.

84 Nanoethics (2011) 5:73–86

Conclusion

There are many formulations and versions of theprecautionary principle, and the debates raised byformulations of the principle have been valuable forrecognizing a changed role for science and technol-ogy in democratic societies. Most attempts at work-able formulations of the principle, however, havebeen met with criticism for either being vacuous ortoo narrow and leaving too much to discretion.Although the UNESCO version makes the bestattempt so far to avoid these pitfalls, it does not fullysucceed, also this version is plagued by vague keyconcepts and questionable normative assumptions.

We suggest instead that the precautionary principleneed to be supplemented by combining the ideal ofbest scientific practice with the insights of Jonas’ethics of responsibility to ensure a sound basis forpolitical decisions on technology regulation. Oncontroversial issues where the stakes are high andfacts contested, such as use of nanotechnology,valuable insights from the debate on precaution isretained, but futile attempts at finding a formulationof a particular principle is replaced by a regulatoryapproach based on a wide scientific evaluation of thevalues and implications of particular technologyapplications. This represents no attempt at solvingthe problems in the definition and application of theprecautionary principle, nor does it avoid the vague-ness problems. We wish to redirect the attentiontowards the issue of scientific and political responsi-bility as an alternative framework for the discussionof how to handle potentially harmful use of newtechnology. This responsibility is aimed at scientistsas we consider expert arguments will and should carrymore weight than public argument since they have theresponsibility for making a thorough and soundassessment of the technology and share their bestopinions with the public and political authorities.Involving lay people should be a way to widen ourperspectives, and we should be careful to avoidshifting the burden of responsibility from politiciansto the general public.

Acknowledgement We will express our gratitude to MatthiasKaiser for his generous criticisms and many suggestions forimprovements to this paper. He obviously does not agree withseveral of our key arguments and is not responsible for anyweaknesses of this paper.

Open Access This article is distributed under the terms of theCreative Commons Attribution Noncommercial License whichpermits any noncommercial use, distribution, and reproductionin any medium, provided the original author(s) and source arecredited.

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