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UK cloners target diabetes cure

The UK has granted its first licence allowing scientists to try to clone human cells for research

THE UK has granted its first licence allowing scientists to try to clone human cells for research. The decision last week was broadly welcomed, but a few vocal critics denounced the plans as both unethical and unnecessary. So just why is such research needed?

In 2001 the UK decided to allow therapeutic cloning – producing embryonic stem cells from cloned human embryos – but each research proposal must be individually approved. Now Miodrag Stojkovic of the University of Newcastle and Alison Murdoch at the Newcastle Fertility Centre at Life have been granted an initial one-year licence.

The team plans to use spare eggs donated by couples having IVF. The eggs will be stripped of their genome, fused with skin cells taken from healthy adults and then given an electrical or chemical jolt to mimic fertilisation. The hope is that a few of the resulting embryos will develop to the blastocyst stage, a bundle of a few hundred cells reached after around five days, and yield viable embryonic stem cells (ESCs) with the potential to turn into any tissue in the body.

It will not be easy. A team at Advanced Cell Technology (ACT) in Massachusetts made the first attempt to clone human cells, in 2001 (although President Bush has restricted federally-funded ESC research in the US, private companies can do as they please). However, none of the cloned embryos developed as far as the blastocyst stage.

So far only one team, led by Woo Suk Hwang at the Seoul National University in South Korea, has come close to succeeding (New Scientist, 21 February, p 6). Hwang’s team obtained 19 blastocysts from 66 eggs, but managed to get ESCs from only one blastocyst, which was cloned from a cell taken from the same woman who donated the egg.

So no one has yet derived human ESCs by cloning cells taken from someone other than the egg donor. Robert Lanza of ACT believes his company has now solved the technical problems, but has no funding to see it through.

The Newcastle team does not have as much cloning experience as the teams in Seoul and ACT, and the eggs they work with may be rejects from women with fertility problems. But if they are successful, the immediate aim is simply to study the characteristics of cloned ESCs and compare them with ESCs taken from normal blastocysts.

After the first year, however, Stojkovic and Murdoch hope their licence will be extended to allow them to clone ESCs from people with various diseases. The idea behind this is to have a limitless source of cells that can be used to study a particular disease, such as Alzheimer’s or Parkinson’s, rather than having to extract tissue samples from patients.

ESC lines have already been created from IVF embryos discarded after they were found to carry disease-causing mutations (New Scientist, 19 June, p 12). But this approach works only for disorders that can be genetically identified before the embryo is implanted. Therapeutic cloning could make it possible to obtain ESC lines from any patient, with any disease.

Stojkovic is particularly interested in studying juvenile diabetes, caused when a person’s immune system destroys the body’s own insulin-producing islet cells in the pancreas. Treating it requires a two-pronged approach: the islet cells must be replaced, and the immune system prevented from destroying the new cells.

Many patients are already being treated with islet cell transplants taken from cadavers, through the “Edmonton protocol”, pioneered at the University of Alberta. But there is a shortage of islet cells. “We have patients who have been waiting over a year for a transplant,” says Jonathan Lakey, director of the programme’s islet isolation facility. “The concept of developing an insulin-producing cell line from embryonic stem cells is very exciting.”

Several groups worldwide have managed to generate insulin-producing cells from ESCs. The advantage of using therapeutic cloning to obtain the ESCs is that the cells used to treat a patient could be derived from that person’s own skin cells, avoiding the tissue mismatches that trigger immune rejection.

However, replacing the lost islet cells with identical cells would trigger the immune system to destroy them again. To get around this, the Newcastle team wants to try to manipulate insulin-producing cells derived from cloned embryos before implantation. “We could change the embryonic stem cells to avoid rejection, or remove surface receptors by which they are recognised,” says Stojkovic.

Such work could offer valuable insights into the causes of diabetes. But as long as hundreds of scarce human eggs are required, it is never going to be a practical method of treating the many millions with diabetes.

Stojkovic will also try to find the key chemicals secreted by the empty egg that tell the skin cell to “rewind” and become like an embryo again. This information should make it possible to sidestep the creation of embryos and turn any cell into any other cell. But the critical chemicals can’t be identified without basic research on cloned embryos, he says.

Making clones

February 1997

Dolly the sheep is unveiled, the first mammal cloned from an adult cell

August 2001

President Bush restricts federally funded research on embryonic stem cells (ESCs) to 60 existing cell lines, many of which turn out to be useless

November 2001

Advanced Cell Technology of Massachusetts announces it has created cloned human embryos, but they do not grow long enough to yield ESCs

December 2002

Clonaid claims the first cloned baby has been born, and says it will soon provide proof. Which we still await

February 2004

A Korean team obtains ESCs from a cloned human embryo

August 2004

The UK’s Human Fertilisation and Embryology Authority grants the first licence in Europe for researchers to attempt therapeutic cloning