About a month ago, shortly before the season break, and very timely to enjoy its Christmas Market (Weihnachtsmarkt), the kick-off meeting of the Project SALAAM (Sharing Advances on Large Animal Models) took place in Munich (Germany), 15-17 December 2014, beautifully organized by Eckhard Wolf and Pascale Chavatte-Palmer, Chair and Co-Chair of this EU-COST Action BM1308. This conference, open to any interested researcher in the field, represented the official launch of the SALAAM project, to discuss about the role of large animal models in Translational Medicine, “Bridging the Gap between Basic and Clinical Research”, as indicated in the SALAAM logo. During these three days, about 120 scientists, including researchers not initially associated with SALAAM (including several ISTT members), gathered at the Gene Center, LMU Munich, to share their views about the role of large animal models in biomedicine.
The meeting started with a welcome address by Eckhard Wolf (LMU, Munich, Chair of SALAAM) who set the stage and underlined the need to use appropriate animal models for succeeding in translational research. In the past, large amount of resources have been devoted to rodents, mostly mice, in biomedicine, where mouse models have become instrumental for the current understanding of how most of our genes work and greatly facilitated the progress in the post-genomic era. However, in spite of mice being widely used in Biomedicine to model human diseases, often mice fail to accurately reproduce the features associated with a given human pathology. Therefore there is an urgent need to develop non-rodent animal models that would mimic aspects of human anatomy and human physiology more closely. Pigs, small ruminants and rabbits appear to be excellent candidates to follow up the preliminary discoveries made in mice, and they are the main purpose of the SALAAM initiative, through all the appointed participants, experts in these large animal models. The conference continued for its first day with lectures by A. Aartsma-Rus (NL), and S. Wildhirt (DE), who described examples of use of large animal models for Duchenne muscular dystrophy and for the development of medical devices, respectively. The initial Ethical perspective on the use of large animals was provided by N. Stingelin (CH). This first day concluded with an interesting key-note lecture by M.M. Mohiuddin (USA) on the recent advances in pig-to-primate cardiac xenotransplantation.
On the second day, the conference presented the very large repertoire of methods and techniques that are currently available for Genetic Tailoring of large animal models. Angelika Schnieke (DE) introduced the state of art for the current genetic engineering of large animals, nicely summarizing many years of techniques and developments that have been successfully applied for the production of large genetically modified animal models. This initial talk was followed by a presentation by Lluis Montoliu (ES) on the use of CRISPR-Cas9 approaches to functionally analyze the role of non-coding genomic sequences, illustrated with some examples tested in mice, depicting the important role of rodents in proof-of-concept type of experiments, before undertaking subsequent experiments in larger animal models. B. Grzeskowiak (PL) presented an innovative set of nanomagnetic gene delivery vectors for transgenesis. Two additional talks illustrated the power of genetic engineering of the pig genome, using transposons (W.A. Kues, DE) or very elaborated gene cassettes for regulating and tracing disease genes (J.E. Jakobsen, DK). The session ended with a presentation from goats, where L. Boulanger (FR) reported the role of FOXL2 as a female sex-determining gene.
The SALAAM conference continued with a session devoted to systematic phenotyping initiatives of large animal models. At first, H. Fuchs (DE), presented the experience and phenotyping pipeline of the German Mouse Clinic, operating within the Infrafrontier consortium, and a good example of successful systematic phenotyping in mice. Next, Pascale Chavatte-Palmer (FR) discussed the achievements and challenges of imaging techniques in large animal models, through her studies on reproduction and fetal development. J. Tibau (ES) presented his interesting studies using pigs to analyze human obesity and to validate the effect of diets on the evolution of fat deposition using tomography approaches. A. Blutke (DE) introduced the impressive Munich MIDY-PIG Biobank initiative, as a unique resource for translational diabetes research. The two last talks presented the use of pigs as models for respiratory infections (K. Skovgaard, DK) or cystic fibrosis (I. Caballero, FR).
The last standard session of this SALAAM conference was devoted to discuss how to select the best animal model. This session began with an interesting presentation by J. Langermans (NL), who shared their initiative of non-human primate biobanking for translational medicine, a collaborative consortium where most of the nonhuman primate research centres in Europe were represented. He also discussed the unique features of non-human primates to investigate devastating diseases affecting us, such as the new infections (i.e. Ebola) or neurodegenerative diseases (i.e. Alzheimer, Parkinson) , often very challenging to be reproduced in non-primate animal models. Next, Antonio Gonzalez-Bulnes (ES) discussed the advantages and challenges of using pigs and sheep animal models, whereas L. Hiripi (HU) presented the unique features of the rabbit models. V. Huygelen (BE) discussed the use of piglets to investigate the human low birth weight cases , and A. Navarrete Santos (DE) further presented rabbits as ideal models for investigating diabetes during pregnancy. Diabetes research was also the focus of the last speaker of the session, G. Pennarossa (IT), whose experimental dessigns are focused on the use of dogs to explore cell therapy-based treatments.
The SALAAM first public conference ended with an excellent and very motivating talk by Karin Blumer (CH) on the ethical aspects of using large animals. She challenged the audience with the question whether “size did matter?” when it comes to Ethics and Animal Models. Her presentation nicely illustrated the different Ethical perspectives existing in the field and, most importantly, the relevant parameters that should be taken into account in order to properly address this question. She presented the “size” of an animal as an accidental attribute, not an intrinsic value, that must not determine its moral status. This presentation triggered an interesting and live discussion among the participants.
On the third and last day, the different working groups of SALAAM gathered first independently to discuss the next initiatives and eventually shared their conclusions in a combined general session. The planned initiatives will include the organization of practical workshops on CRISPR-Cas9 and transposon technologies, the generation of specific pig Cre-transgenic lines for the production of conditional pig mutant animal models, the need to standardize phenotyping protocols associated with additional specific training courses, the preparation of biobanks and associated databases for archiving and sharing tissues from large animal models, and the creation of a group to analyze the implementation of the 2010/63/EU Directive across Europe, the public perception and ethical issues of animal research, and the need for training to adequately communicate results to the public.
Information about future plans, initiatives and activities of the SALAAM EU-COST action will be available from its dedicated web site.
