In the context of a Project of Cooperation and Innovation (PCI) launched by the Swiss State Secretariat for Education, Research and Innovation (SERI), the Universities of Fribourg and Zürich coordinated research activities on non-human primates in the academic domain by creating a “Swiss Primate Competence Centre for Research” (SPCCR), with the goal to unify scientific and ethical procedures at national level.
In the previous article, the Swiss State Secretariat for Education, Research and Innovation (SERI) reports on its efforts to promote research and innovation in Switzerland. Among the various initiatives taken to achieve this goal, in collaboration with the Swiss Conference of Universities (SUK – CUS), the SERI launched in 2013 a Project of Cooperation and Innovation (PCI) aimed at developing and reinforcing centres of national interest in the field of research and innovation. The universities of Fribourg (UniFr) and Zürich (UniZh) submitted a project, with the goal to coordinate at the national level their research activities based on the experimental animal model of Non-Human Primate (NHP). The project financially supported by this PCI program (2013-2016) led to the creation of a Swiss Primate Competence Centre for Research (SPCCR), grouping the activities taking place on the two academic sites, at UniFr and at UniZh. On both sites, research based on the model of NHP was initiated more than 40-50 years ago, without however systematic coordination and cooperation.
Facing new challenges, both scientific and ethical, the senior researchers of the NHP laboratories of UniFr and UniZh decided to unify and coordinate their procedures in order to guarantee the best standards. In particular, the competencies required to work on monkeys are rare and cannot be simply extended from those acquired on other animal models (e.g. rodents), due to the high specificity of NHPs both on the scientific and ethical levels. Indeed, working with NHPs requires a very long training with expert scientists, themselves active in the field for several decades. To this aim, and to train young scientists, a first goal of the SPCCR was to offer in Switzerland a specialised training course of 3 days (LTKE20), recognised by the veterinary authorities, to young scientists active in NHP laboratories or willing to have access to this animal model. In close collaboration with the pharmaceutical industry in Basel, also hosting NHP facilities, the SPCCR organised this training course in autumn 2014, to which about 30 scientists attended during three days, one in Fribourg, one in Basel and one in Zürich. Numerous facets of NHP research, including ethical and welfare issues, were covered in order to prepare the young scientists active in the NHP field to become independent junior group leaders. A similar training course on NHP research will be organised by the SPCCR in winter 2016 for newcomers in the field, but also addressing original aspects not covered in the training course in 2014.
These efforts in the training of scientists working with NHPs also include the technical personal associated with the sites of Fribourg and Zürich, namely the animal caretakers as well as the laboratory technicians. A refined training of the latter category of person is crucial in the sense that they have a long-term contract and thus they are responsible for the transfer of knowledge and competence to the PhD students and post-docs joining the NHP laboratories.
On the scientific point of view, the SPCCR was created with the goal to reinforce the two academic NHP sites, Fribourg and Zürich, by exchanging expertise and competence in various domains, such surgery, anaesthesia, analgesia, animal welfare, conditions of housing, etc. In 2010, the Swiss legislation was modified, introducing new conditions of detention for macaque monkeys. They have to be hosted now in detention rooms of at least 45 m3, for a group of monkeys ranging from 2 to 5 individuals. As compared to the previous guidelines, for the same number of animals, the volume of detention was increased by a factor of 3 (previously 15 m3). The present conditions of detention are illustrated on a video sequence available on the web site of the SPPC: www.unifr.ch/spccr/about/housing
Under the umbrella of the SPCCR, the two academic sites of NHP research in Switzerland, in Fribourg and in Zürich, pursued their long tradition of research in the field of neuroscience. In particular, as of 2000, NHP models of spinal injury (e.g. Freund et al., 2006, 2009), of cerebral cortex lesion (e.g. Kaeser et al., 2011; Wyss et al., 2013; Hoogewoud et al., 2013) and Parkinson disease (ongoing) were developed in order to test essentially two promising therapeutic strategies:
– Neutralisation of neurite growth inhibitors (e.g. Nogo-A) normally present in the adult central nervous system, preventing the regrowth of injured axons, using an antibody against Nogo-A;
– Transplantation of autologous adult progenitor cells.
As shown by the above-mentioned studies, these two therapeutic strategies promote better functional recovery either from spinal cord injury or from lesion affecting the cerebral cortex, paving the way towards clinical tests on patients. These studies gave the opportunity to develop new imaging procedures applied to the NHPs, namely MRI (magnetic resonance imaging) and PET (positron emission tomography). These imaging approaches contribute to a refinement of the NHP procedures, in line with the goal of the 3Rs initiative, to which the SPCCR fully adheres.
An additional goal of the SPCCR is to open its NHP infrastructures to researchers of other academic sites of Switzerland, where such animal model is not available. The SPCCR provides its expertise and competence to host new research projects originating from other institutions. Such collaboration already took place recently in the form of common projects with the Universities of Geneva and Lausanne, resulting for instance in the development of a non-invasive electrophysiological approach in NHPs based on EEG
(Gindrat et al., 2014). As of autumn 2015, a new collaborative project will be initiated together at UniFr with the federal institute of technology of Lausanne (EPFL), with the goal to establish a model of locomotion in macaque monkeys. This model will serve as a pre-clinical trial for the treatment of spinal cord injury based on electrochemical stimulation. In summary, the SPCCR project represents the ideal vehicle to guarantee access to the crucial NHP animal model in Switzerland, indispensable for both fundamental and clinically oriented research.
Freund, P.*, Schmidlin, E.*, Wannier T.*, Bloch J., Mir A., Schwab M.E. and Rouiller E.M. (2009) Anti-Nogo-A antibody treatment promotes recovery of manual dexterity after unilateral cervical lesion in adult primates: re-examination and extension of behavioural data. Europ. J. Neurosci. 29: 983-996.
Freund P.+, Schmidlin E.+, Wannier T.+, Bloch J., Mir A., Schwab M.E. and Rouiller E.M. (2006) Anti-Nogo-A treatment enhances corticospinal tract sprouting and functional recovery after unilateral cervical lesion in adult primates. Nat. Med. 12 (7): 790-792. Gindrat A.D.*, Quairiaux C.*, Britz J., Brunet D., Lanz F., Michel C.M.& and Rouiller E.M.& (2014) Whole-scalp EEG mapping of somatosensory evoked potentials in macaque monkeys. Brain Structure and Function 220: 2121-2142.
Hoogewoud F.*, Hamadjida A.*, Wyss A.F., Mir A., Schwab M.E., Belhaj-Saif A., Rouiller E.M. (2013). Comparison of functional recovery of manual dexterity after unilateral spinal cord lesion or motor cortex lesion in adult macaque monkeys. Front. Neurol. 2013, 4: 101.
Kaeser M*., Brunet J.F*., Wyss A.F., Belhaj-Saïf A., Liu Y., Rouiller E.M.+ and Bloch J.+ (2011) Autologous adult cortical cell implantation enhanced functional recovery of manual dexterity after unilateral lesion of the motor cortex in non-human primates. Neurosurgery 68: 1405-1417.
Wyss A.F.*, Hamadjida A.*, Savidan J.*, Liu Y., Bashir S., Mir A., Schwab M.E., Rouiller E.M.&, Belhaj-Saif A.& (2013) Long-term motor cortical map changes following unilateral lesion of the hand representation in the motor cortex in macaque monkeys showing functional recovery of hand functions. Rest. Neurol. and Neurosci.31: 733-760.
Eric M. Rouiller
University of Fribourg, Switzerland
Tel: +41 26 300 86 09