ORIGIN OF KOREAN CLONED CELLS: Hoo Suk Hwang, the South Korean researcher who fraudulently claimed to have created cells from cloned human embryos, may in fact have stumbled onto the first stem cells made directly from human eggs. Image: © KIM KYUNG-HOON/REUTERS/CORBIS
Researchers say they have confirmed suspicions that embryonic stem cells claimed to be extracted from the first cloned human embryo by discredited South Korean scientist Woo Suk Hwang actually owe their existence to parthenogenesis, a process in which egg cells give rise to embryos without being fertilized by sperm.
A series of genetic markers sprinkled throughout the cells' chromosomes show the same pattern found in parthenogenetic mice as opposed to cloned mice, according to a report published online today in the journal Cell Stem Cell.
The result suggests that, although Hwang deceived the world about achieving the first human cloning, his group was first to succeed in performing human parthenogenesis, which may offer a way of creating cells that are genetically matched to a woman for transplantation back into her body to treat degenerative diseases.
"I think this is an extremely important—and solid—paper," says stem cell researcher Robert Lanza, vice president of research and scientific development at Applied Cell Technology, a regenerative medicine company headquartered in Alameda, Calif., who did not take part in the study. "It conclusively proves that the stem cell line in question was not cloned as claimed, but rather was generated through parthenogenesis."
The result follows on the heels of an announcement last month by another California stem cell company, International Stem Cell Corporation (ISC) in Oceanside, that it had successfully achieved human parthenogenesis for the first time. Last year, Italian researchers claimed to have achieved the same feat but have yet to publish their results.
"The fact that this has now been achieved by two independent groups gives me a far greater degree of confidence," Lanza says.
The new finding brings a measure of closure to a story that first rocked the science world in February 2004, when Hwang and colleagues at Seoul National University announced they had cloned a female donor's cell by transferring its nucleus into one of her egg cells stripped of its nucleus in a procedure known as somatic cell nuclear transfer (SCNT), and harvested embryonic stem cells from the resulting fusion. They published the result the next month in Science.
The claim went up in smoke in January of 2006 after a probe by the university concluded that Hwang had fabricated the evidence, which followed a similarly damning assessment of a landmark paper from the previous year in which the group falsely reported creating 11 cell lines genetically matched to their donors.
A cloned cell should be identical to its donor, but the probe found that of 48 common genetic variations, or markers, present in the 2004 cells, eight did not match their apparent donor. Investigators raised parthenogenesis as the most likely explanation but could not be certain.
Later, during a chance discussion with European colleagues, stem cell researcher George Daley of Children's Hospital Boston and the Harvard Stem Cell Institute learned that they had received samples of the cell line before the work was retracted. "We had read the suspicions that the cell was a parthenote, but also realized that it had never really been proven," Daley says.
To settle the case, they analyzed the genetic sequence of the cell line at 500,000 locations across the genome.
The DNA of any two people will differ on average at one of every 1,000 subunits, or base pairs, Daley says. When a chromosome from a sperm cell joins with that of an egg, these single nucleotide polymorphisms (SNPs or "snips") tend not to match each other.
The same goes for cloned cells. But in contrast, pairs of matching chromosomes in parthenogenetic cells tend to match one another in the middle and differ near the ends because of a genetic mixing process called recombination. In their paper, Daley and colleagues report that the SNPs in the Korean cell line do indeed match toward the center of the chromosomes, similar to five parthenogenetic mouse cell lines that the team created for comparison.