The 2019 3Rs prize awarded to two pieces of novel research

The 2019 3Rs prize has been jointly awarded to Dr Francesca Nunn and Dr Marta Shahbazi for papers describing research that reduces the number of chickens and mice respectively. The 3Rs prize is awarded by the NC3Rs and sponsored by GSK.

Winning papers

- Nunn F, et al (2019). A novel, high-welfare methodology for evaluating poultry red mite interventions in vivo. Veterinary Parasitology. 267:42-46. doi.org/10.1016/j.vetpar.2019.01.011

- Shahbazi, MN, et al (2017). Pluripotent state transitions coordinate morphogenesis in mouse and human embryos. Nature. 552:239-243. doi.org/10.1038/nature24675

Dr Francesca Nunn, a post-doctoral scientist at the Moredun Research Institute

Francesca and colleagues developed and optimized a device to improve the testing of treatments against poultry red mites, reducing the number of hens used in field trials.

Poultry red mites are a blood feeding ectoparasite. They are a global problem for the egg industry, affecting the welfare of laying hens through irritation and anaemia. Mites are controlled using chemicals, however, repeated use has led to resistance and recent research efforts have focused on developing vaccines and novel biopesticides.

Assessment of vaccine control methods is initially done in vitro using blood assays before field trials are conducted, with 750 to 800 hens exposed to mites for each vaccine candidate, with an adjuvant control group. In vitro assays can be unreliable, for example, due to high levels of non-specific mite mortality. As a consequence, vaccine efficacy measured in vitro is not always translated into mite population reduction in field trials.

Francesca developed an "on-hen" mite feeding device that improves the screening of vaccine candidates to avoid unnecessary field trials. The device consists of a mesh pouch containing approximately 100 mites that have been starved for three weeks. The pouch is fitted to the thigh of the vaccinated hen - the mesh is large enough to allow the mites' mouth parts to access the hen's skin but small enough to contain the mites. Four hens are used per vaccine candidate and after three hours, the mesh is removed and the mites are recovered and maintained in 96-well plates for up to six days to assess mortality.

The device has already been used to provide data that has prevented seven vaccines and vaccine delivery methods from going into field trials. The initial pre-screening using the on-hen device involved 56 hens in total, each exposed to 100 mites for three periods of three hours - the field studies would have used almost 5,500 birds exposed to 10,000 mites for 100 days.

The on-hen device has been used by academic and commercial laboratories in the UK and internationally. By varying the size of the mesh, the device has the potential to be used in research on other parasites.

Dr Marta Shahbazi, a research leader at the MRC Laboratory of Molecular Biology

Marta and colleagues have developed advanced 3D cultures of human and mouse embryonic stem cells to mimic the development of the embryo at implantation and the subsequent morphogenesis and formation of the amniotic cavity, providing an opportunity to replace and reduce the use of live mice in some developmental biology studies.

Implantation of an embryo into the uterus is a critical step with a high rate of pregnancies lost at this stage. Studying implantation and other early embryonic events is technically and ethically challenging. The majority of work is carried out in mice, typically genetically modified animals where associated surgery and breeding of large numbers of animals are required.

Marta's research has shown that it is possible to minimise this use with reproducible and novel 3D cultures of mouse embryonic stem cells that reliably mimic development at the time of, and beyond, implantation, avoiding the need for recipient mice for embryo transfer and the subsequent culling of animals to access early stage embryos.

Marta and colleagues have previously described an in vitro method to culture human embryos beyond the point of implantation, overcoming the technical challenges that have traditionally limited the use of human embryos in research. The winning paper builds on this by reporting comparative functional experiments using mouse and human embryonic stem cell 3D cultures that have identified key factors involved in the remodelling of the embryo at implantation to form the amniotic cavity. This has revealed a previously unknown link between cell potency and tissue shape, with a loss of stem cell "naïve pluripotency" (that is the ability to become any cell type in the organism) triggering the formation of the cavity and developmental progression of the embryo. The use of the 3D cultures for these studies replaced the use of 500 mice and importantly by demonstrating that they can be used to answer fundamental biological questions, the research has led to multiple groups worldwide adopting the cultures, further reducing the use of animals.

Professor Kevin Shakesheff, Chair of the NC3Rs Board and 3Rs Prize Panel said: "The vibrancy of research into the 3Rs was evident from the quality and breadth of the papers we considered. The winning papers and authors demonstrate that 3Rs research can the quality of science and unlock new types of experiments with wide applicability. Both papers are making an impact across the world and the prizes are richly deserved."

GSK is incredibly proud of being able to support the important work done by the NC3Rs and it was a real pleasure to participate in the presentation of these awards as the quality of the science was truly outstanding. The ambition to reduce, refine and replace that is at the core of the work that we are happily able to recognise in the winners is more crucial than ever. The need to ensure that every intervention, measurement and outcome helps to move science and the development of medicines forward is especially critical today in the context of Covid19 where great, reproducible, impactful science has to lead the way."

Dr Rab Prinjha, GSK Vice President of Adaptive Immunity and Immuno-epigenetics