The Centre for Aquatic Biotechnology Regulatory Research (CABRR)
The Centre for Aquatic Biotechnology Regulatory Research (CABRR) is a national Centre of Expertise within Fisheries and Oceans Canada (DFO) created in 2008 to conduct research in support of the risk assessment and regulation of fish with novel traits, including genetically engineered fish. The Centre for Aquatic Biotechnology Regulatory Research research facility is located within the Centre for Aquaculture and Environmental Research in West Vancouver, British Columbia.
Canada has one of the world's safest and most effective science‐based regulatory systems for biotechnology. The import and manufacture of all living organism products of biotechnology, including fish, is regulated under the New Substances Notification Regulations (Organisms) under the Canadian Environmental Protection Act, 1999. Living organism products of biotechnology, such as genetically engineered (GE) organisms, are subject to rigorous scientific risk assessment to determine their potential for adverse human health and environmental impacts. Fisheries and Oceans Canada plays a regulatory role in assisting to administer these regulations for fish products of biotechnology (e.g. GE fish) including by conducting environmental and indirect human health risk assessments and recommending appropriate measures to manage any risks.
Researchers at Centre for Aquatic Biotechnology Regulatory Research work closely with regulators at Fisheries and Oceans Canada Headquarters in Ottawa to set research priorities to generate unbiased scientific knowledge needed to inform the risk assessment, and to design regulatory policies and approaches aimed at protecting the environment.
In addition to the above role in support of the regulation of "fish products of biotechnology", researchers at Centre for Aquatic Biotechnology Regulatory Research conduct studies more broadly on the phenotype (e.g. behaviour, physiology, morphology, gene expression, fitness) of fish with novel traits Footnote 1 regardless of whether they are developed through modern biotechnology techniques or through traditional breeding. This scientific knowledge provides insight into the potential ecological effects that escaped or intentionally released fish with novel traits might have on wild populations.
To coordinate, enable and generate regulatory research results related to fish with novel traits and to provide scientific information to inform the risk assessment and regulation of fish with novel traits.
The research objectives of the Centre for Aquatic Biotechnology Regulatory Research are elaborated in Theme 4 of Fisheries and Oceans Canada's Aquatic Biotechnology & Genomics Research and Development Strategy:
- Enable risk assessment science through the identification, development and evaluation of appropriate novel aquatic animal models;
- Conduct studies in support of risk assessment methodology and the design and implementation of regulations;
- Develop and evaluate the efficacy of mitigative measures to prevent interaction between wild and novel aquatic animal strains (containment strategies); and
- Assess potential ecosystem impacts of transgenic aquatic animals.
Projects within each of the above objectives are evaluated on a regular basis and the research focus adjusted based on the needs of the regulatory program. Some specific projects include:
- Development, maintenance and characterization of contained transgenic lines of aquatic organisms to inform regulatory processes
- Assessment of the characteristics of novel organisms that would affect their survival, reproduction and consequences to other organisms in the environment (such as swimming performance, feeding behaviour, predation, energetics, metabolism and disease resistance)
- Development and evaluation of the effectiveness of biological containment (e.g. triploidy and/or transgenic approaches) for preventing interaction of wild and novel aquatic animals in nature
- Evaluation of physiological, morphological and behavioural changes under different environmental conditions to understand phenotypic plasticity and the interaction of genotype and the environment (GXE) effects
An important role of the Centre for Aquatic Biotechnology Regulatory Research is to increase the coordination and sharing of regulatory research results that is being undertaken to address questions and regulatory development pertaining to aquatic organisms with novel traits by:
- Participating in national and international forums to provide and exchange scientific information, research results to inform risk assessment methodology;
- Providing peer-reviewed and other published data on scientific findings, risk assessment theory and methodology; and
- Collaborating on research with other Canadian departments, agencies and institutions and with international research partners.
The research facility of the Centre for Aquatic Biotechnology Regulatory Research (CABRR) is located at the Centre for Aquaculture and Environmental Research (CAER), a fisheries-related research centre since 1968, located on a 7.9 acre site in West Vancouver. It is within this physically contained facility that the Centre for Aquatic Biotechnology Regulatory Research is able to conduct research on fish with novel traits to study their possible effects on the environment.
The unique location of the Centre for Aquatic Biotechnology Regulatory Research facility offers various sources of water such as well water, creek water and sea water which are used in the different types of environments (tanks, artificial streams or mesocosms) in which experiments are conducted to assess parameters influencing the fitness and ecological consequences of novel fish.
Several different tanks sizes are used at various stages of the fish life cycle. The fish are initially reared in hatchery trays, followed by small (200 liters) freshwater tanks before being transferred to the medium (3000 to 5000 liters) sea water tanks where an array of physiological and behavioural parameters can be tested.
To mimic the freshwater environment salmonids utilize in nature, Fisheries and Oceans Canada constructed replicate stream environments with gravel, boulders, woody debris, natural food supplies and natural creek water. The artificial streams better represent environmental conditions found in the wild and offer an important experimental set-up for assessing the characteristics of the fish in semi-natural conditions.
A circulating stream has also been constructed specifically to examine the natural migratory processes of fish in stream environments during different seasons, times of day, and among different treatment conditions. This stream facility is equipped with electronic tag detector systems that allow tracking of migratory tendencies of fish (e.g. upstream vs. downstream migration during smolting, movement between habitat types, etc.).
In addition to normal tank culture facilities, Fisheries and Oceans Canada also constructed three "mesocosm" tanks, each holding 350,000 liters of sea water. These mesocosms are intended to allow growth of fish under conditions that more closely mimics that found in nature and the ocean (e.g. low density, patchy food supply, minimal contact with humans) as compared to small research tanks maintained using standard fish culture practices. As such, the mesocosms are being used to experimentally determine how genetically engineered fish may fare in the open environment, relative to their wild counterparts.
The Centre for Aquatic Biotechnology Regulatory Research also includes modern research laboratories in which genetic technologies to develop and analyze genetically modified fish strains are conducted. Facilities include the capability for DNA sequencing, Quantitative-PCR, Single Nucleotide Polymorphism (SNP) analysis, microarray analysis of gene expression, and general molecular biology.
Key Research Findings
Several key questions are relevant to assessing the environmental risks that genetically engineered fish may have if they were accidentally or intentionally released into the environment, including:
- How well would genetically engineered fish survive and breed in the wild (i.e. fitness)?
- What impacts could genetically engineered fish have on native species and the ecosystem?
- How effective are physical and biological containment methods for preventing genetically engineered fish from reproducing or breeding with native counterparts in the wild?
Several key findings from research conducted at the Centre for Aquatic Biotechnology Regulatory Research contribute to our understanding of the complexity of the answers to these questions.
Genetic engineering of fish may result in enhanced or decreased fitness, depending on the specific environmental conditions. For example, strains of growth-enhanced genetically engineered coho salmon have a very strong drive to eat (see video). Under certain environmental conditions, this enhanced feeding motivation allows the transgenic fish to outcompete wild strains for food resources, thus increasing their likelihood of survival. At the same time, this same enhanced appetite drives the transgenic fish to increase their foraging activity such that they are more willing to abandon the safety of the school to feed. This behavior makes them more susceptible to predation, thus decreasing their likelihood of survival. These two consequences from the same trait (e.g. enhanced feeding) lead to opposing predictions about the ability of genetically engineered fish to survive in the wild, and provide an example of how it can be difficult to reliably assess the net potential effects of transgenic fish on the environment from limited experimental data. Such experiments allow identification of important factors affecting fitness and consequences of transgenic fish, but developing a full understanding of the net consequences of transgenic fish requires significant data examining many aspects of the organisms' physiology, behaviour, and reproduction.
Regulators need to be assured that laboratory conditions accurately simulate environmental conditions in order to rely upon laboratory-generated data on genetically engineered fish to predict how they may grow and behave in the wild. These research results have led Fisheries and Oceans Canada to recognize the need to invest in infrastructure that more accurately simulates conditions in the wild. Three tanks, each of 350,000 liters of sea water, have been constructed at the Centre for Aquatic Biotechnology Regulatory Research research facility, as well as artificial streams to allow examination of paramaters such as food type, habitat complexity, presence of predators, etc. Data from these facilities is showing that strains grown under different conditions do not always show the same morphology, physiology, or behaviour, a response known as phenotypic plasticity. Further, the phenotype of different strains of salmonids (e.g. wild type vs. growth-hormone transgenic) can show different responses to changes in environmental conditions, an effect known as genotype by environment interactions. For example, transgenic fish grown in tank conditions can show very large increases in body size relative to wild-type fish grown under the same conditions. However, transgenic fish grown in semi-natural stream conditions do not show nearly the same growth acceleration as seen in tanks, whereas the non-transgenic fish show the same growth rate. Thus, transgenic fish raised in tank environments are unlikely to accurately represent the characteristics of fish if they had lived in nature (see the picture illustrating the effect of the environment on phenotype).
Methods for containing transgenic fish by inducing sterility are being proposed by proponents of the technology, and such measures would significantly reduce risk by eliminating the potential for transgenic fish to breed and transmit a transgene in an unconfined situation. It is possible to observe 100% efficacy in sterilizing fish using triploid technology when small numbers of fish are examined, however recent laboratory testing conducted at the Centre for Aquatic Biotechnology Regulatory Research on large numbers (~65,000) of triploid coho salmon has revealed an average success rate of around 98%, and a best success in a large-scale trial of 99.8%. A failure rate of 0.2 - 2% for triploidization would result in the presence of 100 to 1000 fertile transgenic fish in a growout population of 50,000 animals. Fertile fish that are accidentally or intentionally released into the environment could reproduce or interbreed with wild counterparts and lead to significant effects on the environment. This insight helps regulators to assess the strength of data in regulatory submissions.
Continued research is important to contribute knowledge to inform risk assessment and regulatory approaches to novel fish.
Overview Publications by the Centre for Aquatic Biotechnology Regulatory Research:
- Devlin, R.H. 2011. Growth Hormone Overexpression in Transgenic Fish. In: Farrell A.P., (ed.), Encyclopedia of Fish Physiology: From Genome to Environment, volume 3, pp. 2016-2024. San Diego: Academic Press.
- Devlin, R.H., Sundström, L. F., Johnsson, J.I., Fleming, I.A., Hayes, K.R., Ojwang, W.O., Bambaradeniya, C., and Zakaraia-Ismail, M. 2007. Assessing Ecological Effects of Transgenic Fish Prior to Entry into Nature. Chapter 6, In "Environmental Risk Assessment of Genetically Modified Organisms, Volume 3: Methodologies for Transgenic Fish" Edited by A R Kapuscinski, K R Hayes, S Li, G Dana. CABI International, USA.
- Devlin R.H, Sundstrom, L.F., and Muir, W.F 2006. Interface of biotechnology and ecology for environmental risk assessments of transgenic fish. Trends in Biotechnology 24: 89-97.
Selected scientific publication on novel aquatic organisms since the creation of the Centre for Aquatic Biotechnology Regulatory Research in 2008:
- Fitzpatrick, JL, Akbarashandiz, H, Sakhrani, D, Biagi, CA, Pitcher, TE, and Devlin, RH 2011. Cultured growth hormone transgenic salmon are reproductively out-competed by wild-reared salmon in semi-natural mating arenas. Aquaculture 312: 185-191.
- Ahrens, R.N.M. and Devlin, R.H. 2010. Standing genetic variation and compensatory evolution in transgenic organisms: A growth-enhanced salmon simulation. Transgenic Res. DOI 10.1007/s11248-010-9443-0
- Sundström, L.F., Lõhmus, M. and Devlin, R.H. 2010. Migratory timing of coho salmon (Oncorhynchus kisutch) smolts is largely independent of a major shift in growth potential: implications for ecological impacts from growth enhanced fish. Ecological Applications 20: 1372-1383.
- Chittenden, C.M., Biagi, C.A., Davidsen, J.G., Davidsen, A.G., Kondo, H., McKnight, A., Pedersen, O.P., Raven, P.A., Rikardsen, A.H., Shrimpton, J.M., Zuehlke, B., McKinley, R.S., and Devlin, R.H. 2010. Genetic versus Rearing-Environment Effects on Phenotype: Hatchery and Natural Rearing Effects on Hatchery- and Wild-Born Coho Salmon. PLoS ONE 5: e12261
- Overturf, K, Sakhrani, D, and Devlin, RH 2010. Expression profile for metabolic and growth-related genes in domesticated and transgenic coho salmon (Oncorhynchus kisutch) modified for increased growth hormone production. Aquaculture 307: 111-122.
- Devlin, R.H., Sakhrani, D., Biagi, C.A, and Eom, K.-W. 2010. Occurrence of incomplete paternal-chromosome retention in GH-transgenic coho salmon being assessed for reproductive containment by pressure-shock-induced triploidy. Aquaculture 304: 66-78.
- Lõhmus, M., Sundström, L.F., Björklund, M. and Devlin, R.H. 2010. Genotypetemperature interaction in the regulation of development, growth and morphometrics in wild-type, and growth-hormone transgenic coho salmon. PLoS ONE 5(4) e9980.
- Phillips, R.B. and Devlin, R.H. 2009. Integration of growth hormone gene constructs in transgenic strains of coho salmon (Oncorhynchus kisutch) at centromeric or telomeric sites. Genome 53: 79-82.
- Tymchuk, W.E., Sakhrani, D. and Devlin, R.H. 2009. Domestication causes large-scale effects on gene expression in rainbow trout: analysis of muscle, liver and brain transcriptomes. Gen. Comp. Endocrinol 164: 175-183
- Lõhmus, M., Björklund, M., Sundström, L.F. and Devlin, R.H. 2009. Individual variation in growth trajectories of wild and transgenic coho salmon at three different temperatures. Journal of Fish Biology 76: 641-654.
- Rehbein H. and Devlin, R.H. 2009. No Evidence for Enhanced Parvalbumin Concentration in Light Muscle of Transgenic Coho Salmon (Oncorhynchus kisutch). European Food Research and Technology 229:579-584.
- Leggatt, R.A., Raven, P.A., Mommsen, T.P., Sakhrani , D., Higgs, D. and Devlin R.H. 2009. Growth hormone transgenesis influences carbohydrate, lipid and protein metabolism capacity for energy production in coho salmon (Oncorhynchus kisutch). Comp. Physiol. Biochem., Part B 154: 121-133.
- Sundström, L.F., Tymchuk, W.E., Lõhmus, M., and Devlin, R.H. 2009. Sustained predation effects of hatchery-derived growth hormone transgenic coho salmon Oncorhynchus kisutch in semi-natural environments. Journal of Applied Ecology 46: 762-769.
- Tymchuk, W.E., Beckman, B., and Devlin, R.H. 2009. Anthropogenic selection in fish has genetically altered the expression of hormones involved in the GH / IGF-I growth axis. Endocrinology 150: 1809-1816.
- Devlin, R.H., Sakhrani, D., Tymchuk, W.E., Rise, M.L., and Goh, B. 2009. Domestication and growth hormone transgenesis cause similar changes in gene expression profiles in salmon. Proc. Natl. Acad. Sci. USA 106: 3047-3052.
- Higgs, D.A, Sutton, J., Kim, H., Oakes, J.D, Smith, J., Biagi, C., Rowshandeli, M. and Devlin, R.H. 2009. Influence of dietary concentrations of protein, lipid and carbohydrate on growth, protein and energy utilization, body composition, and plasma titres of growth hormone and insulin-like growth factor-1 in non-transgenic and growth hormone transgenic coho salmon, Oncorhynchus kisutch (Walbaum). Aquaculture 286: 127-137.
Click here for a complete list of historical publications from the Fisheries and Oceans Canada on assessment of novel organisms.
- Fisheries and Oceans Canada's Aquatic Biotechnology Website
- Canadian Environmental Protection Act, 1999
- New Substances Notification Regulations (Organisms)
- Environment Canada Biotechnology Website
Biotechnology and Aquatic Animal Health Branch
12W129 - 200 Kent, Ottawa, ON, K1A 1E6
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