Redesigning Animal Agriculture

under development as a biopharmaceutical
for the treatment of autoimmune diseases
(Parker et al., 2004). Transgenic livestock
are also being evaluated for the production
of recombinant vaccines. Potential vaccines
against malaria and rotavirus have been produced
in milk of transgenic goats and rabbits,
respectively (Behboodi et al., 2005).
Recombinant human therapeutic antibodies
are also being produced in the milk (Pollock
et al., 1999) and blood (Grosse-Hovest et
al., 2004) of transgenic animals. Moreover,
human polyclonal antibodies have been
produced in the blood of cattle following
the introduction of an artificial chromosome
containing the entire sequence for human
immunoglobulin heavy and light chain loci
into bovine fetal fibroblasts and then creating
calves via NT (Kuroiwa et al., 2002). There
has been an interesting development in the
production of recombinant human butyrylcholinesterase,
purified from transgenic
goat’s milk, as a potential bioscavenger of
organophosphorus nerve agents for affected
military personnel or civilian casualties of
bioterrorism (Cerasoli et al., 2005).
The technology for generating transgenic
livestock as bioreactors is well established,
and there are numerous examples.
But the path to commercialization is fraught
with financial difficulty especially in terms
of the purification costs, the timeframes
involved in rigorous clinical testing and
regulatory evaluation and the risk that the
therapeutic being developed may ultimately
fail. The enormity of these challenges
were exemplified with the recent failure
of PPL Therapeutics, one of the pioneers
of biopharming, caught up in economic
constraints and regulatory uncertainties
(Powell, 2003). It is unclear what the future
holds for the general utility of farm animal
bioreactors in converting forage into valuable
biopharmaceuticals. The use of plants
to directly produce certain therapeutics
appears be a strong competing technology.
Plant-based molecular pharming systems
have successfully produced functional
human pharmaceutical proteins, recombinant
antibodies and vaccines and offer
several advantages over livestock bioreactors,
such as lower production costs, greater
Cloning and Transgenesis 103
scale-up ability and enhanced safety due to
absence of animal or human pathogens (Ma
et al., 2003). Moreover, progress is being
made in mammalian-like, post- translational
processing of proteins, where this is important
for functionality, in biologic ally unrelated
production systems such as plants
(Joshi and Lopez, 2005) and microorganisms
(Gerngross, 2004). Functional proteins
can even be chemically synthesized de novo
(Kochendoerfer et al., 2003). In terms of ethical
acceptance, the public are more likely
to support the use of transgenic plants as
bioreactors rather than animals (Einsiedel,
2005). A more significant environmental
issue with pharming plants is, however,
control over their physical containment and
spread.
Xenotransplantation
The shortage of human donor organs to treat
chronic organ failure and various degenerative
tissue diseases could be overcome by
targeting specific genetic modifications
to generate herds of pigs whose organs
would be immunologically compatible
with humans following xenotransplantation
(Lanza et al., 1997). Pigs are favoured
because of their similarities in organ size
and physiology to humans, short generation
interval and large litter size. Recently, pigs
have been produced that completely lack
the enzyme α-1,3-galactosyl-transferase
(Phelps et al., 2003) in attempts to eliminate
the specific carbohydrate epitope found on
the cell surface in pigs, but not humans, to
counter the complement-based hyperacute
immune rejection that occurs within minutes
of transplantation. However, low but
detectable levels of the gal antigen may still
persist on the pig cells (Sharma et al., 2003).
None the less, initial evidence provides some
encouragement with pig-to-baboon xenografts
surviving for extended periods, up to
83 days for kidneys (Yamada et al., 2005)
and 2–6 months for hearts (Kuwaki et al.,
2005). Subsequent immunosuppressive
drug therapy or additional genetic modifications
could be used to manage the human
body’s other rejection processes to prolong
the functionality of the organ. In using pig