Photo Credits: Crisanti Lab | Imperial College London
Edited by with permission by Frontier
Into the Wild Meets recently sat down with Professor Andrea Crisanti, Professor of Molecular Parasitology at Imperial College London to talk about his latest malaria research.
Your previous areas of interest include immunology and parasitology. When and how did you become interested in mosquitoes?
I am a medical doctor by training, then I did a PhD in immunology. I became interested in the immunology of malaria with a view to make a contribution towards vaccine development, but this was a while ago and I soon realised there was no hope to develop a vaccine against malaria. I also learnt molecular biology and genetics, and became more interested in mosquitos. All the vector control measures that worked to combat malarial transmissions were all directed against the vector, so I thought that the vector was the right bottleneck for transmission. No mosquito, no malaria.
When you talk about your research, mosquitoes don’t jump to mind as charismatic megafauna, how do you inspire the general public to become interested in your research topic?
Our focus isn’t the mosquito; it is the malaria which kills half a million children below the age of five every year. We regard mosquitos as a vector – something that we, if possible, should eliminate. So, our message is simple: if you want to get rid of malaria, you need to get rid of the mosquito which transmits the disease.
Your latest research is about using a gene drive in Anopheles malaria carrying mosquitoes to render the female in the population infertile, ultimately leading the population to collapse – could you talk me through what it involved and the results you came up with?
We have developed a genetic solution that is able to copy itself when gametes are formed in females (eggs) and males (sperm). During this process, a copy of the gene drive (which is inherited by the male or female parents) is then copied to the other chromosome so all the offspring will inherit this genetic modification. Importantly, genetic modifications don’t increase by themselves because there is a 50% probability of inheritance from the father or the mother and so there is only a 50% probability of transmitting to the next generation. A gene drive is a genetic solution that allows a genetic modification to be copied during the process of gamete formation. This means that the probability, rather than being 50% is now nearly 100%. Generation upon generation, the frequency of these genetic modifications then increases to the point that it reaches 100%. When it reaches 100%, it happens that most all of the females have a double copy and at that point, they cannot develop, they cannot lay eggs. That is when the population crashes.
To make the gene drive work you need to identify a gene target that, if destroyed, generates impaired fertility. Since this gene drive is very specific, if the sequence of the target gene changes then it doesn’t work anymore. In principle, you need to choose a sequence that cannot change, because if it changes you lose the function of the gene, and this is what our gene drive does. It is a gene drive that targets the fertility genes that is in principle resilient to resistance.
The gene that has been targeted is extremely conserved, so in principle the sequence of this gene cannot be changed without paying a huge functional price, so if you change it, it doesn’t work. This is very good for us because the end result is that we want to destroy this gene in all of the population, so if it mutates by itself and it is not functional, then it’s ok. The big problem is if it mutates and loses its function. In that case, you have a variant of that gene that surrogates the wildtype gene but is at the same time resistant to the drive.
Photo Credit: Flickr | John Tann
And you found that in the gene doublesex?
We found that in doublesex because this gene is a very intriguing, it is the gatekeeper of the sex differentiation programme. Whether you develop as a male or not, it depends on the activation of genes that orchestrate other genes that determine that you develop as a male. In mosquito, in all insects, the gene is doublesex. Doublesex is like a switch - if you destroy the female bit of the gene then the females will develop as males.
Could gene drive technology be abused if not used carefully?
Gene drive is not a technology that can be done by everybody, it is very complex. Abuse implies something malicious; I don’t believe that the scientific community is malicious because we are moving towards more and more open access and transparency. It is very expensive research that requires a lot of money and a lot of expertise and it is not something you can do in your spare time at home.
Crashing an entire mosquito population sounds like an extreme measure to prevent the spread of malaria. Are there other options?
So, you are thinking that this quantum leap we have seen in gene drive could bring benefits.
Yes, because in principle you remove all the need for logistics and sustainability so these all demand the right action. You also overcome poverty which is human created. At the same time you will release more resources which are currently used for malaria, which could be used for other good purposes.
Photo Credit: Flickr | Javier Díaz Barrera
People might fear the idea of releasing modified mosquitos into the real world – what would you say to that?
I think at the beginning, scientists will probably choose a place (an island) where we anticipate that the spread of the drive would be confined within boundaries and that this will probably provide comfort to everybody. When it works, all these debates about ecological damage and risks will go away because malaria is such a big problem that at that point, rather than having people questioning, we will have a big queue of people asking us to implement the technology. I think you have to reach that tipping point.
I think that when we have released the drive in a confined environment and showed that it works and that it can eliminate malaria. That will be the tipping point.
How would you make sure the gene drive doesn’t spread to other countries?
You cannot. There will have to be a kind of consensus agreement on that, but I am convinced that when you show that the gene drive works and that it can eliminate malaria in an isolated area, people will be forcing us rather than limiting. They will want it to be implemented as quickly as possible rather than worried if it crosses their border.
If you had to sum up the work you’ve done on gene drives, what would you say?
It’s very simple - we are motivated by curiosity, by challenges and by the overall arching aim of doing something good.