How Dolly was produced and the implications for human cloning

Dolly was produced via a process called nuclear transfer, in which the genetic material of a cell is placed into an unfertilized egg that has had its genetic material removed. The two are then fused together either by an electrical pulse, or by introducing a chemical. the development of this newly created embryo can then take place (see figure below).

The process of nuclear transfer.

Figure: The process of nuclear transfer.

Although much research still needs to be done about this process, after many attempts, researchers from the Roslin Institute in Edinburgh, Scotland managed to clone a healthy sheep using nuclear transfer. This was done by treating the cell before inserting it into the egg that had had its genetic material removed. This essentially consisted of growing the cell in culture under specific conditions. In the case of Dolly, the cells were taken from the udder of a six year old ewe and put in culture. The cells were then starved to force them into a dormant state. This had the advantage of greatly increasing the number of donor cells, so as to allow the genetic modification of cells. Then, the scientists would have the option of only selecting the cells which contained the desired genetic modification.

After the fusion of the genetic material of a cell together with an unfertilized egg that had had its nucleus removed, the resultant egg was placed in culture for 7 days. Embryos which grew successfully were then transplanted into female sheep which were at the same stage of the oestrus cycle as the egg, so that the cloned sheep were born naturally.

Cloning by nuclear transfer has been done many times before (see timeline of cloning). What sets the Dolly experiment apart from any previous cloning attempts is that this is the first time the complete genetic material from an adult mammalian cell has been used in the development of a new individual.

Looking to beyond- the potential for human cloning

The successful cloning of Dolly has serious implications for the possiblity of human cloning. It seems to suggest that this process can be used to successfully clone humans. Details of the process might be different as scientists discover new ways of improving the procedure, but the overall technique will remain the same, as suggested in the figure below.

A recipe for making a human cloned cell

Ingredients:

One somatic cell from a donor man or woman

An unfertilized egg from a woman

Procedure:

1) Remove nucleus of somatic cell

2) Remove genetic material of egg

2) Transfer DNA of somatic cell into (enucleated) egg cell

3) Implant egg with DNA from somatic cell into surrogate mother

Figure: How a human clone might be cloned using the method that was used to produce Dolly.

Problem areas with human cloning

Simple, isn't it? Things are not as it seems...

Problem #1) Do the math... over 400 unfertilized eggs were needed to produce 277 recombined eggs. Out of these, only one lamb survived through birth to produce Dolly. Since in vitro fertilization clinics recover an average of 5-10 eggs from each woman donor, it can be concluded that each clone would need 40 volunteers.

Problem #2) Sheep compared to humans are more efficient at reproducing. Sheep usually need to mate only once to get pregnant, but young fertile women have about 30% chance of getting pregnant after each intercourse. If artificial methods of reproducing like in vitro fertilization are used, the rates of getting pregnant drop to 10-20%. It has been estimated that taking all the above factors into account, the chances of producing a human clone are 3-10 times less likely than in humans.

Problem #3) To produce clones from adults, scientists would have to use somatic cells. However, somatic cells are cells that are already differentiated to have a specific function. As a result, many of the genes in somatic cells have been turned off, and scientists do not know how to turn these genes back on. This problem has resulted in many of the pregnancies being terminated, or many of the cloned animals dying in infancy or having abnormalities. As such, the process is not safe to use in humans.

Problem #4) More research needs to be done on the effects of using DNA from older organisms. One area of concern was the fact that a study on Dolly's cells showed that her telomeres, the tips of the chromosomes that protect her genes from damage, were prematurely frayed, mostly likely because her genetic material originated from a 6 year old ewe. This could mean that cloned individuals would have a higher risk of dying prematurely or getting cancer (For the most recent findings of researchers about this issue, click here) .

As such, as of now, it is morally and practically unfeasible to carry out human cloning. However, scientists around the world are carrying out research on animals which are shedding more and more light on how the process can be improved, and possibly used in humans. (Click here for results of subsequent research on cloning after the cloning of Dolly).

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