By Lisa Seachrist
From all outward appearances, the six-month old ewe named Dolly looks like a run of the mill Finn Dorset breed of sheep.
Instead, she is the product of a cloning experiment performed by Ian Wilmut and his colleagues at the Roslin Institute and PPL Therapeutics plc in the outskirts of Edinburgh, Scotland.
“This research is an important first step in improving methods for creating transgenic animals,“ said Ron James, chief executive of PPL Therapeutics.
The experiment, which will appear in the Feb. 26, 1997 issue of Nature, has simultaneously set scientific dogma on its ear and raised a firestorm of ethical considerations.
“We knew well that this experiment would cause ethical concerns, that is why we alerted ethics organizations in the U.K. that the experiment would be published,“ James said.
Since the early 1950’s, scientists have attempted to clone animals as varied as frogs and mice. As those experiments repeatedly failed, the premise that DNA from differentiated or adult sources had somehow lost the ability to support cell division that would produce a new animal approached dogma.
What Wilmut and his colleagues have shown is that the previous failures were failures in technique rather than some inherent characteristic of the DNA,“ said Colin Stewart, director of the laboratory of cancer and developmental biology at the National Cancer Institute-Frederick Cancer Research and Development Center, in Maryland, who wrote an accompanying commentary in Nature.
Previous work in cattle, sheep and mice has shown that scientists could make identical copies of embryos; however, no one had ever produced a clone of a fully-developed adult animal. The team took unfertilized sheep eggs and removed the nucleus leaving the cytoplasm which carries the machinery needed to foster embryonic growth.
Egg nuclei contain only one-half of the DNA needed to produce the embryo that eventually becomes the full grown animal. When the sperm fertilizes the egg, it supplies the other half of the genes as well as a small electrical current that signals the egg to start the initial rounds of cell divisions. The researchers simulated this in the enucleated eggs by inserting nuclei obtained from cultured sheep udder cells. As a result, the egg now had the full complement of DNA needed for embryonic growth. With a small jolt of electricity, the newly “fertilized egg“ began to divide.
The process was far from efficient, however. Of the nearly 300 enucleated eggs, the researchers produced only one cloned sheep.
“The technique, as yet, is highly inefficient,“ Stewart said. “But, I suspect that researchers are going to try the procedure in cattle and pigs.“
Stewart pointed out that one of the biggest determinants as to whether the procedure will work in other animals may depend on when the embryonic DNA must become active to support embryonic development. In mice, at the two-cell stage, the DNA must direct cell divisions. In sheep, the embryonic genome needn’t become active until the eight- to 16-cell stage. “The human embryonic genome is active around the four- to eight-cell stage,“ Stewart said. “This could well prevent the successful cloning of a human on technical grounds alone.“
Nevertheless, such speculations that cloning humans could be possible, has brought visions of cloned Hitlers a la The Boys From Brazil and focused public attention on the ethics of biotechnology as an industry.
“This wasn’t entirely unexpected, but it certainly happened much sooner than most people expected,“ said Carl Feldbaum, president of the Biotechnology Industry Organization (BIO). “It has produced a maelstrom of interest in biotech.“
Feldbaum noted that “Where there are sound reasons to clone animals, we want to be clear that we are absolutely opposed to human cloning. That is just a no-brainer.“
For example, PPL is using transgenic technology to produce human proteins such as alpha 1 antitrypsin in the sheep’s milk. “With current techniques, we only get the gene inserted into six out of 100 animals, half are males that don’t produce milk and we have little control over where the gene gets inserted,“ James said. “Cloning allows us to guarantee that we will have females and that the gene is in the correct place.“
But, James agrees that “there is just no cause or purpose to cloning humans.“
“I have yet to talk to a single person in or out of the industry that supports the concept of human cloning,“ Feldbaum said. “There is just no good reason for it.“
Nevertheless, Feldbaum told BioWorld Today that “the industry needs to take a principled, well-thought out set of positions when it comes to dealing with this subject as well as other that we have yet to consider.“
BIO supports a voluntary ban on research into the cloning of humans similar to the voluntary ban initiated in the early 1970’s to consider the ethics associated with recombinant DNA research. Even so, Feldbaum noted that it is likely that eventually such a ban would have to be written into law and that “law should be international.“
However, enforcing such a law may not be easy. “This is a high-tech procedure, but not beyond the scope of a well-outfitted lab,“ said Ronald Munson professor of bioethics at the University of Missouri, at St. Louis. “It is likely that a wealthy eccentric would choose to grasp at immortality even if it is only their genes that live on.“
Munson maintains that while it may be possible to do, people have such a distaste for the concept it is unlikely to become a common practice. While some may envision armies of cloned super-soldiers, Munson argues that may be affording genes too big a role in the development of a human being.
“We know that twins have identical genomes, yet we understand that they are very separate people,“ Munson said. “Even with identical genomes, a cloned person would be growing up in an entirely different world. Genes are only part of the mix, our experiences and environment shape us as well.“ *