3 July 2006

Hello, Dolly: The sheep that changed the world

By
AFP
PARIS, 3 July 2006 - Ten years ago on Wednesday, a lamb was born in Scotland and the world hasn't been quite the same ever since.
Hello, Dolly: The sheep that changed the world

A 1997 photo of Dolly, the cloned sheep. Credit: AFP

PARIS, 3 July 2006 – Ten years ago on Wednesday, a lamb was born in Scotland and the world hasn’t been quite the same ever since.

Dolly, a Finn Dorset ewe, splashed headlines as the globe’s first cloned mammal, triggering a storm of dreams, dread and ethical polemic that has never abated.

From this event has flowed a river of money, directed into the quest for cures for cancer, heart degeneration, Alzheimer’s and other crippling diseases.

And there have likewise been anguished debate, bitter opposition and the crafting of laws and guidelines to restrict or shape cloning research.

“Where has Dolly taken us?” asked Sue Mayer, a doctor who is a member of GeneWatch, a British watchdog that monitors biotechnology.

“The biggest worry is that she has taken us down a blind alley. Rather than tackling the root causes of disease, we are going for hype and quick fixes which may never deliver. And she’s opened this prospect of reproductive cloning, a door which scientists try to keep open but which we should firmly close.”

The technique that led to Dolly is called somatic cell nuclear transfer and has remained essentially unchanged over the decade.

A mammalian egg is taken, and its nucleus – the DNA programming for making life – is removed.

The nucleus is replaced through a microscopic glass tube by the nucleus of a cell from the animal to be cloned.
The reconstructed egg is then treated with a jolt of electricity and placed in a dish of nurturing chemicals to make it divide, until a few days later it becomes a cluster of cells big enough to be transplanted into the surrogate mother’s uterus.

Dolly, created at the Roslin Institute in Edinburgh, was named after Dolly Parton, the big-busted country and western singer, because the cell that was cloned came from a sheep’s mammary gland.

Her lab name, rather less media-friendly, was 6LL3. It later emerged that the same team, managed by Ian Wilmut, had previously created two sheep clones from embryonic cells. So, strictly speaking, Dolly was the first mammal to be successfully cloned from an adult cell.

After this breakthrough, other cloned species swiftly followed: horses, bulls, pigs, mice, rats, rabbits, cats and dogs and others.

But the miscarriage rate of transplanted eggs is extremely high, and of those embryos that make it to term, many have deformities or (as happened with Dolly) die prematurely: a clear warning to any scientist mad or foolish enough to try to make a cloned baby.

The suspected cause is that the genetic software is not transferred entirely, or is somehow damaged in the transfer. As a result, the machinery malfunctions – genes do not switch on or off as they should in the complex ballet of making proteins.

So if cloning is frustrating, costly and potentially risky, why bother with it?

The most alluring reason is medical.

A cloned lab animal such as a mouse can provide a very useful standardised tool for experiment. And a farm animal that can be engineered and cloned to produce rare pharmaceutical proteins in its milk – Dolly was created with this in mind – could help save lives and ease suffering.

But the most glittering prize of all is to harness cloning to embryonic stem cells, the primitive master cells of early-stage embryos that famously have the power to develop into almost any tissue of the body.

Researchers believe embryonic stemcells can some day be coaxed into regenerative tissue that could repair brain cells, nerves, kidneys, livers and other organs damaged by disease.

So if these stemcells are copies of the patient’s own DNA, they would not be rejected by the immune system.

But here comes the ethical firestorm.

Some religious groups already oppose the use of human embryonic cells, saying that this tissue has the same value as a life.

Yet there is an added queasiness about human cloning that is shared by many others – even if the immediate goal is therapeutic and nothing is created beyond a tiny cluster of cells, a further step will have been taken towards baby cloning.

At the moment, patient-specific embryonic stemcells remain beyond the horizon, and the only scientist to have claimed to have made them, South Korea’s Hwang Woo-Suk, was unmasked in January as a stupendous fraud.

As for reproductive cloning, many countries introduced laws after a renegade sect, the Raelians, claimed in late 2002 to have produced the world’s first cloned baby.

That claim has never been independently confirmed or even examined, and most scientists scoff at it.

That said, many also predict that the first cloned human is only a matter of time.

“The (reproductive cloning) laws that are in place are pretty well-established throughout the world – but there are also laws in place against murder and suicide,” is the shrewd comment of James Bradley, a professor of cell and developmental biology at Auburn University in Alabama.

Key dates in the history of cloning:

1953: Cambridge University scientist James Watson and Francis Crick determine the double-helix structure of DNA, the chemical codebook for creating life

1962: Oxford University biologist John Gurdon clones frogs from differentiated cells.

1963: British geneticist J.B.S. Haldane coins the term “clone,” a derivation of the Greek word “klon”, meaning “twig.”

1996 (5 July): Ian Wilmut and colleagues at the Roslin Institute, Scotland, create Dolly the sheep, the first mammal to be cloned from adult cells. Goal is to have sheep that produce valuable proteins for drugs in their milk.

1998: First cloned mice, an important lab tool for biologists, created by Teruhiko Wakayama and Ryuzo Yanagimachi at the University of Hawaii. First cloned cows, born in Ishikawa Prefecture Livestock Research Centre, Japan.

2000: The first cloned pigs, created by a commercial offshoot of the Roslin Institute. Ultimate goal is to use pigs to grow transplant organs for humans. China creates first cloned goat, but animal dies after 36 hours with lung abnormalities.

2001: Birth of first cloned animal from an endangered species, an Asian ox called a gaur. The clone, created by a Massachusetts company, Advanced Cell Technology, dies 48 hours later.

2002: First cloned rabbit, by researchers at France’s National Institute of Agronomic Research. “Idaho Gem” becomes the world’s first cloned mule, an animal that is sterile. First cloning of a cat, called Cc:, by Texas A and M University, a commercial venture targeted at pet-lovers. A renegade sect, the Raelians, announces that it have created the world’s first cloned baby. The unsubstantiated claim spurs many countries to tighten laws against reproductive cloning.

2003 (14 Feb): Dolly the sheep is put down after developing a lung infection and arthritis. Her premature death is seen by some as a warning that cloning is flawed and dangerous. Ralph, the first cloned rat, is born.

2005: South Korean scientist Hwang Woo Suk claims he has created the world’s first cloned human embryos and used them to make patient-specific stemcells.

2006: Stemcell and cloning research is rocked as Hwang’s claim, which was published in a top peer-reviewed journal, turns out to be one of the greatest frauds in scientific history. A separate claim that he created the world’s first cloned dog, an Afghan hound called Snuppy, is validated.

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