about whether this same restoration would be seen in animals cloned from adult cells, or whether such animals instead will age prematurely and possibly develop health problems usually seen in older animals. While shortened telomere lengths were seen in one sheep (“Dolly”) cloned from adult somatic cells (Shiels et al., 1999), telomere lengths apparently are normal in cattle cloned from adult cells (Lanza et al., 2001; Betts et al., 2001).

BIOMEDICAL APPLICATIONS

In contrast to genetic manipulation of farm animals for production traits, transgenic manipulation for the production of human pharmaceuticals or transplant organs generally is not intended to cause changes that have physiologic effects on the animals themselves. Thus, although unexpected and undesirable phenotypic effects still can occur as a result of gene insertion or cloning technology, there generally are fewer potential animal welfare concerns associated with the production of transgenic farm animals for biomedical purposes than for agricultural purposes (Van Reenen and Blokhuis, 1993).

Pharmaceuticals

Although there is a potential for producing pharmaceuticals in the eggs, blood, urine, or sperm of farm animals (Lubon, 1998; Sharma et al., 1994), the most common method is to produce transgenic cattle or goats that express the protein of interest in mammary tissue. The recombinant protein then is secreted in milk when the female lactates. This poses problems mainly when those proteins either are expressed in non-mammary tissues (so-called ectopic expression) or when they “leak” out of the mammary gland into the circulation (e.g., Lubon, 1998; Niemann et al., 1999). If the protein is active biologically in the species in which it is produced, it can cause pathologies and other severe systemic effects (e.g., Massoud et al., 1996). Rigorous regulation of the expression of the transgene thus is necessary to ensure that the animal welfare consequences of milk-borne pharmaceutical production are minimized, but such regulation currently is difficult to achieve. However, even when a pharmaceutical is confined to the mammary tissue, the expression of particular proteins has been associated with premature lactational shutdown in goats (Ebert and Schindler, 1993) and pigs (Shamay et al., 1992). In pigs, there was evidence that the mammary tissue developed abnormally due to premature expression of the transgene, and that the condition of the mammary gland might have caused lactation to be painful. Similar concerns arise in the case of blood-borne proteins and nutraceuticals (see below) if the products are produced at levels higher than the animal’s normal physiologic levels.



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