How Important Is the Latest Cloning Feat?

Scientists have generated early-stage cloned human embryos, but not stem cells.

Human cloning: Shown here is a three-day old cloned embryo, created from a donor egg and the skin cell of an adult male. Credit: Stemagen

Scientists at Stemagen, a small biotechnology company in La Jolla, CA, reported yesterday that they have for the first time generated cloned human blastocysts--early-stage embryos--from adult skin cells. This is the first step in generating stem cell lines matched to individuals, which are crucial for creating new cellular models of disease and potentially important for future tissue replacement therapies. (See "Next Steps for Stem Cells" and "The Real Stem Cell Hope".) The new findings also confirm that access to fresh eggs from healthy young donors is a key part of successful cloning. Lack of access to human eggs has been the major barrier in the field. (See "Human Therapeutic Cloning at a Standstill".)

Cloned blastocysts have been generated before, but from embryonic stem cells rather than from adult cells. Scientists theorize that embryonic stem cells are easier to turn into blastocysts because of their earlier developmental stage.

Experts in the field have had a mixed reaction to the new work. "It's a nice achievement, but in my view, they haven't crossed the bar," says Evan Snyder, director of the Stem Cells and Regenerative Medicine Program at the Burnham Institute in La Jolla. "The real test will be, can you generate cell lines that are stable and self-renewing and normal?" Others applaud the confirmation of the feasibility of human cloning. "The fact that it can be done is important," says Jeanne Loring, a stem cell scientist at the Scripps Research Institute in La Jolla. "It wipes away that blot on our scientific integrity," she says, referring to a massive fraud unveiled in 2005 in which South Korean scientist Woo Suk Hwang claimed to have generated stem cell lines from cloned human embryos. (See "Stem Cells Reborn".)

To clone an embryo, a process also called nuclear transfer, scientists first strip an egg of its genetic material. Then they insert DNA from an adult cell, such as a skin cell, into the egg. Through an unknown process, the egg turns back the clock on the adult DNA and begins to develop as a normally fertilized egg would. From the embryo, researchers could theoretically collect a specialized ball of cells that can be coaxed to turn into stem cells. So far, however, no one has successfully performed this feat.

Stemagen, a relatively unknown player in the field, probably owes its success to access to human eggs through a close association with a local fertility clinic. (The company was founded by a fertility specialist at the Reproductive Sciences Center in La Jolla.) "We were able to get access to high-quality oocytes and have them in the incubator within one to two hours," says Andrew French, Stemagen's chief scientific officer.

Egg donors and the intended parents gave eggs in excess of those needed for in vitro fertilization to the Stemagen scientists for research. Regulations in many states prohibit compensation for donated eggs for ethical reasons, a requirement that has slowed other cloning efforts.

Starting with 25 fresh oocytes, French and colleagues generated five blastocysts--five- to six-day-old embryos consisting of 30 to 70 cells. Rather than attempting to generate stem cell lines from the embryos, the researchers sent them to an independent company for genetic confirmation of their results. "They showed we had completely removed the DNA from the egg donor and replaced it with DNA from the skin-cell donor," says French. One blastocyst was confirmed as a clone via two DNA-fingerprinting methods, while genetic analysis of two others indicated the likelihood that they were clones.

The next crucial step will be generating stem cell lines from cloned embryos, which many stem cell scientists speculate will be the most challenging step. "That's likely where Hwang failed," says Synder.

French and colleagues are planning such experiments, with results potentially in the next eight to twelve months. "The quality of our blastocysts improved with each experiment," says French. Based on the success rate of previous attempts to make stem cells from regular embryos, he estimates that Stemagen will be able to generate a stem cell line from between five and ten cloned embryos and report the results in the next year. The company aims to sell or license the lines to pharmaceutical companies and others who would use them to test new drugs or develop new therapies.

While human therapeutic cloning has always been an ethically contentious area of research--partly because it requires the creation and destruction of human embryos--it has recently come under greater fire. After the announcement of new techniques for reprogramming adult cells so that they turn into stem cells without first forming embryos, some opponents called for a halt on embryonic-stem-cell research. (See "Stem Cells without the Embryos".)

However, researchers in the field emphasize the need to pursue all reprogramming techniques. "Even though there are other techniques to reprogram a cell that have gotten a lot of press, we still don't know how those compare with the reprogramming you actually see with nuclear transfer," says Snyder. "My feeling is, if we understand nuclear transfer better, we will be able to do the other kind of reprogramming more efficiently."

http://www.technologyreview.com/Biotech/20088/