Korean stem cells unmasked
Disgraced biologist's cell line was first of its kind, but not cloned.
Genetic analysis has confirmed that disgraced biologist Woo Suk Hwang did not clone a human embryonic stem (ES) cell.
But the South Korean scientist's team inadvertently broke new ground by creating the first human stem-cell line to come from an unfertilized egg, say researchers. Other scientists have since replicated the feat, called parthenogenesis.
"It's an unfortunate irony that they didn't know what they had," says George Daley, a biologist at Children's Hospital Boston who led the latest analysis. "It would have been a very important discovery."
By analysing the minute genetic differences between stem cells with different origins, Daley's team has confirmed the conclusion of a January 2006 report from Seoul National University that the cell lines were parthenogenetic, not cloned.
"I'm very pleased that finally we have a sense of closure of what these cells are," says Jose Cibelli, a biologist at Michigan State University in East Lansing and a co-author of the 2004 paper claiming to report the creation of cloned ES cells.
The discovery was an opportunity missed, Cibelli says. "It's very clear that this is a parthenogenetic cell, and probably the first one ever reported. I'm a little disappointed that the Korean group didn't pick this up."
In two papers published in Science in 2004 and 2005, a team led by Hwang claimed to have made ES cells from cloned embryos and ES cells genetically matched to patients. The papers have since been retracted and Hwang fired; he is now standing trial for fraud, embezzlement and breaking bioethical laws.
Daley's team compared the genes of parthenogenetic and cloned mouse ES cell lines with Hwang's cell line. The researchers distinguished between cloned and parthenogenetic ES cells by studying the tiny genetic differences between paired chromosomes.
Cloned ES cells are made from a somatic cell such as skin; half their chromosomes come from the mother, and half from the father. In these cells, the genetic variations between paired chromosomes are spread evenly across the whole chromosome's length.
In parthenogenesis — a form of asexual reproduction found in insects, lizards and sharks, but not naturally in mammals — all the cell's DNA comes from the mother. Pairs of chromosomes are more similar, and what variation there is tends to cluster at the ends of chromosomes.
These differences allowed Daley's team to distinguish parthenogenetic from cloned mouse ES cells. To see if the same applied to human cells, the team analysed 500,000 genetic variations in Hwang's cell line.
The cells show strong evidence of parthenogenesis, with genetic variation concentrated at the ends of chromosomes, they report in Cell Stem Cell1.
"I think the analysis comes as close to unequivocal certainty about the nature of this line as you can get in biology," says Daley. Future claims of cloned stem cells will be subject to similar scrutiny, he says.
The work confirms what many scientists already suspected, says Kent Vrana, a molecular biologist at Pennsylvania State University in State College. "They didn't blaze any trails, but they did a very thorough job," he says.
Parthenogenetic stem cells are promising for therapeutic use, says Vrana, but scientists shouldn't stop trying to make cloned ES cells.
- Kim, K. et al. Cell Stem Cell doi:10.1016/j.stem/2007.07.001 (2007).