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Thursday July 05 06:00 PM EDT
Study: Clones Have Hidden, Dangerous Flaws
By Amanda Onion ABCNEWS.com
Dolly the cloned sheep turns 5 today, but scientists still don't understand why she is abnormally obese. A new study hints to the causes of clones' hidden flaws and sounds a word of caution against cloning humans.
Nearly 98 percent of attempts to clone animals have failed and those that do survive often appear abnormal and grossly enlarged. Now researchers say they have new evidence to explain why.
By tracing specific genes in cloned mice, Rudolph Jaenisch, a biologist at Whitehead Institute at the Massachusetts Institute of Technology and colleagues, found that while clones showed no clear flaws in their genetic make-up, the animals did reveal problems in expressing their seemingly normal genes.
The team traced this gene expression problem not to the cloning process itself, as scientists had suspected the problem might lie, but to the original stem cells that were used to help create the cloned mice.
"We found that embryonic stem cells are unstable — the state of their genes changes a lot," explains Jaenisch. "What was surprising was despite this genetic irregulation, still some embryos developed into pups. This means that those cloned animals that reach birth or beyond may appear normal, but our research shows they're not."
Scientists may have succeeded in cloning sheep, mice, cows, pigs and goats, but Jaenisch says this new research adds to mounting evidence that cloning remains a poorly understood science and one that is not ready to be undertaken with people.
Mark Westhusin, a cloning expert at Texas A&M University in College Station, Texas, points out that problems with genetic expression — the way information in genes is manifested in the body — are difficult to detect and this makes the practice of cloning even more dangerous. "It's not gene mutation, it's gene expression," he says. "This is not something you can set up a test to prevent."
Ryuzo Yanagimachi, a professor of anatomy and reproductive biology at the University of Hawaii and co-author of the study appearing in this week's issue of Science, says "it is outrageous and irresponsible to try human cloning."
The work also casts some uncertainty on the field of stem cell research for fighting disease. In this field, scientists propose using embryonic stem cells to clone adult human cells and tissue, which then can replace diseased tissue of those suffering from heart disease, multiple sclerosis, Alzheimer's and other diseases.
In a press release from Yanagimachi's office, caution is directed toward stem cell researchers, saying the study "is a warning to scientists that they must be very cautious in handling embryonic stem cells" which "may not be normal in a physiological or functional sense."
But Jaenisch feels despite his team's findings that stem cells are unpredictable, therapeutic cloning remains safe. "Even though therapeutic cloning creates embryonic stem cells through cloning, as long as you have some normal cells around and you're not creating an entire clone you counteract any abnormalities," he says.
Bloated Mice, Overweight Dolly
Scientists have already had visible evidence that cloned animals are not normal. Cloned mice have developed into extremely overweight animals, cloned cows have been born with abnormally large hearts and lungs. Even Dolly the sheep, the first cloned animal (who turns 5 years old today), is inexplicably overweight, says Jaenisch. "Look at Dolly — she's fat — as are many cloned mice," says Jaenisch. "Clearly something is going on that we don't quite understand."
While the results of cloning remain mysterious, the process is now well practiced. To clone an animal, scientists insert a cell from an adult into an egg with its genetic material removed. The egg then reprograms the adult cell to develop into an embryo and, eventually, a genetic identical to the owner of the inserted cell.
Tests have shown that inserting embryonic stem cells (which have only been isolated in mice and people) rather than any adult cell, leads to a 10 percent to 20 percent improved cloning rate in mice. Scientists think this may be because it's easier for emptied eggs to reprogram stem cells to develop into embryos.
Researchers have suspected that the process of reprogramming a cell in the emptied egg leads to flaws in clones. But this new research shows, the stem cells, themselves, may be flawed.
Different For Humans?
Despite these and other foreboding findings, Panayiotis Zavos, a reproductive specialist of the Andrology Institute in Lexington, Ky. appears resolved to forge ahead with his recently announced plans to try and clone people. Zavos did not return repeated calls and e-mails to his office, however his office released a statement to ABCNEWS.com saying "Dr. Zavos is not attempting to clone mice but human beings. Rudolf Jaenisch himself has indicated that there are species -to-species variations as one goes about attempting to clone them."
Zavos and his colleague Severino Antinori, a fertility doctor in Rome, have argued that in some respects, it may be easier toclone people due to doctors' long experience with growing human embryos in the laboratory for in-vitro fertilization.
Jaenisch is appalled by such arguments. "The problems with cloning remain biological, not technical — the problem is not getting embryos to survive in a petri dish," he says. "It's ridiculous to assume that humans can produce normal clones when five species of other mammals give you abnormal clones."
-- Swissrose (email@example.com), July 05, 2001