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 Genetic Engineering

Oliver St John, a genetic engineer, talks to Rachel McLeod

 

 

 Oliver and Rachel holding one of the many cages in which the genetically modified mosquitoes are bred

 

 

This interview is about an Oxford University PhD student, Oliver St John working for Oxitec, a company trying to control mosquito numbers to stop the spreading of diseases without using pesticides. 

 

Pesticides work in the sense that they do kill off the insects, but they also kill their natural predators and so any of the target insects that do survive the pesticides won’t be eaten and will be free to reproduce in vast numbers, defeating the purpose of the pesticide in the first place.  The target insects can also adapt quicker than the pesticide, and so in the long run there is not much point in them.

 

 

An Aedes aegypti feeding on blood – only females do this when breeding

Oxitec is using a new technique to control mosquito numbers.  One variation of this RIDL genetic technique kills only females.   They raise mosquitoes that are not infected with any diseases.  All of the mosquitoes’ eggs are injected with a gene which is integrated into their DNA is changed and a new chemical is put into the DNA which kills only the females, and so only the male mosquitoes survive.  The males carry the female-killer but they are not sterile, so they can mate with females in the wild. But all of their surviving offspring will be male because the female offspring are killed by the female-killer DNA that they have inherited.  The offspring of the modified mosquitoes have only one copy of the introduced  DNA, not two copies like their fathers. Only half of their male offspring will carry  the female-killer gene so this gradually gets filtered out of the population over time.  So, new batches of modified males need to be released quite often to keep the number of mosquitoes in the wild low: about once a week.

 

The advantage of this female-killing process over pesticide sprays is that the pesticides kill a broad range of species including insects we like, but Oxitec’s programme only kills the mosquitoes: and only a specific type of them because a mosquito of one type does not breed with another species.

 

Some people are against Oxitec’s work, because they are against changing the DNA of mosquitoes.  However, people are dying of because of mosquito-carried diseases: thousands and thousands of them, so I am with Oxitec.

 

 

Q: Why are you genetically modifying mosquitoes?

Insects are very important spreaders of diseases. They move viruses and parasites between people, so they are responsible for an awful lot of people around the world becoming ill, which is something we want to prevent. The mosquito is the most important insect in terms of carrying disease and transmitting it from person to person. Around the world we have every year about 50-100 million cases of Dengue fever (according to the World Health Organisation (WHO)). We have a million deaths every year from malaria, mainly in Africa, Asia and latin America, so this is an insect that really affects people’s lives, and could affect people in the UK . We have climate change, which is bringing mosquito species into the UK , and so Oxitec is very interested in trying to find ways to prevent mosquitoes from spreading diseases.

 

Q: How does it work?

Oxitec are interested, as a solution, in releasing a type of mosquito in very large numbers that causes the mosquito population to collapse. This is what we call our RIDL technology. We introduce a dominant lethal mutation which kills the offspring of the released male mosquitoes (we only release males because they do not bite).  And so our work here is to genetically engineer these new strains of mosquitoes that produce a male mosquito which is capable of going out into the wild, mating with wild females, and resulting in the death of all progeny, because that will result in the population declining, and so ridding an area of mosquitoes and so hopefully stopping the spread of diseases. We don’t aim to totally eradicate species – but to eliminate them from the towns and cities where lots of people live close together and where disease is spread.

 

Q: What do you spend most of your time doing?

Either looking after the mosquitoes once we’ve generated them, we need to build them up, we need to mate them every successive generation to get these things going. Also I spend a lot of time in the molecular biology lab building these little circles of plasmid DNA that we use to generate new strains of mosquitoes, and then obviously I spend a lot of time injecting them into the mosquito eggs.

[Oliver showed me how he injects mosquito eggs with the new DNA using specially made glass needles and a powerful microscope.  Two people can inject 1,000 eggs in one day and about 10% of the eggs hatch.]

 

 

This picture shows one of the special glass needles being held in a stand.  Oliver uses these tiny needles to inject the new DNA into the mosquito eggs while looking through the microscope.

Q: How do you make this genetic material?

We have is this little circle of DNA, and we construct it by either taking the genes we want from other organisms, so for example we might find this lethal gene in a species of cockroach, a gene that we want, and we look at it and then we can look at the DNA in that organism, and we can actually cut that bit of DNA out; we can take it from one organism and put it into these little circles of DNA. The method is complicated, but once it’s in the circle of DNA we can then move it into the mosquito. So basically it allows us to take something that we like in one organism and put it into another organism.

 

 

The genetically modified DNA includes a fluorescent marker, which makes it possible to identify the type of modification present in mosquito larvae.  Oliver showed me how they glow brightly just like this.  He first put the larvae on ice so that they would not wriggle about – just like putting a cockroach in the fridge!

 

Q: What organism do you get your genes from?

Well, we use lots, actually. A lot of the genes that we work with were originally identified in the fruit fly, the Drosophila species, which is used an awful lot by scientists studying genetics. The fluorescent proteins come from coral. Our simplest constructs harness the mosquitoes’ own genes

 

Q: How long is it until you can release the mosquitoes into the wild?

We have the technology available to do this and have tested it in a house trial. We need to do larger field trials to show that the technology works and is safe.  What we do is genetic engineering and there is some public concern about genetically modifying insects. People are very worried about altered fruit and vegetables, but we’re talking about something that can move around and mate, and so obviously the fear could be greater for GM mosquitoes. Each country must put in place a regulatory system to review the safety to people and environment for their region before we can carry out the necessary field trials and use the technology. Some countries (e.g. USA ) have put scientific regulation in place and others are developing their laws and guidelines. We welcome good scientific regulation.

 

Q: How did you get involved in this job?

I specialised in biological chemistry, but I became more and more interested in the biological aspect of how chemistry affects living things and how they work. But I was also very interested in insects and arachnids. So I went from chemistry and I did a year at the Natural History Museum in London , where I did bio-systematics and bio-informatics, looking at the evolutionary principle as it applies to how molecules change over time, and then eventually, in the end, working at Oxitec, genetic engineering of mosquitoes is actually a lovely combination of biochemistry and entomology.

 

Q: What’s the most exciting thing you’ve done?

So far the most exciting thing has been getting my first transgenic mosquito. Seeing for the first time the marker being expressed in a mosquito, and it’s a really lovely feeling going through the whole process and seeing this animal where you’ve altered a millions of years’ worth of evolution, for your own ends. And that’s quite an impressive feeling, thinking, “I’ve changed this in a way that’s going to help people”.

 

Q: What do you think is the best way to get involved in entomology?

I think people need to see entomology in action, not so much in museums and stuff, but what always interested me was seeing the living animal and how it interacts with the environment and how it behaves, and all the wonderful different behaviours that these things show in the wild. I mean, there’s nothing more interesting to my mind than seeing, say, a spider spinning a web, or seeing a hive of bees go about their business.  I used to be a member of the AES too, and started keeping scorpions when I was thirteen.

 

Q: What does my generation need to do in terms of entomology?

Traditional entomology will not be something that perhaps appeals to your generation so much. I think entomology has become to a great extent an interdisciplinary subject. I mean, I’m a chemist who came into work in entomology, and we have computer scientists coming into entomology. I think what’s so interesting about it is that because it’s involved in things like public health and with crops and how we feed people, and because we use so many different methods to try and combat insects, or we try to use methods to try and preserve them in the wild when they’re endangered, I think that people from many, many different disciplines have an opportunity to come into entomology. I think especially the next generation, as we require more advanced methods, we will have more people trained in lots of different areas, and there will be lots of opportunities for people to come into entomology from a whole different range of disciplines and take part.

 

Q: What parts of entomology do you not like?

I was looking at the evolution of a group of mosquitoes, and I had to dissect the male genitalia of these mosquitoes under a microscope with incredibly fine needles.  Their genitalia are unbelievably tiny and horribly complicated! So that was the bit of entomology I have enjoyed the least; dissecting mosquito genitalia.

 

Q: What is the most embarrassing thing that has happened to you?

Probably letting an entire cage of mosquitoes escape in the room that we keep them in. That wasn’t very good. We had these electrified bats, and it took an awfully long time, swatting mosquitoes out of the air. Yes, that was very embarrassing, because everyone got bitten, which was very bad!

 

Q: If you were to choose only one insect, which one would it be and why?

I suppose it’s going to have to be Aedes aegypti because it’s so important to what we do, and it has such an affect on public health all around the world, especially in Third World countries.  It’s very important that we try and work on it, that we try and find a way to stop it spreading all the diseases that it’s responsible for.  I still have one scorpion, too.  I used to have more than 100, but now that I live in student accommodation, I’m not allowed to keep pets!

 

Special thanks to Ann Kramer, Head of Business Development at Oxitec, for inviting me to visit, showing me around and allowing me to interview Oliver.  For more information on Oxitec see www.oxitec.com