When Dolly the cloned sheep was born 20 years ago on July 5, many hailed mankind's new-found mastery over DNA as a harbinger of medical miracles, such as laboratory-grown transplant organs.

Others trembled at the portent of a "Brave New World" of identical humans farmed for spare parts or as cannon fodder.

As it turns out, neither came to pass.

Human cloning - complicated, risky and ethically contentious - has largely been replaced as the holy grail of regenerative medicine by other technologies, say experts.

"It has not lived (up) to the hype," said Dr Rosario Isasi of the University of Miami's Institute for Bioethics and Health Policy.

"It was like a eureka moment: that we will finally be able to understand more (about) the mechanisms of disease, be able to maybe use it as a treatment for infertility. But that has not happened."

Dolly was the first mammal cloned using a technique called somatic cell nuclear transfer (SCNT). It involves removing the DNA-containing nucleus of a cell other than an egg or sperm - a skin cell, for example - and putting it into an unfertilised egg from which the nucleus has been removed.

In Dolly's case, the gene-encoding cell was taken from a mammary gland, which saw the ewe named after buxom country singer Dolly Parton. Once transferred, the egg reprogrammes the mature DNA back to an embryonic state with the aid of an electric jolt, and starts dividing to form a single- parent embryo.

No human is known to have been created in this way.

Cloning as a human reproductive technique is a global no-no. Apart from ethical objections, safety is a key concern. In animals, only a few cloned embryos survive to birth, and many have health problems later.

Experts say moral opposition to cloning as a means of reproduction has clouded opinion on the technique's potential usefulness in regenerative medicine.

Mainly people fear that scientists will not be able to resist the temptation to play God. "With ethical safeguards in place, there's... no way to go into reproductive applications," said Dr Isasi.

Yet, many people "fear that slippery slope... that one thing leads to another, leads to another, until there is a bad result".

"That's the main concern. That is probably what has held back the use of the technology."

Investment in therapeutic cloning research has dwindled, and few countries - among them Belgium, China, Israel, Japan, South Korea, Britain and Singapore - allow the creation of embryos for experimentation. In the United States, it is not explicitly illegal.

In therapeutic cloning, scientists harvest stem cells from a very early-stage embryo - called a blastocyst - a hollow ball of about 100 to 200 cells. Coaxing these "blank", juvenile cells into specialised liver or blood cells, for example, holds the promise of curing disease or repairing damaged organs.

If grown from the patient's own DNA, the risk of transplant rejection is dramatically lowered. But producing stem cells this way involves destroying embryos, another moral quagmire.

While a handful of scientists have succeeded in creating stem cells through SCNT, none has been grown into a functional human organ.

Cloning may not have found a direct application in medicine, but it has yielded many spin-off technologies, experts say.

"The whole field has moved to IPS cell research," pointed out Professor Julian Savulescu, who heads Oxford University's Uehiro Centre for Practical Ethics.

Induced pluripotent stem (IPS) cells are created by stimulating mature, already specialised, cells back into a juvenile state - basically cloning without an embryo.

The Nobel-capped discovery is the new focus in regenerative medicine, though the jury is out as to whether IPS cells work as well as embryonic ones.

Another spin-off is mitochondrial gene transfer, a new way to plant parental DNA into a healthy egg to create an embryo free of harmful mutations carried by the mother.

Associate Professor Aaron Levine, a bioethicist at Georgia Tech, said cloning's biggest impact on human health is likely to come from animals raised to produce organs, tissue or biological drugs that will not be rejected by the human immune system. "I think human cloning will disappear," he said.

"I think there's just ultimately not enough demand, not enough that you can do through cloning that you can't do through other things."

AGENCE FRANCE-PRESSE