GM mosquitoes - threat or friend?

The article from GeneWatch UK that claims Oxitec tried to conceal the results of a five-year-old study from regulators is completely wrong in fact and, indeed, irresponsible. Oxitec was founded with the purpose of finding better ways to combat diseases spread by insects, rather than wholesale reliance on toxic and broad spectrum insecticides. Dengue is an intractable disease spread by the Aedes aegypti mosquito that affects more than 50 million people annually, mostly in dense urban environments. There is neither medication nor vaccine for this disease. Combating this mosquito relies largely on the use of larvicides added to water or chemical insecticides sprayed - or, in some cases, released as fogs by helicopters into whole neighbourhoods.

Over the last few decades this invasive mosquito has spread around the world and, with it, the number of dengue cases has increased. In spite of the availability and use of insecticides, in the last 50 years, incidence has increased 30-fold. Our approach is dramatically different in using genetically engineered sterile males to search for females, resulting in non-viable offspring. Male mosquitoes do not bite or spread disease. This approach is in evaluation in a number of countries and potentially could become an important new tool in combating the mosquitoes that spread disease. Both field and laboratory results are extremely promising.

The institutions who determine the acceptability of any new public health technology are that nation's regulators. By causing unfounded anxiety outside of the regulatory process, GeneWatch UK risks consigning more than 50 million people to "break bone" flu. We are is committed to full transparency in the regulatory process. This means sharing all research with these experts, who are in a position where they regularly evaluate risk-benefit relationships. Oxitec has been completely open with the regulators and collaborators and has not concealed any information. The fact that GeneWatch UK obtained this information from regulators is, indeed, proof that regulators have the information.

The specific study referred to was done in 2006-7, within an external independent laboratory. They found a high level of survival of our mosquitoes in the apparent absence of tetracycline, which was a strange result. We and they investigated and found the food they used for the mosquitoes was contaminated with tetracycline. While this was a clear case of contamination we have, of course, carried out dose-response studies to determine whether the tetracycline levels that can be found in the environment are likely to lead to survival of our mosquitoes. While tetracycline can be found in the environment in isolated areas, it is not present in sufficient quantity to ensure survival of the mosquitoes.

But the place where such risk assessments are made is within the regulatory process, within each country. GeneWatch UK has ample opportunity to participate in that process, but instead it seeks to create public concern by going outside of the process through a scaremongering approach. GeneWatch UK also alleged yesterday that Oxitec is "using poor regions in the global south, such as cities in the north east region of Brazil, as its laboratory for genetically modified mosquitoes". This insinuation that we are somehow targeting exploitable populations is also particularly irksome and patronising. Dengue is associated with tropical climate and about two fifths of the world population are at risk. Non-governmental organisations risk undermining the chance of a real solution coming to cultures, who have a real problem.
Hadyn Parry, Oxitec chief executive - Oxford, UK

If Oxitec has evidence that tetracycline contamination is not a problem, why has it not published this? Why did Oxitec black out the evidence about the 15 per cent survival rate from public versions of its laboratory protocol? And why did the company conduct its first trials in the Cayman Islands, where there is no biosafety law to regulate the release of GMOs?

Evidence from elsewhere suggests that tetracycline contamination is widespread in agriculture and in sewage, including mosquito breeding sites. The comment about Brazil was made by Friends of the Earth and reflects their own concerns about Oxitec's experiments in their own country. The company has understandably lost trust because it has not been open with the public in the countries where it has released GM mosquitoes into the wild. GeneWatch accepts that dengue is a serious disease, but Oxitec's technology suffers from a fundamental flaw which will limit its effectiveness as well as posing risks to health and the environment.
Helen Wallace - GeneWatch UK

Thank you Oxitec, for clearing that up. I have been interested in the promise of SIT for a while now, and I'm glad some good is coming of it. Could you elaborate on one point for me, please? If the males receive tetracycline from some source and do not die, do you know whether they pass on the dependence on tetracycline to their descendants? Is their offspring affected at all?
Niek Beaujean - Dublin, Ireland

Oxitec has made these data available to regulators and potential users of this technology, along with a vast range of other data relating to the use, benefits and limitations of our technology. These pressure groups now trying to scare the public know this perfectly well – they admit they obtained the information from a regulatory package we submitted.

For those not familiar with our technology, we aim to develop a clean, environmentally-friendly technology to tackle some of the world's major pest problems – in particular dengue, an intractable mosquito-borne disease for which the main current measure is extensive use of broad-spectrum chemical toxins.

Regarding the availability of tetracycline in the environment, in summary: our lead strain of Aedes aegypti, OX513A shows no increased survival at tetracycline concentrations 2-20x the highest we see in the literature for waste water or run-off. Furthermore, Aedes aegypti breeds in clean water (rainwater or stored human drinking water). This mosquito is occasionally found in more polluted environments, but even in these rare circumstances there is not enough tetracycline available to affect the success of our technology.
Helen Wallace wonders, perhaps rhetorically, why we have not published these data.

Such negative "it's not a problem" data are difficult to publish in the scientific literature as they are not seen as of wide or fundamental interest. One could imagine an infinite series of "it's not a problem" publications. In fact, we encouraged our collaborators to publish these data and they did indeed attempt to do so but failed for exactly this "your findings are not of sufficient general interest" reason. So we simply provide the information to regulators and others who do have a specific interest.

The pressure groups could have contacted Oxitec or our collaborators to find out any or all of the above items. One has to wonder why they chose not to do so, preferring instead to make up inferences and allegations when simple research and fact-checking would have been so easy. We have extended such an offer privately following their previous spurious allegations and now repeat that – if in the future you are interested in portraying the situation accurately rather than issuing scare stories of your own imagination, please contact us with any concerns. Naturally, this offer extends to any member of the public, press or other organisation who has any concern or question regarding any aspect of our technology or its delivery.
Luke Alphey, co-founder and chief scientist of Oxitec - Oxford, UK

Helen Wallace raises important points. Oxitec has not given a convincing account of why it blacked out the evidence on survival, or why it started its trials in a country devoid of biosafety laws. And Oxitec's rejoinder that we should just leave it to local regulators is less than convincing, if it's the case that Oxitec's own staff have been closely involved in developing the risk asessment guidelines used by regulators.
Sam Mason - UK

Niek - interesting question. The transgene is inherited as a single dominant trait. The released males have two copies - "homozygous" in the jargon. If and when they mate with wild females, their offspring inherit one copy. This kills them - in the case of OX513A as late larvae or early pupae - if they develop in the absence of tetracycline. If they somehow survived, e.g. due to presence of improbably high levels of tetracycline, they would pass on the trait to half of their offspring which would again need tetracycline to survive (the other half would not inherit, would be wild type, non-transgenic and not need tetracycline).

The same applies to a different version of our technology, the use of a female-flightless trait, where males are expected to live and pass on the flightless trait to females. More on both versions of that technology on our website. Another related aspect may be of interest - what about inheritance of tetracycline from the female mosquito to her offspring? For example if she mated one of our engineered males and took her blood meal from a human being treated with tetracycline (not very likely, I realise, but we need to consider all possibilities). We tested this and found that even feeding female mosquitoes very high levels of tetracycline, far higher than they could get from real blood, did not lead to any survival of offspring.
Luke Alphey, co-founder and chief scientist of Oxitec - Oxford, UK

Oxitec's claims of openness are completely undermined by the fact that they conducted their trial in the Caymans, in secret. What they really want is advanced notice of any criticism so that they can continue to control the flow of information.
Jonathan Matthews - GMWatch

Gene Watch UK appears opposed to any form of GM activity for pest control and is scaremongering. Compared to the toxic use of pesticides across Africa - which are increasingly ineffective - the Oxitec type solution is to be applauded. I hope they develop a solution for Malaria and the Tsetse Fly in due course. Dr Wallace should come and see the devastating effect on our environment of the use of pesticides and the human suffering caused by Malaria. We need new technologies and solutions to save our planet and alleviate poverty. As for tetracycline contaminated tins of cat food - I would suggest closing that problem down not on the unlikely event of one of Oxitec's mosquitoes tucking in to it.
Jason Drew - director - AgriProtein

Sam - regarding publication, this is addressed in my post above - which may have crossed with yours due to time delay of moderation. We went to the Cayman Islands because we were invited to do so by the Cayman Islands Mosquito Research and Control Unit, an arm of the Cayman Islands goverment. It is responsible for mosquito control in the Cayman Islands and, as a responsible agency, seek better means of achieving this - which our technology may be able to provide. It is not the case that the Cayman Islands have no biosafety law.

Indeed, I doubt there are any countries for which that would be true - though I have not attempted any comprehensive survey. We and many others contribute to the development of regulations in this area; one key role for technology developers in this regard is to keep regulators informed of what might be coming in the years ahead. As a small UK company, we do not have the muscle to influence the regulators in other countries, other than by rational argument; even if we wished to do so.

One useful aspect of the scrutiny of outside sceptics is to help regulators assemble a comprehensive list of potential harms, the likelihood and consequence of which they can then duly assess. In this respect, the more independent views of the technology the better. Poorly researched scaremongering is not the way to do it though; fortunately regulators can recognise poor-quality data and arguments from any source, whether for or against any proposed action.
Luke Alphey, co-founder and chief scientist of Oxitec - Oxford, UK

High survival rates? It appears only when tucking into poisoned cat food in a lab.
Rachel Sandford - Botswana

Friends of the Earth? If they wasted less of my donations on the huge NGO jamboree on Durban beach, with 8,000 attendees dancing and drinking that kept me awake till 4am, and more of my donations helping get rid of pesticides that don't work and trying science that might work - there might be progress on our planet.
Helen Edmonds - Durban

The last time (9 months ago) when I checked the Cayman Islands Parliament's webpages, I could find no evidence that a biosafety law had been passed. So obviously the field releases were undertaken in a country - actually Cayman Islands are not an independent country, but a UK overseas territory with some degree of autonomy - that had no biosafety law. According to Oxitec, that has changed now. Is there a link for this biosafety law?
Hartmut Meyer - ENSSER, Germany

Rebound in tropical diseases - get real – they are already endemic and causing massive human suffering and death. Have you ever seen a person suffering from dengue fever or breaking bone disease? They spend most of their time when not on pain-relief drugs screaming. The effect of excessive use of pesticides on land causes allergies in humans today – potential allergies – give me the dengue prevention first and worry about possible hypothetical allergies once my dengue fever wears off.
Pan Yiannakou - Limassol, Cyprus - GPAM

Dengue transmission could be suppressed by infecting mosquitoes with natural virus-blocking bacteria.
Sam Mason - UK

Luke Alphey, straight from the horse's mouth, I appreciate you taking the time. Keep up the good work. Another question occurs to me: can you give some indication of how easily/quickly you can modify a new mosquito for this purpose? We could imagine, for example, that a subgroup of Aedes aegypti would not be attracted to your archetype, allowing this subgroup to persist. Alternatively, because of the small starting population, genetic flaws might arise in your breeding population, making your archetype less successful in the wild.
In both scenarios, the ability to nab a free mosquito and quickly modify it would be invaluable. Could you? You are right in saying that negative results are hard to publish in a journal. Nevertheless, they would be interesting to read, I'm sure. If they are written up as an article, perhaps you could make them available via your website.
Niek Beaujean - Dublin, Ireland

Lot of unscientific and illogical straw man type nonsense being spouted here. e.g. when NGOs and the public ask for companies to publish evidence about the risky products, they are generally not bothered if it is published in a peer reviewed journal or merely stuck onto the company or regulators' websites. Our purpose is to scrutinise it and invite independent scientists to comment on it. And the idea of publication is to not black out inconvenient evidence.

For a thorough demolition of the notion that pesticides (which are the only 'choice' being given by pro-GM lobby if one rejects GM insects) ever effectively eradicated any disease carrying insect, see the book Merchants of Doubt. It's well referenced and scientific in approach. The only answer to, say, malaria has always turned out to be improved sanitation and removal of breeding grounds for mozzies. The mozzies only get resistant to pesticides, including DDT. We don't need your wretched GM insects and we don't need pesticides either. Just the political will to implement tried and tested methods to eradicate these diseases, as malaria already has been in North America.
Elisa Trimble - Exeter, UK

The folly of the GM mosquito at first seemed to be a godsend, but as with all GM products there is the unforeseen waiting to trap the unwary. But to use an anitbiotic to me seems to be unwise. These are vaulable drugs and to corrupt them for such an aim, however superficially beneficial, seems to be misaimed. All one can say in mitigation is that a test site in Florida is to be welcomed.

After all, the United States is the home of GM products. Whatever one does to try and trick nature seems to have a nasty habit of misfiring. All the present GM crops, without exception, have a very sad downside. Perhaps, like alchemy, GMs might sometimes be a success. At present, the technique has reached the stage of not turning lead into gold .
David Morgan-Davies - Normandie, France

I believe the Cayman Islands suffers from wild populations of Dengue fever-carrying mosquitoes. It is also an island, so there is natural containment. Where does the author think Oxitec test its Dengue fever solution mosquitoes in the wild - Oxford street?
Justine Kanter - London

Niek Beaujean - another good question. Assortative mating, as you describe, is a interesting issue. It would take, perhaps, two or three years to generate an entirely new strain depending on the species. However, a quicker solution would be to introgress the existing transgene into the new/problematic genetic background. This should work unless the 'new version' is, in fact, a completely different species with an insurmountable mating barrier, even under lab conditions. This is often not the case even for different species within a species complex, let alone different populations of the same species.

Regarding pesticides, I don't suggest that insecticides can never be effective. Of course not. They are mainstays in agriculture, and successful both historically (e.g. DDT) and currently (e.g. insecticide (pyrethroid)-impregnated bed nets), though their ongoing effectiveness can be threatened by insecticide resistance, a current concern for bednets. However, dengue poses particular problems that make pesticides less effective than one would wish. Current dengue control programmes place heavy reliance on insecticides because there is nothing better, not because they work so well that no alternatives are needed. Modifying mosquitoes, whether by putting single genes or whole bacterial genomes into them is one approach worth pursuing, as are drugs and vaccines, for example. All of these methods have potential difficulties - technical difficulties in development, evolution of resistance, acceptance/compliance rates, to name just a few. None is likely to provide a single 'magic bullet' to solve the problem; certainly we don't claim that for our approach. Rather they are likely to provide public health programmes with a wider range of tools that can be combined into integrated pest/disease management programmes that combine the best features and covering the limitations of each.
Luke Alphey, co-Founder and chief scientist of Oxitec - Oxford, UK

I have read these comments with interest and, based on some field experience with NGO's in poor countries, would bring things down to a more practical level by asking the following questions. What is the opinion of people actually living in dengue-affected areas likely to be with respect to any new technologies? How many of the correspondents have actually suffered from either dengue fever or malaria? How many dengue areas are actually subject to tetracycline contamination? Why doesn't GeneWatch appear to trust either Oxitec or the regulatory authorities? If GeneWatch manage to stall or delay the development of this technology, what do they intend to tell the people in dengue areas?
James Otter - Hampshire UK

James Otter asks what is the opinion of those in the dengue-affected areas. Yet Oxitec's GM mosquito trials in the Caymans appear to have been conducted without any public consultation, let alone the informed consent of local people.
Sam Mason - UK

Luke Alphey, I thank you again. I've signed up to your newsletter, and hope to hear more. Your website lists a lot of articles. Any reading you might recommend?
Niek Beaujean - Dublin, Ireland

We are lucky in the UK not to be troubled by local transmission of diseases such as dengue and malaria - which affect millions in developing countries and Oxitec is to be applauded as a small British company developing and applying new technology to tackle such problems. They are right in conducting field trials of their dengue mosquito control system in these countries, in order to evaluate it and thereby to demonstrate to the local health and regulatory authorities that it is safe and effective in the circumstances where it would actually be used in practice once approved.

In Rio de Janeiro State alone last year, there were reported to be 160,000 cases of dengue and 131 deaths with 3,000 people employed to try to contain transmission of the disease and 4,000 health assistants required for rapid response and diagnosis. What would our attitude be to promising new control methods if these statistics applied to London, Manchester or Birmingham?

National regulatory authorities need to be provided with all the facts and local evidence required to be able to review the risks and benefits of new treatments, but it appears that the risk of dengue increasing through survival of mosquitoes on tetracycline contaminated larval habitats is miniscule and the benefits of an effective new control approach would be massive.
Dr Julian Entwistle - Xenex Associates, UK

"GM mosquitoes - threat or friend?" Definitely a threat. Has nothing been learned from the disaster of myxomatosis, which was similarly "introduced" into Australia to kill rabbits and which led to so much unnecessary death and suffering all over the world?
Mike - UK

Gene modification of our food is bad enough with all its negative impact on people and the environment globally. Let alone, creating GM insects for it's horrid impact on humanity. Such a sad existence we are born into these days.
Evelyn Padua - Queensland, Australia

I'm intrigued by the last two posts. Mike, how do you make your connection with myxi? Evelyn, how can reducing the incidence of dengue fever have a horrid impact on humanity? It sounds wonderful to me and is exactly the type of thing modern science should be doing for the benefit of humanity.
Ifor Phillips - Faringdon, UK

I have followed the posts in response to the original statements from Greenwatch UK with interest. Not only as a trained scientist with some understanding of vector bourne diseases, but also as a European citizen who wants to live in a healthy and hygenic world. In today's world, I am sure that nobody with an educated understanding of any scientific discapline would expect to see any break-through technology such as that developed by Oxitec being used in the wider environment - without being able to demonstate to whichever appropriate compentent authority a detailed scientific justification for their statements and a clear understanding of the potential environmental impact.

This may not have been the same when compunds such as DDT were first available. But, make no mistake, that information is expected in today's world and governments have every right to demand this and reject unsubstantiated information. Governments do not take the decision to trial novel technologies lightly, they take it in consultation with their own scientific staff along with specialists from the World Health Organisation and other respected bodies. If organisations such as Greenwatch UK were prepared to engage, listen and contribute to a balanced scientific debate and assessment - their presence I am sure would be more than welcome at the table too.

Dr Wallace states that civil society groups have called for an immediate halt to any field trials and a re-assessment of the risks posed by the technology. Would she please state who these civil society groups are and substantiate with scientic evidence, not anecdotal comments their reasons for this inflamatory statement. Perhaps, Dr Wallace would also like to inform those engaged with the debate of her own scientic qualifications as a director of GeneWatch UK.

Having lived and worked in so called "less-developed countries" for more than 30 years - I can assure the previledged, articulate and educated members of today's European society that they might find their own values changed if they lived with the daily threat of being bitten by a potentailly deadly vector bearing mosquito. More citizens of this globe live with this daily threat than live without it.

Many factors are driving such vector bourne insects ever closer to Europe, will the messages change when they can no longer sit in their own parks during the summer months for fear of a similar threat as has happened in vast areas of the United States since the arrival of West Nile Virus vectored by a close relative of the dengue mosquito. Mosquitoes are not bound by country borders.

The sooner we accept that science is never perfect, but has delivered enourmous benefit to mankind the better. Do those who scaremonger about this exciting new technology with many inherent benefits and advantages over current mosquito control practices want to go back to a world without antibiotics, vacines or contraception? None of them had perfect science, but all of them have had a positive impact on our global heath.
Rob Fryatt - UK

As a mere mortal, it is hard to know who is telling the unbiased truth. What I do believe is that in the past companies developing GM products have done very poor evaluation of new products with safety testing that is unlikely to show all problems. Safety regulators are rubber stamping test results that are unverified. Developers have also refused to make seed available for well designed independent safety tests. If the products are as good as claimed it would make excellent business sense to have as many researchers as possible demonstrating how good they are.

If Oxitec tried to hide a 15 per cent failure rate, I am very worried. I don't know what the effect of GM mosquitoes breeding in the wild would have – probably no one can know - but honesty is essential. I don't want anyone suffering from nasty diseases, hunger, thirst or poor housing. The only statistic that I am certain of is that unless the world population stops rising and the rich share with the poor, the number of people suffering is only going to rise. GM mozzies are not going to reduce total suffering on their own, and may cause further problems.
Peter Muskus - Scotland

I do not support the release of GM mosquitoes.
Betsy van der Lee - Forres, Scotland

Up to 15% survival rate of offspring if they get enough tetracycline, up to 3 per cent if they don't - instead of the 80+ per cent of standard mosquitoes. So the mosquito population will go down drastically if this doesn't work, even more so if not much tetracycline is available. Sounds good to me.
Just on the points that Dr Wallace brought up, it sounds like a good deal. Cut the dengue problem down without sickening people with harmful pesticides. Maybe they can help with malaria, too. And I always hate it when the government comes door to door putting that white powder in our drinking water vat to stop the mosquitoes. Was there a reason for incorrectly stating that the Caymans has "no biosafety law or regulation"? Dr Wallace, have you done any thing to check for risks? That's what I want to know before bringing geongineered mosquitoes here
Bill Williams - Belmopan, Belize