ARTICLE IN PRESS
InsectBiochemistry
andMolecular
Biology
Insect Biochemistry and Molecular Biology 35 (2005) 649–660
www.elsevier.com/locate/ibmb

Ethical, legal and social issues of genetically modifying
insect vectors for public health
Darryl Macera,b,c,
aEubios Ethics Institute, Japan
Eubios Ethics Institute, New Zealandc
RUSHSAP, UNESCO Bangkok, 920 Sukhumwit Road, Prakanong, Bangkok 10110, Thailandb

Accepted 11 February 2005

Abstract
The use of genetically modiﬁed (GM) insects for control of human disease can be consistent with common ethical norms ofinternational society to reduce human suffering. This paper considers a range of ethical issues including animal rights, informed
consent, community consensus and environmental viewpoints. Each community needs to decide its own priorities for methodology
of disease policy guidance for ethical genetic engineering, and to negotiate with neighbouring countries. The approach to geneticallymodify insects raises few intrinsic ethical issues; however, important environmental and human health concerns need to be assessed
before release of any GM insects. The policy that each community adopts should be the product of open dialogue involving all
sectors of society. It can be expected that this process will take years and not all communities will endorse genetic control approaches
to insect vectors.
r 2005 Published by Elsevier Ltd.
Keywords: Genetically modiﬁed insects; Bioethics; Animal rights; Environmental ethics; Biosafety; Public health; Informed consent; Public opinion

1. The ethics of disease prevention
There is global support for the efforts to improveexisting and develop new approaches for preventing,diagnosing, treating and controlling infectious diseases
that cause loss of human life (Macer, 2003). The ethicalprinciple that lies behind the idea of preventing, treating
and controlling disease is that human life is somethingworth saving. There is however considerable ethicaldebate over the most ethical measures for achieving
these goals, including the extent to which risks to humanhealth, damage to the environment and other livingorganisms, and economic costs are balanced in societiesthat have a range of worldviews and social structures.

Corresponding author. RUSHSAP, UNESCO Bangkok, 920
Sukhumwit Road, Prakanong, Bangkok 10110, Thailand.
E-mail address: d.macer@unescobkk.org.

0965-1748/$ - see front matter r 2005 Published by Elsevier Ltd.
doi:10.1016/j.ibmb.2005.02.010

Certain principles basic to resolving ethical dilemmas
can help decision makers make more informed policy
decisions. The principle that we should love the life
given to us (self-love) implies that each person should begiven autonomy (self-rule) to work out how to balance
the ethical dilemmas and choices themselves. The
Universal Declaration of Human Rights of 1948
speciﬁcally set as a baseline that all human beings
possess equal rights, and should be given a chance toexercise their autonomy. One of the fundamental humanrights is a right to health, and working towards giving
every person a chance to grow up free of disease is the
ethical foundation of public health. If a person does notpossess some basic level of health, he/she cannot evenface many of the choices commonly accepted as normal.
Poverty also restricts the choices of many people(Azevedo and de Moraes Marcilio Cerqueira, 2002),
especially in areas faced with infectious insect borne
diseases.

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D. Macer / Insect Biochemistry and Molecular Biology 35 (2005) 649–660

Justice simply means that if we want others torecognize our autonomy, we have to recognize theirs
as well. There are at least three different meanings of theconcept of justice: compensatory justice—meaning thatthe individual, group, or community, should receive
recompense in return for contribution; procedural
justice—meaning that the procedure by which decisions
about compensation and distribution are made is
impartial and includes the majority of stakeholders;and distributive justice—meaning an equitable allocation of, and access to, resources and goods (Macer,2003). There are ethical questions about how a society
should represent procedural justice when there aremajor divisions within the society on particular issues.
The process of consensus building and reachingcommon ground may be preferable for many cultures
rather than confrontations.
At present there is great inequality between rich andpoor nations in the direction and priorities of research,and in the distribution of and access to beneﬁts thatmight come from this research. Under any ethicaltheory, the presence of diseases that threaten the lives
of not just one but more than a billion people worldwide
provides a compelling need for efforts to eradicate thediseases. There is wide diversity in the risks thatmembers of each community face from infectious
diseases due to: individual genetic variation in resistanceto infectious disease agents; a person’s nutritional stateand immediate environment; a family’s economic
situation with respect to providing barriers to vectors
and disease; access to both preventative and therapeutic
medicines. These variations can be regarded as a type oflottery. Working towards better global equity is a goalthat attempts to even out the lottery that people areborn into. This is ethically mandated by Rawlsian justice(Rawls, 1971), which argues that efforts should be madeto minimize the variation in all social factors because no
one knows before they are born into which situation
they will be born, so everyone would wish for equal
opportunity and equal exposure to risk. All should havea chance to be born and grow up in an environment freeof infectious diseases, if that can be achieved.
The ethical principle of beneﬁcence supports thedevelopment of science and medicine, and its provision
to those who suffer. A universal ideal found throughout
human history is that it is better to love doing goodthings than bad things, and to love our neighbour as
ourselves. Humans have used technology in efforts tomake their lives easier and better for thousands of years,
and the ethical principle of beneﬁcence argues that weshould continue to make life better. This ethicalprinciple is based on the general motivation insidepeople to love doing good rather than harm, and may be
expressed as love or compassion (Boyd et al., 1998).
Efforts that work for the betterment of others in society
have a universal moral mandate.

The ethical principle of non-maleﬁcence, or do noharm, would make us reasonably cautious about
premature use of a technology when the risks are notunderstood. Recently some have advocated a total
precautionary principle for genetic engineering, which
would mean that no technology with more than 0% risk
should ever be attempted (Ho, 1998). This has also
entered the Cartegena Protocol on Biosafety, which isan International Legally Binding Agreement that
regulates international movement of living modiﬁed
organisms (LMOs) (CBD, 2000). Because no humanaction has 0% risk, the principles of both beneﬁt andrisk are used to assess technology and are central to any
public health program (Callahan and Jennings, 2002).
The ethical issues raised by biotechnology arecommonly termed bioethics dilemmas, although when
we examine the actual moral questions they may not be
so novel and are often related to areas of applied ethics
that were debated long before we had modern biotechnology (Comstock, 2000). There are several basic
theories of ethics. The simplest distinction that can bemade is whether they focus on consequences, actions or
motives. Consequential arguments are the criteria
applied to assess the ethics of biotechnology applications, i.e. whether they contribute to the greater good byimproving the well-being of all. Consequential arguments state that the outcome can be used to judge
whether an action was ethically correct or not. An
action-based argument looks at the morality of the act
itself, so that the actual action to cause harm itself is an
unethical action regardless of the consequences ormotives. Motive-based theories of ethics, including
virtue-based ethics, judge an action based on the
motivation of the action. For example, if the act wasdone with good intentions or not. Another separationthat is used is between deontological theories, which
examine the concepts of rights and duties, andteleological ones, which are based on effects andconsequences. If we use the image of walking along
the path of life, a teleologist tries to look where decisions
lead, whereas a deontologist follows a planned direction.
The objects and subjects of ethics can be viewed interms of ecocentric, biocentric or anthropocentric
concerns. Ecocentric concerns, that value the ecosystem
as a whole, are used when expressing environmental
concerns. The reverence for all of life (Schweitzer, 1966)
can apply to the whole ecosystem or to every member ofit. Biocentric thinking puts value on the individualorganism, for example one tree or one animal. Anthropocentric thinking is focused on the human individual.
There is a trend for more ecocentric views to be included
in recent legislation, with protection of ecosystems fortheir own value. While it can be useful to isolate distinct
issues, as will be done in this report, it is not realistic toseparate human/nature and social interactions. This isbecause almost all of human life is a social activity,

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involving many relationships with people and theecosystem. Different ethics are implied when humanactivity, e.g. agriculture or urbanization, attempts todominate nature or to be in harmony with theenvironment.
Despite the fact that there are a variety of deﬁnitionsof health, disease, disability, and what is a meaningful
human life, working to alleviate disease and empower
individuals to reach their potential are universal goals
for the progress of humankind. The basic ethicalprinciples of autonomy, justice, beneﬁcence and nonmaleﬁcence can be applied to help decision-making in arange of bioethical dilemmas in medical and environmental ethics. There is some debate over whether further
principles can always be derived from these over the
precise terminologies in each ﬁeld (Weed and
McKeown, 2001), but the general consensus is thatthese four principles are fundamental in a range ofcultures (Beauchamp and Childress, 1994; Macer, 1998;
Tsai, 1999). The emphasis on individuals may bequestioned more in developing countries. There are also
theories of ethics based on community, which argue that
individuality, autonomy or rights of a person are notsuited to the community structure of society.

2. Bioethics and molecular entomology
This paper examines some philosophical issues overthe use of genetic engineering on insects for publichealth purposes. There is a long history of altering the
behaviour of disease vectors so that they cannot
transmit pathogens to humans (Spielman and D’Antonio, 2001). Insects have also long been the targets ofattention in agriculture as well as in medicine. While
there are few intrinsic ethical concerns about killinginsect pests, as discussed below, ecocentric approaches
to ethics do raise some objections to modiﬁcation of
ecosystem components, and these need to be taken more
seriously.
People of all cultures have developed biotechnologies
as they live together with many species in the wider
biological and social community. A simple deﬁnition of
biotechnology is the use of living organisms (or parts ofthem) to provide goods or services. Over ﬁve millennia
of classical plant and animal breeding have seen theemergence of agricultural societies, and modern biotechnology is built on that. Since the mid-1990s, foods
produced from genetically modiﬁed organisms (GMOs)
have been sold in a growing number of countries (James,
2004). There has been ﬁerce international debate overthe environmental and human health aspects of GM
foods, but no harmful effects of GM foods on humanhealth have been shown scientiﬁcally (FDA, 2001).
There is greater concern over the environmental impactof gene transfer in the environment. A number of651

governments have considered the issues and concerns
people have raised about genetic engineering, and there
is a wealth of useful material in the reports andsubmissions made to them (United Kingdom Royal
Commission, 1989; New Zealand Royal Commission,2002). Reports have also been made by independent
organizations on the ethical issues (Nufﬁeld Council on
Bioethics, 1999a).
New technology has been a catalyst for our thinking
about bioethics, and has been a stimulus for research
into bioethics in the last few decades. Genetic engineering allows genes to be exchanged in a controlled manner
between different species. Since its invention in 1974, it
has conjured up images of hope and dread. Public
opinion is mixed. With the emergence of genomic
sequencing, we now have the DNA sequence of humanbeings, dozens of pathogens, and some disease vectors,
e.g. Anopheles gambiae (Holt et al., 2002; Morel et al.,2002). It is therefore not surprising that molecularentomology, the study of DNA and the proteins it
encodes in insects, is emerging as a serious scientiﬁc
approach for insect control (Atkinson et al., 2001;
Robinson et al., 2004).
The general approach has global support beyond the
dreams of individual scientists. The UNDP/World
Bank/WHO Special programme for Research andTraining in Tropical Diseases (TDR) has been developing the ideas of genetic control of insect vectors since a1991 meeting on use of genetically modiﬁed (GM)mosquitoes to replace disease vectors. TDR’s Steering
Committee for Molecular Entomology has outlined athree-pronged effort towards developing GM mosquitoes for malaria control, with similar approaches for
dengue fever and Chagas’ disease (TDR, 2002). First in
the process for each disease is to study host–parasite
interaction; second is to develop methods to transformthe vector; and third is to look at population ecology
and genetics and at how to replace a population ofharmful vector insects with a population of non-harmful
insects. Social factors need to be carefully considered(TDR, 2000; Macer, 2003).
While there is debate over the use of funds to combat
infectious disease using genomics and biotechnology as
opposed to implementing practical measures to curb
vectors and pathogens in the ﬁeld (Curtis, 2000), it is
widely agreed that the former approach will be a major
strategy in the future (Hoffman, 2000; James et al.,2001). A common way to insert DNA for genetictransformation of insects is to use transposons or viruses(O’Brochta and Atkinson, 1998). A number of papers inthis issue of the journal describe the advances that are
being made in this ﬁeld. Most attention has been given
to efforts to genetically transform insects in thelaboratory, and to test their behaviour before releasing
them into the environment. A mechanism that would
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D. Macer / Insect Biochemistry and Molecular Biology 35 (2005) 649–660

objective of these studies, except for the approach using
sterile insects.
Transposable elements can contribute to genome
evolution in nature, but the way they invade the genome
and are regulated remains one of the major questions in
population genetics. Effector molecules must be identiﬁed that will induce the anti-pathogen phenotype in thevector, and mechanisms are needed to drive the effector
system into the vector population (Beaty, 2000). The
latter step raises more ethical issues about the safety anddesirability of changing the entire vector population,and possibly related species.

3. Intrinsic ethical issues of genetic engineering
The conclusions of studies of ethical issues inherent to
the process of genetic engineering compared to traditional methods of animal and plant breeding, are thatthe only signiﬁcant differences in the process are themore precise control of genetic engineering and whether
the DNA involves cross-species gene transfer that does
not occur in nature (Nufﬁeld Council on Bioethics,
1999a; Comstock, 2000; Macer, 2003). One of the key
questions is whether there is an intrinsic value of genetic
integrity at an organism and ecosystem level thathumans should not change. In the attempt to prioritize
issues given in Table 1, it assumes that there are somepersons in the community that place intrinsic value uponnative fauna including insects. One way to consider thisquestion is to note that cross-species DNA transfer does
occur in nature between all species, even of different
kingdoms, and that the genomes of insects are subject togenetic ﬂux in nature. In this sense, because the DNAchange can be precisely designed, an actual targeted
genetic change through genetic engineering should besafer than a natural change because it is more undercontrol. Given the results of public opinion surveys thatﬁnd opposition to cross species gene transfer (Macer,
1994; Macer and Ng, 2000), if the DNA change is madeusing DNA within the same species entirely, then thisconcern can be removed. In this way of thinking there
may not be any new intrinsic ethical dilemma from themodiﬁcation of DNA structure in genetic engineering as
it simply mimics the natural ways organisms use tochange genetic structure. However, the scientiﬁc detailsof the targeting process, and the intentional nature areimportant for some persons.
Another argument used in these discussions concerns
the telos (purpose) of an organism. A teleologicalexplanation describes phenomena by their design,
purpose, or ﬁnal cause. Teleology is the branch ofmoral philosophy dealing with the cause and effect of anaction, the belief that there is purpose and design innature, and consequently, with the belief in the existenceof a Creator. There are concerns that the ability to alter

the telos of an animal has profound implications(Munro, 2001). If one believes that every organism hasa purpose, then the telos is an intrinsic concern, andgenetic engineering alters the telos or ‘being-ness’ of anorganism. However, it is debatable whether changes andcontrol through genetic engineering are signiﬁcantly
different from changes made by humans to animals andplants in farming and modern life. It is basically an issueof human control of nature, and there is debate over theextent to which humans should control nature (Reiss
and Straughan, 1996; Bruce and Bruce, 1998; Comstock,2000). If we consider this issue in a historical context, we
see that humans in many afﬂuent cultures havecontrolled nature in signiﬁcant ways, e.g. by concreteriver banks, irrigation and sanitation projects. However,
especially in some developing countries, limited resources have meant that control of nature has been less.
However, sociological evidence has found that a numberof people object to human control of nature, regardlessof whether it poses a risk (Macer, 1994).

4. Animal rights concerns
Another concern in ethics when discussing animals istheir capacity to suffer or feel pain. If insects do not feelpain or sense feelings, then the most prevalent ethicalapproach for animals would argue that there is nothing
intrinsically wrong in manipulating them (Singer, 1976).
However, if we consider the idea of making so-calledvegemals, animals that do not feel pain, we are still
manipulating life for human purposes without considering the interests of the animal (Macer, 1989). The
concern is that living organisms should not merely betreated as a means to the ends desired by humans.
Animal rights concerns about the genetic modiﬁcationof higher animals, e.g. mammals or birds, mean there ismore ethical concern about modifying sentient animals,
and more public concern, than if insect vectors wereengineered. In addition to so-called intrinsic concerns(pain, sentience, consciousness), there are also extrinsic
values placed on some animals by human society. For
example, some animals are national symbols and people
have greater concern about harming them. There arealso biodiversity concerns about endangered animals,
some of which are expressed in the Convention on
Biological Diversity.
While perhaps only followers of the Jain religion inIndia regularly refrain from killing insects that arehuman pests, there are still some people who may object
to killing mosquitoes. It is not known if manipulating
the insects so that they would not be a human pest
would be more acceptable to persons with theseecocentric world views than traditional methods ofinsect control that attempt to eradicate a whole insect
population.

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653

Table 1
Ethical priorities in community engagement over genetic methods of vector control
Expected beneﬁts

Negative concerns

Autonomy/justice(1) Prevent human disease.
(2) Less health and environmental damage
compared to insecticides.
(3) Less environmental change compared tocivil engineering approaches to vector
control.
(4) Development of social consensus processthat can be applied to other public policy.
(5) Emergence of informed choice andempowerment of individuals leading togreater personal responsibility for healthchoices.
(6) Sites of ﬁeld trials could be promised to be
beneﬁciaries of more permanent use.
(7) Modiﬁed mosquitoes would not be killed,
so the vector species would remain alive.

(1) Risk of damage to the environment from
ecological changes under ecocentric and/or
biocentric views.
(2) Possibility of horizontal transfer of thetransgene(s) to non-target organisms.
(3) Modiﬁcation of one ecosystem component,
altering the telos (purpose) of an organism.
(4) Indigenous persons place higher value on
the unmodiﬁed the native fauna.
(5) Human control of nature.
(6) Greater concerns over mobile genetic
elements compared to ‘‘sterile’’ vectors.
(7) Unforseen consequences on human health.
(8) Intellectual property issues.

(1) Regulatory systems for oversight need toﬁnd proper balance between expected
beneﬁts and precaution.
(2) Education materials and process, after a 2way development process.
(3) Whether consent is required from every
individual, including children.
(4) Options for those who refuse to be
involved, e.g. alternative insecticide
protection methods.
(5) Inequality in access to the modiﬁed
mosquitoes.
(6) Roles of external persons, e.g. activists,
media, NGOs, commercial actors.
(7) Payment mechanisms for trials, andinsurance for accidents.
(8) Sustainability of intervention.

Note: This summary table includes issues under the three headings in an order suggested for most endemic countries, with a component indigenous
population that has a non-industrialized and non-Western scientiﬁc worldview, but the priority for each community could be found after community
engagement, which may also identify new issues.

Those who subscribe to an ecocentric viewpoint mightargue that the ecosystem as a whole would beneﬁt froman intervention that left the mosquitoes in the ecologicalcommunity, with the elimination of the disease-causing
pathogen from the vector, if the alternative was
eradication of the vector species. In this case the total
number of species affected by this type of genetic
modiﬁcation of vectors would be signiﬁcantly less than
the number of species affected by use of insecticides(Macer, 2003). However, there are still those who believe
there should be no human modiﬁcation of the ecosystem. This actually should argue that there should be no
direct or planned modiﬁcation of an ecosystem byhumans, since human activity modiﬁes almost all
ecosystems, including those where humans are notdirectly a component member.

5. Consent from trial participants
Recognition of the ethical principle of autonomy
means that all participants need to give informed
consent to an intervention that has a reasonable riskof causing harm (Annas, 1989). There are signiﬁcantdifﬁculties in obtaining individual informed consent insome developing countries (Ekunwe and Kessel, 1984;
Angell, 2000; Alvarez-Castillo, 2002), but by adequate
investment of time and provision of suitable materials, it
should be possible to obtain informed consent fromindividuals at direct risk, even though the exact culturalinterpretation of the informed consent process may vary
between countries (Nufﬁeld Council on Bioethics,

1999b). There are risks of direct or indirect harm tohuman beings from the original pathogen-transmitting
vector, so a trial needs to be done to show that there isgreatly reduced risk of harm from the modiﬁed vector.
This is the whole purpose of the project to create
modiﬁed vectors, to reduce risks. Until a trial is made wecannot be sure that there will be no risk and that thewhole enterprise has been successful.
The risks may not just be those that arise directlyfrom the ability of the vector to carry the target
pathogen. There could be a negative impact on humanhealth by altering the behaviour of blood-feeding
insects. In the case of insects that cannot be conﬁned
to a particular population, whether they ﬂy or ﬂoat to
new places, notions of ‘‘human subject’’ and ‘‘informed
consent’’ need to be extended. There are basic ethicalissues involved in vector collection and studies in theﬁeld. Firstly, many such studies have relied on a
researcher waiting for the vector to land on a humanhost, and then capturing it hopefully before the vector
has transmitted the pathogen to the ‘‘bait’’. In fact, anyﬁeld studies in which human beings are exposed to thepathogens raise the question as to why some otherintervention is not used in that area.
The approach developed for population genetics
studies may be useful where the community and local
authorities are involved in the decision-making process.
Informed consent requires information to be provided,
so disseminating information about the plans andprogress of the project, and obtaining the consent ofany person potentially affected by the release oftransgenic insects, is important for the ethical conduct

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of research trials, whether or not national guidelines
require this, or even exist. Other lessons show us thatpeople who lack the means to express their preferences
may have been abused by the lack of individual orcommunity consent for research in anthropology (Fine,
1993; Kleinman, 1999) and epidemiology (Capron,
1991; Dickens, 1991; Gostin, 1991; Chee et al., 1996).
If a study involves humans, oversight by an ethics
committee or institutional review board (IRB) is
necessary. In an increasing number of countries, suchcommittees are established by law and are charged withcertain legal responsibilities, typically about the conductof research or clinical practice at local or national level.
An IRB is a group of persons from a range of disciplines
who meet to discuss the ethical issues of particularsubmitted procedures and review the beneﬁts, risks andscientiﬁc merit of the application. The IRB usuallyrequires that each human subject in a medical trial gives
informed consent to be involved in the project. Model
ethical guidelines on the establishment and procedures
for an IRB have been produced by an international
consultative committee for TDR (WHO, 2000). These
guidelines however are not sufﬁcient for the broad
question of how to obtain informed consent for a publichealth intervention involving thousands of persons
where the beneﬁts are not demonstrated.
Ethics or bioethics committees include groups ofpeople set up to adjudicate about bioethical matters. An
IRB is in a sense an institutional ethics committee, but atypical IRB works through a large number of applications and often excludes the broader social discussion
and representation that is seen in a regional or national
bioethics committee. There are also national variationsin the laws to deﬁne membership and scope of work, andterms used. The project to introduce transgenic insects
will need an ethics committee with a broad overview,and speciﬁc regional ethics committees to consider the
local issues.
To consider the issue at a local level, as required for
obtaining appropriate informed consent, it is essentialthat a local ethics committee (and/or IRB if associatedwith an institution) open to the communities involved isestablished. There are cultural differences in the way
informed consent should be taken (Levine, 2001;
Alvarez-Castillo, 2002). The accepted norm in international ethical guidelines is seen for example in themodiﬁed Helsinki Declaration (World Medical Association, 2000) and the draft Council for International
Organizations of Medical Sciences (CIOMS, 2001)
guidelines. In cases involving bilateral research collaboration, the most stringent ethical standards of the twocountries should be applied. This creates problems for
non-literate populations, and for populations whose
common sense social assumptions are different. It is
desirable that internationally agreed standards areapplied, and that there are few points of difference

between these standards even for simple clinical trials of
drugs. The ultimate decision procedure should be
decided by the local ethics committee, but international
consistency and guidance will be essential.
Although the control population for the study may
continue to face the same high risk of contracting thedisease, recent trends in research ethics debate whether
we can leave control groups without any treatment.
Therefore, ethically there may need to be some othervector reduction measures given if making any interventional study in an area. While those designing ethicalguidelines on placebo-controlled trials (e.g. Helsinki
Declaration) were thinking of placebo controls on
clinical trials of potential medical drugs, we can ask
the ethical question whether researchers have an
obligation to the local population to use the best
available means of disease control whenever they enteran area for a study. This practically means that, as well
as studying the new method, a researcher may ethicallybe compelled to also provide the best available provenalternative to the study population. There may be times
when the provision of the proven alternative to the areaof study alters the dynamics of the disease so that theresults of the vector ﬁeld trial differ from what theresults would have been had no established alternative
been provided.
Before and during the intervention, there may beprivacy concerns when questionnaires are administeredand personal data are stored. For public healthpurposes, it is essential that all information about
individuals involved is linked to other data, but toensure privacy, the data should only be identiﬁable to a
speciﬁc person by a coding frame that is not in acomputer linked to a network.
Children are therefore one of the targets of publichealth interventions, with presumed consent from thetherapeutic imperative that they want to be involved inprogrammes that will avoid disease. Some compulsory
vaccination programmes have faced criticism thatconsent is not obtained even from the surrogate
decision-maker, the child’s parents. In each family there
may several adults, and more children, which raises
questions of whether consent is required from every
individual. The local cultural norms need also to beconsidered. However, an appropriate mechanism may
be one in which the views of everyone of reproductiveage (let us call this the level of adult maturity) aregathered, and consent sought from these persons both asindividuals and as a family. The agreement and understanding of children in the community should be sought
through suitable materials. However, children should
not be exposed to direct risk from therapeutic trials
unless there is no alternative. In the case of a child living
in a community that was involved in a GM vector trial,
no direct risks to the human population would be
expected so the consent issue is not a major hurdle. On a

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more positive note, children in fact could be a very
powerful means to involve the community in a processof community engagement through schools. Sincechildren are at higher risk from many of the diseases
in question, they stand to beneﬁt more, and mostparents may want to be involved in the trial because of
the potential beneﬁt to their children rather thanthemselves.

6. Environmental risks and public consensus
The human community also needs to consent to theenvironmental risks of a trial as these represent potential
harm to other members of the biological community as
well as other members of the human community.
Globally people vary in the importance they ascribe to
the environment, or parts of it. Especially in areas wheremore traditional world views are found, we may see
greater value given to parts of the environment that areforgotten in the modern industrial mindset (Table 1).
We also see variations between persons in all cultures as
to their images of nature and what is life (Macer, 1994).
Some people are willing to sacriﬁce themselves for theenvironment. Examples such as the preservation ofsacred groves in India for thousands of years, evenduring times of severe crisis and human death (Gupta
and Guha, 2002), show that in some cultures almost all
people are willing to die rather than damage that part ofthe environment they cherish. This behaviour is often
linked to religious beliefs in the afterlife.
A variety of potential broader ecological, environmental and health risks are associated with the release of
GMOs. Environmental risks can be considered fromboth anthropocentric and ecocentric-based approaches.
The risks identiﬁed include the possibility of horizontaltransfer of the transgene to non-target organisms, andpossible disturbance of insect ecology (Hoy, 1995;
Nufﬁeld Council on Bioethics, 1999a). There have also
been concerns expressed in some cultures, e.g. New
Zealand, over the need to value the native fauna andﬂora, which is considered by many in the Maoricommunity to be something not to modify (New
Zealand Royal Commission, 2002). While human beings
cannot consent for other organisms to be modiﬁed, very
few persons suggest that any consent is required except
for possibly sentient animals.
One of the main concerns of releasing GMOs isenvironmental risk (FAO, 2001; Aultman et al., 2000).
This risk has been successfully controlled in over 10 000
international ﬁeld trials of GMOs (USDA, 2002). Whilst
the methods used for monitoring ﬁeld trials are argued
to be inadequate by those campaigning against GMOs,
to date there has not been a signiﬁcant adverse eventfrom GMO release for the health of any non-target
organism, including humans, in the ecosystem (Com-655

stock, 2000). New ethical issues about GM arthropod
vectors and their symbionts and/or pathogens should be
subject to extensive open discussions and forums.
Any risks to the agricultural systems of ruralcommunities also require assessment, as animal diseases
transmitted by vectors are important to farming
families. In addition, there may also be risks to wild
animals in surrounding areas, which in some ecocentric
environmental views have more intrinsic rights to be left
undisturbed than farm animals (Rolston, 1994). This
calls for broad ecological understanding of the impact,beyond public health. There is also the possibility for
GM vectors to spread to areas beyond the initialexpectations, which needs to be considered whenplanning the geographical extent of information andcommunication programs.
In the year 2001, the ﬁrst US ﬁeld test of a GM pinkbollworm, a cotton pest, was conducted. It followed
very soon after the development of methods to transform the bollworm (Peloquin et al., 2000), suggestingthat some researchers may go to ﬁeld trials within 1–2
years of transforming an insect species. About 3600
moths were studied in a ﬁeld enclosure of more than one
hectare, after being modiﬁed with green ﬂuorescentprotein (GFP) as a tracing gene. This was based on theidea that a lethal gene can be introduced to kill theprogeny of both engineered moths and moths whichbreed with them (Dalton, 2001). In the short term
however, the presence of GFP means that the sterile
insects can be readily distinguished in the ﬁeld. This
itself is a signiﬁcant advantage because currently farmers
may have to release up to 60 times the number of sterile
insects in the ﬁeld to control bollworm, but thesenumbers might be brought down 12-fold if the sterile
insects can be easily identiﬁed in the ﬁeld. This type oftrial had an important consequence of preparing
regulatory systems for oversight of GMOs/LMOs, but
still most countries in the world have not establishedsystems for oversight of GM insect ﬁeld releases (Pew,
2004).
Although there have been numerous public opinion
surveys on the release of different GMOs, there havebeen few surveys asking people their views on introducing GM vectors or pathogens for disease control. One
general feature of the surveys is that GM plants are
considered less threatening than GM microbes, animals
and humans. In a 2003 national sample in Japan, one
third thought it would be acceptable to use genetic
engineering to make mosquitoes unable to be a vector
for human diseases like malaria or Japanese encephalophy, and only 16% said it would not, while half said
they did not know. There was 54% approval forenvironmental release of mosquitoes that do nottransmit human disease, which is the same as the
support for release of GM disease resistant crops, with
19% disagreeing (Inaba and Macer, 2003).

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Although knowledge is important for acceptance ofbiotechnology, it is not a predictor of acceptance. In
surveys of scientists and the public in Japan in
1991–2000, for example, well-educated scientists were
often just as sceptical of biotechnology as the generalpublic, and shared the same types of concerns (Macer
and Ng, 2000). The failure of the government authorities
in public health has led to higher public trust in NGOs,
including environmental groups. The media has also
disproportionately reported negative aspects of genetic
engineering because these appeal to people (Durant,
1995). Thus the late 1990s saw a dramatic drop in public
support for biotechnology in every country surveyed. It
is therefore important that scientiﬁc knowledge be
accurately shared with all, that this process be open,
and that all opponents are involved in discussion.
If the trial covers an area with a local population of
100 000 persons or more, it is unrealistic and unlikelythat informed consent can be given by all people in thearea. There will always be some people who are against
any proposition, no matter how much others value it,
but the opponents cannot be moved from their houses
for the period of the trial. So a procedure that is neither
paternalistic nor paralytic needs to be developed. Afterthe process of consultation and dialogue to seek
informed consent, there still needs to be a procedure
to supply relevant information to all persons in the area
so that the minority who disagree with the trial have theoption to leave. In developing countries, many may notrealistically be in either a position to achieve social
consensus or for persons to actually leave the area.
Other options may be to provide additional insecticide
resources to households that object to the study and are
afraid of the GM insects presence. The mechanisms forsocial consensus in biotechnology are not well understood in the afﬂuent countries that have been debating
GMOs, and even less is known in developing countries.
Public opinion studies suggest that people may responddifferently to theoretical and real situations.
Recognizing the autonomy of people as a groupdemands that we apply the consent model to more thanisolated individuals. The introduction of GM vectors
and pathogens requires community consent, so a process
for seeking group consent needs to be developed foreach community (Kleinman, 1999). The question ofwhether every citizen has to consent to public healthinterventions is not a new one (Kass, 2001), but with thecurrent social transition from a paternalistic society to
informed consent and informed choice, this key concern
is appearing in all societies, although at different speeds.
Any initial trial may be subject to the philosophy ‘‘notin my backyard’’. Socially powerful persons are
generally more effective at preventing trials they
perceive to be risky in their area, or, conversely, atattracting social resources towards themselves and awayfrom weaker persons in the community. Ethically it isimportant that risks and beneﬁts are shared equally, andone way to ensure this would be a commitment to the
local community that, if the trial is successful, the fullscale intervention would include them from the beginning. In this way, any risks borne by a local population
would subsequently be rewarded by that population
being the ﬁrst group to beneﬁt from the knowledge
gained when the full-scale safe and effective control
programme is implemented. The ﬁeld trial must therefore come with a commitment to the local communitythat ﬁnancial resources will be available and thatsustainable use of the control tool will be affordable.

7. Ethics of technology choices
Issues include the ethics behind research into, andlater ﬁnancing of, technological products that attemptto ‘‘ﬁx’’ a problem rather than invest in increasing theecological knowledge base to ‘‘prevent’’ the problem.
There is considerable preference for deterministicscience over ‘‘softer’’ educational systems like ﬂexible
learning. It is clear that not all local communities will
share the modern scientiﬁc world view that technicalhealing is better for them, so there needs to be ﬂexibility
in the approaches available to eradicate disease. In thepast, paternalistic interventions were taken on the behalfof citizens; however, civil rights movements haveempowered people to take these decisions themselves.
A number of ethical issues have been raised ininternational debates over the morality of patents, andthere have been strong calls against the patenting of
medical innovations. Laws on intellectual property vary
between countries, despite attempts to harmonize theselaws among industrialized countries and members of theWorld Trade Organization (WTO). A number ofdeveloping countries are not members of the WTO,
and often the major controversies over whether acountry will join WTO is related to intellectual property
rights (IPR).
Practical guidance for ethics committees needs to beclariﬁed on public health interventions. One key
problem is identifying who is speciﬁcally at risk, andwhat the particular risk is. In vector release studies,everyone in the area may be at risk. These complex
questions are made more manageable through breaking
down the concerns people have into manageable areas.
Deﬁning a minimum standard of protection for research
participants in trial and control populations for GMO
interventions is the key point. This issue is not speciﬁc to
GM vectors and pathogens, but it is crucial to consider
the beneﬁt/risk equation.
Most concerns can be the subject of better information and education. Gathering satisfactory scientiﬁcdata by conducting ﬁeld trials, and understanding
ecological issues (Scott et al., 2002), are the main

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criteria required prior to release for most people. The
remaining concern, and one which is also found inscientists as well as the public, is that genetic engineering
is somehow unnatural. This is an issue that needs greatersocial discussion. However, if presented with the threatof contracting disease, most people have few concerns
about using other ‘‘unnatural’’ remedies such as
pesticides and medical drugs. Given that most mosquitoes do not transmit disease to humans, it is, arguably,
not unnatural to change a mosquito that does transmit
diseases into one that does not. There is a need for
public opinion studies in the communities before therelease, during the process of community engagement,
and after the study, if we wish to really understand theopinions and concerns that people have.

8. Regulation
The internationally accepted principles of risk assessment for GMOs take into account: relevant technicaland scientiﬁc details of the recipient or parentalorganism, the donor organism(s), the vector, theinsert(s) and/or characteristics of modiﬁcation, theGMO, and the methods for detection and identiﬁcationof the GMO including speciﬁcity, sensitivity andreliability; as well as information relating to intended
use, information on location and geographical, climaticand ecological characteristics, and the foreseen healthimpact of the intervention (Macer, 2003). The ethicalprinciple of non-maleﬁcence is the underlying basis forattempting to avoid harm and the regulation of humanactivity.
What is a particularly relevant point in the development of GM insect vectors unless it is based on sterile
insect methods (Alphey et al., 2002; Robinson et al.,2004), is that in order for a vector programme to be
successful, the modiﬁcation must spread throughout thewild population of a vector. This means that deliberate
infection with the transgene may be the target of
introducing the GMO. In order to deﬁne the parameters
associated with the speed and extent of spread of thegenetic modiﬁcation under real conditions, extensive
trials are necessary. Some vectors may transmit morethan one pathogen, so any intervention programme may
have complicated effects on the distribution of disease.
Concern over possible safety and environmental risks
raised by biotechnology prompted the WHO, United
Nations Environment Programme (UNEP) and United
Nations Industrial Development Organization (UNIDO) to identify and study the various safety issues
involved. As a result, a UNIDO/UNEP/WHO/FAO Ad
Hoc Working Group was formed in 1990 to work out
practical guidelines through a series of consultations
with international experts and scientists from developing
countries. In 1991, the UNIDO/UNEP/WHO/FAO

657

Working Group on Biosafety brought out a Voluntary
Code of Conduct for the Release of Organisms into theEnvironment. The code sets out general principles and aframework and guidelines to be adopted at national,
regional and international levels to facilitate the safe
application of biotechnology. The scope of this document covers ‘‘GMOs at all stages of research, development, use and disposal, while focusing on release to theenvironment. It covers, but is not limited to, GM plants,
animals (including for example, insects, molluscs andﬁsh), and microorganisms and their products and byproducts’’ UNEP, 2002.
The International Centre for Genetic Engineering andBiotechnology (ICGEB) provides assistance in biosafety
training for the development of genetic engineering inmany countries (ICGEB, 2002). Some issues also relate
to the proposed Code of Conduct in Biotechnology
being developed under the Commission on Genetic
Resources for Food and Agriculture (CGRFA). UNDP
(2001) and FAO generally support the development ofgenetic technology while considering the beneﬁts andrisks of the organisms. The capacity of countries toestablish committees to adequately address ethical,
social and scientiﬁc concerns needs to be strengthened.
The Scientists’ Working Group on Biosafety of theEdmonds Institute (1998) in Washington, DC, USA,recommended that ﬁeld trials of vectors geneticallyengineered to reduce disease should be small scale interms of the area of dispersal of the vector. ‘‘In the caseof an anti-malaria or anti-dengue intervention, such aﬁeld trial could involve a single village or an isolated
cluster of adjacent villages. No large-scale release should
be attempted until the effectiveness is shown in the ﬁrst
trial’’. Thus, while there is general international
consensus in the UN system that selected use of GMOs
should proceed, there are groups within society that
continue to be cautious. There are also countries whose
political regimes do not accept GMOs, and these
attitudes depend on political elections, including theprinciple of democracy. National sovereignty should ofcourse be respected, but GM vectors may spread beyond
a national border.
The Cartagena Protocol on Biosafety to the Convention on Biological Diversity is an advance informed
agreement procedure on the safe transport, handlingand use of LMOs resulting from modern biotechnologythat speciﬁcally focuses on transboundary movements of
LMOs. The parties to this protocol agreed to ensure that‘‘the development, handling, transport, use, transfer andrelease of any LMOs are undertaken in a manner thatprevents or reduces the risks to biological diversity,
taking also into account risks to human health’’. It wasalso noted that ‘‘the parties are encouraged to take into
account, as appropriate, available expertise, instruments
and work undertaken in international forums withcompetence in the area of the risks to human health’’

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D. Macer / Insect Biochemistry and Molecular Biology 35 (2005) 649–660(CBD, 2000). In the Cartegena Protocol, ‘‘a living
modiﬁed organism means any living organism thatpossesses a novel combination of genetic material
obtained through the use of modern biotechnology.
Modern biotechnology means the application of either
in vitro nucleic acid techniques, including the recombinant DNA and direct injection of the nucleic acid into
cells or organelles, or the fusion of cells beyond thetaxonomic family, that overcome natural physiologicalreproductive or recombination barriers and that are nottechniques used in traditional breeding and selection’’.
This deﬁnition of a LMO is now accepted in international law in general because of the Protocol. The actual
term ‘‘LMO’’ is still not as widely used as ‘‘GM
organism’’, the term that has been used for two decadesin academic and media debates.
One useful development of the Cartegena Protocol
umbrella is the establishment of biosafety clearing
houses, which are contact points in each member
country. The Protocol also includes risk assessment
and risk management once agreement is reached, as well
as development of capacity building in biotechnology
research. Many developing countries do not have theeconomic or scientiﬁc capacity needed to examine theproducts of modern biotechnology (Chinsembu andKambikambi, 2001). Information related to GM vectors
should be linked to the same biosafety clearing houses.
The United States Department of Agriculture(USDA) has reported the results and approval procedures for six trials of GMOs. These include ﬁeld trials oftransgenic mites, nematodes, ﬂies, spruce budworm, andpink bollworm, as discussed above (USDA, 2002). The
ﬁeld trials of transgenic nematodes and predatory mites
were intended to study the risk to the environment ofthese transgenic organisms and the stability of thetransgenes under controlled conditions. The genetic
modiﬁcations did not affect infectivity of the nematodes,
however the ﬁeld performance of the transgenic mites (inFlorida) was dramatically different to in the laboratory
due to differences in relative humidity, and the ﬁeld
experiment was terminated after 3 weeks because
populations of both predatory mites and prey spider
mites declined rapidly. Few individuals in the population contained the transgene. At the end of these ﬁeld
trials, all the transgenic organisms and hosts weredestroyed. The American Committee of Medical Entomology has also produced guidelines (ACME, 2002).

values on risk assessment. A universal minimal standardof risk assessment applicable to disease vectors needs tobe deﬁned, as diseases cross national and continental
borders.
Before ﬁeld release of transgenic insects, researchers
must assess all the scientiﬁc and social issues associatedwith GM vectors and develop safety precautions toaddress potential risks. The scientiﬁc and social risks
should be minimized through careful design of thevector system, relevant laboratory experience, andcareful choice of the site including considering appropriate social and cultural factors. Even if there are notperceived to be any realistic risks, a procedure for theirevaluation should be set up so that new information canbe gathered and interpreted. This procedure may involve
establishing a specialized ethical review committee under
the auspices of an international body such as TDR tooffer advice to researchers on the ethics of projects.
There should be prior environmental, medical andsocial studies for site selection, and the most appropriate
site chosen on the basis of these data. Information
should be exchanged as broadly as possible with
community leaders, members of the local community,
and the mass media. Consent should be obtained fromthe communities involved. Speciﬁc mechanisms to
obtain individual and group consent need to be
developed for public health interventions. A contingency plan for aborting a ﬁeld trial needs to be
developed.
Commitment to the local communities involved inﬁeld trials should be made such that they will be the ﬁrst
beneﬁciaries of more permanent use of a GM vector
should results indicate that this is appropriate. Intellectual property concerns should not be barriers to
implementing public health measures using GM vectors
or their symbionts and/or pathogens. Prior negotiation,
including possible involvement to allow access to thelatest technology, is preferable to confrontation. The
data should be made available to all in order to beneﬁt
from global expertise and develop international consensus. There is a need for an ongoing and active processof ethical analysis, through a variety of forums, that will
provide us with the conclusions about where it is ethicalto conduct these type of studies.
Ethically, we have to consider what are core ethicalvalues for modiﬁcation of nature for human needs. The
ethical principle of beneﬁcence demands action toeliminate hunger and disease. We must do this while
preserving the environment for the future.

9. Conclusion
There are a variety of ethical issues that are raised
from the use of GM insects (Table 1), but the mostchallenging may be the process of informed consent forindividuals and communities. Each community orsociety needs to be given a chance to set consensus

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