388 
Monitoring Stem Cell Research 
article is to provide such a basis and to contribute to a more rational 
discussion that is founded on scientific evidence rather than on 
misconceptions or misrepresentations of the available scientific data. 
I. Introduction 
It is important to distinguish betv\^een “reproductive cloning" and 
"nuclear transplantation therapy" (also referred to as “SCNT" or 
"therapeutic cloning"). In reproductive cloning a cloned embryo is 
generated by transfer of a somatic nucleus into an enucleated egg 
with the goal to create a cloned individual. In contrast, the purpose 
of nuclear transplantation therapy is to generate an embryonic stem 
cell line (referred to as "ntES cells") that is “tailored" to the needs of 
a patient who served as the nuclear donor. The ntES cells could be 
used as a source of functional cells that would be suitable for 
treating an underlying disease by transplantation. 
There is now experience from cloning of seven different 
mammalian species that is relevant for three main questions of 
public interest: 1) Would a cloned human embryo be "normal"? 2) 
Could the problems currently seen with cloning be solved in the 
foreseeable future? 3) Would ES cells derived from a cloned human 
embryo be “normal" and useful for cell therapy? The arguments 
advanced in this article are strictly based on molecular and biological 
evidence that has been obtained largely in the mouse. I will not 
attempt to review the cloning literature but only refer to selected 
papers on cloned mice. The relevant literature on cloning of 
mammals can be found in recent reviews (Byrne and Gurdon, 2002; 
Gurdon, 1999; Hochedlinger and Jaenisch, 2002b; Oback and Wells, 
2002; Rideout et al., 2001; Wilmut, 2001; Young et al., 1998). 
n. Most cloned animals die or are bom with abnormalities 
The majority of cloned mammals derived by nuclear transfer (NT) die 
during gestation, and those that survive to birth frequently display 
“Large Offspring Syndrome", a neonatal phenotype characterized by 
respiratory and metabolic abnormalities and enlarged and 
dysfunctional placentas (Rideout et al., 2001; Young et al., 1998). In 
order for a donor nucleus to support development into a clone, it 
must be reprogrammed to a state compatible v\hth embryonic 
development. The transferred nucleus must properly activate genes 
important for early embryonic development and also suppress 
PRE -PUBLICATION VERSION 
