Investigating insects: Oxitec's novel approach

In the past 10 years, research teams have built biomechanical body parts, printed synthetic meat and mapped the human genome. They might even have discovered the legendary Higgs boson.

But despite these advancements in science and medicine, malaria, dengue fever and crop damage caused by insects remain a growing problem.

Dengue cases have increased 30-fold since the 1960s and malaria kills more than 500,000 each year, while agricultural pests cause famines around the world. Yet there are no approved vaccines for either disease and until now, the most popular method of pest control has been spraying harmful pesticides and keeping fingers crossed.

“In public health, there is a mindset that the best you can do is spray chemicals and try not to make the problem any worse. The idea that you can solve it is completely novel,” says Hadyn Parry.

Parry is the CEO of Oxitec, a company founded in 2002 after researchers at Oxford University’s zoology department developed a method of sterilising insects that could wipe out disease-carrying species and provide a safer, more affordable way to reduce the population of agricultural pests such as fruit flies and bollworms.

Researchers have been working on sterile insect techniques (SITs) for years, but all have so far relied on radiation. As Parry explains, this method is costly and works only on a limited number of species.

“People have tried traditional SITs with mosquitos and have never been able to make it work. It has been impossible to find the perfect dose of radiation that will damage the species enough so it can’t breed, but not so much that it’s unfit.”

We’ve had to patent with an idea of where we’re going to need patents in 10 years’ time or more.

Instead of radiation, Oxitec uses genetic engineering to breed insect strains that are healthy, but produce offspring that will die before reaching adulthood. Where possible, the company breeds only the non-damaging sex of each species (such as male mosquitos, which do not bite), meaning that unlike radiation techniques, it can wipe out local pest populations without causing further environmental damage.

Depending on an insect’s life cycle, it can take between two and four years to develop a healthy ‘sterile’ strain. This is done in laboratories, where the insects are fed on artificial diets and put through rigorous tests to check their fitness. Oxitec then carries out cage trials in the insect’s natural environment and, if these trials are successful, the sterile strain is released into the wild.

This development process can take up to 10 years, and perfecting the pre-release rearing method is key to Oxitec’s success.

“This has to be perfected so that we can release millions of insects in the field. Otherwise, the technique is not cost-effective,” he says.

These rearing methods make up the bulk of Oxitec’s patent portfolio and while the company is heavily involved in drawing up patent claims, its patent prosecution is handled externally by law firm Marks and Clerk.

“Most of our IP is around how DNA is inserted into the insects and how we make sure it’s stable and safe. We’re also developing patents around the rearing and release of insects for species that no-one has addressed before. And as the company develops, there’s a lot of scope for patenting at the molecular end and in terms of the technology’s application, such as production and monitoring techniques,” says Parry.

While SITs already exist, Oxitec’s genetic engineering methods are unique, meaning the company has had little trouble patenting its inventions.

“There is some existing prior art, such as on how to rear insects on a large scale, but other SITs are so limited in the number of insect species they can be applied to that it doesn’t produce much.”

Oxitec’s work is so research intensive that Parry believes it would be extremely difficult for anyone to copy the company’s ideas before it could stop them.

“Anyone wanting to copy our technology would have to go through the same 10 year research and development cycle, so time is on our side. The easiest way to copy us would be theft, but then we’d also have commercial law on our side,” he adds.

The geographical scope of Oxitec’s work offers added IP protection, as any companies wanting to emulate its technology would have to go through the same national regulatory approval process. Because of the limited threat of infringement, Parry says the company assumes an open and transparent approach to its inventions.

“If someone calls me and asks, ‘can I film in your laboratories?’ I always say yes. We open our doors to everyone and have had radio and TV crews visiting our Brazilian labs for weeks,” he says.

Of course, Oxitec has to keep some information confidential.

To ensure trade secrets are not leaked, the company chooses its employees and research partners carefully.

“A lot of our IP protection is built on trust. That’s probably the best form of protection you can have— although we do have contracts as well,” he says.

While most companies begin by prosecuting patents in China, the US and Europe, most of Oxitec’s work is done in developing countries. And as dengue fever is found in more than 100 countries, a tactical approach to patent prosecution is essential.

“When you first file for patent protection, you can’t file for the whole world, so you make a selection. Over time though, this selection may not be as accurate as you might have thought, so we’ve had to patent with an idea of where we’re going to need patents in 10 years’ time or more. Having that foresight has perhaps been our biggest challenge.”

Oxitec has already carried out successful tests in Cayman, Malaysia and Brazil. The company has now been asked to develop sterile dengue strains in Florida, Bolivia and Paraguay.

“We’ve proved that we can transfer our technology to different countries, and that people in those countries can be trained to use our techniques. If we can prove beyond doubt that the sterile strain of the dengue-carrying Aedes aegypti is effective, then we’re hoping we’ll secure the funding to start working on Anopholes [the mosquito that spreads malaria].”

If its success continues, Oxitec’s work could have a tremendous global impact and could save millions of lives. But for Parry, it doesn’t stop there—he would also like to see the company’s technology applied to cattle pests and insects that mankind has caused to move out of their natural habitat.

“In France, for example, they have a pest called red palm weevil. It’s a major pest in the Arab world, where it destroys oil and date palms and now, it is ruining the palm trees that are central the scenery and culture of France’s south coast. You couldn’t even dream of removing infestations of invasive species using chemicals, but it’s possible with sterilisation,” he says.

Ten years ago, Oxitec was set up because the technology it had developed was so novel that there was no network through which to license it. As the company continues to grow, Parry is aware that other companies may try to replicate Oxitec’s success, but at the moment, it’s in a league of its own.

“When a young company develops a new small molecule drug, it knows there are tens or hundreds of companies out there with very good synthetic chemistry capabilities who will take your drug and try to modify or copy it. In our world, there simply aren’t people with mosquito-rearing abilities, but I’m sure there will be in time,” he adds.