BIOTECH: Cloning: Buyer Beware

From: Robert J. Bradbury (
Date: Wed Jul 11 2001 - 17:29:27 MDT

As a point of interest, there is an article in the July 6th 2001
issue of Science:
  Humpherys, D. et al,
  "Epigenetic Instability in ES Cells and Cloned Mice"

> Cloning by nuclear transfer (NT) is an inefficient process in which most
> clones die before birth and survivors often display growth abnormalities.
> In an effort to correlate gene expression with survival and fetal
> overgrowth, we have examined imprinted gene expression in both mice
> cloned by nuclear transfer and in the embryonic stem (ES) cell donor
> populations from which they were derived. The epigenetic state of the
> ES cell genome was found to be extremely unstable. Similarly,
> variation in imprinted gene expression was observed in most cloned
> mice, even in those derived from ES cells of the same subclone. Many
> of the animals survived to adulthood despite widespread gene
> dysregulation, indicating that mammalian development may be rather
> tolerant to epigenetic aberrations of the genome. These data imply
> that even apparently normal cloned animals may have subtle abnormalities
> in gene expression.

I believe that I've commented on this previously in postulating that
faulty imprinting of epigenetic information may be a possible cause
of the low efficiency of cloning. This paper would appear to cast
some doubts on that -- in that you can get adults even with
"widespread gene dysregulation". Of course there may be
selection effects at work here, i.e. one set of dysregulated
genes results in an adult (with wierd spin on gene regulation)
while another set of dysregulated genes results in fetal termination.
So perhaps the jury is still out.

The big picutre depends to a large degree on the fraction of genes
that carry parental "imprinting" and their significance in development
to fetal/adult maturity. It may be true that modern medicine, including
C-sections for larger than average size babies, may mitigate the
value/importance of gene imprinting. (The "imprinted" genes I
know of are involved in the male/female tradeoff in the male's
desire to foster large newborns vis-a-vis the female's desire
to manage resource consumption and maternal birth risk.)

The bottom line re: cloning with current technology is that you
may not get what you expected. Cloned organs may fail prematurely
and whole body clones may not provide a full lifespan. Until the
full impact of epigenetic imprinting is understood, lobbying for
"real" availability of cloned organs or bodies seems premature.
Yes, they may be better than nothing, but they probably do not
carry the Original Equipment Manufacturer (OEM) warranty.


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