Replicator review

    Nature has implemented a peer-review policy for strong claims.

    The transfer of a nucleus from a somatic cell of one organism into an enucleated germ cell of another for therapeutic or reproductive cloning is now well-established in many species, but has proved notoriously difficult to do in primates. Indeed some experts have concluded that it simply couldn't be done. Woo Suk Hwang's high-profile paper reporting that it had worked in human cells turned out to be fraudulent, making the goal seem even more elusive.

    Nature has now published what we expect to be the final word on whether nuclear transfer can work in a primate — a paper by J. A. Byrne et al. showing not only that it is possible to clone primate embryos by somatic-cell nuclear transfer but also that precious embryonic stem cells can be derived from the embryos (see page 497). If embryonic stem cells live up to their promise, the technology could be used to derive patient-tailored stem cells. Even if they don't, the ability to clone primate embryos means that researchers may be able to create cell lines from patients with disorders such as Parkinson's disease and diabetes, and use them to screen drugs and examine cell pathology (see page 462).

    Nature took the unusual step of soliciting an independent verification of the paper during the process of peer review (see D. S. Cram et al. Nature doi:10.1038/nature06456; 2007). This is the first time that Nature has obtained second-party replication ahead of publication. It should not be seen as reflecting a mistrust of scientists in the cloning field or scepticism about this particular research group. Rather, our actions fulfilled a statement in an Editorial (see Nature 439, 243; 2006) that was conceived in the aftermath of the Hwang affair: “Keeping in mind the principle that extraordinary claims require extraordinary proof, Nature may in rare cases demand it.”

    The decision was partly pragmatic — the corroborating experiment was straightforward and an expert was willing to do it on a timescale that would not delay publication of the paper. It was also based on history. Past fraud is no reason to submit an entire discipline to unusually tough review, but a history in stem-cell research of difficulties in replication of genuine claims carries some weight. The experiments are tough to do, there are many 'moving parts' in nuclear transfer and, given the importance of the conclusions of this work, it is desirable to be doubly robust in excluding the possibilities that embryos were a result of parthenogenesis, cell-line contamination or sample mishandling. (A blog discussion of peer-review challenges in stem-cell research and the peer-review reports for the paper by Byrne et al. can be found at Nature Reports Stem Cells;

    “Researchers should consider maintaining tissue samples, and trying to establish and fulfil requirements that may go beyond the routine.”

    So Nature asked a team led by Alan Trounson of Monash University in Victoria, Australia, an expert on human embryonic stem cells, to obtain tissue samples from the donor animals and stem-cell lines, and to test for the origins of the stem cells' nuclear and mitochondrial DNA by genotyping. In successful nuclear transfer, the mitochondrial DNA will come from the oocyte donor and the nuclear DNA from the somatic-cell nuclear donor. An Oregon veterinary surgeon, Theodore Hobbs, collected tissue from the animals, coded it, observed DNA preparation in the authors' lab, and then shipped the samples to a laboratory at University of Southern California, where Monash scientist David Cram conducted the analysis.

    Nature will continue to evaluate the need for such validation on a case-by-case basis. Meanwhile, researchers should consider maintaining tissue samples, and trying to establish and fulfil requirements that may go beyond the routine, as Byrne et al. did for their cloning paper. In that way, remarkable scientific developments can remain as free as possible from unwarranted speculation and controversy.

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    Replicator review. Nature 450, 457–458 (2007).

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