Dolly's Legacy

Nuclear transfer--used to clone Dolly and now owned by Geron--may help scientists develop more potent stem-cell therapies















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Image: GERON CORPORATION

NUCLEAR TRANSFER, the first step in creating a clone, involves inserting the nucleus from an adult somatic, or differentiated, cell into the emptied cytoplasm of an egg cell. The egg cell then reprograms the adult cell's genes so that it behaves like an all-purpose stem cell.

Since early May, when Geron Corporation acquired Roslin Bio-Med, there has been nervous speculation about what the marriage might mean. Geron, the biotech wunderkind, last made big news in November 1998 when scientists they funded--James A. Thomson of the University of Wisconsin and John D. Gearhart of Johns Hopkins--independently isolated two sorts of so-called human pluripotent stem cells. These cells that have tremendous therapeutic potential because they can develop into any other type. Roslin Bio-Med is the firm established to commercialize nuclear transfer, the method researchers at Roslin Institute used to clone Dolly the sheep in 1997.

Might not the two be ideal parents for the first human clone? Last week, headlines around the world aired that suspicion: "Science 'weeks from cloning human embryo,'" London's Daily Mail shouted on June 15; "Cloned embryos planned," echoed the Montreal Gazette. Similar stories appeared the same day in the Daily Telegraph and Boston Herald.

But the situation it is not so simple. Geron, which promptly denied the accusation, does have scientists at an undisclosed location conducting experiments in which they transfer the nuclei of adult cells into human eggs already relieved of their own--the first step in creating a clone, Dolly-style. But instead, after five to ten days, the researchers are removing pluripotent stem cells from the resulting ball of 100 or so and analyzing them.

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Image: GERON CORPORATION

PLURIPOTENT STEM CELLS, first isolated in humans last November, can be transformed into any other type of cell, making them the ideal raw material for fashioning replacement parts. By reactivating telomerase, an enzyme that reknits the frayed ends of genes in older cells that have undergone many divisions, scientists can extend the life span of the new parts.

Why is this work not quite human cloning? For one thing, most scientists maintain that a 10-day old embryo is not yet a life because the nervous system hasn't developed, an event that begins around day 14. Less controversial is the argument that creating human embryos for the sake of harvesting stem cells doesn't really serve Geron's purposes. Although such harvested cells could be cultured as say, liver cells for treating hepatitis or dopamine-producing cells for Parkinson's, the resulting transplants would likely be rejected by patients' immune systems.

It is in this regard that Geron's motivation in purchasing Roslin's cloning technique becomes clear. Nuclear transfer hinges on the fact that, somehow, factors in an egg cell's cytoplasm can reactivate all of the genes in adult cells so that they behave like stem cells. All adult cells contain an organism's entire set of genes, but they shut off all save those genes they need to function as hair, blood and so forth.

If Geron can learn what chemicals in an egg cell's cytoplasm reprogram an adult cell's nucleus--the aim of their current experimentation--they can avoid using embryos altogether. In that case, any cell from a patient could be used to whip up perfect tissue matches--histocompatible in the parlance of immunology--for treating a range of conditions.



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