AW0521 - Determining potential impacts of Precision Breeding on Animal Welfare FINAL REPORT

1. Introduction of the Genetic Technology (Precision Breeding) Act in 2023 paved the way for the use of precision breeding technologies (e.g., genome editing) in livestock in England. However, while recognising that there may be major benefits inferred by increased disease resistance and other traits, concern has been raised about the possible wider effects of the use of the technology on animal welfare. This project aimed to understand the current situation with respect to level of use and development of precision-bred animals and to consider what welfare indicators should be used to assess welfare in general, and for specific types of edits.2. A mapping and scoping phase indicated that few companies have initiated data collection or development of precision-bred animals that might be present in/be imported into England. The pig and fish sectors were the only sectors to indicate that development has commenced. Mapping suggested that the first animals are bred in research/university environments where animals are kept under the auspices of ASPA. Apart from the fish and pig sectors, the chicken, cattle and sheep sectors also expressed some interest in developing precision-bred animals in the near future (I.e.., in the next 5 years). For the equine sector, only a few stakeholders expressed some interest in using precison-breeding technologies to improve specific traits such as disease resistance or resilience to environmental stress, but there is no intention to use PB in equine breeding practice in the immediate future. 3. Expert consultation and a review of the literature indicated that the Five Domains Model was the most appropriate of current animal welfare models to use to build indicator lists. This model includes nutritional state, health, environmental responses, behavioural interactions and mental state. While most animal welfare assessment protocols assess the effects of housing and management on welfare outcomes for animals, it is biological functioning that is the most important aspect to assess in the precision breeding context.4. Welfare assessment indicator lists were drawn up for the three main species that are in the most advanced stage of use of precision breeding. These were pigs, poultry and salmon. Indicator lists were constructed that drew on industry handbooks, current animal welfare assessment schemes and relevant literature. These indicator lists aimed to facilitate a holistic assessment of overall animal welfare to detect changes in functioning across the Five Domains. The indicator lists contain welfare indicators that assess the animal across its EVID4 Evidence Project Final Report (Rev. 06/11) Page 3 of 21lifetime, compared with a control group of the same breed and same age and sex ratio. Three levels of assessment were considered: basic, enhanced and enhanced plus. The basic level of assessment does not fully cover the five domains in all three species, so SRUC strongly recommends that the enhanced level of assessment is adopted.5. In addition to the overall welfare assessment indicator lists, three cases studies were considered to determine how and when to add additional welfare indicators to these lists. The aim was to cover welfare-related traits and production-relate traits. To this end, the specific traits considered were PRRS virus, avian influenza and the hypothetical case of myostatin in fish. As animals carrying these edits are not available for inspection, a risk assessment was limited to ‘consequence characterisation’: ie., identifying possible consequences of gene editing on welfare. These case studies showed that a wider consideration of the edit and the pathways involved needs to be investigated. In addition to the overall holistic assessment using the Basic, Enhanced or Enhanced Plus levels, assessment using additional welfare indicators that are relevant to the specific edit may be required.6. Three webinars/workshops were held to present results to stakeholders. In addition, a meeting was held with equine stakeholders and numerous discussions were held with individual stakeholders to gain information on aspects of precision breeding

AW0521 - Determining potential impacts of Precision Breeding on Animal Welfare FINAL REPORT

1. Introduction of the Genetic Technology (Precision Breeding) Act in 2023 paved the way for the use of precision breeding technologies (e.g., genome editing) in livestock in England. However, while recognising that there may be major benefits inferred by increased disease resistance and other traits, concern has been raised about the possible wider effects of the use of the technology on animal welfare. This project aimed to understand the current situation with respect to level of use and development of precision-bred animals and to consider what welfare indicators should be used to assess welfare in general, and for specific types of edits.2. A mapping and scoping phase indicated that few companies have initiated data collection or development of precision-bred animals that might be present in/be imported into England. The pig and fish sectors were the only sectors to indicate that development has commenced. Mapping suggested that the first animals are bred in research/university environments where animals are kept under the auspices of ASPA. Apart from the fish and pig sectors, the chicken, cattle and sheep sectors also expressed some interest in developing precision-bred animals in the near future (I.e.., in the next 5 years). For the equine sector, only a few stakeholders expressed some interest in using precison-breeding technologies to improve specific traits such as disease resistance or resilience to environmental stress, but there is no intention to use PB in equine breeding practice in the immediate future. 3. Expert consultation and a review of the literature indicated that the Five Domains Model was the most appropriate of current animal welfare models to use to build indicator lists. This model includes nutritional state, health, environmental responses, behavioural interactions and mental state. While most animal welfare assessment protocols assess the effects of housing and management on welfare outcomes for animals, it is biological functioning that is the most important aspect to assess in the precision breeding context.4. Welfare assessment indicator lists were drawn up for the three main species that are in the most advanced stage of use of precision breeding. These were pigs, poultry and salmon. Indicator lists were constructed that drew on industry handbooks, current animal welfare assessment schemes and relevant literature. These indicator lists aimed to facilitate a holistic assessment of overall animal welfare to detect changes in functioning across the Five Domains. The indicator lists contain welfare indicators that assess the animal across its EVID4 Evidence Project Final Report (Rev. 06/11) Page 3 of 21lifetime, compared with a control group of the same breed and same age and sex ratio. Three levels of assessment were considered: basic, enhanced and enhanced plus. The basic level of assessment does not fully cover the five domains in all three species, so SRUC strongly recommends that the enhanced level of assessment is adopted.5. In addition to the overall welfare assessment indicator lists, three cases studies were considered to determine how and when to add additional welfare indicators to these lists. The aim was to cover welfare-related traits and production-relate traits. To this end, the specific traits considered were PRRS virus, avian influenza and the hypothetical case of myostatin in fish. As animals carrying these edits are not available for inspection, a risk assessment was limited to ‘consequence characterisation’: ie., identifying possible consequences of gene editing on welfare. These case studies showed that a wider consideration of the edit and the pathways involved needs to be investigated. In addition to the overall holistic assessment using the Basic, Enhanced or Enhanced Plus levels, assessment using additional welfare indicators that are relevant to the specific edit may be required.6. Three webinars/workshops were held to present results to stakeholders. In addition, a meeting was held with equine stakeholders and numerous discussions were held with individual stakeholders to gain information on aspects of precision breeding

Bacterial microcompartment-directed polyphosphate kinase promotes stable polyphosphate accumulation in E. coli

Processes for the biological removal of phosphate from wastewater rely on temporary manipula-tion of bacterial polyphosphate levels by phased environmental stimuli. In E. coli polyphosphate levels are controlled via the polyphosphate-synthesizing enzyme polyphosphate kinase (PPK1) and exopolyphosphatases (PPX and GPPA), and are temporarily enhanced by PPK1 overexpression and reduced by PPX overexpression. We hypothesized that partitioning PPK1 from cytoplasmic exopoly phosphatases would increase and stabilize E. coli polyphosphate levels. Partitioning was achieved by co-expression of E. coli PPK1 fused with a microcompartment-targeting sequence and an artificial operon of Citrobacter freundii bacterial microcompartment genes. Encapsulation of targeted PPK1 resulted in persistent phosphate uptake and stably increased cellular polyphos-phate levels throughout cell growth and into the stationary phase, while PPK1 overexpression alone produced temporary polyphosphate increase and phosphate uptake. Targeted PPK1 increased polyphosphate in microcompartments eight-fold compared with non-targeted PPK1. Co-expression of PPX polyphosphatase with targeted PPK1 had little effect on elevated cellular polyphosphate levels because microcompartments retained polyphosphate. Co-expression of PPX with non-targeted PPK1 reduced cellular polyphosphate levels. Thus, subcellular compartmentali-zation of a polymerizing enzyme sequesters metabolic products from competing catabolism by preventing catabolic enzyme access. Specific application of this process to polyphosphate is of potential application for biological phosphate removal

Carbon and nitrogen isotopic ratios of urine and faeces as novel nutritional biomarkers of meat and fish intake

Purpose Meat and fish consumption are associated with changes in the risk of chronic diseases. Intake is mainly assessed using self-reporting, as no true quantitative nutritional biomarker is available. The measurement of plasma fatty acids, often used as an alternative, is expensive and time-consuming. As meat and fish differ in their stable isotope ratios, δ13C and δ15N have been proposed as biomarkers. However, they have never been investigated in controlled human dietary intervention studies. Objective In a short-term feeding study, we investigated the suitability of δ13C and δ15N in blood, urine and faeces as biomarkers of meat and fish intake. Methods The dietary intervention study (n = 14) followed a randomised cross-over design with three eight-day dietary periods (meat, fish and half-meat–half-fish). In addition, 4 participants completed a vegetarian control period. At the end of each period, 24-h urine, fasting venous blood and faeces were collected and their δ13C and δ15N analysed. Results There was a significant difference between diets in isotope ratios in faeces and urine samples, but not in blood samples (Kruskal–Wallis test, p < 0.0001). In pairwise comparisons, δ13C and δ15N were significantly higher in urine and faecal samples following a fish diet when compared with all other diets, and significantly lower following a vegetarian diet. There was no significant difference in isotope ratio between meat and half-meat–half-fish diets for blood, urine or faecal samples. Conclusions The results of this study show that urinary and faecal δ13C and δ15N are suitable candidate biomarkers for short-term meat and fish intake

Author correction : a global database for metacommunity ecology, integrating species, traits, environment and space

Correction to: Scientific Data https://doi.org/10.1038/s41597-019-0344-7, published online 08 January 202

Author correction : a global database for metacommunity ecology, integrating species, traits, environment and space

Correction to: Scientific Data https://doi.org/10.1038/s41597-019-0344-7, published online 08 January 202

Effects on mortality of a nutritional intervention for malnourished HIV-infected adults referred for antiretroviral therapy: a randomised controlled trial.

Malnourished HIV-infected African adults are at high risk of early mortality after starting antiretroviral therapy (ART). We hypothesized that short-course, high-dose vitamin and mineral supplementation in lipid nutritional supplements would decrease mortality

Should Research Ethics Encourage the Production of Cost-Effective Interventions?

This project considers whether and how research ethics can contribute to the provision of cost-effective medical interventions. Clinical research ethics represents an underexplored context for the promotion of cost-effectiveness. In particular, although scholars have recently argued that research on less-expensive, less-effective interventions can be ethical, there has been little or no discussion of whether ethical considerations justify curtailing research on more expensive, more effective interventions. Yet considering cost-effectiveness at the research stage can help ensure that scarce resources such as tissue samples or limited subject popula- tions are employed where they do the most good; can support parallel efforts by providers and insurers to promote cost-effectiveness; and can ensure that research has social value and benefits subjects. I discuss and rebut potential objections to the consideration of cost-effectiveness in research, including the difficulty of predicting effectiveness and cost at the research stage, concerns about limitations in cost-effectiveness analysis, and worries about overly limiting researchers’ freedom. I then consider the advantages and disadvantages of having certain participants in the research enterprise, including IRBs, advisory committees, sponsors, investigators, and subjects, consider cost-effectiveness. The project concludes by qualifiedly endorsing the consideration of cost-effectiveness at the research stage. While incorporating cost-effectiveness considerations into the ethical evaluation of human subjects research will not on its own ensure that the health care system realizes cost-effectiveness goals, doing so nonetheless represents an important part of a broader effort to control rising medical costs