Controversy erupted when scientists created Dolly, the first fully grown mammal to be cloned. Now, Duke researchers have reported that humans are theoretically easier to clone than other animals because they possess a growth-suppressing gene that prevents gross developmental abnormalities.
"We're reporting valid information, but anything we report may be used negatively," said Randy Jirtle, a primary investigator of the study and professor of radiation oncology. "[The cloning debate] has now moved more from, OCan we do it?' to OShould we do it?' and that's where we should be--society has to decide what rules it will follow and there hasn't been a good discussion about it."
Humans and other primates inherit two copies of a gene called insulin-like growth factor II receptor, or IGF2R, from their parents. When active, IGF2R is a receptor that degrades cell growth during embryogenesis. However, non-primate animals, including sheep, pigs, mice and cows, have only one copy of this gene because one of the genes is affected by a rare process known as genetic imprinting.
With imprinting, crucial information in the gene sequence of one IGF2R gene is damaged, and the gene's function is turned off. Without this second copy, these animals are more susceptible to developing cancer and suffering from fatal cloning complications such as immature lung development, reduced immunity, enlarged hearts and large offspring that may kill the fetus and the mother.
Previously, it was debatable whether IGF2R is imprintable in primates, but Jirtle and lead author Keith Killian have concluded that the receptor cannot be imprinted in humans.
After examining tissues from 100 human samples, Killian and Jirtle looked at tissues from Primate Center ringtail lemurs, tree shrews and flying lemurs, and did not find any imprinting on IGF2R in any of these species. The closest species to humans in which imprinted genes were first observed was rodents.
Because mice and rats comprise 90 percent of animals used in research, the scientists believe these findings have implications in interpreting and applying scientific findings in the future.
"The biggest significance of our research is that it's a reminder that humans are not sheep and rodents," said Killian. "We found a very important genetic component that makes a fundamental difference between us and other animals."
Furthermore, because IGF2R cannot be imprinted in primates, humans are less susceptible to certain cancers compared to non-primate animals. The immutable IGF2R also protects humans against bearing abnormally large offspring.
"Natural selection did not tolerate or allow [the imprintable gene] to continue in the primate lineage, and it's not known why, but clearly whatever the reason, the need was more important in primates than in rodents," said Killian.
Jirtle and Killian are now identifying additional regulatory genes that are imprinted and trying to determine the roles they play in causing behavioral disorders and cancer. Their current research was published last week in Human Molecular Genetics.
These findings undermine arguments of those who are against cloning because of safety concerns. "It's almost as if mother nature removed the Olight switches' entirely from the gene 70 million years ago. IGF2R can never inadvertently be turned off in humans, so we would never be at risk of any growth abnormalities. To a certain degree, human cloning has been made easier because of this," said Jirtle.
However, Jirtle emphasized that his goal is neither to clone nor actively support cloning humans. There are still about 50 genes that are imprintable in humans, and if these genes are altered in any way, they can lead to developmental abnormalities as well. "Cloning humans has been likened to the Mount Everest of biology," he said. "Quite frankly, I don't really want to climb Mount Everest."
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