Kenneth A. Oye, Gene Drives: Mechanisms, Applications and Risk Governance Issues
•Download as PPTX, PDF•
3 likes•1,106 views
January 26, 2018 In the United States, two major federal laws apply to vertebrate animals used in laboratory research. The first of these two statutes, the Animal Welfare Act (AWA, under the US Department of Agriculture), celebrated its fiftieth anniversary in 2016. The second statute, the Health Research Extension Act of 1985 (also referred to as the Public Health Services Act, or PHS Act), which is similar to the AWA, applies specifically to work funded by the US Public Health Service (i.e., agencies under the Department of Health and Human Services). Understanding laboratory animal law is necessary and fundamental for all researchers relying on results from animal research, laboratory animal veterinarians, institutional officials, Institutional Animal Care and Use Committee (IACUC) members and veterinarians in training. They require familiarity with both the scope and particulars of these laws. Different parties interested in or impacted by laboratory animal laws can have significantly different perspectives about the scope or efficiency of the regulations or their implementation. The Roundtable on Science and Welfare in Laboratory Animal Use of the Institute for Laboratory Animal Research, the Petrie-Flom Center for Health Law Policy, Biotechnology and Bioethics, and the Animal Law and Policy Program of Harvard Law School convened this pre-workshop webcast and a workshop to discuss the future of federal laboratory animal law in the United States. For more information, visit our website at: http://petrieflom.law.harvard.edu/events/details/future-directions-for-laboratory-animal-law-in-the-united-states
More Related Content
What's hot
What's hot (20)
Similar to Kenneth A. Oye, Gene Drives: Mechanisms, Applications and Risk Governance Issues
Similar to Kenneth A. Oye, Gene Drives: Mechanisms, Applications and Risk Governance Issues (20)
More from The Petrie-Flom Center for Health Law Policy, Biotechnology, and Bioethics
More from The Petrie-Flom Center for Health Law Policy, Biotechnology, and Bioethics (20)
Recently uploaded
Recently uploaded (20)
Kenneth A. Oye, Gene Drives: Mechanisms, Applications and Risk Governance Issues
- 1. National Academy of Sciences Workshop on Future Directions for Laboratory Animal Law Harvard Law School January 26, 2018 ON GENE DRIVES MECHANISMS, APPLICATIONS AND RISK GOVERNANCE ISSUES Kenneth A. Oye Director, Program on Emerging Technologies Professor, Political Science and Data, Systems and Society Massachusetts Institute of Technology This presentation is based on research, meetings, and safety /security programming supported by NSF Division of Molecular and Cellular Biology, NSF Directorate for Environmental Research, and NSF Directorate for Engineering; Open Philanthropy Project; DARPA Safe Genes; the International Risk Governance Council; MIT Center for Biomedical Innovation and MIT International Policy Laboratory.
- 2. GENE DRIVES WHAT IS A GENE DRIVE / SELF PROPAGATING GENETIC ELEMENT? Mendelian: 50% odds genetic alteration will pass to next generation IFF fitness or reproductive edge, THEN propagate Gene drive: 99.5% odds alteration will pass to next generation Edit whole population without fitness or reproductive edge FOR WHAT APPLICATIONS? Control invasive species • Limit population of invader by reducing fitness or reproductive success Reduce herbicide or pesticide resistance • Edit plants or insects to increase sensitivity to controls Control vector borne diseases like malaria, dengue, zika, lyme • Editing vector to not carry disease / Eradicating vector WITH WHAT RISK GOVERNANCE ISSUES? Environmental and security effects Fit with existing regulations Technological safeguards Current status of debate over risks
- 3. GENE DRIVES WHAT IS A GENE DRIVE / SELF PROPAGATING GENETIC ELEMENT? Mendelian: 50% odds genetic alteration will pass to next generation IFF fitness or reproductive edge, THEN propagate Gene drive: 99.5% odds alteration will pass to next generation Edit whole population without fitness or reproductive edge FOR WHAT APPLICATIONS? Control invasive species • Limit population of invader by reducing fitness or reproductive success Reduce herbicide or pesticide resistance • Edit plants or insects to increase sensitivity to controls Control vector borne diseases like malaria, dengue, zika, lyme • Editing vector to not carry disease / Eradicating vector WITH WHAT RISK GOVERNANCE ISSUES? Environmental and security effects Fit with existing regulations Technological safeguards Current status of debate over risks
- 5. HOW GENE DRIVES BIAS INHERITANCE A Altered genes (blue) and wild type (grey) ~ 50 % odds B Altered gene with gene drive and wild type ~ 100 % odds Gene drives cut homologous chromosomes lacking alteration and cause cell to copy altered gene and the gene drive ------ Inheritance biasing “selfish” genetic elements evolve 2003 Burt proposes gene drive design to alter wild population 2012 Charpentier/Doudna/Anderson/Church/Zhang Cas9/CRISPR 2014 Esvelt/Church propose Cas9/CRISPR to create gene drives
- 6. MENDELIAN AND GENE DRIVE INHERITANCE OF ALTERED GENE
- 7. MENDELIAN AND GENE DRIVE INHERITANCE OF ALTERED GENE
- 8. MENDELIAN AND GENE DRIVE INHERITANCE OF ALTERED GENE
- 9. MENDELIAN AND GENE DRIVE INHERITANCE OF ALTERED GENE
- 10. GENE DRIVE BASICS Gene drives exist in nature / inheritance biasing “selfish genes” Purpose built gene drives proposed (Burt, 2003) CRISPR enabled gene drives proposed (Esvelt et al, 2014) Works with sexually reproducing plants & animals with short reproduction cycles Specify target sequence to be cut and replacement sequence to be inserted Gene drive systems specific to species / subspecies / alteration TECHNICAL ISSUES OUTSTANDING Design of gene drive systems Robustness of systems with mutation Precision of editing with mutation Localization drives Immunization drives Reversal drives Burt A, 2003, “Site-specific selfish genes as tools for the control and genetic engineering of natural populations,” Proceedings of the Royal Society of Biological Sciences, Vol: 270, Pages: 921-928, ISSN: 0962-8452
- 11. GENE DRIVES WHAT IS A GENE DRIVE / SELF PROPAGATING GENETIC ELEMENT? Mendelian: 50% odds genetic alteration will pass to next generation IFF fitness or reproductive edge, THEN propagate Gene drive: 99.5% odds alteration will pass to next generation Edit whole population without fitness or reproductive edge FOR WHAT APPLICATIONS? Control invasive species • Limit population of invader by reducing fitness or reproductive success Reduce herbicide or pesticide resistance • Edit plants or insects to increase sensitivity to controls Control vector borne diseases like malaria, dengue, zika, lyme • Editing vector to not carry disease / Eradicating vector WITH WHAT RISK GOVERNANCE ISSUES? Environmental and security effects Fit with existing regulations Technological safeguards Current status of debate over risks
- 12. APPLICATIONS TO INVASIVE SPECIES TIGER MOSQUITO, ARGENTINE ANT, MIRROR CARP, HOUSE MOUSE
- 13. APPLICATIONS TO INVASIVE SPECIES ISLAND CONSERVATION: GENE DRIVE AS “POWER-TOOL” FOR RATS
- 14. APPLICATIONS TO HERBICIDE AND PESTICIDE RESISTANCE
- 15. VECTOR BORNE DISEASESAPPLICATIONS TO DISEASE VECTORS INSECTS AND MAMMALS
- 18. CONTROLLING VECTOR BORNE DISEASE USUAL OPTION (NOT VECTOR DISEASE SPECIFIC) IMMUNIZATION/VACCINATION OF HUMAN POPULATION TARGETTING THE VECTOR, REDUCING EXPOSURE CUT VECTOR POPULATION ENVIRONMENT - DRAIN SWAMP CUT VECTOR POPULATION KILL - INSECTICIDE, FLOCK ERADICATION CUT EXPOSURE TO VECTOR BEDNETS, DEET
- 19. CONTROLLING VECTOR BORNE DISEASE USUAL OPTION (NOT VECTOR DISEASE SPECIFIC) IMMUNIZATION/VACCINATION OF HUMAN POPULATION TARGETTING THE VECTOR, REDUCING EXPOSURE CUT VECTOR POPULATION ENVIRONMENT - DRAIN SWAMP CUT VECTOR POPULATION KILL - INSECTICIDE, FLOCK ERADICATION CUT EXPOSURE TO VECTOR BEDNETS, DEET CUT VECTOR POPULATION OXITEC – LARGE N GM STERILE MOSQUITO
- 20. CONTROLLING VECTOR BORNE DISEASE USUAL OPTION (NOT VECTOR DISEASE SPECIFIC) IMMUNIZATION/VACCINATION OF HUMAN POPULATION TARGETTING THE VECTOR, REDUCING EXPOSURE CUT VECTOR POPULATION ENVIRONMENT - DRAIN SWAMP CUT VECTOR POPULATION KILL - INSECTICIDE, FLOCK ERADICATION CUT EXPOSURE TO VECTOR BEDNETS, DEET CUT VECTOR POPULATION OXITEC – LARGE N GM STERILE MOSQUITO CUT VECTOR POPULATION IMPERIAL – GENE DRIVE SEX RATIO IMMUNIZE VECTOR MIT - GENE DRIVE AND WHITE FOOTED MOUSE
- 21. GENE DRIVES WHAT IS A GENE DRIVE / SELF PROPAGATING GENETIC ELEMENT? Mendelian: 50% odds genetic alteration will pass to next generation IFF fitness or reproductive edge, THEN propagate Gene drive: 99.5% odds alteration will pass to next generation Edit whole population without fitness or reproductive edge FOR WHAT APPLICATIONS? Control invasive species • Limit population of invader by reducing fitness or reproductive success Reduce herbicide or pesticide resistance • Edit plants or insects to increase sensitivity to controls Control vector borne diseases like malaria, dengue, zika, lyme • Editing vector to not carry disease / Eradicating vector WITH WHAT RISK GOVERNANCE ISSUES? Environmental and security effects Fit with existing regulations Technological safeguards Current status of debate over risks
- 22. 22
- 23. ENVIRONMENTAL ISSUES Mutation of gene drives inevitable, will alter effects Lateral gene transfer may reduce discrimination Immunization and reversal may not be effective Diseases borne by vectors will evolve Environmental effects will vary by species and alteration SECURITY ISSUES Gain-of-function enabling ability to host diseases Suppression of crops and livestock in traditional agriculture Suppression of pollinators and other keystone species Immunization drives may protect self and allies from effects Reversal drives may be withheld for economic or political gain Security implications uncertain - note ingenuity and creativity
- 24. INTERNATIONAL SECURITY 1925 GENEVA PROTOCOL • Prohibits “bacteriological methods of warfare” • Extends (by analogy) to viral agents . . . and more? UN BIOLOGICAL WEAPONS CONVENTION • Article 1 “general purpose criterion” bans development, production, or stockpiling of agents that have no justification for prophylactic, protective, and other peaceful purposes. • National measures and Australia Group Guidelines rely on lists of organisms and toxins
- 25. INTERNATIONAL ENVIRONMENT Transborder movements inevitable, effects complex CARTAGENA • Article 17 “Unintentional Transboundary Movements and Emergency Measures” notify if released organism likely to have significant adverse effects on biodiversity or health. • Other provisions treat movement of organisms as trade issue, with controls through ordinary border measures. NAGOYA-KUALA LUMPUR SUPPLEMENT • Article 27 - Parties to adopt process to define rules on liability and redress for damage from trans-border movements
- 26. USES OF LEAD TIME Science nerds: Assess environmental and security effects, flag sources of uncertainty, direct research at uncertainty • Effect of possible instability of drives on environment • Effect of lateral gene flow on diffusion of alterations • Improve test methods - mesocosms and microcosms Technology geeks: Modify organisms and uses to minimize risks by designing, testing and incorporating safety features • Develop and test immunization and reversal drives • Develop and test degradation methods to localize effect Policy wonks: Identify and address gaps in policy, fund research, foster informed public debate . . . . • Functional approach -- not just lists of pathogens • Gaming / “white hat hacking” to flag misuses • Public debate over benefit/risk in advance of release > US NSABB, UN BWC, NRC Gene Drive Study, IEGBRR
- 28. SOME REACTIONS OMG Don’t tell the muggles They will panic No need to alarmBesides the magic is not ready.
- 29. SOME REACTIONS OMG Don’t tell the muggles They will panic Don’t let Voldemort know. Classify all information needed to create gene drives
- 30. SOME REACTIONS OMG Don’t tell the muggles They will panic Don’t let Voldemort know. Classify all information needed to create gene drives Malaria is nature’s way of controlling human population Don’t eradicate malaria “Kelly from Millbury”
- 31. SOME REACTIONS OMG Don’t tell the muggles They will panic Don’t let Voldemort know. Classify all information needed to create gene drives Malaria is nature’s way of controlling human population Don’t eradicate malaria Gene drives would affect the global commons We need global discussion of values and decision processes
- 32. THE MAGIC WAS READY In drosophila (January 2015) and anopheles (October 2015)
- 33. MOST WIZARDS ARE ACTING RESPONSIBLY Code of Conduct
- 34. MOST WIZARDS ARE ACTING RESPONSIBLY Code of Conduct
- 35. WIZARDS USING PATENTS TO INDUCE RESPONSIBLE CONDUCT OCTOBER 2016
- 36. YOUNG WIZARDS LEARN FAST - iGEM NOVEMBER 2016 College students try to hack a gene drive — and set a science fair abuzz STATNEWS 12/14/2016
- 37. FDA IS ADAPTING FDA Guidance for Industry on Regulation of Intentionally Altered Genomic DNA in Animals (2009, revised 2017) Altered genomic DNA in an animal is considered a drug if it affects the structure or function of the body of the animal. Each specific alteration is considered to be a separate new animal drug, subject to new approval requirements. Factors affecting exercise of enforcement discretion include: • Is there anything about the article that poses human, animal, or environmental risk? • Does the animal with altered DNA pose any more of an environmental risk than its counterpart? • Could disposition of animals with altered DNA pose human, animal, or environmental risks? • Are there other safety questions not adequately addressed by the sponsor? Exception: Guidance does not include articles intended to prevent, destroy, repel, or mitigate mosquitoes for population control. Such products are pesticides regulated by EPA.
- 38. Kenneth Oye, Maureen O’Leary and Margaret F. Riley Science, 18 August 2017NIH IS REFLECTING Science, August 18, 2017
- 39. FUNDERS ARE FINANCING GENE DRIVE RESEARCH Gates Foundation $75 million to Target Malaria Tata Trust $70 million to UCSD DARPA $65 million to Safegenes TATA TRUST
- 40. FUNDERS ARE SETTING GUIDELINES FOR RESEARCH Science, Policy Forum December 1, 2017 Tata
- 41. FUNDERS ARE SUPPORTING TECHNICAL SAFEGUARDS WORK Immunization, Reversal and Localization Designs and Testing “Daisy Chain Gene Drives for Alteration of Local Populations,” Nobel et al, Responsive Science, June 2016
- 42. NGOS ARE CRITICAL OF GENE DRIVE FUNDING
- 43. ACADEMIES & INTERNATIONAL ORGANIZATIONS DELIBERATE UN BIOLOGICAL WEAPONS CONVENTION MEETING OF EXPERTS GENEVA AUGUST 2014 INTERNATIONAL EXPERTS GROUP ON BIOSECURITY REGULATION BERLIN AUGUST 2015 NATIONAL ACADEMY OF SCIENCES PANEL WASHINGTON DC 2015-2016 NORTH CAROLINA STATE DELIBERATIVE WORKSHOP RALEIGH MARCH 2016 EUROPEAN UNION SYNERGENE AMSTERDAM JUNE 2016 OECD GENE EDITING WORKSHOP OTTAWA OCTOBER2016 IUCN WORLD CONSERVATION CONGRESS HAWAII SEPTEMBER 2016 UN CONVENTION ON BIODIVERSITY COP13 CANCUN DECEMBER 2016
- 44. 44 NGOS CALL FOR MORATORIUM ON RESEARCH AND RELEASE
- 45. SOME DISCUSSION QUESTIONS What are benefits and costs of a moratorium on research and release? Risks of uncontrolled release, need for info & technical safeguards What additional information is needed to provide a basis for decisions? On effectiveness of disease eradication and vector control applications On safety / environmental / security effects On technical safeguards to localize or reverse effects of drives What conditions should be imposed on research? Physical or genetic isolation? Technical safeguards to localize, immunize, reverse? Who should impose conditions… and how? Researchers/Regulators/Funders/Patent Holders/Oversight Committees What should those charged with animal research oversight do now? Legal: Respect existing regulations and guidance . . . but gaps are huge. Political: Identify gaps and seek changes in regulations and guidance. Duty to protect: Go beyond what is legally required to begin to fill gaps.
- 46. Synthetic Biology Policy Group Evan Appleton, Harvard Medical, Postdoc Church Lab Pete Carr, MIT Lincoln Laboratory, Head Synthetic Biology Unit Courtney Diamond, MIT Biology and Political Science, UROP PoET Kevin Esvelt, Professor, MIT Media Lab and Synthetic Biology Center Samuel Weiss Evans, Professor Tufts STS and Fellow Harvard STS Michael J. Fischer, Professor MIT Anthropology and STS Lily Fitzgerald, MIT TPP and Esvelt Lab, formerly Gingko Bioworks David Gillum, ASU Biosafety Officer and ABSA International Consular Natalie Kofler, Yale, Research Scientist, School of Forestry and Environment Todd Kuiken, NC State, Sr Res Scholar Genetic Engineering & Society Center Shlomiya Bar-Yam Lightfoot, MIT Postdoc PoET Phiona Lovett, MIT, Administrative Assistant PoET Jeantine Lunshof, Professor, Groeningen; Harvard Med, Ethicist, Church Lab Leonard Miller, Sullivan and Worcester LLP Piers Millett, Oxford Future of Humanity Institute and iGEM, formerly UNBWC Yusuke Mori, Cabinet Office of Japan Kenneth A.Oye, Professor, MIT Political Science and IDSS, Director PoET Megan Palmer, Stanford, Senior Research Scientist CISAC Larisa Rudenko, MIT Visiting Scholar, PoET Meicen Sun, MIT doctoral candidate Political Science Katherine Von Stackelberg, Senior Research Scientist, Harvard Public Health Ed Woll, Sullivan and Worcester LLP; former Vice President Sierra Club Mass