The Alternatives in Research Challenge

The Alternatives in Research (AiR) Challenge is a program intended to stimulate innovative research that advances medical progress through the use of methods that do not involve animals.
The program focus is on biomedical research, given that animal use in this area far exceeds that in safety testing and scientific education.

Awardees of the first AiR Challenge Grants, at $20,000 each, have been announced, working with new methods to address cancer, Alzheimer's and autism:

Erika Darrah, PHD and Eleni Tiniakou, MD
Johns Hopkins University School of Medicine, Baltimore, MD
Harnessing the Human Immune System to Identify Candidate Epitopes for Cancer Vaccine Development.
Immunology research has relied heavily on animals to model the complex cellular interactions that occur during immune responses. Despite the scientific advancements made using this approach, it is inherently flawed due to the significant differences that exist between humans and model animals. This is particularly problematic for the study of highly complex diseases such as autoimmunity and cancer. We have recently shown that autoimmunity and cancer may represent two sides of the same coin, with the anti-self immune responses arising in patients with autoimmune diseases also being potent anti-cancer tools, and vice versa. In patients with cancer and the autoimmune disease scleroderma, who make antibodies to the PolR3 protein, we found that mutations in PolR3 present in the patients' cancer could stimulate immune responses against both the normal and mutated versions of the protein. We recently developed a method to study human immune responses ex vivo by harnessing the specificity and sensitivity of a patient's own immune system to reveal the immunogenic "hot spots" within proteins. We plan to use this method to identify epitopes from normal and mutated versions of self-proteins that promote potent immune responses in patients with scleroderma, to identify potential candidates for cancer vaccine development.

Melissa Herbst-Kralovetz, PHD and Pawel Laniewski, PHD
University of Arizona, Phoenix, AZ
Vaginal Bacteria as Oncogenic Drivers: Using a Human 3-D Endocervical Epithelial Cell Model to Investigate Bacterial Influence on Hallmarks of Cancer.
Recent studies have emerged to identify two key bacterial species: Atopobium vaginae and Sneathia sp. to be associated with three major complications of obstetric and gynecologic health: preterm birth, pelvic inflammatory disease and gynecologic cancer. Our central hypothesis is that Atopobium and Sneathia can cause local inflammation, disrupt epithelial barrier integrity and promote pathophysiological changes in the female reproductive tract (FRT) that contribute to cancer development. To test our hypothesis, we developed and characterized a novel human 3-D endocervical epithelial cell model using bioreactor technology. We demonstrated that our model recapitulates functional and structural characteristics of parental tissue and can be utilized to study host-microbe interactions and cellular functions related to the hallmarks of cancer. This model allows us and others to replace the use of animal products (serum-free medium) and laboratory animals for cancer-related studies. We propose a reductionist approach using the 3-D epithelial model with Atopobium and Sneathia to determine the impact on cell signaling pathways that may promote pathological damage and represent changes in the tissue microenvironment during cancer development. The overall goal is to elucidate the microbe-specific mechanisms that promote the establishment of a harmful inflammatory microenvironment that influence the hallmarks of cancer.

Lena Smirnova, PHD
Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
Testing for Autism Toxicants by Gene Environment Interaction
Autism is a main concern of developmental neurotoxicity (DNT). The recent dramatic increase of autism cannot be explained solely by genetics or exposure to environmental chemicals. We hypothesize that it is rather the interplay of both. A combination of three cutting edge technologies (pluripotent stem cell (iPSC) technology, CRISPR-CAS9 gene editing and 3D human-relevant microphysiological systems) will allow for the first time to produce a brain model with autistic genetic background. The exposure to critical chemicals such as pesticides will allow screening gene environmental interactions. This will replace animal models for DNT and autism, which are of limited predictivity for humans. To generate the model, we used iPSC with mutation in the chromodomain helicase DNA-binding protein 8 (CHD8), one of the major genetic risk factors of autism. In our preliminary data, we found that CHD8 heterozygous knockout brain organoids are more susceptible to pesticide, chlorpyrifos, than controls and that clorpyrifos reduces CHD8 protein level in both knockout and control organoids. We aim to further characterize this synergy by studying functionality and molecular signatures (gene/miRNA, metabolic perturbations) of exposure in knockout and control organoids. This will allow to derive an animal-free test strategy for chemicals causing autism in genetically vulnerable embryos.

Xianmin Zeng, PHD
XCell Science, Novato, CA
Effect of ApoE Isoforms on Alzheimer's Disease
Genetic variants in the apolipoprotein E (ApoE) locus are associated with Alzheimer's disease (AD) and other chronic diseases. Among the gene alleles encoding the three major isoforms, the ApoE4 allele is the strongest genetic risk factor for late-onset AD, ApoE3 is largely neutral, and ApoE2 is protective. How ApoE isoforms predispose to AD, or protect against it, is incompletely understood. By combining induced pluripotent stem cells (iPSC) and precise CRISPR/cas9 gene editing technology, it is now feasible to generate otherwise isogenic iPSC lines with ApoE alleles. We have made progress toward the generation of these lines and in this proposal will create iPSC lines with all three major ApoE alleles (ApoE2/2, ApoE2/2 and ApoE2/2) and their combinations, differentiate them into neurons and astrocytes, and assess cellular phenotypes associated with AD. We will compare and contrast the effects of ApoE2 and ApoE4, looking for specific mechanisms by which these alleles are protective or sensitizing to AD, respectively. This unique approach offers the possibility of identifying potential prognostic and diagnostic markers, and developing and refining therapeutic targets for AD, as well as other cognitive disorders.

In the next phase, ARDF will seek proposals for an AiR Challenge Prize that will award up to $350,000 to a single recipient who presents a research plan that is most likely to succeed in having an impact on a biomedical research field and an impact on replacing animal use.

The AiR Challenge program is intended not only as a means of rewarding scientists, advancing biomedical progress, and sparing animals from suffering. It is also intended to help dispel the outdated notion that an interest in medical progress and a concern for animals are inexorably in opposition; indeed, finding better non-animal approaches to researching human disease is a win-win for humans and animals. The ARDF is also seeking to broaden the understanding and appreciation for alternative methods not only among scientists, but also among the general public, thought-leaders, media representatives, and patients and patient-advocates.


Scientific Advisory Committee

ARDF is grateful to members of the Scientific Advisory Committee (SAC) for the AiR Challenge program, which advises ARDF on criteria and selection of grants and prizes. Members of the SAC serve as individuals and volunteers, and their affiliations are listed for identification purposes only. ARDF is responsible for all final decisions and activities of the AiR Challenge program.

Chairman, Raymond R. Tice, PhD

Dr. Tice received a PhD in Biology in 1976 from Johns Hopkins University (Baltimore, MD). He was employed by the Medical Department at Brookhaven National Laboratory (Upton, NY) from 1976 to 1988, by Integrated Laboratory Sciences, Inc. (Durham, NC) from 1988 to 2005, and by the National Institute of Environmental Health Sciences (NIEHS) from 2005 to 2015. At NIEHS, he served as the first Deputy Director of the National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) and in 2009 as the first Chief of the Biomolecular Screening Branch within the NTP, where he was the NTP lead on the US interagency Tox21 initiative. Dr. Tice retired from NIEHS in January, 2015. Among his achievements and awards, he served as president of the Environmental Mutagen and Genomics Society, was one of the recipients in 2008 of the North American Alternative Award from the Humane Society of the United States and Proctor & Gamble, and he received in 2016 the William and Eleanor Cave Award for Advancing Alternatives from the Alternatives Research & Development Foundation.

Kim Boekelheide, MD, PhD

Kim Boekelheide is Professor of Pathology and Laboratory Medicine at the Brown University School of Medicine. He received his BA from Harvard University, and MD and PhD from Duke University. His research examines fundamental molecular mechanisms by which environmental and occupational toxicants induce cellular injury and male reproductive effects. Current projects include the development of novel in vitro approaches to safety assessment and the discovery of sperm molecular biomarkers that reflect testicular injury. He is Associate Director of the Brown University Superfund Research Program and Director of the Brown University Center to Advance Predictive Biology. His research has been continuously funded by the National Institute of Environmental Health Sciences since 1985 and he has received several awards including a Burroughs Wellcome Toxicology Scholar Award (1994-1999), and the Lifetime Achievement Award (2015) from the Reproductive and Developmental Toxicology Specialty Section of the Society of Toxicology.

Larry Carbone, DVM, PhD

Larry Carbone is the Director of the University of California Animal Care and Use Program, and Senior Veterinarian in the UCSF Laboratory Animal Resource Center. He has worked in laboratory animal care in the academic setting as animal care staff, veterinarian, researcher and IACUC member for over 35 years and is specialty board-certified in Animal Welfare (ACAW) and Laboratory Animal Medicine (ACLAM). Following his DVM training at Cornell University, he stayed on as laboratory animal veterinarian and as PhD candidate in Science and Technology Studies. His dissertation on the intersection of ethics, history and epistemology in laboratory animal welfare policy became his 2004 book What Animals Want: Advocacy and Expertise in Laboratory Animal Welfare Policy (Oxford University Press). His research in animal welfare science and policy focus primarily on pain management for laboratory animals, and on how scientists write about animal pain in their research publications.

Suzanne Fitzpatrick, PhD

Dr. Suzanne Fitzpatrick is the Senior Advisor for Toxicology in the Office of the Center Director at Center for Food Safety and Applied Nutrition at the US Food and Drug Administration. Dr. Fitzpatrick is a board certified toxicologist here in the US and in Europe. She is the FDA lead for Tox 21 and is also an FDA Representative to ICCVAM. She is in charge of all toxicology research at CFSAN. Dr. Fitzpatrick represents CFSAN on several FDA Committees and Work Groups including the FDA Biomarkers Group, the NIH FDA Biomarkers Group, the FDA Senior Toxicology Workgroup, the HHS Environmental Justice Committee, and the FDA/NCATS/DARPA Collaboration on Organs/Human on a Chip. She represents FDA at several outside committees, including ILSI HESI Emerging Issues, ILSI North America, NRC Emerging issues Committee, and the OSTP Subcommittee on Toxics and the Environment. Dr Fitzpatrick is the FDA representative to the Federal Children's Environmental Health Task Force. Dr. Fitzpatrick is an FDA representative to several OECD Committees including the Work Group on Non-Genotoxic carcinogens, OECD Validation Management Group-Non-Animal and the OECD Advisory Group on Molecular Screening and Toxicogenomics. She is very active in the Society of Toxicology including serving on the planning committees for Future Tox I, II, III, and IV. She is on the planning committee for the 10th World Congress on Alternatives. Dr. Fitzpatrick is a Past President of the American College of Toxicology. Dr. Fitzpatrick is an Adjunct Professor at Johns Hopkins University. Dr. Fitzpatrick received her BA from the University of California at San Diego and her PhD from Georgetown University.

Thomas Hartung, MD, PhD

Thomas Hartung is the Doerenkamp-Zbinden-Chair for Evidence-based Toxicology with a joint appointment for Molecular Microbiology and Immunology at Johns Hopkins Bloomberg School of Public Health, Baltimore. He holds a joint appointment as Professor for Pharmacology and Toxicology at University of Konstanz, Germany; he also is Director of Centers for Alternatives to Animal Testing of both universities with the portal AltWeb.

CAAT hosts the secretariat of the Evidence-based Toxicology Collaboration, the Good Read-Across Practice Collaboration, the Good Cell Culture Practice Collaboration, the Green Toxicology Collaboration and the Industry Refinement Working Group. As PI, he heads the Human Toxome Project, funded as an NIH Transformative Research Grant.

He is the former Head of the European Commission's Center for the Validation of Alternative Methods (ECVAM), Ispra, Italy, and has authored more than 500 scientific publications.

Jeffrey Kahn, MPH, PhD

Jeffrey Kahn is the Andreas C. Dracopoulos Director of the Johns Hopkins Berman Institute of Bioethics. He is also Levi Professor of Bioethics and Public Policy, and Professor in the Department of Health Policy and Management in the Johns Hopkins University Bloomberg School of Public Health. His research interests include the ethics of research, ethics and public health, and ethics and emerging biomedical technologies. He speaks widely both in the U.S. and abroad, and has published four books and over 125 articles. He is an elected member of the National Academy of Medicine and a Fellow of the Hastings Center, and has chaired or served on committees and panels for the National Institutes of Health, the Centers for Disease Control, and the Institute of Medicine/National Academy of Medicine, where he is currently chair of the Board on Health Sciences Policy. His education includes a BA in microbiology (UCLA, 1983), MPH (Johns Hopkins, 1988), and PhD in philosophy (Georgetown, 1989).

Karin Gabrielson Morton

Karin is a senior policy advisor at the Swedish Fund for Research Without Animal Experiments, with 25+ years of experience of funding research to replace animal experiments as well as communication and lobbying in this field. Karin also lectures about replacing animal experiments at Lab Animal Science and other courses at several universities. She is a member of the Swedish Central Animal Experimental Ethics Committee and the Swedish National Committee on the protection of animals used for scientific purposes which serves as the steering committee of the new (2017) Swedish National Center for 3Rs. Karin served on the Supervising Board of ReProTect, a project funded by the European Commission to develop and evaluate alternatives to animal experiments in reproductive toxicology testing. Karin has also served as a board member of ecopa (the European consensus platform on alternatives) and chaired the Swecopa.

Maurice Whelan, PhD

Prof. Maurice Whelan is head of the Chemical Safety and Alternative Methods Unit of the Directorate for Health, Consumers and Reference Materials of the European Commission's Joint Research Centre (JRC), based in Ispra, Italy. He also heads the European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) of the JRC, established under EU Directive 2010/63 on the protection of animals used for scientific purposes, which builds on the 20 years of activities of ECVAM, the European Centre for the Validation of Alternative Methods. Priorities of his work include the development, validation and promotion of alternative approaches to animal testing both for regulatory safety assessment of chemicals and for applications in biomedical research. Whelan is the EU co-chair of the OECD Advisory Group on Molecular Screening and Toxicogenomics that is responsible for the OECD programme on Adverse Outcome Pathways, and he is a member of the Steering Committee of the European Partnership for Alternative Approaches to Animal Testing (EPAA).