By Sean Henahan, Access Excellence
Edinburgh (2/24/97) The birth of a little lamb named Dolly, cloned from a sheep's udder, may usher in a new era of genetic engineering, and bring with it new consideration of the ethical and scientific issues involved in cloning.
Scientists who asserted that a mammal could not be cloned from an adult cell must be feeling a bit sheepish. Dolly is the first viable offspring ever derived from adult mammalian cells. The procedure used was deceptively simple -- the researchers removed an unfertilized oocyte (egg cell) from an adult ewe and replaced its nucleus with the nucleus of an adult sheep mammary gland cell. This egg was then implanted in another ewe, and Dolly was the result. Dolly is now seven months old and appears normal in every respect, the scientists report.
This remarkable experiment answers one of the biggest questions facing geneticists in the past 30 years, whether the genetic material of differentiated cells from adult animals undergoes some kind of irreversible modification, rendering it useless for cloning. The study suggests that, with careful handling, the genetic material of such cells can indeed be introduced into an egg cell, and that normal cell development and differentiation, culminating in live birth, can occur.
Other research teams have managed to clone tadpoles and cattle from embryo tissue. Indeed, the same researchers that produced Dolly had only last year raised seven other sheep from oocytes whose nuclei had been replaced with nuclei from either fetal or embryonic tissue. (Campbell, K. H. S. et al., Nature 380, 64-66; 1996). But Dolly is a first -- the only animal ever cloned from genetic material of adult cells.
The researchers built on this knowledge, using a similar process with the adult cells that had proved useful in their earlier experiments with fetal cells. The process depends on the experimental protocol which forces the donor cell (the cell that is to provide the nucleus) into a `quiescent' state, so that it is not replicating its DNA or dividing. This appears to make the nucleus more susceptible to re-programming by the recipient egg cell.
Cloning: A Special Report
In the current experiment, the researchers managed to produce live births derived from three cell populations: 9-day old embryo, 26-day fetal and 6-year old mammary gland. Nearly two-thirds of the reconstructed embryos did not survive. However, eight ewes did give birth. Only one of these, Dolly, resulted from adult-cell nucleus cloning.
"The birth of this lamb shows that during the development of that mammary cell, there was no irreversible modification of genetic information required for development to term. This is consistent with the generally accepted view that mammalian differentiation is almost all achieved by systematic sequential changes in gene expression brought about by interactions between the nucleus and the changing cytoplasmic environment," noted Ian Wilmut, the lead scientist, of the Roslin Institute, Edinburgh, Scotland.
The implications of this work are far-reaching, and not limited to sheep. It seems probable that the same methods used to produce clones of sheep would work with other mammals, including humans.
"There is no clinical reason why you would clone humans. Why would you make anoth er human being?'' said Dr.Wilmut. "`We think it would be ethically unacceptable and certainly would not want to be involved in that project.''
"I can think of no ethical reason to apply this technique to human beings, if in fact it can be applied,'' concurred Carl Feldbaum, president of the Biotechnology Industry Organization, which represents about 700 companies and research centers in the United States and abroad. "The biotechnology industry exists to use genetic information to cure disease and improve agriculture. We opposed human cloning when it was a theory. Now that it may be possible, we urge that it be prohibited by law.''
Cloning farm animals might allow a farmer to replicate a disease resistant cow that was an especially good milk producer. However, too many clones in a herd could reduce essential genetic diversity to a dangerous level, leaving the animals vulnerable to disease and unexpected problems.
On the positive side, cloning livestock could allow the creation of animal herds that can be farmed for milk, blood and organs. Indeed, a company that supported the sheep cloning research is already farming animals genetically engineered to produce human proteins with a potential use for the treatment of cystic fibrosis.
Similar methods might be used to "farm" treatments for hemophilia and emphysema, and could lead to a better understanding of other diseases including BSE (Mad Cow Disease), the researchers note. Cloning could also prove a great advance for genetic researchers studying gene expression, aging and cancer.
It may not be that farfetched to imagine that one could clone one's dead relatives, or even one's self. Aldous Huxley described such a world in his novel "Brave New World". The breakthrough is also likely to excite interest in cloning extinct species where a compatible living host can be found (eg elephants and mastodons).
The research is reported in the Feb. 27, 1997 is sue of Nature.
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