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Unexpected Perils of Cloning
Adult DNA lacks vital information embryos need to develop properly
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Dateline: 3/12/01

Scientists are discovering that cloning mammals leads to unanticipated, and potentially disastrous problems. These findings, released the same month other researchers announced disastrous problems with fetal-cell transplants into Parkinson's patients, show that mammalian embryos are much more complex than scientists had been willing or ready to admit.

Despite the widely hyped apparent success in sheep cloning with "Dolly," most cloned animals still die in-utero. Most of those who survive to birth die quickly from defects of the heart, lungs, kidneys, brain, or immune system. Rudolf Jaenish, professor of biology at the Massachusetts Institute of Technology, says, "I doubt there are any normal clones whatsoever."

Embryonic development in clones seems to progress abnormally. Mature cells seem to lack the information for proper gene activation needed for successful embryonic development.

French geneticist Jerome Lejuene frequently pointed out during his lifetime that embryos are not the unsophisticated blobs of tissue most people perceive them to be. Their DNA actually contains more information than the DNA of an adult. Not only does the embryo's DNA contain information about what the mature adult will be like, but it also contains the information on how to build the structures of the organism. The earliest embryonic cells contain the most genetic information, most importantly the information about how and when to trigger development of different types of cells and structures.

In order to get the DNA in an adult cell to behave like the DNA in an embryonic cell, the DNA has to be "reset," after a fashion -- made to "forget" its development and specialization.

Researchers point out that the entire maturation and aging process seems to be programmed into the DNA at conception. DNA from adults does not seem to have the ability to trigger development at the proper time. This might lead to problems in seemingly normal clones as developmental milestones approach, or during aging.

The researchers who cloned Dolly the sheep reported in May of 1999 that she had damaged DNA. Tiny strands of DNA at the end of chromosomes -- called telomeres -- are shorter in Dolly and other cloned sheep than in sheep produced the old-fashioned way.

Each time a cell divides, the telomeres shorten. Dolly, who was cloned from the DNA of a 6-year-old sheep, had telomeres that were about 20 percent shorter than she should have had at her age. This particular abnormality was not unexpected, the researchers said, because cultured cells in laboratories have shortened telomeres, too.

But the problem of shortened telomeres can effect not just cloning of whole individuals, but also cloning of organs.

Mark Westhusin, professor of veterinary physiology at Texas A&M, said that cloning "is a model for failed mammalian development."

Westhusin was involved in a project, begun in 1998, to clone a bull named Chance. Chance had become a pet and was trained for TV and film appearances. But at 21, Chance was facing his mortality. After 189 attempts to clone a viable embryo, Westhusin's team finally achieved the birth of Chance's clone, Second Chance.

Second Chance had immature lungs and high blood pressure at birth, and quickly developed Type II diabetes, anemia, a yeast infection, and evidence of immune system defects. The team managed to provide intensive care to the calf, and after nearly dying, Second Chance survived. But Westhusin was profoundly affected by the experience. He said, "No one who actually has any experience with cloning wants anything to do with this."

Chinese researchers also ran into troubles when their cloned goat died 36 hours after birth, due to abnormal lung development. The Chinese cloning experiments were aimed at developing a means of cloning giant pandas, and not cloning humans.

French researchers identified similar problems when a cloned cow died at six weeks of age due to abnormal development of lymphoid tissues. The calf appeared healthy at birth but suddenly exhibited a dramatic fall in its red blood counts.

These discoveries, however, are not diminishing many researchers' eagerness to clone human beings. A team of American and Italian researchers still expect to clone a human being within the upcoming year.

Some studies even indicate that the host mother may also suffer fatal risks from carrying a cloned fetus.

Fetal clones are typically abnormally large -- sometimes twice the normal size. The cloned embryo also doesn't seem to be able to trigger appropriate milk production in the mother. This might indicate other flaws in the maternal/fetal symbiosis during the gestation of clones.

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