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On December 21, 2010, 6000 genetically modified (GM) mosquitoes were released in an uninhabited forest in Malaysia. The purpose of the deliberate release was a limited “marked release and recapture” (MRR) experiment, a standard ecological method in entomology, to evaluate under field conditions, the flight distance and longevity of the sterile male Aedes aegypti strain OX513A (My1), a GM strain. As with any other GM technologies, the release was received with mixed responses. As the scientific community debate over the public engagement strategies for similar GM releases, dengue incidence continues to rise with a heavy toll on morbidity, mortality and healthcare budgets. Meanwhile the wild female Aedes aegypti continues to breed offspring, surviving and evading conventional interventions for vector control.

This paper describes the extensive biosafety review process and stringent regulatory protocols at national level and public engagement before the limited MRR field trial. Our experience has shown that public engagement is an important component of field releases to provide information, receive feedback on public perceptions and gain public trust through the transparency of the process.

Research background

  1. Top of page
  2. Research background
  3. Biosafety review process
  4. Public engagement
  5. Discussion
  6. Acknowledgements
  7. REFERENCES

Aedes aegypti is well known as a vector of dengue and chikungunya viruses. The Aedes aegypti OX513A (My1) strain was developed by Oxitec Ltd., a spin-off company founded by the University of Oxford, UK. The strain contains a lethal genetic element that is repressed during laboratory rearing by the addition of tetracycline[1]. This repressible system represents a built-in biocontainment, preventing the GM mosquito from establishing in the wild. The OX513A (My1) strain has been extensively studied for more than 60 generations in the Institute for Medical Research (IMR), Malaysia. The origin of this strain was a cross between a transformed Rockfeller strain and a Malaysian strain of Aedes aegypti. These experiments were carried out at the Medical Entomology Unit of IMR. This laboratory started functioning early in 1902, pioneered by the British to study the taxonomy and control of malaria vectors. From its modest beginnings, the unit is now the World Health Organization (WHO) Collaborating Centre for Ecology, Taxonomy and Control of Vectors of Malaria, Filariasis and Dengue, working closely with the Vector-borne Diseases Division of the Ministry of Health, Malaysia to enable health authorities to utilize research findings to control and eradicate vector borne diseases in Malaysia.

Aedes aegypti is well known as a vector of dengue and chikungunya viruses

Experiments on OX513A (My1) were carried out in an arthropod level 2 containment laboratory (ACL-2) and in a semi-field ACL-2 house to study physical and biological traits including male mating competitiveness. The OX513A (My1) strain has the ability to mate with female wild type Aedes aegypti and produce offspring that will die as larvae or pupae. The experiments conducted by IMR indicated that OX513A (My1) showed promise as a new vector control tool, that is, circumvents the adverse effects of chemical pesticides [2–4]. While the female mosquito bites humans for a blood meal, male mosquitoes do not have the anatomical features to feed on blood. Therefore, a limited MRR under field conditions was proposed to evaluate the dispersal patterns and longevity of the GM mosquitoes in the environment, using males only [5]. Permission was sought from regulators for a limited release of OX513A (My1), as the information that could be gained was considered an important prerequisite for any subsequent larger-scale evaluation of the strain and technology for vector control in Malaysia.

Biosafety review process

  1. Top of page
  2. Research background
  3. Biosafety review process
  4. Public engagement
  5. Discussion
  6. Acknowledgements
  7. REFERENCES

The Malaysian Biosafety Act was passed in 2007, as part of Malaysia's obligations to both the Cartagena Biosafety Protocol (CPB) and the Convention of Biological Diversity (CBD) to regulate the import, export and handling and release of living modified organisms (LMOs) and products of LMOs. There are essentially two regulatory processes: approval and notification. Notification to the National Biosafety Board (NBB), who is the competent authority, is required for contained use in the laboratory, i.e. all R&D activities involving modern biotechnology, import for contained use and export of LMOs. A certificate of approval, issued by the NBB is required for the release and importation of LMOs and products of LMOs. The law also requires mandatory risk assessment and risk management of risks that may be caused by LMOs as well as emergency response plans from researchers and proposers of modern biotechnologies to ensure safe and responsible use. NBB makes its decision based on recommendations by the National Genetic Modification Advisory Committee (GMAC), policy and public considerations.

Importation of the OX513A (My1) mosquito and eggs, testing in quarantine conditions and testing in a confined field house was preceded by appropriate regulatory approval from the competent authorities at the time, including the GMAC. IMR's Institutional Biosafety Committee (IBC) reviewed the research proposals, the biocontainment aspects in the design of the semi-field house and the biosafety practices in the ACL-2 laboratory used for rearing these mosquitoes. The IBC received the application for the field trial in 2008. The expert scrutiny by the IBC and the Institutional Medical Research and Ethics Committee (MREC) and continuous improvement process took more than a year before the application for a limited MRR trial was submitted to the NBB. The application form used in the submission provided comprehensive details of the LMO including the gene construct, methodologies, stability and safety with a dossier of research data and publications from containment experiments comparing the OX513A (My1) and wild type Aedes aegypti.

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The principles of risk assessment used by the expert GMAC panel followed closely the Roadmap for Risk Assessment of LMOs, specifically the additional guidance to conduct a Risk Assessment on Living Modified Mosquitoes, according to Annex III of the CPB produced by the Ad Hoc Technical Expert Group (AHTEG) on Risk Assessment and Risk Management of the Convention on Biological Diversity [6]. A Risk Matrix was developed identifying potential hazards, and then adding a value/rank for the likelihood of each hazard as well as its consequences. The GMAC assessment also involved meetings with the applicants for exhaustive information exchange. For their assessment the GMAC also reviewed data from the Cayman Island GM Aedes aegypti mosquito release.

Public engagement

  1. Top of page
  2. Research background
  3. Biosafety review process
  4. Public engagement
  5. Discussion
  6. Acknowledgements
  7. REFERENCES

Public consultation is mandatory in processing any application for release under the Malaysian Biosafety Act. Public announcements were made in two national newspapers in two major languages, twice with a gap of two weeks. At the first announcement of the field trial in the national newspaper, the National Biosafety Department uploaded information (Fact Sheet) about the proposed field trial and called for input from the public on the National Biosafety Department website (www.biosafety.nre.gov.my). As it was the first time public consultation was done in Malaysia for release of LMOs, the Department of Biosafety took the initiative to write to nine environmental non-governmental organizations (NGOs) inviting comments on the proposed field trial. Input from local as well as the global community regarding the field trial were received for a period of thirty days from the date of the first announcement.

In order to have a comprehensive assessment, GMAC also requested for meetings with scientists from NGOs to obtain their views on the proposed field trial. One group, the Third World Network (TWN) provided feedback on several issues, which, where appropriate, were taken into consideration by GMAC in the risk assessment process.

The applicants further took their own initiative to disseminate relevant information about the proposed field trial to the local community nearest to the release site. Posters were distributed in four major languages, Bahasa Malaysia, the national language, English, Mandarin and Tamil. Permission was also sought from local councils and community leaders regarding the field trial and site selection. A scientific forum was conducted at the Malaysian National Academy of Sciences and the public were invited to this forum. In addition, risk communication workshops were conducted for scientists, project managers and health professionals in selected districts to prepare them as spokespersons for the project. The applicants together with the local authorities briefed the residents in two public talks in two languages, Bahasa Malaysia and Mandarin.

Thirty-two responses were received by the National Biosafety Department during the consultation from NGOs, private companies and also layman or the general public. Assessment of the feedback from the public engagement could be divided into four categories: information seeking, positive, neutral and negative. Some of the feedbacks were from individuals who wrote in or called to seek information about the field trial. There were individuals and groups who fully supported and welcomed the proposed field trial. These were individuals who were concerned with the alarming rise in dengue cases in Malaysia and were open to try new methods to control it. Some supported the field trial if issues raised by experts were addressed by applicants; many groups though were neutral, leaving the decision to the expert review. A few individuals and groups were concerned with the use of the GM technology and cited alternative methods for dengue control. A few objected to the field trial due to uncertainties, being unfamiliar with the technology and its impact to the environment. Information from local as well as the global community regarding the field trial was submitted to the NBB to facilitate the assessment and final decision on the approval process. After the decision was made by the regulators to approve the field trial with terms and conditions, the basis of the decision and all issues and concerns raised were consolidated into a fact sheet and uploaded in the National Biosafety Department website. A press conference was also arranged by the Biosafety Department to announce the NBB's decision and provide information to the public on the approved field trial. Subsequent to the approval, the field trial was conducted in a forested land in Benteng District, in the State of Pahang [7]. A summary of the biosafety regulatory process before approval of the limited MRR field trial is shown in Figure 1.

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Figure 1. Genetically modified mosquitoes: from laboratory to field. Flowchart showing a summary of the biosafety regulatory process, public engagement and approximate time frame before the deliberate release of sterile male genetically modified Aedes aegypti mosquitoes in a limited MRR field experiment.

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Discussion

  1. Top of page
  2. Research background
  3. Biosafety review process
  4. Public engagement
  5. Discussion
  6. Acknowledgements
  7. REFERENCES

Applicants and regulators in Malaysia were aware of the importance of public engagement for the field trial involving the release of the sterile male Aedes aegypti strain OX513A (My1). For the applicants, public engagement was important to gain public trust through dissemination of information about the objectives of the field trial and other relevant issues including dengue transmission, dengue morbidity data and present strategies for vector control. Public consultation was also linked to compliance with regulatory requirements for approval. For the regulators, the feedback from the public strengthened the assessment and review process, although it involved a continuous and lengthy process of extracting additional data from applicants. Our experience showed that despite executing a well planned transparent public engagement process that was relevant for a release in an uninhabited site, there was still some dissatisfaction from some community groups.

Public engagement was important to gain public trust through dissemination of information about the objectives of the field trial

Scientific groups have criticized the shortcomings of the public engagement processes undertaken for field trials of GM mosquitos. The Malaysian field trial has also been compared with the Cayman Island field trial, conducted in 2009, for lack of transparency and public engagement. The Cayman Island field trial involving a similar strain of Aedes aegypti mosquito, OX513A (My1), constituted the first known large scale release of GM mosquitoes in the world. Unlike Malaysia, which has a comprehensive biosafety legislation for regulating LMOs, the Cayman Islands does not yet have an enacted legislation relating to the deliberate release of genetically modified organisms. The open field trial was carried out by the Cayman Islands' Mosquito Research and Control Unit, which has a mandate from Parliament to conduct research activities for mosquito control as enshrined in the Mosquito (Research and Control) Law (2007 Revision) [8]. Malaysia is a Party to the CPB and under Article 23 of the CPB, Parties are obligated to have a public consultation before any release of LMO into the environment. Consistent with this provision, it is a mandatory requirement under Section 14 (c) of the Biosafety Act to get public input in the decision making process for any release activities. Applicants also require prior consent from the relevant state government before approval is granted for undertaking any open field release of LMO.

The terms “public engagement” and “public consultation” refer to different processes

Our knowledge and best practices on the public engagement process have evolved from important concepts in community development, anthropology, sociology, environmental health and ethical guidelines in public health [9, 10]. This evolving process was seen as an important move to create a more democratic and deliberative approach to communicating science and medicine and build stronger links between professional scientists, the lay public and other communities through greater openness and engagement. The terms “public engagement” and “public consultation” have often been used interchangeably, but they refer to different processes. Engagement is generally raising awareness of science and the issues it raises among the public. Consultation, that is consulting the public on issues, contributes to, and feed into some decision making process. For the consultation process, it would be more appropriate to engage focus groups and relevant administrative authorities who have the necessary capacity and are able to act in the best interests of the populations they serve.

There were some concerns that applicants did not get individual informed consent from communities at the trial site. Individual informed consent is a process aptly used in research when individuals partake actively on a one-to-one basis for example in clinical drug or vaccine trials. The field trial was also reviewed by the National Medical Research Ethics Committee. It was widely acknowledged that it is impossible and impractical to get approval from every individual when the research was not intrusive and involved a field release in an uninhabited area.

The fact remains that due to the complexity of this process, we do not have a clear mechanism or guideline for effective communication and outreach especially for health-related projects. This is further complicated by negative perceptions in some quarters over the use of GM technology. The development of effective communication messages should explain the risk and benefit of the GM technology for interruption of dengue transmission and communicate findings of the field trial to the public. Various prevention strategies were used by vector-borne disease control authorities to reduce mosquito burden but despite these strategies the alarming rise of dengue cases and mortality remains a major problem. A likely solution would be an integrated vector control strategy and to review new strategies such as transgenics but these methods have to be evaluated in the field for efficacy such as the field trial carried out in Malaysia. In the public health context, therefore, risk benefit analysis should form an integral part of the GM regulatory framework [11]. If the scientific evidence from the risk benefit analysis demonstrates an expectation of significant disease reduction with low ecological risks, the precautionary principle in the GM regulatory framework should not impede meaningful benefits for human health. However if human value cannot be determined or ecological risks are high, caution should be exercised in the approval process of future releases [12].

An international guidance on public engagement would definitely assist researchers and regulators of future releases with a comprehensive communication plan that ensures transparency and a mechanism to respond to feedback following public consultation. In the meantime, countries planning GM releases should establish a working group to develop models for effective stakeholder or community engagement from an early stage. The IMR learned valuable lessons in the public engagement process from our personal experience as well as the successes and failures of open field releases conducted in Cayman Islands and Brazil.

Countries planning GM releases should establish a working group to develop models for effective stakeholder or community engagement from an early stage.

Brazil is the third country that conducted a suppression trial involving the large-scale release of the Oxitec strain of Aedes aegypti mosquitoes. The project was carried out by the University of Sao Paulo and permission was granted by Brazil's National Biosecurity Technical Commission (CTNBio) in December 2010. Scientists involved in the project reported an overwhelming positive support for the project from all sectors of the community. IMR organized an intensive biosafety workshop on GM mosquitoes in September 2011 and invited Brazilian scientists to share first hand information on the public engagement process. The IMR is working closely with regulators and stakeholders towards effective community engagement from lessons learnt in the open field release in the uninhabited site. Although approval with terms and conditions included release for a limited MRR trial in an inhabited site, IMR has postponed the project, until an improved, effective communication plan can be implemented. The communication plan proposed would adopt a proactive approach before any trial begins with advertorials, engagement of journalists, media interview and distribution of flyers from door to door at the trial site. The relationship and trust would also be established through meetings with residents allowing specific concerns on GM vector control to be addressed and for direct feedback. This will ensure a more systematic and coordinated public engagement and communication plan for any future releases involving GM mosquitoes.

Acknowledgements

  1. Top of page
  2. Research background
  3. Biosafety review process
  4. Public engagement
  5. Discussion
  6. Acknowledgements
  7. REFERENCES

The authors would like to thank the Director General of Health and the Director General of the Department of Biosafety, Ministry of Natural Resources and Environment for permission to publish this paper.

The authors declare no conflict of interest.

REFERENCES

  1. Top of page
  2. Research background
  3. Biosafety review process
  4. Public engagement
  5. Discussion
  6. Acknowledgements
  7. REFERENCES
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