To augment and expand upon the findings of the Nonhuman Primate Evaluation and Analysis Part 1: Analysis of Future Demand and Supply study report, which was derived from historical analyses, supplier interviews, and user surveys, an expert panel forum was convened by the NIH on “Challenges in Assessing Nonhuman Primate (NHP) Needs and Resources for Biomedical Research.” A forum was conducted August 23-24, 2018 and brought together program officers from the NIH ICOs that sponsor the majority of NHP studies, leading researchers who use NHPs and represent a broad spectrum of scientific areas, and NHP resource managers from the academic, government, and commercial sectors. The objectives of the meeting were to:

• Forecast the future uses of NHPs in biomedical research
• Discuss and determine the scientific advances that are driving the future research
• Define the relevant and emerging NHP models that will be required for future biomedical advances
• Assess the capabilities of the existing resources and their ability to adapt to future needs, including an examination of the timeframe needed for expansion and, if expansion is not possible, what additional resources or infrastructure would be required
• Address the challenges in the resource planning process

The forum was designed with the assistance of an organizing committee comprised of experts in NHP research and resource management and was intended to examine demand and supply from the perspective of each of the three groups of attendees: program sponsors who broadly generate demand based on their funding priorities, researchers who have specific NHP needs, and resource managers who must manage their breeding colonies and provide specialized populations and research capabilities to meet the needs of researchers. The discussions and potential solutions identified by forum participants were further evaluated by the organizing committee after the conclusion of the meeting and synthesized into a set of key recommendations for NIH consideration.

• Nonhuman Primate Evaluation and Analysis Part 1: Analysis of Future Demand and Supply

• Nonhuman Primate Evaluation and Analysis Part 2: Report of the Expert Panel Forum on Challenges in Assessing Nonhuman Primate Needs and Resources for Biomedical Research

“Strengthening Research Resources: Integration, Innovation, and Standardization,” the Twelfth Comparative Medicine Resource Directors Meeting, was held August 7-8, 2018 in Rockville, MD. All Resource Directors funded by the Office of Research Infrastructure Programs (ORIP)/Division of Comparative Medicine (DCM) were invited to attend. This biennial meeting offers a forum for the exchange of information among grantees and NIH Program Officers provide useful information to DCM-funded Resource Directors and for developing synergistic working groups, interactions, and collaborations. A primary objective was to generate broad interests in Resources, discuss “lessons learned,” and to convey a sense of what’s been done and what can be done in the future. Another important objective was to allow Resource Directors the opportunity to discuss optimization of administrative processes. ORIP Program Officers and others from various NIH Institutes, Centers, and Offices (ICOs) contributed to scientific discussions to further enhance national use of DCM-funded resources.

On July 30, 2018, the Office of Research Infrastructure Programs (ORIP) convened a workshop on “Defined Reference Diets for Zebrafish and Other Aquatic Biomedical Research Models: Needs and Challenges”.  Aquatic animal species, such as zebrafish (Danio rerio), are powerful models for studying human development, behavior, genetics, and disease. The ability to produce transgenic and mutant lines provides biomedical researchers with many options for developing models of human diseases and for developing relevant therapeutic approaches. Different facilities and laboratories use a variety of diets and feeding protocols to maintain these models. In many laboratories zebrafish are reared with a combination of live feed (ex vivo) and/or one of many undefined commercial diets. Commercial diets used in zebrafish husbandry differ significantly in ingredient and nutrient composition and often contain preservatives, lakes, dyes, antinutritional factors, or bioactive food compounds. Studies indicate that the length, weight, sexual maturation, fecundity, and mortality of zebrafish can vary significantly with different diets. Unfortunately, impacts of diet on zebrafish health and behavior and corresponding implications for zebrafish research outcomes are not well described. Currently, the daily dietary nutrient requirements of almost all nutrients have not been investigated. There is also no consensus among aquatic facilities, researchers, and commercial vendors on nutritional requirements at various life stages (i.e., larval, juvenile, and adult) or for particular research applications to minimize husbandry variations among aquatic facilities or laboratories. Complicit in this lack of consensus is a community-wide lack of understanding of the role of nutrition in animal development, health, and research outcomes. To address this gap, the Office of Research Infrastructure Programs (ORIP) is sponsoring a workshop to bring together members of the zebrafish scientific community, with expertise in zebrafish and other aquatic and relevant models, for a day of discussion. The workshop attendants will assess the needs and challenges of developing defined diets and optimized feed management strategies that will support normal zebrafish development and physiology and will facilitate the analysis of phenotypes in a standardized nutritional environment. Standardization and education will promote rigor and reproducibility in some zebrafish studies and enhance the power of zebrafish and other aquatic models in biomedical research.

Objectives:

• Review diet development strategies, where available, in other biomedical model species.
• Assess the current nutrition status of zebrafish.
• Describe the need for defined diets for maintenance and experimental stocks, including assessment of life stage requirements.
• Discuss the potential impact of defined diets on genetic stocks used in biomedical research, their effect on development, physiology and expressivity of disease/mutant phenotypes.
• Identify obstacles and evaluate strategies that may lead to a successful consensus, acceptance, and implementation of defined diets among the different scientific community stakeholders.
• Define an educational approach to informing the community and associated partners (journals, organizations, granting agencies, etc.)
• Determine whether/how the approach to develop a defined diet for zebrafish could be applied to other aquatic models, and animal models in general.

Speaker Presentations

• Session 1 Videos: Historic perspectives, current diets, ingredient considerations, and feeding management in the husbandry of zebrafish and other animal models: a comparative analysis.
• Session 2 Videos: The impact of diet variation on health and experimental outcomes of zebrafish and other aquatic models.

On September 11-12, 2017, the Office of Research Infrastructure Programs (ORIP) convened a workshop “Zebrafish and Other Fish Models: Description of Extrinsic Environmental Factors for Rigorous Experiments and Reproducible Results”. The workshop brought together stakeholders, including facility managers, veterinarians, investigators, journal editors, and representatives from industry, for plenary and break-out sessions on how to account for extrinsic environmental factors. Specifically, the sessions focused on the effects of external environmental conditions on experimental outcomes and the need to strengthen experimental data with extrinsic environmental factors. The participants addressed questions on how to collect, manage, and share such data to benefit facilities and to improve robustness and reproducibility of experiments. The participants developed a draft of guidelines on extrinsic data formats and contents for inclusion in publications; the guidelines will be shared with a broader peer community for comments and edits, before they are published as a white paper.

On September 6, 2017, the Office of Research Infrastructure Programs (ORIP) at National Institutes of Health (NIH) convened a workshop on the “Tagging and Identification of Animal Resources.” The goals of the workshop were to provide participants with (1) a thorough review of the current challenges and possible solutions for the reporting and unique identification of research resources, including model organisms used in biomedical research; (2) an overview of the Resource Identification Initiative (RII or Initiative) to create and maintain biological resource identifiers for NIH-supported animal repositories; and (3) a hands-on session for Resource Directors and NIH staff on acquisition and use of unique Research Resource Identifiers (RRIDs) to identify research resources and conduct citation analysis of their usage. Participants included representatives from academia, industry, and publishing. 

The Cryopreservation of Aquatic Biomedical Models Workshop was held on January 7, 2017 in Birmingham, Alabama. Aquatic animal species such as zebrafish, medaka, Xiphophorus, and Xenopus are increasingly valuable to biomedical researchers because they provide critical clues to the biological mechanisms that underlie human health and disease. Although considerable resources have been invested to generate transgenic, knockout, and mutant lines of many of those aquatic species, reliable and cost-effective approaches for long-term preservation of these valuable lines are still lacking. Currently, cryopreservation of sperm is the sole and proven method for the long-term maintenance in many aquatic models, with no other approaches available to aquatic researchers. To address this gap, the National Institute of Health’s Office of Research Infrastructure Programs (ORIP) sponsored a workshop, whose objectives were to (1) assess the status of germplasm cryopreservation in various aquatic models; (2) identify the obstacles, opportunities, and priorities that may address the need for improved methods; and (3) evaluate novel and emerging research and technologies that might lead to the successful preservation of other germplasm formats. Approximately 25 participants, including experts in the field of cryopreservation of aquatic models, representing the cryopreservation scientific community at large attended the workshop, despite the severe weather that affected the area where the workshop was held. Discussions during the different sessions resulted in specific, actionable recommendations to ORIP, as described in the accompanying report.

Drosophila melanogaster is widely used in the biomedical research community to study development, model human diseases and undertake high-throughput drug discovery. However, reliable and cost-effective approaches for long-term preservation of Drosophila stocks are lacking. To address this gap, the Office of Research Infrastructure Programs in the Division of Program Coordination, Planning and Strategic Initiatives and the National Institute of Neurological Diseases and Stroke co-sponsored a workshop titled “Cryopreservation of Drosophila Strains” in Orlando, Florida on July 13, 2016. The objective of this workshop was to evaluate the potential and practicality of developing efficient preservation methods for long-term storage of Drosophila stocks.

The Office of Research Infrastructure Programs in the Division of Program Coordination, Planning, and Strategic Initiatives convened on September 10-11, 2015 a Symposium titled “Linking Disease Model Phenotypes to Human Conditions” at the Fishers Lane Conference Center, Rockville, MD. Over 120 participants, including 58 NIH representative from 16 Institutes and Centers, attended the meeting. Among participants were foreign scientists, representatives from other government agencies, such as FDA and US Army, and the biotech and pharma industry. The purpose of the Symposium was to discuss the current status of phenomics and its role in closing the gap that exists between biomedical research and clinical medical practice.

Over 600 participants attended the 16th annual Merial-NIH Symposium at the campus of UC Davis, California, hosted by the College of Veterinary Medicine.  More than 450 veterinary students from 33 academic institutions were represented at the symposium, including 26 veterinary colleges from the United States, two from Canada, and two from Europe as well as five other research centers and universities, including NCI/NIH. Other participants included University Program Directors and representatives from the NIH, Merial, Burroughs Wellcome, the Association of American Veterinary Colleges, the American Veterinary Medical Association (AVMA), and the Howard Hughes Medical Institute. Students attending the symposium included veterinary students participating in summer research programs as well as DVM/PhD students and postdoctoral veterinarians in research training programs. The symposium theme of “Solving Complex Challenges at the Interface of Humans, Animal and their Environment” emphasized the impact of the One Health concept on local, national and global sustainability as well as human and animal health and scientific discovery.

On April 7–8, 2015, the Office of Research Infrastructure Programs (ORIP) in the Division of Program Coordination, Planning, and Strategic Initiatives, sponsored a workshop on the NIH campus entitled, One Health: Integrating the Veterinary Scientist into the Biomedical Research Enterprise.  One Health is defined as the integrative effort of multiple disciplines working together to attain optimal health for people, animals and the environment. The purpose of the workshop was to identify how the concept of One Health can advance the NIH mission in regard to both basic and applied research, including training of the biomedical work force, concentrating on the veterinary scientist.

The Medaka Model for Comparative Assessment of Human Disease Mechanisms Workshop was held on December 18, 2014 in Austin, Texas. The central purpose of this workshop was to assess current use and to project the future resource needs of the American medaka research community. The workshop sought to spur discussions of issues that would promote more informative comparative disease model studies. Finally, workshop attendees met together to propose, discuss, and agree on recommendations regarding the most effective research resources needed to enable scientists in the United States to perform experiments leading to impacting experimental results directly relevant in human disease research.

The 7th Aquatic Animal Models of Human Disease Conference was organized by Dr. Ronald Walter (Texas State University) and was held on December 13-18, 2014 in Austin, Texas. Approximately a hundred scientists, junior faculty, students and postdoctoral researchers from academic institutions in 10 different countries (the USA, Canada, Japan, Germany, Hong Kong/China, Singapore, Taiwan, South Korea, Italy and Spain) attended the meeting. The meeting provided a forum to highlight scientific developments using aquatic species (natural and genetically engineered), as well as to discuss pressing topics that the aquatic research community consider important to advance the use of aquatic species as models for biomedical research. In general, the sessions covered the following research areas: Translational, Aquatic Genomes, Toxicology, Regeneration, Cancer, Developmental Disease, Stem Cell, Infectious Disease, Aging, Metabolic Disease and Aquatic Environments.

“Animal Models Impacting Human Disease,” the Tenth Comparative Medicine Resource Directors Meeting, was held August 12-13, 2014, in Bethesda, Maryland. All Resource Directors funded by the Office of Research Infrastructure Programs (ORIP)/Division of Comparative Medicine (DCM) were invited to attend. This biannual meeting provides a forum to (1) Exchange new information, advances, and ideas among grantees and NIH staff members from several Institutes and Centers (ICs), (2) Increase collaborations and sharing among DCM-funded Resources and between these Resources and various NIH ICs, (3) Inform Resources and NIH staff about accomplishments and challenges, and (4) Identify Resource-related scientific advances on evolving animal-human correlations, emerging technologies, and reproducibility in animal models of human disease.

More than 460 veterinary students from 45 academic institutions were represented at the symposium, including 29 veterinary colleges from the United States, three from Canada, two from the Caribbean, four from Europe, and two from Australia as well as five other research centers and universities, including NCI, NIH. Other participants included University Program Directors and representatives from the NIH, Merial, Burroughs Wellcome, the Association of American Veterinary Colleges, the American Veterinary Medical Association (AVMA), and the Howard Hughes Medical Institute. Students attending the symposium included veterinary students participating in summer research programs as well as DVM/PhD students and postdoctoral veterinarians in research training programs. The symposium theme of “One Health” emphasized the impact of veterinary medicine on global sustainability as well as human and animal health and scientific discovery.

On October 28 and 29, 2013, the NIH convened a workshop entitled, “Animal Models and Personalized Medicine.” The goals of the workshop were: 1. to discuss the status of human personalized genomics and the use of comparative functional genomics in other organisms to interpret patient information for clinical use; 2. to review the current status of the development and use of the personalized animal models based upon a variety of animal species; 3. to evaluate the potential use of personalized animal models for translational medicine applications and; 4. to develop the consensus and provide recommendations to the NIH regarding the potential strategic initiatives which would make a valuable contribution to the field.

On October 28 and 29, 2013, the NIH convened a workshop entitled, “From Tank to Bedside:  Zebrafish and Translational Research” on October 29 – 30, 2013 at the Natcher Conference Center on the NIH Campus.  The objectives of the Workshop were: 1)  to provide input to the NIH on the current status of projects and technologies that directly inform studies related to human health using the zebrafish as an animal model; and 2) to provide advice to the NIH on initiatives that can enhance the use of zebrafish in translational research.  For the purpose of the workshop, translational research was defined broadly as investigations that are directly related to aspects of human disease, with the eventual goal of finding the cause of illness and treating it in the clinic.

Over 600 participants attended the 13th annual Merial‐NIH Symposium at the Kellogg Center, East Lansing, Michigan, hosted by the College of Veterinary Medicine at Michigan State University. Over 435 veterinary students from 36 veterinary schools, including 27 from US institutions, three from Canada, two from the Caribbean, three from France, and one from Holland, were represented at the symposium as well as veterinary students training at NCI, NIH. Other participants included University Program Directors as well as representatives from the NIH, Merial, Burroughs Wellcome, the Association of American Veterinary Colleges, the American Veterinary Medical Association (AVMA), and the Howard Hughes Medical Institute. Students attending the symposium included veterinary students participating in the summer research program, DVM/PhD students and postdoctoral veterinarians in research training programs. The over‐riding theme of the symposium was “Comparative Medicine: Meeting Global Needs”.

The Division of Comparative Medicine (DCM), within the Office of Research Infrastructure Programs (ORIP) / DPCPSI / NIH-OD, funds Special Emphasis Research Career Awards (SERCAs) in Pathology and Comparative Medicine. These K01 awards are intended specifically to assist graduate veterinarians who have experience in animal/comparative research to become independent investigators in areas related to biomedical science. Since its inception more than 30 years ago, an independent evaluation of the program has not been done. Therefore, in 2012 the DCM assessed the extent to which the program is achieving its original goals.

In the “pre-genomic” era, efforts to functionally annotate human and animal genomes provided information regarding the structure and biological activity of individual genes, leading to a better understanding of the genetic basis of a variety of human monogenic diseases. In the “post genomic” era, sequencing of entire genomes and development of complex bioinformatic tools such as the human HapMap have revealed specific alleles associated with monogenic as well as complex diseases in humans. One of the most frequently used approaches to verify that particular genetic changes lead to human disease is to recapitulate and test these changes in genetically-modified animal models.

“Evolution of Disease Models Resources,” the Ninth Comparative Medicine Resource Directors Meeting was held in Bethesda, Maryland. Principal Investigators were invited to attend if they held resource-related grants or contracts from the Division of Comparative Medicine, Office of Research Infrastructure Programs, Division of Program Coordination, Planning, and Strategic Initiatives, Office of the Director. This biannual meeting provides a forum to exchange information among grantees and extramural program staff members from many NIH Institutes and Center and the NIH Office of the Director, and to highlight activities of the DCM-supported resource centers. At this meeting, 26 presentations and more than 50 posters highlighted aspects of “Strengthening DCM Resources’ Impact in Biomedical Research,” “Strategies for Linking Genotypes with Phenotypes,” and “Promoting a Resource.”