In research, animal care committees advocate the implementation of the Three Rs principles- reduce, refine and replace. However, the unique conditions required for animals involved in xenotransplantation make these goals difficult to achieve.

Primary Welfare Concerns in Xenotransplantation:

Invasiveness of procedures

• Production of transgenic animals:
  • Hormone injections to induce super-ovulation
  • Embryos surgically harvested from breeding animals
  • Males are vasectomized to induce pseudo-pregnancy in surrogate females
  • Surgical embryo transfer to surrogate females
  • offspring often delivered by caesarean section (major surgery)
• Frequent screenings involving tissue and blood samples to determine genetic inheritance and ensure animals are pathogen-free
• Animals involved in pre-human clinical trials (often nonhuman primates):
  • Major surgery
  • Pain and suffering if xenograft is rejected
• Animals used as donors:
  • Major surgery
  • Use of certain anaesthetic agents may be prohibited because they may be harmful to the human recipient
  • Sequential organ procurement has been suggested for kidneys; animals would be subjected to multiple organ harvesting surgeries

 

Animal Wastage

• Many animals used in the production of transgenic animals
  • CRISPR has substantially reduced the number of animals used for this purpose, but there are concerns that this technology could lead to an increase in transgenic animal production in general
• A surplus of animals are kept for the propagation of useful germ-lines for future experiments
  • Can be refined by cryopreservation of gametes
• Animal sacrifices:
  • In breeding after blastocysts/embryos are harvested
  • If the animal does not inherit the desired gene
  • If the animal is exposed to a potential pathogen

Unintended Genetic Outcomes

• Off-target mutations (common with HR)
  • Less frequent when CRISPR is used
• Unanticipated outcomes of intentional gene modification:
  • Deletions and insertions of genes can result in behavioural and physiological changes in unexpected ways (may not be apparent to the researcher)
  • Example: pigs modified to express CTLA4-Ig to improve immuno-tolerance became immunocompromised and resulted in premature death

Sterile Rearing Environment

• Animals to be used as donors must be certified pathogen-free
• Environments are restrictive
• Often raised in isolation, deprived of social interactions
• Natural foodstuffs, rooting and bedding materials are often prohibited (may be contaminated)
• Often weaned prematurely, causing distress to mother and piglet