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Home My WebLink AboutMIT Presentation_201708241059120196Preventing Tick-Borne Disease Kevin M. Esvelt, PhD Assistant Professor, MIT Media Labphoto: Janice Haney Carr Our proposal We propose to permanently break the transmission cycle between white-footed mice (the primary reservoir of Lyme disease) and ticks in order to reduce the number of infected ticks and consequently human infections. Controlled releases of Lyme immune mice will introduce immunity to a large fraction of the native mouse population. Open, Community-Driven Science •Clear benefits to citizens •Discussions before experiments •Safeguards agreed upon early •Developed/run by nonprofit groups •Independent monitoring and analysis •Open and responsive science The project is only a concept and can only move forward if embraced by the community It could supplement, not replace, existing control efforts Background Last December, we held a workshop involving island citizens, scientists, ethicists, NGOs and regulators before starting experiments or seeking funding Workshop Takeaways: Island citizens must agree to the following… •The veto points that stop the project •Which approach should be chosen for trials •Where the initial field trial should be held (e.g. uninhabited island(s) ) •Who will perform ecological monitoring and effectiveness tests •Requirements for local release •Any other decision deemed important by the community Thoughtful, Measured Approach •Federal and state regulations must be followed throughout FDA, EPA, State Fish & Wildlife were present at the initial workshop and must approve •All efforts will be guided and monitored by local and national ecologists •Trials will be sequential: uninhabited islands, then small islands, etc. We are not proposing anything anticipated to spread beyond the island No gene drive! (to be explained later) Tick-borne disease is an ecological problem The spirochetes that cause Lyme disease persist by moving between mice and ticks White-footed mouse Black-legged tick B. burgdorferi B. burgdorferi Tick-borne disease is an ecological problem White-footed mouse Black-legged tick B. burgdorferi B. burgdorferi Ticks pass the spirochetes to humans, causing Lyme disease (a similar cycle holds for other tick-borne diseases) Lyme disease Tick-borne disease is an ecological problem White-footed mouse Black-legged tick What if white-footed mice were no longer infected? Relevant study #1 By-hand vaccination reduced Borrelia prevalence by •42% in mice •25% in ticks This study did not control for unvaccinated mice migrating into the area. Tsao JI, Wootton JT, Bunikis J, Luna MG, Fish D, Barbour AG (2004) PNAS Relevant study #2 An oral bait-delivered vaccine reduced tick infection rates by •25% when deployed for 2 years •76% when deployed for 5 years This study did not control for unvaccinated mice migrating into the area. Increase in mouse antibody levels was barely statistically significant. This study also had issues with proper controls. Richer LM, Brisson D, Melo R, Ostfeld RS, Zeidner R, Gomes-Solecki M (2014) J. Inf. Dis. Breaking the cycle If every mouse produced antibodies conferring total immunity from birth, the reservoir of B. burgdorferi would likely collapse Important: Some few ticks could become infected from residual secondary reservoirs, but the rate would be far lower than today No infected mice No infected ticks No infected people Breaking the cycle How might we identify the best antibodies and give them to the island mouse population? Vaccinate mice and identify those that are most resistant Sequence their antibodies to identify which ones are most protective Encode multiple protective mouse antibodies in the mouse genome Release mice for field trial 1: Determine ecological safety and efficacy Release mice for field trial 2: Reduce incidence in populated areas Timeline Funding •Initial MIT support •Philanthropic funding, possibly from multiple sources, for scale-up Other projects of comparable scale require funding in the low tens of millions Mice Immunity Options Option 1: Protect mice from the Lyme spirochete only This should not affect other species, but would not prevent other tick- borne diseases. Option 2: Immunize mice vs ticks This should also prevent babesiosis, anaplasmosis, and ehrlichiosis. It would reduce the tick population, which may have side-effects. Option 3: Do both Implementation Release immune mice constituting ~10% of local population, 4-5x per year •Mouse populations normally fluctuate by >50% over the course of a year •The mouse population would be at most 150% of ‘normal’ •Bait stations should be used to reduce populations near commercial and residential areas Local reductions will not affect the spread of resistance in the population Questions for the citizens of Nantucket •Is this project one you might wish to pursue? •What criteria must be met for you to consider releasing mice on Nantucket? •Should mice be immunized vs Lyme, vs ticks, or both? •Where should the first field trial(s) be held? •Which independent group(s) should do the monitoring and assessment? Note There will be outside interest and media attention due to the novelty of this approach and the possibility of spreading resistance to the mainland using drive systems If successful, we could consider spreading antibodies to the mainland No Need for Drive Systems on Nantucket There is no need for a drive system on Nantucket due to the size of the island A daisy drive system could spread resistance faster with fewer mice, but again, there is no need to use one Leading By Example Pioneering a local and grassroots approach to guide science, technology development, and local ecological management – with decisions made using New England town hall democracy – could help other communities decide similar questions www.sculptingevolution.org Guide CRISPR Genome Guide CRISPR Edited DNA Genome CRISPR+ Edited DNA+Guide RNAs Guide CRISPR Gene Drive AgricultureSustainable ConservationEcologicalHealthHuman This is worth considering. It could solve many problems, but could also do great harm. How are you sure of this? Are our tests thorough enough? It’s far too risky. The precautionary principle says we mustn’t risk it Isn’t that easy for us to say? Even so, the biotech box is probably too dangerous. If it could solve the problem, why not try it? The risks are almost certainly worth it, even if the side effects are comparatively bad. We need to be sure that it’s our technology – developed and tested here. WTF, mate? Worth a shot, no? Not like we haven’t got a lot of ecological problems to solve. Or make worse! Eh, it’s more or less reversible. Gene DriveGlobal Daisy Drive CRISPR+ Edited DNA+Guides Daisy Drive Daisy Drive Daisy Drive Daisy Drive Generations Daisy Drive Generations Frequency Populationin Local Daisy Drive Generations Frequency Populationin Local Daisy Drive Generations Frequency Populationin Local MaximumFrequency # of Daisy Elements