Unsafe cloning

Scientists confirm the previous suspicion that reproductive cloning is not only inefficient, but also unsafe

 
Published: Wednesday 15 August 2001

-- (Credit: Ruby Bagchi)scientists have found an evidence to show that even seemingly normal-looking clones may harbor serious abnormalities affecting gene expression that may not manifest themselves as outward characteristics. The findings, reported by researchers at the Whitehead Institute for Biomedical Research and University of Hawaii, confirm the previous suspicion that reproductive cloning is not only inefficient, but also unsafe ( Science , July 6, 2001).

In the study, scientists from Rudolf Jaenisch's laboratory and Ryuzo Yanagimachi's laboratory sought to examine the mechanisms underlying poor survival and gross overgrowth in cloned animals. They made mouse clones from embryonic stem ( es ) cells and monitored the activity of imprinted genes--developmental genes that are controlled by special tags that do not affect the base sequence itself.

Scientists found to their surprise that much of the problem lay in the make up of the donor embroynic stem cells, which they found to be extremely unstable in culture. As they divide in culture, these cells lose the tags that tell an imprinted gene to be either turned on or off during development.

The researchers found that even clones made from sister stem cells had differences in their gene expression. Despite this instability, many embryos survived to adulthood, suggesting that mammalian development is surprisingly tolerant to aberrant gene regulation. "This suggests that even apparently normal clones may have subtle aberrations of gene expression that are not easily detected in the cloned animal," says Jaenisch.

The cloning procedure involves removing the nucleus, or the genetic command centre, of an egg and replacing it with the nucleus from an adult cell or an embroynic stem cell. Ideally, the egg resets the developmental clock of the nucleus back to a state compatible with early embryonic growth and gives rise to a new organism that is genetically identical to the donor cell.

T he embroynic stem cells are unique in that they can give rise to an entire organism without using the nuclear transfer procedure. The researchers found that animals developed from mouse embroynic stem cells by this technique exhibited irregular gene expression just as animals derived from nuclear transfer using embroynic cells confirming that these abnormalities likely existed in the cells before the cloning procedure was performed.

"However, despite their instability, it is important to remember that embryonic stem cells when combined with normal cells--as in making chimeras or when used in transplantation--may function fine.

In other words, embroynic cells might work fine when used as cell therapy, but when they are used to make whole animal would likely produce organisms that are abnormal," says Jaenisch.

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