Genetic control of mosquitoes OXFORD INSECT TECHNOLOGIES HEALTHY PEOPLE HEALTHY ENVIRONMENT Luke Alphey, Founder and Chief Scientific Officer Visiting Professor in Zoology, University of Oxford
Dec 27, 2015
Genetic control of mosquitoes
O X F O R D I N S E C T T E C H N O L O G I E S HEALTHY PEOPLE HEALTHY ENVIRONMENT
Luke Alphey, Founder and Chief Scientific OfficerVisiting Professor in Zoology, University of Oxford
Oxitec Ltd
Based in Oxford, UK,30 employees
Founded in 2002 to commercialise new technology from Oxford University
Control of insects Agricultural pests
Public Health (mosquitoes)
Injecting DNA into mosquito eggs
Introduction Why?
Pest insects cause $$bn damage and transmit major diseases
How?
Engineered sterile males
RIDL®: Release of Insects carrying a Dominant Lethal genetic system
Genetics, molecular biology
When?
Initial strains successfully tested in field
Marker-only moth: USA 2006
RIDL mosquitoes: Cayman Islands 2009, Malaysia 2010, Brazil 2011
Increased Risk of Vector Borne Disease Dengue - growing global pandemic
Over 100 million cases annually Severity increasing No specific medication or vaccine
Chikungunya - emerging threat 1.8 million cases in last 6 years
(WHO) Reunion (2005) had 266,000 cases
and 254 deaths Italy (2007) – 197 cases and I death
Oxi
tec/
Nim
mo
Dengue control
WHO
RIDL®
RIDL
WHO
A Genetic Solution Release engineered sterile
males to prevent mosquito reproduction and so control dengue “birth control for mosquitoes”
Sterile male mosquitoes actively seek females Find mosquitoes better than
human inspectors
Based on Sterile Insect Technique How it works
Rear millions of insects Sterilise with irradiation Release over wide area Sterile males mate with wild
females: progeny don’t survive Pest population declines
Species-specific Used for over 50 years
New World Screwworm Eradicated
RIDL insects are genetically sterile Repressible Release homozygous males
X
RIDL: fail-safe / replacing radiation
Introgression of genes through male line
X
Bi-sex lethal Female-specific lethal
effectortTAtetOpromoter
Antidote (Tc)
death
RIDL®: molecular biology
Thomas et al. 2000 Science 287: 2474-6Fu et al. 2010 PNAS 107: 4550-4
Controllable Gene Expression
Female specificity
Female death
Act4-tTA + tetO-DsRed
OX3545F
effectortTA
tetO + promoterpromoterAct4
(DsRed)
Flight muscles only
OX3604C RIDL mosquitoes
Males FemalesFlightless mosquitoes cannot survive in wild (or find hosts). Unable to mate even in laboratory. Males have normal flight
ability, as have females given antidote as larvae.
fsRIDL phased trials – large lab cage trials
RIDL cage trials performed in Colorado State University (Megan Wise, Bill Black) showing suppression of target population
RIDL insects are genetically sterile Repressible Release homozygous males
X
RIDL: fail-safe / replacing radiation
Introgression of genes through male line
X
Bi-sex lethal Female-specific lethal
Development trials First open release Grand Cayman 2009
mating of RIDL males to local females excellent mating competitiveness provided data for suppression trial 2010
10km
500m
0
Each Area approx 16 Ha (40 acres)
No conventional control for Aedes aegypti
Release period May-Oct 2010 with pre- and post-release monitoring
Cayman field trial 2010
1-Apr 1-May 1-Jun 1-Jul 1-Aug 1-Sep 1-Oct0
20
40
60
80OVITRAP INDEX treated (A) & non-treated (C)
EE - Area C Polynomial (EE - Area C)EE - Area A
Ovi
trap
Inde
x (%
)
Trial was complete success; all endpoints met Clear suppression from early August
Sustained release of RIDL OX513A males can suppress a field population of Aedes aegypti mosquitoes Maximum degree of suppression limited by immigration
GM mosquitoes can perform successfully in the field
500m0
Bringing new technology to the field
Technical
CommunityRegulatory
RIDL
effectortTAtetOpromoter
Antidote (Tc)
death
Nature
Regulatory Progress
The USDA completed (2008) an Environmental Impact Statement (EIS) on the use of autocidal technology (RIDL) in fruit flies and PBW Record of Decision: this is the environmentally preferred alternative
North American Plant Protection Organization (NAPPO) standard signed late 2007
MosqGuide: WHO/TDR develop guidance for use of GM mosquitoes for disease control
Oxitec transgenic insect approvals Multiple movement and contained trial approvals (Medfly, Mexfly, pink
bollworm, Aedes aegypti, Ae. albopictus) Open field release approvals in the USA (PBW 2006,7,8)
Released 15 million Oxitec pink bollworm from aircraft over 2500 acres (2008)
Community Engagement
Focus Group: reactions to Oxitec approach
• breakthrough!• good news• kills larvae• good – something worth trying going forward• provides immediate solution / result in preventing
Dengue• seen as a long term solution cf other methods which
are all seen as short term• some even welcome the research team to test the
technique in their community
From TNS Malaysia
Community engagement
• Malaysian Health Minister Datuk Seri Liow Tiong Lai “We see it as the most efficient and fastest way in eradicating Aedes mosquitoes from our local environment,” Liow said, adding that Aedes is not a species endemic [native] to Malaysia. Monday 11th Oct 2010
Frequently Asked Questions
Will the genetic modification spread outside the release area?
The released mosquitoes and their progeny will die so this is a ‘self limiting’ approach, with no permanent change to the wild mosquito population. The large fitness cost (and no component advantage) also prevents spread.
Do mosquitoes provide valuable ecosystem services (e.g. food chain, pollinators)?
Aedes aegypti originated in Africa and only achieved pan-tropical distribution in the 1930s. Therefore in most countries it is not a native species. There are no birds, fish or other insects that feed exclusively on it and therefore reducing the number of Aedes aegypti is most unlikely to have negative impacts on the environment.
If one mosquito suppressed, will a worse one replace (niche replacement)?
Aedes aegypti it occupies an unusual, human-associated niche normally empty in its absence. Aedes albopictus, a potential alternative, is an inferior vector of dengue. RIDL strains are also available for Aedes albopictus.
Can we release enough (feasibility, economics)?
Long history of success and data from SIT implies ‘yes’, as do modelling and data so far.
Acknowledgements
O X F O R D I N S E C T T E C H N O L O G I E S HEALTHY PEOPLE HEALTHY ENVIRONMENT
Greg SimmonsBob Staten (rtd)Tom Miller (UCR)
IMR, Malaysia
Lee Han LimPI: Tony James
PI: John Mumford
Angi HarrisBill Petrie
Thank you…