Frequently Asked Questions : Genetically Sterile Insects.

How close are Oxitec’s products to field use?

Oxitec has several products in various stages of laboratory and field trials. Oxitec’sproducts
pass through several stages of rigorous testing, analogous to the stepwise evaluation for a
drug or vaccine. Many of these tests are performed by independent laboratories outside
Oxitec. Beyond the laboratory, later stage trials include testing in confined field conditions,
e.g. in field cages, and in open field conditions.

Following earlier tests in the laboratory and in field cages, Oxitec’slead strain of pink
bollworm was successfully tested in open field releases in Arizona, performed by the United
States Department of Agriculture (USDA-APHIS-CPHST).

Oxitec’s lead strain of Mediterranean fruit fly was successfully tested in confined field
(glasshouse) conditions in Oxford, in collaboration with Oxford University and also in Austria,
in collaboration with the International Atomic Energy Agency (IAEA) Entomology Unit.

At the request of the Government of Malaysia, the Institute for Medical Research (under
Malaysia's Ministry of Health) is planning to conduct open field trials subject to regulatory
and ethical clearance. Oxitec will provide all background information and technical support
on its RIDL strain to the evaluating agency (Institute for Medical Research, IMR). IMR has
already conducted a detailed evaluation of Oxitec’s lead strain of Aedes aegypti (the
mosquito that transmits dengue and chikungunya) in confined field conditions.

What are the likely human impacts from using RIDL mosquitoes for dengue control?

We would expect a rapid reduction in the wild mosquito population, leading to a reduction in
disease transmission. This reduction in mosquitoes and disease would take place over a
period of a few months.

Dengue, malaria, and other mosquito-borne diseases are transmitted exclusively by adult
female mosquitoes. Adult males do not bite, and larvae are aquatic organisms, harmless to
humans. Females bite to obtain a blood meal, which gives them the nutrients they need to
produce lots of eggs. Males do not need to do this; infact they do not have the female’s
specialized mouthparts and so are literally incapable of biting humans.

RIDL mosquitoes are just like wild mosquitoes in this respect – and indeed in essentially all
respects except for being genetically sterile. Males will be sorted from females before
release, so that the insects released will be the harmless, non-biting, sterile males.

What are the likely ecological impacts?

RIDL insects will have no adverse effects on insects or birds that eat them – in all such
cases they are just like normal insects. The RIDL system affects only those insects that
inherit it from one of their parents, and works by causing subtle adjustments to their cells in a
way that is not toxic to organisms that eat those cells, including the bacteria and fungi that
decompose dead insects. No antibiotic resistance genes are used to create the RIDL
insects.

Disease-transmitting mosquitoes and agricultural pests are already suppressed by other

methods, typically by spraying insecticides. The precise, species-specific nature of RIDL will
minimisethe ecological impact of controlling the pest insect (‘non-target effects’) while still
providing good control. RIDL is therefore exceptionally benign to the environment.

What will happen to the food chain if you control the pest insect?
Most of our current targets are insects that are not native to the places where they are major
pests. So, for example, Aedes aegypti, the mosquito that transmits dengue and
chikungunya, originated in part of Africaand was accidentally spread around the world by
man. Similarly, Mediterranean fruit fly is only native to a part of Africa, and pink bollworm to
Australia. In other regions, these insects are recently introduced exotic species and it is
unlikely that any native species is substantially dependent on them, e.g. for food. In the
specific instance of mosquitoes, other studies have found that they do not make up a
significant proportion of the diet of their various predators. So, although various things (fish,
birds, other insects) will eat them if they find them, few if any actually depend on them, and
probably none on one particular species, even where it is native.

Disease-transmitting mosquitoes and agricultural pests are already suppressed by other

methods, typically by spraying insecticides. The precise, species-specific nature of RIDL will
minimisethe ecological impact of controlling the pest insect (‘non-target effects’) while still
providing good control. RIDL is therefore exceptionally benign to the environment

Can the insect persist in the environment?

No. A RIDL strain is genetically sterile and the offspring cannot develop to adults. To control
the pest, RIDL insects will be released regularly, for example once or twice a week, to make
sure that there are always RIDL males around to mate with wild females and so suppress
the target population. Releases are so frequent because these species (fruit flies, moths,
mosquitoes) are very short-lived and will only live for a week or two as adults. But this
means that the RIDL insects will disappear from the wild very quickly if releases are stopped,
or outside the release area. Of course, this would also mean that the pest population was
no longer being controlled by RIDL, and so it would tend to increase; that would then require
an alternative control method, such as insecticides.

Can the genes be transferred to other species?

The various insect species will not interbreed with each other in the wild, and even in
laboratory conditions cannot form fertile hybrids. These mating barriers restrict the genes to
the single species. Predators, parasites and prey will potentially be exposed to proteins and
DNA from the modified insects by ingestion. Everything any animal eats contains DNA and it
is very hard, or impossible, for organisms to take up and incorporate genes by this route.
There is no known instance of this of having occurred. As the DNA is not conferring a
selective advantage to the cell or the organism the genetic modification would be rapidly lost
from any population..

How do you know it will work?

RIDL is essentially an improved version of the Sterile Insect Technique (SIT). RIDL makes
SIT more effective and applicable to a wider range of insects, for example to mosquitoes.
SIT has been used successfully for more than 50 years for control of flies such as fruit flies
and screwworm, and moths such as the pink bollworm and codling moth. It can be described
as “birth control” for insects. SIT involves the sustained release of a large number of sterile
insects over a wide area to mate with the wild pest population. The offspring of the wild
females that have mated with a sterile male do not develop, leading to a decline in the target
pest population

Why has SIT not been used in mosquitoes previously?

Mass-release of males sterilised by radiation (the Sterile Insect Technique, SIT) has
controlled or locally eliminated several major agricultural pests, however it has not been
used for mosquito control because radiation damages male mosquitoes to the extent that
they are unable to compete successfully for mates. Oxitec’s RIDL technology overcomes this
problem by eliminating the need for radiation – the males are made sterile by genetics.