If Snuppy is cloned by 'nuclear transfer', then there must be no 'virtual genetic identity'

Dianne N. Irving
January 7, 2006
Reproduced with Permission

Hurray! TIME Magazine has it right! Yes, as I and others have been trying to say for a long time now, there is no such thing as "virtual genetic identity" between an embryo cloned using the "nuclear transfer technique" (and its stem cells), and the patient-donor. That is, the product of nuclear transfer is not "genetically identical" to the donor, nor is it a "twin" of the donor. Impossible. This is no small "picky" matter, as if there is not "genetic identity" then any such stem cells injected into patients will cause severe immune rejection reactions in those patients. The body's immune system is startlingly sensitive -- and likes scientific accuracy.

Any stem cells derived from human embryos cloned by nuclear transfer would match only the nuclear DNA of the donor cell; their mitochondrial DNA would not match, because the mitochondrial genes in the stem cells come from the "foreign" mitochondria of the enucleated oocyte used during nuclear transfer (with the exception of when a female donor uses her own oocytes).

The only other way there could be a perfect genetic match -- i.e., "genetic identity" -- between the nuclear DNA and the mitochondrial DNA of the stem cells and the donor would be if the embryo were cloned using the "twinning" method (blastomere separation, blastocyst splitting, blastocyst division, etc. -- now used as "infertility treatments" in IVF clinics). In this case, the cells of the twins would be "genetically identical"; but neither the nuclear DNA nor the mitochondrial DNA of the stem cells of either twin would match a patient-donor (because the nuclear DNA contains male chromosomes from the fertilization technique, and the mitochondrial DNA comes from the female oocyte used in fertilization).

Therefore, as noted in the TIME article below, if only the nuclear DNA of the stem cell and the patient-donor is tested by DNA profiling techniques, then the question as to whether the embryo who was produced by "nuclear transfer" matches the patient-donor still remains undetermined. The DNA profiling must test both the nuclear and the mitochondrial DNA of the stem cells and of the donor cell.

In the case of Snuppy the dog, if the DNA profiling tests both the nuclear and the mitochondrial DNA and finds a "match", then Snuppy was not cloned by nuclear transfer as Hwang claims. Rather, the dog was probably cloned using the "twinning" technique. (Which means that there is probably a "Yuppy" around somewhere). Only if the nuclear DNA of Snuppy's cells match the nuclear DNA of Snuppy's supposed "donor" -- and the mitochondrial DNA of Snuppy's cells do not match the mitochondrial DNA of his "donor" -- can it be concluded that Snuppy was cloned using the nuclear transfer method.

I rest my case.

See Irving, "How can either 'nuclear transfer' or 'twinning' produce Hwang's 'patient-specific stem cells'?", (December 17, 2005), at: http://www.lifeissues.net/writers/irv/irv_112retraction.html

and, "When is 'not-self' really 'self'? International Research Ethics Standards Require Hwang's Team to Retest Its Stem Cells" (December 6, 2005, at: http://www.lifeissues.net/writers/irv/irv_111reteststemcells.html.


TIME Magazine
January 3, 2006

Is Snuppy the Puppy for Real?

With Hwang's scientific credibility in shambles, the status of the world's most famous dog hangs in the balance. The embattled scientist maintains that Snuppy is the world's first canine clone, and he even hired an independent Korean DNA lab, HumanPass Inc., to verify that assertion. The verdict: HumanPass CEO Seung Jae Rhee told TIME last week, "There is no dispute about these results, and so I am 100% certain on Snuppy's authenticity." But since HumanPass is in essence working for Hwang, that's hardly good enough for the investigative panel at Seoul National University, which is carrying out independent tests, or for the editors of Nature, who have ordered an investigation.

If Snuppy really was cloned from the ear cell of a 3-year-old male Afghan named Tai, it shouldn't be tough to prove, even to those outside investigators. As long as they have tissue samples from both the clone and the parent, they should be able to determine whether DNA in the nuclei of both animals' cells is identical--the first hallmark of a true clone. Ian Wilmut, the Scottish scientist who created Dolly the sheep in 1996, had to provide such samples to prove to skeptics that he had created history's first mammalian clone.

Even with the controversy raging over his stem-cell paper, Hwang could have forestalled some of the questions about Snuppy if he had offered one additional bit of confirming proof in his original paper in Nature. That piece of critical evidence comes from the animals' mitochondria, tiny energy-producing structures within each cell. While most of a mammal's DNA resides in the nucleus, there's also some in the mitochondria. (Nuclear DNA forms the animal's basic genetic blueprint; mitochondrial DNA contains instructions for making proteins involved in various metabolic functions within the cell.)

Mitochondrial DNA is passed down from the mother as part of the egg's genetic contribution. Identical twins, for example, have the same nuclear and mitochondrial DNA, since they're produced when a single egg is fertilized and the resulting embryo splits in two. With a clone, the situation is different. Because the cloning process that Hwang says he used to create Snuppy involves two dogs--one for the nucleus and another for the egg--Snuppy's mitochondrial DNA should not match Tai's. That's what Rhee's scientists say they've found and what Hwang undoubtedly hopes the university and Nature will find as well. Final, ironclad proof of Snuppy's provenance would involve showing that the dog's mitochondrial DNA matches that of his egg donor. It's not clear, however, whether that test is being done.

From the Jan. 09, 2006 issue of TIME magazine