RA&RM of Living Modified Mosquitoes

Dear Forum participant,

The Discussion Group on “Risk Assessment and Risk Management of Living Modified Mosquitoes” is now open for discussions at http://bch.cbd.int/onlineconferences/mosquitoes_ra.shtml . The objective of this discussion is to provide input to the AHTEG Sub-working Group (SWG) for the preparation of a guidance document on this topic.

An initial outline of the guidance material being prepared by the SWG is attached to this message (the attachment is visible only in the Forum website on the link above). This document provides a basis for the discussions. An introduction to the work of the SWG as well as guiding questions and suggested reading materials are also available to assist in the discussions. The guiding questions are also copied below for ease of reference.

You may reply to this posting or create a new “thread” of discussion by email following the appropriate link below, or directly from the online Forum in the link above. In order to post your contribution through the online Forum, you must be signed-in to the BCH.

Your contribution is very important. We are looking forward to your views on this topic.

If you need any assistance, please do not hesitate to contact us at: riskassessment.forum@cbd.int .

Thank you and best regards,
Manoela

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** Guiding questions **

The following questions were prepared to assist in the discussions on this topic:

· What should be the focus of the SWG-LMM?
  a) all LM mosquitoes known to cause serious human diseases or
  b) a specific mosquito specie causing a specific disease or
  c) specific trait/genetic modification?

· What existing guidance documents are useful examples and can help in identifying specific approaches for the risk assessment of LM mosquitoes?

· What are the potential risks or adverse effects the risk assessment of LM mosquitoes should focus on?

· Given the current status of LM Mosquitoes development, what uncertainties should be addressed?

The categories of GM mosquito strategies that are being considered should be expanded. The existing terminology used for the strategies has led to misunderstanding, been widely promulgated in the literature, and misinterpreted even by fairly well-informed individuals. I will suggest some alternative names in a separate posting.

Using the existing terminology, two categories are listed in the Initial Outline: (1) population replacement strategies and (2) population suppression.

POPULATION SUPPRESSION STRATEGIES

This category of strategies is correctly named “population suppression.” These are refinements of the sterile insect technique (SIT) which has been successfully (and safely) applied to several other insects and has proven effective in a few trials against mosquitoes. The Outline Document mentions one strategy that properly belongs in this class, RIDL, but I would like to provide a more comprehensive list. Three improvements to SIT are anticipated: female elimination, sexual sterilization and marking.

Example 1: Release of Insects carrying Dominant Lethals (RIDL [1]). This technology creates insects which are viable, or whose progeny are viable, only under specific conditions provided in the laboratory or factory and which are not found in the natural environment. While in some instances a gene is introduced by mating into wild populations, the individuals that receive it die. The transgene is therefore genetically contained. The transgene however has a very high fitness penalty so that it is expected to be rapidly eliminated from the target population.

Example 2: Conventional SIT with transgenic sex separation. Only male mosquitoes can be released since females are able to transmit disease and are a biting nuisance. Transgenic mosquitoes have been produced for this purpose. Several species of mosquitoes have been produced which carry a marker (DsRed) and a beta-tubulin gene that causes eGFP expression in the testes [2]. Males can be selected using a modified flow cytometry device called COPAS (Union Biometrica). It is anticipated that these male mosquitoes would be sexually sterilized by the conventional means of irradiation. It should be noted however that irradiation sterilization that is used in SIT is not completely effective. Therefore, it is likely that the marker would be transmitted to wild progeny.

Example 3. A variation of RIDL exists which allows female elimination by sex-specific expression of a female lethal gene [3]. Released males also carry this gene and, if not sterilized by some means, can confer this gene to their progeny, females of which also die.

Example 4. Transgenic augmentation of classical SIT has been accomplished in which a transgene provides a definitive marker for the released material. This can be invaluable when the presence of even one wild insect may require extensive control measures in response. This is the first use of transgenesis that has been applied in the field releases of the pink bollworm (Pectinophora gossypiella). Because conventionally marked moths are difficult to distinguish from wild type, the fluorescent marker provides unequivocal marking. Numerous strains of mosquitoes have been created that would be useful for this purpose, but I am aware of no plans to release them. However, the strain described in Example 2 above provides marker function in both the released males and the sperm of the females they mate.

Example 5. Homing endonucleases (HEGs [4]) have been used to create male sexual sterility [5] by targeting sequence on the X chromosome. Like RIDL, the transgene is contained in nature by the sexual sterility.

POPULATION REPLACEMENT STRATEGIES

While other ideas have been put forth, the following are under active investigation and molecular tools are available to create them.

Example 1: Homing endonucleases could be used in a strategy of this type in addition to the suppression approach mentioned above. They would be used to alter the host genotype of wild populations specifically at particular DNA sequences. The most likely scenario is that the target site would be within a gene that is necessary for diseases transmission or reproduction of that species via sex-ratio distortion. Because HEGs that are implemented would be inherited at rates higher than that of a normal allele, they have the potential to spread through populations. It is important to note that except for the targeted gene, the wild genotype would not be (deliberately) affected and would continue to undergo recombination and selection normally.

Example 2: The medea element is a potential gene drive system that could carry an effector and spreads in natural populations of its natural host, Tribolium castenaeum.[6]. Attempts are underway to introduce it to mosquitoes. It is hoped that it will provide the benefit of reducing drive –effector dissociation.


1. Alphey L, Andreasen M: Dominant lethality and insect population control. Mol Biochem Parasitol 2002, 121:173-178.
2. Catteruccia F, Benton JP, Crisanti A: An Anopheles transgenic sexing strain for vector control. Nat Biotechnol 2005, 23:1414-1417.
3. Thomas DD, Donnelly CA, Wood RJ, Alphey LS: Insect population control using a dominant, repressible, lethal genetic system. Science 2000, 287:2474-2476.
4. Burt A: Site-specific selfish genes as tools for the control and genetic engineering of natural populations. Proceedings of the Royal Society B: Biological Sciences 2003, 270:921-928.
5. Windbichler N, Papathanos PA, Crisanti A: Targeting the X chromosome during spermatogenesis induces Y chromosome transmission ratio distortion and early dominant embryo lethality in Anopheles gambiae. Plos Genetics 2008, 4.
6. Beeman RW, Friesen KS: Properties and natural occurrence of maternal-effect selfish genes ('Medea' factors) in the Red Flour Beetle, Tribolium castaneum. Heredity 1999, 82:529-534.

I agree that the description of technology development should be expanded.

There are many different approaches being developed, and they can be usefully categorized in two ways.

First, one can categorize different approaches in terms of the effect on the mosquito population. There are many ways to reduce disease transmission, but most approaches are either aiming to affect mosquito demography (i.e., fertility, mortality, and sex ratio), or mosquito competence (the ability of individual mosquitoes to support development and transmission of the parasite). Targeting mosquito demography can be useful because dengue and malaria are transmitted only by females that are relatively old, and anything that reduces the number of old females should help reduce transmission, including reducing the total number of mosquitoes, or biasing the sex ratio towards males, or increasing adult female mortality. All of these possibilities are being investigated. Reducing mosquito competence can also obviously be useful. In principle, there are even more ways that could be developed (e.g., changing host seeking behaviour), though I'm not aware of anyone working on that at the moment.

The second way to categorize the different strategies is whether the construct is self-limiting (meaning that it will disappear from the population of its own accord over a period of 1 or more generations) or self-sustaining (meaning it will tend to spread though the population over a period of generations and maintain itself at a high frequency). Self-limiting constructs need recurrent innundative releases to have an effect, whereas self-sustaining constructs need smaller-scale innoculative releases and more time. The release of sterile males is an example of a self-limiting release, whereas self-sustaining constructs are more analogous to traditional biological control programmes. Self-sustaining approaches require a gene drive system, and ones currently under development include driving sex chromosomes, homing endonuclease genes, MEDEA elements, and engineered underdominance. Gene drive systems for vector control are reviewed by Steven P. Sinkins & Fred Gould Gene drive systems for insect disease vectors. Nature Reviews Genetics 7, 427-435 (June 2006) | doi:10.1038/nrg1870.

Austin Burt

A Proposal to Limit this Discussion to Population Suppression Technologies

Three options are offered for narrowing the scope of the discussion. Choosing the third, "specific trait/modification" would allow the discussion to narrow to what is likely to be the first implementation of GMM, specifically modifications used for the class of strategies called "population suppression." While the “population replacement” strategies ultimately are theoretically more powerful, those very characteristics will require much more safety and sustained efficacy testing. Nor are any of these technologies ready for even semi-field contained testing. Therefore, it is unlikely that any of these will be released in open field trials in the near future.

On the other hand, technologies such as RIDL (a population suppression technology) are being field tested now and technology development per se is not preventing implementation. Similarly, use of transgene markers for monitoring and sex selection and sexual sterility effected by HEGs would fall into the same application group and are available for use.

There are several reasons that selecting such technologies will make this discussion more relevant and tractable:

1. The duration of the effect is limited by the release activities. Therefore, concerns about persistence of transgenes in the environment and their spread are largely eliminated.

2. Because the strategies involve genetic sterility, the likelihood that mutations will be selected and transmitted is minimized.

3. The effects of releases of this kind of mosquitoes are similar to that accomplished by conventional methods such as insecticides and source reduction. Therefore, the epidemiological consequences are well known.

4. If unanticipated effects occur, halting the releases will allow the pre-release state to naturally return. Therefore, considerations such as species replacement can be monitored during the release program and addressed before they become an irreversible problem.

5. The spatial effect of the release of the GMM is limited to the immediate vicinity of the activities. Because mosquitoes do not migrate long distances, there is no long-distance effect that might be seen if dispersing progeny acquired a transgene.

Regarding the guiding question "What existing guidance documents are useful examples and can help in identifying specific approaches for the risk assessment of LM mosquitoes?"  I would like to draw attention to the Environmental Impact Assessment on the Use of Genetically Engineered Fruit Fly and Pink Bollworm in APHIS Plant Pest Control Programs conducted by the United States Department of Agriculture. This document is the world’s first Environmental Impact Statement (EIS) on any kind of transgenic organism, either plant or animal, prokaryote or eukaryote.   This programmatic EIS is also a major part of the world’s first official government regulatory process on any transgenic insect.  It was published October 2008 and is on the Internet at: http://www.aphis.usda.gov/plant_health/ea/geneng.shtml


The attached file describes the EIS and has been written by Dr Robert Rose for a recent (May 2009) WHO/FNIH Technical Consulation Meeting on Genetically Modified Mosquitoes.

I have followed the discussion on this thread with great interest, and I would like to support many of the views that have been expressed so far.  I would agree that while ethical and legal issues are important considerations for government decision making, they are not part of an environmental risk assessment and are therefore outside the scope of this AHTEG.  Further, the concept of “informed consent” as used here, and as has been pointed out by others in this forum, is problematic for the reasons that experts have outlined.  Reading the “adverse effects” section, much of what is presented here is hypothetical without evidentiary support. 

As, I have mentioned in my previous post to the abiotic stress forum, it is important to keep in mind that with this SWG we are not attempting to craft a new standard or even a new guide to conducting risk assessments under the Protocol.  The work of the AHTEG is not intended to produce a new obligation for Parties but to help those who wish to perform risk assessments in accordance with Annex III. 

The Annex is a well-crafted and generally applicable document.  What is needed to support risk assessments, then, is not a set of specific instructions for reviewing a particular living modified organism, in this case a mosquito (which would seem contrary to the general principle of case-by-case assessments from paragraph 6 of Annex III), but rather a useful collection of available information that can help risk assessors obtain what information they need and guidance on how to use that information when performing an assessment.

The first step in this process is to assemble a solid baseline of available information.  By advancing to develop a draft before doing a thorough review and analysis of existing information, we are running the risk of being counterproductive or even of providing incorrect guidance.  We have yet to identify what specific need we’re trying to fill, and it is unclear how this guidance will relate to Annex III, or the Roadmap, which is still in development.  If we skip to drafting a guidance document, we run the risk of contradicting the Roadmap or generating unhelpful confusion. 

In the U.S., we have been working with government and public sector experts on LMO mosquitoes to try to identify this relevant information and post it to these forums.  Relevant information includes what is known about LMO mosquitoes and their intended uses.  It also includes information on other, similar pest control strategies including the sterile insect techniques that have been discussed here, as well as some additional alternative control methods.  Although transgenic mosquitoes are currently being used only in small scale, carefully contained research, there are examples of other transgenic insects being developed for use in eradication programs.  We will continue to post documents as we identify them and we appreciate the references that have already been assembled.  We look forward to a thorough discussion of these and other materials in the AHTEG.

Best,
Dave Heron

References:

Alphey L, Beard CB, Billingsley P, Coetzee M, Crisanti A, Curtis C, Eggleston P, Godfray C, Hemingway J, Jacobs-Lorena M, James AA, Kafatos FC, Mukwaya LG, Paton M, Powell JR, Schneider W, Scott TW, Sina B, Sinden R, Sinkins S, Spielman A, Touré Y, Collins FH.  (2002) Malaria control with genetically manipulated insect vectors.  Science 298:119-121.

Alphey, L., Nimmo, D., O'Connell, S., and Alphey, N. (2008). Insect population suppression using engineered insects, In Transgenesis and the management of vector-borne disease, S. Aksoy, ed. (Austin, Texas: Landes Bioscience), pp. 93-103.

Association of State and Territorial Health Officials. 2008. Before the Swarm: Guidelines for the Emergency Management of Mosquito-Borne Disease Outbreaks. A Project of the Mosquito Control Collaborative. Publication 0807001, 22pp. http://www.astho.org/pubs/BeforetheSwarm-PDF.pdf

Anonymous. Florida State Public Health Pesticide Applicator Manual, Chapter 3. Mosquitoes. http://entnemdept.ifas.ufl.edu/fasulo/vector/chap03.pdf

Anonymous (2009) Mosquito wars. Bull World Health Organ 87:167–168.

Benedict MQ, D’Abbs P, Dobson S, Gottlieb M, Harrington L, Higgs S, James A, James S, Knols B, Lavery J, O’Neill S, Scott T, Takken W, and Toure Y (2008) Guidance for contained field trials of vector mosquitoes engineered to contain a gene drive system: Recommendations of a scientific working group. Vector-borne Zoonotic Dis. 8:127-166.

Brelsfoard CL, Sechan Y and Dobson SL (2008) Interspecific hybridization yields strategy for South Pacific filariasis vector elimination.  PLoS Neglected Tropical Diseases 2:e129.

Bremen, JG, Alilio MS and White NJ (2007) Defining and Defeating the Intolerable Burden of Malaria III. Progress and Perspectives. Am. J. Trop. Med. Hyg. 77(Suppl 6), pp. vi–xi.

FAO/IAEA/USDA manual for product quality control and shipping procedures for sterile mass –reared tephritid fruit flies.  http://www-naweb.iaea.org/nafa/ipc/public/ipc-mass-reared-tephritid.html.

Federici, B A (2007) Bacteria as biological control agents for insects: Economics, Engineering, and Environmental Safety. Chapter 2, pp. 30-61, In  "Novel Biotechnologies for Biological Agent
Enhancement and Management" J. Gressel and M. Vurro, Editors). Springer-Verlag Berlin & Heidelberg.

Franz AW, Sanchez-Vargas I, Adelman ZN, Blair CD, Beaty BJ, James AA, Olson KE (2006) Engineering RNA interference-based resistance to dengue virus type 2 in genetically modified Aedes aegypti. Proc Natl Acad Sci U S A. 103(11):4198-203.

Fu, G., Condon, K. C., Epton, M. J., Gong, P., Jin, L., Condon, G. C., Morrison, N. I., Dafa’alla, T. H., and Alphey, L. (2007). Female-specific insect lethality engineered using alternative splicing. Nature Biotechnology 25, 353-357.

Gong, P., Epton, M., Fu, G., Scaife, S., Hiscox, A., Condon, K., Condon, G., Morrison, N., Kelly, D., Dafa'alla, T., et al. (2005). A dominant lethal genetic system for autocidal control of the Mediterranean fruitfly. Nat Biotech 23, 453-456.

Gould F, Huang Y, Legros M, and Lloyd AL (2008) A Killer–Rescue system for self-limiting gene drive of anti-pathogen constructs. Proc Biol Sci. 275: 2823–2829.

Greenwood B, Fidock DA, Kyle DE, Kappe SH, Alonso PL, Collins FH and Duffy PE (2008) Malaria: Progress, perils and prospects for eradication. J Clin Invest 118:1266-1276.

Helinski ME, Hassan MM, El-Motasim WM, Malcolm CA, Knols, BG, and El-Sayed B (2008) Towards a sterile insect technique field release of Anopheles arabiensis mosquitoes in Sudan: irradiation, transportation, and field cage experimentation. Malaria J 7:65-75.

IAEA-TECDOC -1438 Status and risk assessment of the use of transgenic arthropods in plant protection. Proceedings of a technical meeting organised by the Joint FAO/IAEA Programme of Nuclear Techniques in Food and Agriculture and the Secretariat of the International Plant Protection Convention Rome 8-12 April 2002.  http://www-pub.iaea.org/MTCD/publications/PDF/te_1483_web.pdf

ISPM 3 – Guidelines for the export, shipping import and release of biological control agents and other beneficial organisms  IPPC Phytosanitary Measures #3. http://www.nappo.org/Standards/NEW/RSPM26-e.pdf

Ito J, Ghosh A, Moreira LA, Wimmer EA and Jacobs-Lorena M  (2002) Transgenic anopheline mosquitoes impaired in transmission of a malaria parasite. Nature 417, 452-455

James, A (1992) Mosquito Molecular Genetics: The Hands That Feed Bite Back. Science 257:37-38.

James, A.A.  (2005)  Gene drive systems in mosquitoes: rules of the road. Trends in Parasitology 21, 64-67.

Kay BH and Nam VS  (2005) New strategy against Aedes aegypti in Vietnam.  Lancet  365: 613-617

Kelly-Hope L, Ranson H, and Hemingway J. (2008) Lessons from the past: managing insecticide resistance in malaria control and eradication programmes Lancet 8:387:389.

Lavery JV, Harrington LC, and Scott TW. (2008) Ethical, Social, and Cultural Considerations for Site Selection for Research with Genetically Modified Mosquitoes.  Am. J. Trop. Med. Hyg., 79:312–318.

McMeniman CJ, Lane RV, Cass BN, Fong AW, Sidhu M, Wang YF, O'Neill SL. (2009) Stable introduction of a life-shortening Wolbachia infection into the mosquito Aedes aegypti. Science 323:141-4.

Metzger, M.E. 2004. Managing mosquitoes in stormwater treatment devices. University of California, Division of Agriculture and Natural Resources Publication 8125, 11 pp, http://www.ucmrp.ucdavis.edu/publications/managingmosquitoesstormwater8125.pdf

Mills A, Lubell Y and Hanson K (2008) Malaria eradication: the economic, financial and institutional challenge. Malaria J. 7(Suppl 1):S11.

Montesinos, E (2003) Development, registration and commercialization of microbial pesticides for plant protection. Int. Microbiol 6: 245–252.

Morens, DM and Fauci AS (2008) Dengue and hemorrhagic fever. JAMA 299(2):214-216.

Phuc, H. K., Andreasen, M. H., Burton, R. S., Vass, C., Epton, M. J., Pape, G., Fu, G., Condon, K. C., Scaife, S., Donnelly, C. A., et al. (2007). Late-acting dominant lethal genetic systems and mosquito control. BMC Biology 5, 11

Rose, R.I. 2001. Pesticides and public health: Integrated methods of mosquito management. Emerging Infectious Diseases, 7(1): 17-23.

Scott TW, Takken W, Knols BGJ and Boete C. (2002) The ecology of genetically modified mosquitoes. Science 298:117-119.

Sinkins SP and Gould F (2006) Gene drive systems for insect disease vectors. Nat. Rev. Gen. 7:427-35.

Strickman, D., S.P. Frances, and M. Debboun. 2009. Prevention of Bug Bites, Stings, and Disease. Oxford University Press, NY, 352 pp.

Thomas MB and Read AF (2007) Can fungal biopesticides control malaria? Nature Reviews Microbiology 5:377-383.

Wilder-Smith A, Gubler DJ. (2008) Geographic expansion of dengue: the impact of international travel. Med Clin North Am. 92:1377-90, x. Review.

Willott, E. 2004. Restoring nature, without mosquitoes? Restoration Ecology, 12(2): 147-153.

Windbichler, N., P. A. Papathanos, and A. Crisanti.  (2008)  Targeting the X chromosome during spermatogenesis induces Y chromosome transmission ratio distortion and early dominant embryo lethality in Anopheles gambiae. PLoS Genet. 4:e1000291.

World Health Organization. 2003. Guidelines for Integrated Vector Management, trial edition. 30 pp. http://www.afro.who.int/vbc/framework-guidelines/guide_integrated_vector_management.pdf

POSTED ON BEHALF OF DAVID ANDOW

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David Heron’s suggestion to provide as much available information as possible is an excellent idea, and helps meet the goals of the BCH. It is a necessary step and essential to have.  However, it is
insufficient risk assessment because it is backwards looking, and
would result in basing the next risk assessment on information of the past.  Clear guidance as to the possible content and methods for risk
assessment is needed.  This guidance must achieve several delicate
balances, including a balance between being to prescriptive on the one hand and having no specific meaning on the other, and a balance
between being too futuristic (e.g., purely imagined technologies and
risks) and being mired in the past (e.g., accepting the formulation of the problem from the past).
In relation to this, the risk assessments conducted by the USDA for
genetically engineered sterile crop pests will be very useful in terms of some of the methods for analyzing and characterizing risk.
However, the identification of ecological hazards is not general
enough to address the GM mosquito case.  Because the sterile insects
considered by USDA have been agricultural pests, the identified
ecological hazards are centered on the agricultural fields where the
insects will be applied and be most abundant.  In addition, these
documents tend to argue or strongly imply that because the insects are pests, any positive ecological role that they may have is largely overshadowed by their pest status.  Finally, the risk assessments rely heavily on the fact that the released insects are sterile and incapable of reproduction.  There will be analogous arguments that can be used to address GM mosquitoes, but the published arguments will not always extend, so it is quite important that the framework for GM mosquitoes is sufficiently general.
Regarding informed consent.  The term may have too much baggage to be useful in the context of GM mosquitoes, however, the concept of
“community consent” may be too restrictive.  What is needed is a term that indicates that people must be informed and give consent, without implying which people, at what level of organization (individual, family, community, etc), what kind of consent is to be granted, and how it is to be documented.  For lack of a better term, this can be called “informed consent in the broad sense”.  All of these components need to be considered and specified in specific GM mosquito contexts.
“Informed consent” (sensu lato) is a critical risk management measure and depending on its structure, it would have considerable
implications for how a risk assessment would need to be conducted.
The guidance documentation may need to indicate this complex and
subtle relation better than it does at present.

***********************************************
David Andow
Distinguished McKnight University Professor, Insect Ecology
Department of Entomology
219 Hodson Hall
University of Minnesota
St. Paul, MN 55108 USA
612-624-5323 (office)
612-625-5299 (fax)
***********************************************
GMO ERA Project

POSTED ON BEHALF OF DR. S. S. VASAN

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Apologies for joining late... I had problems registering myself that Manoela was so kind to solve. But I understand I am not alone. Can we make this process simpler to enable wider participation and feedback in future?

Firstly, if a mosquito is artificially infected with a naturally-occurring strain of Wolbachia, or a mutant such as wMelPop (or popcorn) – it is not clear to me whether it is considered a ‘Living Modified Mosquito (LMM)’. Even if it is not, it is important to bring it within the remit of the AHTEG discussion because they do share key features (e.g. species-specificity) as well as issues of potential concern to regulators and the public (e.g. self-propagation similar to ‘refractory’ mosquitoes with gene-drive system(s)). I already see comments raised in this forum on ‘recall’, for instance.

I could count 12 initiatives (including this one) which are looking at biosafety, risk analysis and Ethical-Social-Cultural (ESC) aspects to be considered prior to and during the possible deployment of LMMs. It would be better for everyone (especially the public) if we coordinate and compare notes. The open-acces Asia-Pacific Journal of Molecular Biology and Biotechnology (APJMBB) has commissioned four special issues (‘Transgenic Insects: From Laboratory to Field’) during 2009-11 to publish proceedings of the different initiatives in this area, so as guest editor I welcome you to submit articles.

One of the 12 key initiatives that is conspicuously absent in the discussion forum is the WHO/TDR-Sponsored ‘MosqGuide’ project headed by Professor John Mumford at Imperial College London. I request to visit their site http://www.mosqguide.org.uk.

Alongside ‘MosqGuide’, the WHO/TDR has also set up three ‘Regional centres for training in biosafety assessment for human health and environment using genetically modified vectors’, one each for Asia, Africa and Latin America, funded during 2008-2010. The idea is that these four initiatives will iteratively feed into each other to produce and validate guidance for potential deployment of LMMs.

I am fortunate to be associated with the Asian centre which met in June 2009. It had extensive discussions on ESC aspects, especially ‘informed consent’, resulting in unanimous conclusions as well as topics for further deliberation in future meetings. I will be happy to forward the details to the Chair of AHTEG with TDR’s permission, but the following conclusions they arrived at reinforce some of the points mentioned in this discussion forum:

‘There is a moral obligation to evaluate LMMs which show promise to reduce burden of diseases.’

‘Informed individual ethical consent is virtually impossible in this case [i.e. open release of a LMM], therefore what is feasible is ethical consent by proxy’.

‘A credible proxy is one which has respectability and public standing in order to be taken seriously by decision-makers and the public.’

‘In addition to Government-appointed review committees, professional bodies can be a credible proxy, especially if they have a statutory status and if they are provided with sufficient information to conduct an independent peer-review.’

‘Credible proxies should give due consideration to all concerns raised to decide which ones are valid and which are frivolous.’

‘Regional organisations such as SAARC, ASEAN, etc. should play a greater role .’

Before I conclude, I would like to add a sentence or two about the UNDP-sponsored workshop on risk assessment of transgenic insects (series-1) held in Kuala Lumpur last year. It is one of the 12 initiatives and perhaps the first instance of a workshop dedicated to training on science-based risk analysis for a hypothetical release of a LMM. Its proceedings will come out this year in the APJMBB special issue.

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Dr. S.S. Vasan
Oxitec Sdn Bhd
ssvasan@gmail.com