The future is here - how theory has grown into a virtual reality

Astonishing breakthroughs show that the controversial technology's potential to treat incurable conditions is rapidly advancing

THE breakthroughs in therapeutic cloning reported yesterday by South Korean scientists address many of the key issues that need to be resolved if this promising technology is to benefit patients.

Last February the team led by Woo Suk Hwang of the Seoul National University became the first in the world to clone a human embryo and use it to create stem cells.

Their latest advances, published today in the journal Science, go much further than this. Astonishing progress over the past year has laid to rest enduring concerns that their early results were a fluke, and shows that cloning can be done in ways that might allow its potential to be realised.

The research has also made the process of cloning much more efficient and reveals insights that could improve it still further.

“This time last year, the Koreans had done this once but there was still doubt that it might have been a freak incident that would not be possible to repeat,” Professor Alison Murdoch of the University of Newcastle upon Tyne, whose own team has also cloned a human embryo, said. “The Koreans have now shown they can do it again and again, and make stem cells. What was a theoretical promise a year ago is now a real possibility.”

Dr Hwang’s group has made three crucial advances, each of which would in itself be a major step forwards.

First, the newly created embryos are unarguably clones. In the 2004 study, the researchers produced 30 embryos by taking adult cells from female volunteers, and transplanting the nuclei into eggs donated by the same women.

As both the egg and adult cell donors were identical, it was impossible to establish beyond doubt that true cloning had taken place. It remained possible that the eggs had divided spontaneously — a phenomenon known as parthenogenesis — or that cloning was feasible only with eggs and adult cells from the same person, a problem that would make it useless for male patients.

The study has ruled this out. The scientists created 31 cloned blastocysts — embryos of 100 cells or so — and 11 embryonic stem cell lines, and in only one case was the adult cell donor the same as the egg donor. Genetic tests have proved that the others are clones.

The Newcastle scientists’ results offer further proof that cloning is genuinely possible in humans: they also used eggs and nuclei from different sources.

The Korean team has also produced cloned embryos and stem cells with DNA that specifically matches those of sick patients for the first time. All the cell donors suffered either from spinal cord injuries, juvenile diabetes or a genetic immune system disorder called congenital hypogammaglobulinaemia.

The genetic tests they conducted have proved not only that the clones carry these disease traits, but that they are compatible with the immune systems of the donors.

This is critical if cloned stem cells are to be medically useful: their potential lies in their capacity to act as laboratory models of genetic disease, or to form replacement tissue that can be transplanted without danger of rejection by the body’s immune system.

The third critical advance is one of efficiency. In 2004, Dr Hwang needed 242 eggs from 16 volunteers, to create 30 cloned blastocysts and a solitary colony of viable stem cells. One of the most telling criticisms of that study was that with a one in 242 success rate, it might never be conceivable to harvest sufficient cloned embryonic stem cells for laboratory use, never mind for transplant therapies.

This time, 185 eggs from 18 women were used to create 31 cloned blastocysts, but these produced 11 useful lines of stem cells. An average of 17 eggs was required for each stem cell line, and when the eggs were taken from women aged under 30 the success rate was one in 14 — a 16-fold improvement on the research published last year. The improvement is down to better culture techniques for encouraging stem cell growth.

The greater success seen with eggs from younger donors suggests one way of improving the efficiency of cloning still further.

Professor Gerry Schatten of the University of Pittsburgh, who helped Dr Hwang to prepare his latest paper for publication, said: “Last year they stunned us with a proof of principle. The fact that they have now produced so many stem cell lines, that they are perfectly immuno-compatible and that they have improved efficiency by 16 times is just amazing. This is landmark stuff.”

Q What is cloning?

A It involves creating an embryo that is genetically almost identical to an existing person.

Q How is this done?

A Using a process known as cell nuclear transfer, the technique used to create Dolly the Sheep. The nucleus, containing most of a person’s DNA, is removed from an adult cell. It is then injected into an egg which has had its own nucleus removed. The resulting embryo is tricked into dividing, using electricity and chemicals.

Q What is it used for?

A Scientists are interested chiefly in “therapeutic cloning” — creating cloned cells that may be useful for studying and treating disease. “Reproductive cloning” is the creation of a cloned human being.

Q What is therapeutic cloning?

A The idea is to produce a cloned embryo that is genetically similar to a patient, perhaps with a disease such as diabetes. This can then be used to extract embryonic stem cells that have the same DNA as that patient.

Q What is an embryonic stem cell?

A These are master cells found in early-stage human embryos, which can form any tissue in the body.

Q Why are they useful?

A In the short term, embryonic stem cells that carry the genes of a patient will be valuable for studying the progression of his or her disease, and for investigating new treatments.

In the longer term, scientists hope to use cloned embryonic stem cells to create replacement tissue, which could be transplanted back into the patient to cure disease. As the cells would have the same DNA as the recipient, there would be no risk of rejection by the body.

Q What sort of diseases might be treated?

A Any condition in which a particular kind of cell is damaged or diseased. Good examples include type 1 diabetes, in which insulin-producing islet cells in the pancreas malfunction; Parkinson’s disease, in which dopamine neurons in the brain go wrong; or paralysis caused by damage to the spinal cord. Replacements for these cells could be grown and then transplanted.

Q Are embryonic stem cells and cloning the only options?

A Not necessarily, but most scientists think they are the most promising ones. Some studies have suggested that adult stem cells, such as those found in the spinal cord, will also be useful for treating disease. The likelihood is that adult stem cells will work for some conditions, but that embryonic tissue and cloning will be needed for others.

Q How far away are we from real treatments?

A Progress is unlikely to be swift. Scientists have yet to discover how to turn stem cells reliably into particular tissue types. The cells can only be grown using animal products at present, raising safety issues. Many years of research and safety tests will be required before trials can begin on seriously ill patients. Use of cloned stem cells as a laboratory model carries greater immediate promise. These will be useful for testing drugs that might treat conditions such as motor neuron disease.

Q What about reproductive cloning?

A The more efficient cloning techniques pioneered by the Korean team could in theory make this easier. However, scientists are almost unanimous that human reproductive cloning is not safe. Reproductive cloning is illegal in most countries.

Q What other ethical objections are there?

A People who believe in the sanctity of the embryo, particularly Roman Catholic groups, object to all forms of cloning, and indeed all embryonic stem cell research. There are also concerns about the ethics of women donating the eggs needed for therapeutic cloning, who must undergo risks to their health without any immediate benefits.

Q Who is researching cloning in Britain?

A The Newcastle team that has produced Britain’s first human clone, and a group at the Roslin Institute in Edinburgh, headed by Professor Ian Wilmut, which wants to create cloned embyros to study motor neuron disease.

By Mark Henderson

The Times, May 20, 2005

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