HomeMy WebLinkAboutPreventing Tick-Borne Disease PresentationPreventing Tick-Borne
Disease
Kevin M. Esvelt, PhD
Assistant Professor, MIT Media Lab
17 August 2017 photo: Yousur Al-Hlou/ The New York Times
The proposal
To stably reduce the incidence of tick-borne disease by
breaking the transmission cycle between white-footed
mice (the primary reservoir) and ticks
Controlled releases of resistant mice would introduce
immunity to most or all of the native mouse population
Released mice would be genetically altered, but 100% mouse
A percentage of the Nantucket’s white-footed mice naturally express
antibodies against the Lyme-causing spirochete Borrelia burgdorferi
Open, community-driven science
•Clear benefits to citizens
•Discussions before experiments
•Safeguards agreed upon early
•Developed/run as a nonprofit
•Independent monitoring and analysis
•Open and responsive science
This project can only move forward if embraced by the community
It could supplement, not replace, existing control efforts
Thoughtful, measured approach
•The Steering Committee must secure federal, state and local approval
•All efforts will be guided and monitored by local and national ecologists
•Trials will be sequential: uninhabited islands first, then inhabited
Changes are not anticipated to spread beyond the island. No gene drive!
Guiding principles for eco-engineering:
•Rule 1: Make the smallest possible change capable of solving the problem
•Rule 2: Start local and only scale up if warranted
Tick-borne disease is an ecological problem
The pathogens that cause Lyme and other diseases persist by
moving between mice and ticks
White-footed
mouse
Blacklegged
tick
B. burgdorferi
B. burgdorferi
Tick-borne disease is an ecological problem
Ticks pass the pathogens to humans, causing disease
Lyme disease
White-footed
mouse
Blacklegged
tick
B. burgdorferi
B. burgdorferi
Tick-borne disease is an ecological problem
White-footed
mouse
Blacklegged
tick
B. burgdorferi
B. burgdorferi
What if white-footed mice could not become infected?
Breaking the cycle
If every mouse produced antibodies conferring effective
immunity from birth, the main reservoir of tick-borne
pathogens would likely collapse
Important note:
Some ticks could become infected from residual secondary
reservoirs, but the rate should be far lower than today.
No infected mice Few infected ticks Few infected people
Technical team
Dr. Kevin Esvelt
MIT
Dr. Sam Telford
Tufts
Joanna Buchthal
MIT
Dr. Jeantine Lunshof
MIT/Harvard
John Min
MIT/Harvard
Dr. Linden Hu
Tufts
Byong Kang
MIT
Sisi Sarkizova
Broad Institute
Plus: Tom Watson (Arc Bio) , Alison Tisdale (MIT) and Tanja Petnicki-Ocwieja (Tufts)
Technical challenges
house mouse
white-footed mouse
Technical background
Nantucket is home to between 50,000 and 500,000
white-footed mice throughout the year
Two types of antibodies
Anti-Lyme Antibody
Protects mice from the
Lyme spirochete only
Antibody target: OspA
an outer surface protein on
Borrelia burgdorferi
Anti-tick Antibody
Protects mice from all
pathogens carried by
black-legged ticks
Antibody target: subolesin,
a tick salivary protein
How to make mice heritably Lyme resistant
Step 1: Inject white-footed mice with
surface markers from B. burgdorferi
Dr. Sam Telford
Step 2: Isolate B cells with antibodies
that target the pathogen
Byong Kang
How to make mice heritably Lyme resistant
Sisi Sarkizova
Step 3: Sequence DNA
from B cells
Step 4: Identify anti-Lyme antibody gene
sequences
How to make mice heritably Lyme resistant
Step 5: Integrate antibodies into
the mouse genome using CRISPR
John Min
Harvard/MIT
Joanna Buchthal
MIT
Engineering milestones
Next up (~6 months)
-Synthesize anti-Lyme antibodies
-Test anti-Lyme antibodies in mice
-Immunize mice with subolesin (anti-tick)
Recent advances
-Isolated B cells with anti-Lyme antibodies
-Sequenced B cells to identify gene sequences
Timeline
~2 years to engineer
immune mice
~3 years to
generate
enough
mice for a
small island
Build heritably
immune mice
Release on an
uninhabited island
Release on an
inhabited island2+ years to
evaluate
effects and
raise
enough
mice for a
large island
Implementation
Release immune mice in early spring
•Introduced mice would increase the local mouse population
to at most 300% of ‘normal’ for that time of year
•For context, mouse populations often fluctuate by >500%
over the course of a year
•Bait stations could be used to reduce populations near
commercial and residential areas
Local reductions will not impact the spread of resistance
Project status
Local Presentations
•Jun 2016: Nantucket Board of Health meeting
•Jul 2016: Martha’s Vineyard health agents meeting
•Jul 2016: Edgartown Library presentation with Professor Sam Telford and Dr.Michael Jacobs
•Oct 2016: Martha’s Vineyard All-island Board of Health meeting
•Jan 2017: Nantucket Board of Health meeting
•Mar 2017: Edgartown Board of Health meeting
•May 2017: Aquinnah Board of Health meeting
•May 2017: Presentation at Martha’s Vineyard Regional High School
Project Management
•Jul 2016: Nantucket BOH agrees to jointly develop project management plan
•Jul 2017: Nantucket and MV Steering Committees have full membership (All 6 Vineyard BOHs
selected a representative for MV’s Steering Committee)
Project management
Nantucket Steering Committee
•Danica Connors
•Dr. Howard Dickler
•Dr. Kevin Esvelt
•Dr. John Goldman
•Dr. Emily Goldstein Murphy
•Dr. Sam Telford
Data Safety
Monitoring Board
Independent of the Steering
Committee, MIT, funding
agencies or representative
communities
Size and makeup TBD
Project Manager
Joanna Buchthal
Reports to the Steering
Committee
Proposed decision points
1st Evaluation Point: After immune mice have been created in the lab
-Project go/no go recommendation by DSMB
-If go, project must secure ...
•Regulatory approval for next phase
•Approval for the use of an uninhabited island from the land owner/local
government involved
•Continued interest by the Boards of Health
2nd Evaluation Point: After uninhabited island field trial
-Project go/no go recommendation by DSMB
-If go,project must secure ...
•Regulatory approval for next phase
•Warrant proposed by the Board of Health at a Town Meeting
•Warrant approved at a Town Meeting
Funding
•Initial MIT & Tufts support
•Greenwall Foundation
•Rainwater Foundation
•Recommended for CDMRP Tick-Borne Disease Award
•Philanthropic funding for scale-up
Other projects of comparable scale require funding in
the millions for operations and evaluation
Questions for the citizens of Nantucket
•Is this project still one you might wish to pursue?
•Should mice be immunized vs Lyme, vs ticks, or both?
–Current plan is to do both
•What criteria must be met for you to consider releasing
mice on the island?
•Any suggestions to improve project governance?
•Project name? How about ‘Mice Against Ticks’?
esvelt@mit.edu
buchthal@mit.edu
egoldstein@mariamitchell.org
For more information:
www.responsivescience.org
Questions or Concerns?