Introduction research on the TSEs, including studies to elucidate

Livestock Production Science 62 2000 287–316 www.elsevier.com locate livprodsci Risks of transmission of spongiform encephalopathies by reproductive technologies in domesticated ruminants A.E. Wrathall Veterinary Laboratories Agency Weybridge, New Haw, Addlestone, Surrey KT15 3NB, UK Abstract This paper considers whether transmissible spongiform encephalopathies TSEs or prion diseases could be spread by artificial insemination, embryo transfer and other more advanced reproductive technologies which are used for genetic improvement and also for purposes such as production of recombinant drugs for medical use. Although the technologies are most used in cattle, they are increasingly used in sheep, goats and deer as well, all of which can be naturally affected by TSEs. In general, provided appropriate precautions are taken, the risks of TSE carriage specifically by the gametes spermatozoa and oocytes or by in-vivo-derived embryos per se appear to be negligible, but further research, some of which is already in progress, will be helpful to give assurance on this point. Greater concerns relate to the many biological products that are used in the technologies, e.g. pituitary hormones used for the superovulation of donors, and various tissues and blood products used in semen and embryo culture transport media, some of which have the potential to carry TSE infectivity if derived from infected animals. The myriad instruments and items of technical equipment that are used also give cause for concern because if they become contaminated with TSEs they may, due to their construction, be impossible to sterilise properly. Crown Copyright  2000 Published by Elsevier Science B.V. All rights reserved. Keywords : Transmissible spongiform encephalopathy; Reproductive technology; Embryo transfer; Disease control; Ruminants

1. Introduction research on the TSEs, including studies to elucidate

their routes of transmission. Awareness of the transmissible spongiform en- Unconnected with TSEs, but nevertheless cephalopathies TSEs — also known as prion dis- momentous, was the revelation early in 1997 that a eases, particularly scrapie in sheep and bovine cloned sheep ‘Dolly’ had been produced in Edin- spongiform encephalopathy BSE, has risen burgh, Scotland, by transfer of the nucleus from an dramatically in the past decade. The possibility of a adult cell Wilmut et al., 1997. This has also zoonotic link between BSE and new variant Creut- stimulated new research and a vigorous debate on the zfeldt–Jakob disease nvCJD in man, first reported implications of cloning and other reproductive tech- in March 1996 Will et al., 1996, added ‘fuel to the nologies in farm animals, including possible risks of fire’ and precipitated the so-called ‘beef crisis’ in the diseases such as TSEs being spread by their use UK, Europe and in other parts of the world. In the Evans, 1999. These risks are small but they cannot wake of this there has been a huge increase in be dismissed altogether. The possibility, for example, 0301-6226 00 – see front matter Crown copyright  2000 Published by Elsevier Science B.V. All rights reserved. P I I : S 0 3 0 1 - 6 2 2 6 9 9 0 0 1 6 3 - 3 288 A .E. Wrathall Livestock Production Science 62 2000 287 –316 of a cloned, transgenic animal transmitting TSE to enable more oocytes from preferred females to be infectivity via recombinant products destined for utilised. Then in the third category is a range of medical use is an alarming but not implausible techniques, some relatively new, such as sexing, scenario if sanitary precautions are overlooked. This cloning and genetic modification, which select or paper explains how TSE transmission risks might modify gametes and embryos to obtain offspring arise in reproductive technologies and how they with specific characteristics. Taken together, these should be avoided. Topics covered include the technologies not only supplement what can be following. achieved by conventional breeding but also enable the production of new foods, industrial products, and • Brief summaries of the reproductive technologies drugs for use in human medicine. in domesticated ruminants. • Conventional disease transmission risks via re- 2.2. Selective breeding productive technologies. • Differences between conventional infectious dis- Although not strictly a reproductive technology it eases and the TSEs. is apposite to mention selective breeding because • Natural TSE transmission, especially during re- susceptibility to some TSEs is strongly affected by production in ruminants. genetic factors. Selective breeding enables promising • Risks of TSE transmission via reproductive tech- individuals to be identified and genetic lines to be nologies, and their control. selected and improved in respect of commercially important characteristics. One of these characteristics is disease resistance, and selection for resistance to

2. The reproductive technologies conventional diseases, such as mastitis and lameness,