Appendix N. 
393 
fiii) Cloned animals develop serious problems y\rith acre 
The generation of adult and seemingly healthy adult cloned animals 
has been taken as evidence that normal cloned animals can be 
generated by nuclear transfer, albeit with low efficiency. Indeed, a 
routine physical and clinical laboratory examination of 24 cloned 
cows of 1 to 4 years of age failed to reveal major abnormalities 
(Lanza et al., 2001). Cloned mice of a corresponding age as that of the 
cloned cows (2-6 months in mice vs. 1 - 4 years in cows) also appear 
"normal" by superficial inspection. However, when cloned mice were 
aged, serious problems, not apparent at younger ages, became 
manifest. One study found that the great majority of cloned mice died 
significantly earlier than normal mice, succumbing with immune 
deficiency and serious pathological alterations in multiple organs 
(Ogonuki et al., 2002). Another study found that aged cloned mice 
became overweight with major metabolic disturbances (Tamashiro 
et al., 2002). Thus, serious abnormalities in cloned animals may often 
become manifest only when the animals age. 
Firm evidence about aging and “normalcy” of cloned farm animals 
is incomplete or anecdotal because cloned animals of these species 
are still comparatively young (relative to their respective normal life 
span). For example, the premature death of Dolly (Giles and Knight, 
2003) is entirely consistent with serious abnormalities in cloned 
sheep that become manifest only at later ages. Also, two of the 
analyzed cloned cows developed disease soon after the study on 
"healthy and normal cattle" (Lanza et al., 2001) had appeared: one 
animal developed an ovarian tumor and another one suffered brain 
seizures (J. Cibelli, pers. comm.). While it carmot be ruled out that 
these are “spontaneous" maladies unconnected with the cloning 
procedure, a more likely alternative is that these problems were 
direct consequences of the nuclear transfer procedure. 
(iv) Are there anv "normal" clones? 
It is a key question in the public debate whether it is ever possible to 
produce a normal individual by nuclear cloning, even if only with low 
efficiency. The available evidence suggests that it may be difficult if 
not impossible to produce normal clones for the following reasons: 1) 
As summarized above, all analyzed clones at birth showed 
dysregulation of hundreds of genes. The development of clones to 
birth and beyond despite widespread epigenetic abnormalities 
suggests that mammalian development can tolerate dysregulation of 
many genes. 2) Some clones survive to adulthood by compensating 
for gene dysregulation. Though this ‘ compensation assures 
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