Transgenesis may affect farm animal welfare: A case for systematic risk assessment C. G. Van Reenen 1 , T. H. E. Meuwissen, H. Hopster, K. Oldenbroek, Th. A. M. Kruip, and H. J. Blokhuis Institute for Animal Science and Health (ID-Lelystad), Division of Animal Sciences, 8200 AB Lelystad, The Netherlands ABSTRACT: This paper considers (potentially) harmful consequences of transgenesis for farm animal welfare and examines the strategy of studying health and welfare of transgenic farm animals. Evidence is discussed showing that treatments imposed in the con- text of farm animal transgenesis are by no means bio- logically neutral and may compromise animal health and welfare. Factors posing a risk for the welfare of transgenic farm animals include integration of a transgene within an endogenous gene with possible loss of host gene function (insertional mutations), inappro- priate transgene expression and exposure of the host to biologically active transgene-derived proteins, and in vitro reproductive technologies employed in the pro- cess of generating transgenic farm animals that may result in an increased incidence of difficult parturition and fetal and neonatal losses and the development of unusually large or otherwise abnormal offspring (large offspring syndrome). Critical components of a scheme for evaluating welfare of transgenic farm animals are identified, related to specific characteristics of transgenic animals and to factors that may interact with the effects of transgenesis. The feasibility of an Key Words: Animal Welfare, Farming, Risk Assessment, Transgenic Animals 2001 American Society of Animal Science. All rights reserved. J. Anim. Sci. 2001. 79:1763–1779 Introduction A transgenic (or genetically modified) animal is one whose genome contains DNA of exogenous origin that has been introduced through experimental manipula- tion (Jacenko, 1997). Since the early 1980s, when for the first time transgenic mice were generated, research with transgenic animals has evolved into a major scien- tific field. During the last 15 yr transgenesis has been 1 Correspondence: P.O.Box 65 (phone: +31 320 23 82 03; fax: +31 320 23 80 94; E-mail: c.g.vanreenen@id.wag-ur.nl). Received October 2, 2000. Accepted March 26, 2001. 1763 evaluation of welfare of transgenic farm animals in practice is addressed against the background of the objectives and conditions of three successive stages in a long-term transgenic program. Concrete steps with regard to breeding and testing of transgenic farm ani- mals are presented, considering three technologies to generate transgenic founders: microinjection, electro- poration and nuclear transfer, and gene targeting in- cluding gene knockout. The proposed steps allow for unbiased estimations of the essential treatment effects, including hemi- and homozygous transgene effects as well as effects of in vitro reproductive technologies. It is suggested that the implementation of appropriate breeding and testing procedures should be accompanied by the use of a comprehensive welfare protocol, speci- fying which parameters to monitor, at which stages of the life of a farm animal, and in how many animals. Some prerequisites and ideas for such a protocol are given. It is anticipated that systematic research into the welfare of farm animals involved in transgenesis will facilitate the use of the safest experimental proto- cols as well as the selection and propagation of the healthiest animals and, thereby, enable technological progress that could be ethically justified. extended to livestock, with the aim of benefiting human health, but also to improve animal production (Pinkert and Murray, 1999). At the same time there is growing concern about health and welfare of the animals in- volved in transgenesis research (e.g., Masood, 1997; Mench, 1999). However, few studies have been con- ducted to evaluate the welfare of transgenic farm ani- mals. Moreover, although scientists or companies di- rectly involved in the production of transgenic farm animals have recognized the importance of animal wel- fare (e.g., Pinkert and Murray, 1999; Pharming, 2000), they generally fail to specify concrete steps to monitor and prevent possibly adverse effects of transgenesis on animal health and welfare (see also Klotzko, 1998). We argue that opinions on welfare of transgenic farm animals should be based on relevant biological data