The Year in Review: Science

Stem cells the great breakthrough

Two of the most significant science events of 2007 occurred within the space of a fortnight. The first was when scientists announced that they had been able to clone dozens of embryos from an adult monkey a technical feat that had eluded researchers since the announcement on cloning Dolly the sheep back in 1997. The second breakthrough happened when researchers showed that it was possible to convert human skin cells into the equivalent of embryonic stem cells, which could then be used to make beating heart-muscle and brain cells in the test tube.

In fact, both studies were related, in that they are part of the huge international effort into the potential uses of stem cells in regenerative medicine. Stem cells are the "mother" cells of the body and if they come from an early embryo no more than a few days old they are capable of developing into any of the dozens of specialised tissues of the body, from insulin-making pancreatic cells to the message-transmitting nerve cells in the spinal cord.

Eventually, the aim is that scientists will be able to come up with an easy and reliable way of making embryonic stem cells from tiny fragments of skin taken from a patient. In this way, replacement parts can be made in the laboratory and transplanted back into the appropriate organ or tissue of the patient without the risk of rejection.

One way to achieve this would be to make cloned human embryos from skin cells and human eggs, and then extract the stem cells from these early embryos. Another would be to convert skin cells directly into embryonic-like stem cells, which would bypass the ethical and moral concerns over the creation and destruction of human embryos. Either way, such stem cells could then be grown in the laboratory for repairing damaged organs or tissues in situ, which would provide a vital alternative to organ transplants.

Scientists had shown that it was possible to use the Dolly cloning technique which involved the transfer of a skin cell's nucleus to an "empty" unfertilised egg with its own nucleus removed to create cloned embryos from a range of species. But despite much effort, no one had shown that this was possible with monkeys, which suggested that there might be insuperable barriers to creating cloned embryos from adult primates including humans. The suggestion gained currency after the announcement of cloned human embryos being created in South Korea, which subsequently turned out to be based on fraudulent research.

This year, however, Shoukhrat Mitalipov of the Oregon National Primate Research Center proved that no such technical or biological barrier exists. He and his colleagues developed a new microscopic technique that is less damaging to the eggs of primates because it does not use ultraviolet light and dyes, which seem to harm primate eggs. As a result, he has managed to produce scores of cloned monkey embryos, and managed to extract stem cells from some of them although as yet the team has not been able to produce any cloned offspring.

Professor Alan Trounson of Monash University in Australia, who was asked to double-check Shoukhrat's results to make sure they were valid, said that the findings show once and for all that it is possible to produce cloned human embryos for stem-cell research. "This is 'proof of concept' for the primate. It has been thought by some that it would be extremely difficult in monkeys and humans but those of us who work in animals such as sheep and cattle thought that success rates would be much like that achieved in these species," Professor Trounson said.

But no sooner had the ink dried on Shoukhrat's scientific paper (which was published in the journal Nature) than another study was published (in the journal Cell) which in some ways seemed to make the monkey-cloning work redundant. A group of Japanese scientists, led by Shinya Yamanaka of Kyoto University, showed that it may not be necessary to produce cloned embryos in order to extract embryonic-like stem cells from a patient. Instead, they found, you can turn skin cells directly into the stem cells without using human eggs or embryos.

Yamanaka was following up earlier work that he had carried out using mouse skin to create stem cells. This time, however, he used human skin cells from a 36-year-old woman which were genetically engineered with four genes known to be involved in the "reprogramming" of a cell's nucleus. In other words, the genes effectively turned back the developmental clock of the skin cells to make them more like the cells of an early embryo.

As a result, the reprogrammed skin cells were able to be coaxed into becoming two of the 220 specialised cells of the body. The scientists reported that they had been able to tinker with the growth medium bathing the woman's skin cells in the laboratory to turn them into beating heart-muscle and brain cells. Other tests suggested that they should be able to convert the skin cells into any of the other specialised cells, which would be extremely useful for treating diseases such as diabetes, Parkinson's or heart disease.

Professor James Thomson of the University of Wisconsin-Madison, who in 1998 was the first scientist to isolate human embryonic stem cells, mirrored the Japanese findings with his own research (published in the journal Science) and exclaimed that the "the world has changed" because of it. It could mean, for instance, that there would be no need to make human embryos bitterly opposed in the White House and Vatican in the search to find easy ways of making embryonic stem cells from a patient's skin cells.

"The induced cells do all the things embryonic stem cells do. It's going to completely change the field. The idea of cells becoming things they don't normally become is suddenly viable," Professor Thomson said. "The new results may not eliminate the controversy [over cloned human embryos] but it may be the beginning of the end of that controversy."

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