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Â Appendix A Workshop Agenda CARE, USE, AND WELFARE OF MARMOSETS AS ANIMAL MODELS FOR GENE EDITINGâBASED BIOMEDICAL RESEARCH A Roundtable on Science and Welfare in Laboratory Animal Use Workshop October 22-23, 2018 Keck Center 500 Fifth Street NW Washington, DC, Room 100 Workshop Context The New World primate, the common marmoset (Callithrix jacchus), is a research model of increasing importance for biomedical research in the United States and globally. Marmosets present certain advantages compared to more traditional nonhuman primate species and may be particularly useful for the development of new disease models using genetic engineering (achieved using the CRISPR/Cas9 technology) and as- sisted reproductive technologies. Germline transmission of a transgene in marmosets was first shown in 2009 while mapping of their genome was published in 2014. Production of transgenic models of disease in marmosets is currently being tested in the United States and in Japan among others. However, a number of concerns have been voiced with respect to the increasing popularity of marmoset animal models based on the advent of genetic engineering/gene editing. Planned by an ad hoc committee, the Roundtable on Science and Welfare in Laboratory Animal Use will host a public workshop to explore and address these concerns. Workshop Objectives Invited experts and speakers from academia, industry, non-profit organizations and government agen- cies will convene for this 2-day public workshop to: 1. Examine the availability of marmosets in the United States and abroad. 2. Discuss animal welfare and ethical considerations stemming from the use of wildtype and genet- ically modified marmosets. 3. Discuss standards of housing and care, dietary needs and feeding requirements for wildtype as well as genetically modified marmosets in captivity. 4. The presentations and discussions at the workshop will be captured in a workshop proceedings. 58 Prepublication Copy
Appendix AÂ AGENDA MONDAY, October 22, 2018, Keck 100 8:00AM Welcome and Introduction to Workshop Workshop Co-Chairs: JAMES FOX, Massachusetts Institute of Technology SAVERIO CAPUANO, Wisconsin National Primate Research Center Roundtable Director: LIDA ANESTIDOU, Institute for Laboratory Animal Research 8:10AM Keynote: The Historical Use of Callitrichids SUZETTE TARDIF, Southwest National Primate in Biomedical Research and Current Trends Research Center Introduction JAMES FOX Session 1 â Marmoset Availability 8:40AM Current State of Affairs: Analyzing Session Moderator: the Numbers SAVERIO CAPUANO Objectives: ï· Inform on the status of marmoset population in the United States ï· Present one countryâs approach to meeting its marmoset-dependent research needs ï· Present a perspective on the conflict between conservation, bioprospecting and biomedical research ï· In the context of anticipated demand for marmosets, discuss an equitable, sustainable and fair control of and access to marmoset resources (numbers, tissues and genetic material; how supply lines are established and the role of wild caught marmosets) globally Speakers: JON LEVINE, Wisconsin National Primate Research Center ERIKA SASAKI, Central Institute for Experimental Animals, Japan MARIA ADELIA BORSTELMANN DE OLIVEIRA, Federal Rural University of Pernambuco - UFRPE, Brazil SAVERIO CAPUANO Q&A with the audience 10:10AM COFFEE BREAK 10:30AM Genetic Diversity in Times of Session Moderator: Increased Demand JAMES PICKEL, National Institute of Mental Health Objectives: ï· Examine the prospect and application of a Species Survival Plan for marmosets, including its role in the exchange of genetic information (+ small colonies) ï· Discuss elements of genetic and microbiological characterization of marmosets o Do the provenance and genetic background of marmoset colonies play a role in choosing research questions o Maintain marmoset colony genetics ï· Discuss the genetic diversity in Japanâs marmoset colonies ï· Analyze the need for and role of genetic diversity in marmosets used in biomedical research (genome sequencing) ï· Present a chip-based genomic analysis Speakers: KENTON KERNS, Smithsonian National Zoo and Conservation Biology Institute JOANNA MALUKIEWICZ, Arizona State University YASUHIRO GO, National Institute of Physiology, Japan JEFFREY ROGERS, Baylor College of Medicine RICARDO DEL ROSARIO, Broad Institute Prepublication Copy 59
Care, Use, and Welfare of Marmosets as Animal Models for Gene EditingâBased Biomedical Research 11:45AM Maintain and Track Genetic Diversity in Session Leader: Marmoset Colonies - Facilitated Discussion JAMES PICKEL with the Audience ï· What is the contribution of genetic diversity to marmoset-based animal models? ï· What are some of the most common problems encountered in tracking genetic diversity? ï· What are some of the potential solutions in maintaining said diversity? ï· It appears likely that the US marmoset research population will include a number of breeding colonies that are each relatively small, raising questions as to how to best maintain the overall population to ensure genetic viability. o What are the specific goals of genetic management of the marmoset population â e.g., outbreeding? Definition of founder populations? Enrichment or elimination of certain lineages based on either genotype or phenotype? o What can we learn from other institutions that manage numerous, small breeding populations â e.g., zoos? o What mechanisms can be used to either encourage or enforce broad population genetic management? o What would be the costs and benefits of plans to genotype or sequence every marmoset in research? 12:30PM LUNCH (Lunch will not be provided. There is a cafeteria on the 3rd floor of this building) Session 2 â Marmosets as Research Models 1:30PM Using Marmosets in Biomedical Research Session Moderator: MARINA EMBORG, Wisconsin National Primate Research Center Objectives: In order to showcase the versatility of marmosets as animal models, panelists will use examples of different research questions to discuss: ï· Aging research with marmosets ï· Marmoset-based infectious disease research under biocontainment conditions ï· The development of marmoset-based neuroscience models ï· Genomic editing in marmosets ï· Using behavioral tests (fMRI) and neuroimaging analysis for model verification Speakers: CORINNA ROSS, Texas A&M University, San Antonio JEAN PATTERSON, Texas Biomedical Research Institute JAN LANGERMANS, Biomedical Primate Research Center, The Netherlands ERIKA SASAKI AFONSO SILVA, National Institute of Neurological Disorder and Stroke Q&A with the audience 3:30PM COFFEE BREAK 3:45PM Ethical Considerations Regarding the Session Overview: Use of Marmosets in Research ERIC HUTCHINSON, Johns Hopkins University Objectives: ï· Discuss the ethics of genetically modifying the marmoset, a nonhuman primate ï· Analyze the ethical imperative of being cognizant of your knowledge before starting research with marmosets (small colonies; transport; stress) Speakers: ADAM SHRIVER, Oxford University, United Kingdom STEVEN NIEMI, Harvard University 4:45PM Facilitated Discussion with the Audience Session Leader: ERIC HUTCHINSON 5:30PM End of Day 1 60 Prepublication Copy
Appendix AÂ TUESDAY, October 23, 2018, Keck 100 8:15AM Opening of Day 2 and Recap of Day 1 SAVERIO CAPUANO 8:30AM Highlights of the workshop on Transgenic MARINA EMBORG and Chimeric Neuroscience Research: Exploring the Scientific Opportunities Afforded by New Nonhuman Primate Models Session 3 â Marmoset Husbandry 8:45AM Select Topics in Marmoset Husbandry Session Moderator: JACO BAKKER, Biomedical Primate Research Center, The Netherlands Objectives: ï· Highlight marmosetsâ nutritional needs and daily dietary management ï· Provide an overview of marmoset-specific behavior and enrichment ï· Discuss marmosetsâ reproductive cycle and ways of controlling it ï· Present basic elements of Specific Pathogen Free marmoset colonies ï· Explore options for harmonization of marmoset husbandry from a global perspective Speakers: MICHAEL POWER, Smithsonian National Zoo and Conservation Biology Institute NANCY CAINE, California State University, San Marcos DAVID ABBOTT, Wisconsin National Primate Research Center TAKASHI INOUE, Central Institute for Experimental Animals, Japan JACO BAKKER 10:25AM Facilitated Discussion with the Audience Session Leaders: SUZETTE TARDIF JACO BAKKER There is considerable variation in the husbandry and management of marmosets. Such variation may impede efficient and effective use of this species as a research model and may lead to irreproducible studies. ï· What are the areas of management that are most likely to vary and have the potential to affect animal welfare? ï· What are the areas of management that are most likely to vary and have the potential to affect study outcomes? ï· What mechanisms can we use to gather information on this variation and assess its effects? ï· How do we encourage evidence-based decision-making regarding husbandry and management? ï· How do we best disseminate such evidence-based management information to the broader community? 12:00PM LUNCH (Lunch will not be provided. There is a cafeteria on the 3rd floor of this building) Session 4 â Marmoset Veterinary/Clinical Care 1:00PM Select Topics in Marmoset Veterinary Care Session Moderator: ERIC HUTCHINSON Objectives: ï· Provide a framework for an overall health management of marmoset colonies ï· Discuss common clinical presentations in and treatments for marmosets ï· Provide an overview of basic elements of anesthesia and analgesia for marmosets ï· Present basic facts and practical aspects of marmoset reproduction ï· Discuss key features of marmoset pathology Prepublication Copy 61
Care, Use, and Welfare of Marmosets as Animal Models for Gene EditingâBased Biomedical Research Speakers: CASEY FITZ, Wisconsin National Primate Research Center JESSICA IZZI, Johns Hopkins University ANNA GOODROE, University of Houston MONIKA BURNS, Massachusetts Institute of Technology KEITH MANSFIELD, Novartis 2:40PM Facilitated Discussion with the Audience Session Leader: ERIC HUTCHINSON Session 5 â Improving Research Practices that Depend on the Use of Marmosets: Key Messages and Future Actions 4:00PM Closing Session â Improving Research Session Leaders: Practices that Depend on the Use of JAMES FOX Marmosets: Key Messages and Future SAVERIO CAPUANO Actions 4:30- Workshop Adjourns 4:45PM 62 Prepublication Copy