MadSci Network: Molecular Biology

Re: what technology breakthrough lead to being able to clone

Date: Wed Mar 15 13:30:26 2000
Posted By: Irene Yan, Post-doc/Fellow, Vertebrate Embryology, Rockefeller University
Area of science: Molecular Biology
ID: 947360238.Mb

To understand what cloning is and what led to it, I’ll have to give you a 
little bit of the background on embryology.  As you might know, embryology 
studies the processes that develop a whole organism from a single cell: 
the egg.  In other words, embryologist are interested in understanding how 
can a one single cell develop into multiple different cell types 
(differentiation) that constitute a healthy adult organism.  Each cell 
type (differentiated cell) has its own set of proteins that are necessary 
for its function.  For example, the red blood cells have hemoglobin, which 
other cells don’t.  However, all the different cells in a single organism 
have the same nucleus, with the same genetic information.  Thus, for the 
differentiated cells to have different proteins some genes in the nucleus 
are turned on or off, this is a process known in embryology 
as “restriction of nuclear potency”.  As you can imagine, it is important 
to understand how can a single egg with one nucleus give rise to so many 
different cells that derive different gene expression patterns from the 
same original nucleus.  Sometimes, the changes that a differentiated cell 
exerts on a nucleus can be difficult to reverse or change. A good way of 
thinking about it is in terms of a “specialized nucleus”.  As the embryo 
develops into an adult organism, the nucleus of each cell becomes more and 
more specialized.
	Cloning is a process where the nucleus from one individual is 
transferred into another cell and generates an individual that is 
genetically identical to the nucleus donor.  The initial cloning 
experiments were done by transferring nucleus from one embryo to an 
enucleated activated egg (nuclear transfer technique).  The activated egg 
is obtained by pricking an egg with a clean glass needle, stimulating it 
to undergo all the changes that occur after fertilization, without 
actually providing it with a sperm.  After its activation, the chromosomes 
can be removed from the egg, and replaced with the nucleus of the donor 
cell.  But, for a successful cloning to occur, it is important to start 
with a donor nucleus that is not irreversibly specialized, or it wouldn’t 
be able to give rise to all the different cells that constitute an 
organism.  Therefore, when a differentiated cell donates the nucleus, 
its “specialization” must be reversed.  In other words, the specialized 
nucleus must be “reset” to its original naďve state.  The factors 
important for “reseting”the nucleus in the recipient egg cytoplasm are 
still unknown.  In the early cloning experiments, the problem of resetting 
a nucleus was avoided by using early embryos as donors, thus using nuclei 
that had not undergone extensive specialization.   Recent advances now 
allow scientist to transfer nuclei from differentiated cells (more 
specialized nuclei).  These advances include knowing which stage of the 
cell cycle at which the donor nucleus must be obtained.  Also, using 
ovulated oocytes increased the frequency of successful clones. Both of 
these modifications increase the chances of the differentiated nucleus to 
be reset.
 	In summary, the present cloning technology involved a series of 
discoveries that were culminated in the generation of Doll, the lamb, in 
1998.  My private opinion is that the breakthrough discovery that allowed 
cloning was done by Robert Briggs and Thomas King in the 1950s with the 
first nuclear transfer experiment, done in frogs.  All the posterior 
advances are all built on the concept that nuclear transfer can generate 

You can read more about cloning at:

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