Seoul National University report removes any lingering doubts, but says cloned dog was genuine
By Ivan Oransky | January 10, 2006
A summary released today by Seoul National University (SNU) of an investigation into the work of Hwang Woo-Suk confirmed what many have feared and believed true since ethical and scientific doubts about his work began to surface in November: All of the human cloning claims made by Hwang were fabricated.
The only bright spot in the investigation for the researcher, who resigned from SNU in December following an earlier report, was that Snuppy, the Afghan hound the team reported cloning in Nature in August, is a genuine clone. This conclusion matched the preliminary findings of an independent investigation by Nature, also released today.
"The research team of Professor Hwang does not possess patient-specific stem cell lines or any scientific bases for claiming having created one," the authors of the SNU report write in their summary, referring to a then-heralded 2005 Science paper in which Hwang's team claimed to have establish 11 patient-specific human embryonic stem cell lines through transfer of somatic cell nuclei. The report also found that a "forerunner cloned cell line" described in a 2004 publication in Science "resulted from the fusion of a non-enucleated egg and a nearby polar body, which initiated a parthenogenetic process," rather than through cloning, and that the results in that article "including DNA fingerprinting analyses and photographs of cells have also been fabricated."
Elaine Ostrander, of the National Human Genome Research Institute, Bethesda, Maryland, who conducted the independent tests for Nature on Snuppy and Tai, his genetic donor, said that the 16 microsatellite nuclear DNA markers she and colleague Heidi Parker tested were identical in both hounds, which would be expected if the dogs were clones. The findings also make it highly unlikely that Tai and Snuppy are simply highly inbred cousins, given that of the 16 nuclear markers, 8 were heterozygous, Parker said. "We would have expected homozygous markers if they were inbred," she noted. Parthenogenesis ? in which the egg is "tricked" into thinking it's fertilized -- had been ruled out earlier because the process would give rise to a female, and both dogs are males.
What was "really important," Ostrander told The Scientist, was the fact that Parker identified 12 differences between Snuppy's and Tai's mitochondrial d-loop sequence markers. Those markers would be expected to show such differences, given that the donor egg was a mixed breed dog. Had the researchers simply taken a tube of Tai's blood, divided it in half and falsified the tubes, the mitochondrial DNA markers would have been identical, Ostrander said. That also rules out another scenario, that Snuppy and Tai were delayed twins, perhaps created using in vitro fertilization, with one embryo split off at the blastocyst stage and then implanted into a surrogate years later to create the appearance of a clone, she added.
"We invite any other scenarios but within the obvious explanations, the data that we have rule them out," Ostrander said. "The important point is that the mitochondrial differences aren't one or two, they're in a dozen places. The work was blinded, and everything was done twice. The quality of data was certainly the best we could generate."
The acts of fabrication in the human cloning studies "are none other than deceiving the scientific community and the public at large," the authors of the SNU study say in their summary, which calls for "a severe penalty" by academia. The stage is now set for a government prosecution of Hwang and his colleagues, who have been barred from leaving the country.
"These individuals cannot be regarded to represent science in Korea," the SNU authors note, in a nod to the blow the scandal has leveled against South Korean science. "We have numerous well-qualified researchers whose works are globally recognized, and we also have a world-class research capability in biological sciences that will ensure a successful partaking in the field of stem cell biology."
The authors add that the scandal "will not have a large impact" on Korean science. "Rather, we are certain that this learning experience will be a stepping stone for better execution and management of scientific research and contribute to scientific advancement in this country. The young scientists who courageously pointed out the fallacy and precipitated the initiation of this investigation are our hope for the future."
Speaking of Snuppy, Ostrander added that it's always good practice to send samples to outside labs for validation. "That was certainly one of the things that the group responsible for cat cloning did. That's something that will undoubtedly become part of the gold standards of these experiments. Few of these have been done, so there isn't yet a set of criteria. I could imagine that coming out of this."
Links for this article
SNU statement on reportS. Pincock, "Hwang admits ethics lapses," The Scientist, November 28, 2005.S. Pincock, "Hwang faked results, says panel," The Scientist, December 23, 2005.I.Oransky, "First dog cloned," The Scientist, August 3, 2005.