The Hindu : Stem cells and cloning

Online edition of India's National Newspaper
Friday, Feb 20, 2004

Opinion

Opinion - Leader Page Articles

Stem cells and cloning

By N. Gopal Raj

The creation of the first cloned human embryos, enabling the recovery of stem cells, holds out mixed prospects.

A PREDOMINANTLY South Korean team of scientists has succeeded in creating the first cloned human embryos, cutting a biological Gordian knot. It is a step that permits the recovery of stem cells, which can potentially be used to treat a wide range of ailments. Unfortunately, the Korean success also makes the cloning of whole humans, termed "reproductive cloning," that much easier and therefore more likely to happen.

"This is an exciting announcement because it means a potential advance in exploiting the therapeutic potential of stem cells," said Richard Gardner, chair of Britain's Royal Society working group on stem cells and cloning, but added: "This announcement does not make attempts at human reproductive cloning any more desirable, ethical or safe."

Stem cells are unspecialised cells that are capable of replicating themselves for long periods of time. Under suitable conditions, they can also differentiate and become specialised cells performing specific functions, be it as a muscle cell required for flexing a joint, a nerve cell carrying electrical impulses or one of the many secretory cells providing vital chemicals needed by the body. More than 200 known cell types make up the human body. A cut is easily healed, but many cells and organs do not recover after they are damaged. A spinal injury leaves people paralysed. Heart and brain tissue are destroyed after a heart attack or stroke. For people whose liver or kidneys are failing, finding a suitable donor for an organ transplant offers the only hope. If stem cells can be reliably transformed into those specialised cells and implanted in the body without immune rejection, scientists believe that a whole range of health problems, from heart and brain disease to arthritis, spinal paralysis and diabetes, could be treated and perhaps even cured.

Such treatment and therapy could be many years away. Several fundamental questions remain as scientists seek to understand how things work at the molecular level inside cells and are affected by the environment around them. "For researchers and patients, there are many practical questions about stem cells that cannot yet be answered," observed a report prepared by the National Institutes of Health in the United States. Predicting the future of stem cell applications was impossible, particularly given the very early stage of the science of stem cell biology, the report noted.

"We are only at the end of the beginning," Robert Nerem, Director of the Georgia Tech/Emory Center for the Engineering of Living Tissues in the U.S., warned at a recent conference in Thiruvananthapuram on tissue engineering and stem cell technologies. There was, he said, a long way to go to realise the vision of creating spare body parts and rebuilding broken down bodies.

Embryonic stem cells are coveted because they have the ability to differentiate into all cell types. These stem cells are extracted from the human embryo when it is less than a week old, forming a tiny ball of cells known as the blastocyst. The South Korean achievement has been in cloning human embryos. The scientists extracted the DNA-bearing nucleus from women's eggs and transplanted genetic material taken from mature cells into those eggs, in a procedure known as "somatic cell nuclear transfer." The modified eggs were coaxed into multiplying and forming blastocysts, from which stem cells could be taken. Until now, cloning embryos through somatic cell nuclear transfer had seemed an almost insurmountable hurdle in primates. So much so that Gerald Schatten of the University of Pittsburgh School of Medicine, who had tried hundreds of times to clone monkeys, was quoted last year in the journal, Science, as saying that it was as if someone had drawn a sharp line separating old-world primates (including humans) from animals such as sheep, cattle, mice, rabbits and cats, that could be cloned.

Creating embryonic stem cells by using somatic cell nuclear transfer was needed to pursue at least two important avenues of investigation, say Bruce Alberts, president of the U.S. National Academy of Sciences, and fellow scientists. Writing in Science, they noted that creating stem cells with the patient's own nuclear genome might eliminate tissue rejection. Besides, creating stem cells that were genetically identical to mature cells in people with heritable diseases offered "an unprecedented opportunity to study genetic disorders as they unfold during cellular development."

However, if the cloned embryo were placed in a mother's womb and allowed to develop, it is not impossible that a cloned human being might be born, the genetic twin of the person whose DNA was transferred to the egg. Since Dolly the sheep, the first mammal to be cloned through somatic cell nuclear transfer, was born in 1997, many other animals have been cloned using similar methods. With the exception of "cowboy cloners" (a phrase used by Lord Robert May, president of Britain's Royal Society), scientists and science academies around the world are completely opposed to any reproductive cloning of humans. But as the InterAcademy Panel on International Issues, a grouping of more than 60 national academies of science, emphasised in a statement calling for a "universal ban" on reproductive human cloning, cloning for research and therapeutic purposes must be permitted.

Somatic cell nuclear transfer-based cloning is still inefficient, noted Ian Wilmut, who led the team that created Dolly, and other scientists in an article published recently in Nature Reviews Genetics. Their article, titled "Human cloning: Can it be made safe", points out that experience with other mammals showed that any attempt to clone humans was "inherently unsafe" at this point of time. Clones were lost right from the earliest developmental stages and throughout pregnancy, and some that survived to term died prematurely from various abnormalities. The factors that led some cloned animals to develop normally while others did not were not understood. "Scientists should not condone human reproductive cloning, even without taking into account the equally important ethical and moral issues," they stated.

The InterAcademy Panel on International Issues pointed out in its statement on human cloning: "It is not beyond the bounds of possibility that scientific knowledge would advance to the point where reproductive cloning by somatic cell nuclear transfer might be accomplished without undue risk. Such a situation would not of itself warrant the lifting of a ban on the practice, which would still face strong ethical, social and economic objections."

Stem cells are also to be found after birth. For years, blood-forming adult stem cells have been extracted from the bone marrow and blood stream, and given to cancer patients whose own stem cells had been depleted by high doses of radiation or chemotherapy. These stem cells are needed to replenish continually various blood cells. In the last decade, scientists have found adult stem cells in many other body tissues such as those of the eye, liver, muscle, skin, the intestinal lining, pancreas, and even the pulp of teeth. Scientists at the L.V. Prasad Eye Institute in Hyderabad have developed a technique that uses stem cells from the eye in order to repair damage to the cornea of the eye, and thus restore sight.

There is evidence too that these adult stem cells can differentiate into cells of other tissue types, and not just the cells of the tissue where they are found. It has been found, for instance, that blood-forming adult stem cells can produce heart muscle cells and nerve cells.

So why not use adult stem cells and avoid the ethical and moral issues that beset embryonic stem cells? As yet no population of adult stem cells had been isolated that was capable of forming all the kinds of cells of the body, points out the National Institutes of Health report. Moreover, adult stem cells were rare, and often difficult to identify, isolate and purify. Nor were adult stem cells able to replicate indefinitely when cultured. However, results just published involving slightly more specialised cells, called progenitor cells, suggest that genetic modification might produce adult stem cells that are immortal.

The InterAcademy Panel on International Issues took the view that it was not possible to conclude from scientific findings so far that adult stem cells had proved sufficiently versatile and that there was, therefore, no need to derive stem cells from very early human embryos. "Research on both adult and embryonic stem cells is vital for a proper evaluation of the prospects of stem cell research for the treatment of serious disease and injury," it said.

But the InterAcademy Panel also pointed out that clinical viability of cloning for therapeutic purposes remained to be established. The cost of such customised treatment and obtaining an adequate supply of unfertilised human eggs were both important issues, apart from scientific challenges involved. As cloning was at present an inefficient process, many eggs would be required to make a single embryonic stem cell line.

A long-term goal, said the InterAcademy Panel, would be to learn to re-programme mature cells into stem cells, thus providing a way of obtaining stem cells, genetically compatible with the patient, without any need for the use of eggs and embryos.

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