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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?