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Cloning

I am a 53 year old woman who underwent removal of her uterus after two operations for uterine fibroids. I insisted on keeping my ovaries, however, to prevent premature menopause. By now I assume that my eggs are greatly deteriorated and heroic attempts to fertilize them would likely result in an unhealthy fetus. However, is there a way to retrieve healthy DNA from other cells in my body, implant my DNA in the nucleus of a donor egg whose own DNA has been removed, fertilize my egg(s)with my husband's sperm, implant the egg(s)in a donor womb, and obtain a healthy fetus that is genetically like my husband and me?

-A curious adult from Washington D.C.

March 8, 2005

You are right that females have a loss of fertility with aging. Fewer eggs are made by the ovaries and those older eggs have a greater chance of having problems. It does seem reasonable to put a body cell's more healthy DNA into someone else's egg.

Unfortunately, its much more complicated than it sounds. DNA from any other type of cell has twice as much DNA as an egg. So far there is no good way to put only half of that cell's DNA into an egg. Also, DNA from a body cell has a hard time directing the formation of a normal baby.

In everyday human reproduction, a sperm fertilizes an egg, and the newborn's genes come from both parents. Half are in the egg, and the other half are carried in the sperm. These genes are found in the nucleus on coiled linear chains called chromosomes.

Most of your body cells (known as somatic cells) have 46 chromosomes, in 23 pairs, with one from each parent. When a cell divides, the chromosomes are copied and each daughter cell receives an identical set of 46.

Egg cells (oocytes) and sperm are special non-somatic cells, created by a unique cell division called 'meiosis'. The cell divides twice leaving each egg and sperm with 23 chromosomes.

The divvy-ing up of the chromosomes during meiosis is an intricate dance. Mishaps that lead to egg or sperm having even one extra or missing chromosome causes serious disease. Around half of early pregnancy losses are due to embryos having the wrong number of chromosomes (click here for more details).

When egg and sperm come together, the full amount of 46 chromosomes is restored. Combining 46 chromosomes from a body cell with 23 more chromosomes from a sperm would be genetic overload.

To use somatic cell DNA in reproduction, its chromosome number needs to be reduced from 46 to 23. Can somatic cell chromosomes complete meiosis if placed in an egg? In fact it's very tricky to get those rearranging chromosomes to sort in a radically different pattern.

So far this has only been attempted in mouse cells, by combining a somatic cell nucleus just about to divide with a very young oocyte that has not begun meiosis. Timing in this experiment is crucial and the results were not perfect.

There were mistakes in how the chromosomes sorted out. Scientists are hopeful that further research will let them make artificial eggs ready for fertilization by sperm.

But, that's not the only hurdle. Besides the amount of DNA, the origin of the DNA placed in an egg also affects the embryo.

The DNA of egg and sperm is different in form from the DNA in body cells. The chromosomes are specially arranged and tagged before the sperm fertilizes the egg (click our previous answer here for more details). This ensures that the right genes are active at the proper time and place during development.

In specialized body cells, like a nerve or muscle cell, the chromosome arrangement is very different. The genes needed for early development are shut down. Research shows that somatic cell DNA cannot guide embryo growth normally.

What about Dolly the sheep? Dolly is called a clone because her DNA came entirely from a single body cell. That cell's nucleus was put into an egg that had its own nucleus removed. This intricate procedure is called nuclear transfer. The egg is then jolted to begin dividing using chemicals or an electrical current.

Didn't it work just fine? Although Dolly appeared normal at first she actually died early and had serious health problems. In the many kinds of animals tested so far, only a very small fraction clones are ever born. It turns out that early growth is usually very abnormal. The problems come from the wrong genes being turned on or off as well as the trauma of the procedure.

Your suggestion is different from cloning because the offspring will have two genetic parents. However, it also involves delicate handling of an egg and DNA. And it similarly requires body cell DNA to perform unaccustomed tasks.

Your idea may become reality in the future. Scientists are working on advancing these technologies for many purposes. Cloned animals with special qualities may have several uses. For example, to study disease, make drugs, or revive rare species.

Also, cloning produces embryonic stem cells that can be transformed into many cell types. Scientists are working on ways to use these cells to restore damaged tissue in serious human diseases like diabetes and Parkinson's.

By Dr. Robin Kimmel, Stanford University


Older eggs can have extra chromosomes


Cell division is tricky!


Taking out an egg's nucleus can be tricky too