A paper published via Nature's advance online publication program on November 14 reports that scientists have managed to generate embryonic stem cell (ESC) lines from an adult rhesus monkey.

The researchers used a variant on the procedure of so-called somatic cell nuclear transfer. Since Dolly the sheep was cloned in 1996, marking the first cloning of a mammal, the cloning of many species has become more or less a routine (if still inefficient) procedure. But achieving the same in primates, especially given the political and ethical issues surrounding any work with human cells, has been a much greater scientific challenge.

Part of the problem is that the egg cells of primates are fragile, and tend to be damaged by the dyes and ultraviolet light that are used to remove the egg nuclei during egg retrieval. Shoukhrat Mitalipov, assistant scientist in the division of reproductive medicine at the Oregon Primate Research Center, and his colleagues were able to modify those techniques through use of an imaging system that allowed them to see the nuclei without stains, using polarized rather than ultraviolet light. The researchers also changed the culture medium of the cells in ways that promoted the oocyte's so-called nuclear remodeling, though the exact reasons for their success remain to be worked out at a molecular level.

Using this method, Mitalipov and his group used skin cells from an adult male rhesus macaque to reprogram oocytes taken from a total of 14 females. The scientists observed a blastocyst formation rate of 16 percent, and were able to generate two ESC lines (one of which was chromosomally abnormal, with a translocation in the Y chromosome). Mitalipov told reporters at a press conference that his team had been developing the techniques "for several years now," and that his team's efficiency of generating blastocysts has improved from the 0.7 percent rate reported in Nature, although it is still not at a level that would allow clinical applications.

Expression profiling showed that the cells expressed ESC markers, and the cells were able to develop into cell types from all three embryonic germ layers, including heart cells and neuronal cells.

In 2005, South Korean researchers falsely claimed that they had managed to efficiently create patient-specific stem cells originating from all three major layers of the embryonic germ line. Presumably mindful of that highly public debacle, Nature took the unusual step of publishing a paternity test of sorts along with the paper by the Oregon group: an independent verification by scientists from Australia's Monash University, showing that the genetic material of the mitochondria in the cytoplasm was indeed from the female donors, while the DNA in the nucleus was from the male. (See BioWorld Today, Jan. 11, 2006, and Dec. 19, 2005.)

ESC science has always been subject to the degree of public interest usually reserved for presidential candidates or celebrity shenanigans, and the current paper was no exception: It was released early, essentially in response to a leak.

According to a report by the Associated Press, the research had first been presented at a scientific conference earlier this year, to "limited media attention at the time." But a London newspaper reported on the research last week, setting off the "continued speculation" that ultimately led to its advance publication.

The reason for the widespread public interest in embryonic cloning is mainly the specter of reproductive cloning, followed by the possibility of creating tissues for transplant that are genetically matched to the recipient. Such tissues could be transplanted without worries about rejection, and could be useful in conditions such as immunodeficiency, diabetes, Parkinson's disease, and spinal cord injury.

Researchers and ethicists have differing priorities on both the ethical and the research fronts. Reproductive human cloning is universally condemned by scientists and ethicists alike, the near-term ethical problems of therapeutic cloning lie in the ethics of oocyte donation and questions of how to adequately explain the risks and rewards of the procedures for the purposes of obtaining informed consent. (See BioWorld Today, May 20, 2005.)

And while some researchers are interested in using patient-specific stem cells to cure disease, the near-term applications of the findings are likely to be more pedestrian, if no less useful. Indeed, some researchers question that transplant tissues are a viable role for ESCs. In a "News and Views" article accompanying the Nature paper, Ian Wilmut - the creator of Dolly the Sheep - and his colleague Jane Taylor state that patient stem cells could be a great tool for studying the molecular mechanisms of disease. But, they add, "realistically, a careful examination of resources and the time required to produce differentiated cells for treatment purposes suggests that large-scale use of stem cells would be impractical."

Mitalipov was more optimistic about the possibilities of using stem cells for treatments, noting that ultimately, the approach depends on the efficiency of generating lines. That efficiency continues to improve, and will improve further as the research on the problem reaches what he termed "critical mass."

He also said that, by studying just how the eggs manage to the adult cell nuclei in greater detail, it might be possible to make a stem cell without breaking eggs. "The egg is a natural system that [generates ESC lines] pretty efficiently," he said. "If we understand how the egg does it, we should be able to do it directly without using eggs."