Closing In on Cloning

By John S. DeMott

In 363 tries, three rare mice and hints of things to come

In the book and movie The Boys from Brazil, a demented Nazi doctor uses blood and tissue cells from Adolf Hitler to clone dozens of copies of the German dictator in the hope that at least one of them will seize power and conquer the world. Though the cloning of human beings is likely to be confined to fantasy for decades--perhaps forever--other kinds of cloning have long been possible. The Greek word klon means twig, and the simplest kind of vegetable cloning consists of cultivating cuttings from a plant. By the mid-1950s scientists had succeeded in cloning amphibians, producing frogs that were genetically identical to each other and carried the inherited characteristics of only a single parent. Most animal cloning has been done by transplanting nuclei into egg cells to produce an entire organism from a single cell. But the cloning of higher forms of life, like mammals, is hard to achieve. Mammal eggs are microscopic, ten to 20 times smaller in diameter than frogs' eggs, and vastly more difficult to manipulate. Consequently, the barriers to cloning laboratory mice had, until now, proved insurmountable. But last week the word was out that biologists had successfully done just that.

The work was carried out in Switzerland by Karl Illmensee of the University of Geneva and Peter Hoppe of the Jackson Laboratory in Bar Harbor, Me., both veteran researchers in cell biology. Their breakthrough was not in conception --since the procedures for cloning are familiar. It lay rather in the surgeon-like skill and persistence with which they used microscopic instruments to transplant nuclei from cell to cell.

First they scooped a mass of embryonic cells from the womb of a pregnant gray mouse. Using microscopes and a micropipette much finer than a human hair, they sucked out the cells' nuclei and, one by one, transplanted each into a recently fertilized egg extracted from another mouse. That mouse was black and functioned as a kind of genetic control.

The researchers drew out the egg and sperm nuclei that were already in the black mouse's egg so that their genetic information could not influence the resulting clone. Next they cultured the cell in a solution of nutrients until it divided and grew into an early embryo, which was then inserted into the womb of a third mouse, this one white. The white mouse gave birth to a gray mouse, genetically identical to the original embryo.

In 363 tries, Illmensee and Hoppe managed to produce three such mice. The high failure rate was due mainly to the delicacy and complexity of the microma-nipulative technique involved. In subsequent experiments, however, Illmensee and Hoppe had better luck. They generated several mice from a single embryo, all genetically identical to each other and thus true clones.

Almost every cell in an organism contains all the genetic information needed for reproducing the entire organism. But getting that information to turn on or, as biologists put it, to "express" itself, is the main problem in animal cloning. It has been done now with immature cells. But as cells become differentiated, they seem to lose the ability to release genetic instructions for anything other than what they have become. A red blood cell can become only another red blood cell, for example. For that reason, Illmensee and Hoppe were only able to clone mice from embryonic cells that had not yet differentiated into cells for skin, bones, brains, eyes and other parts of the body. So far, there have been no undisputed reports of cloning from mature animal cells.

Nonetheless, the Illmensee-Hoppe mice, if they are produceable in large numbers, open many new avenues for research. The mice are, in fact, less important as clones than as vehicles for experiments in embryology, cell differentiation and immunology as well as in the study of birth defects and cancer. They enable medical researchers to introduce variables into otherwise genetically identical subjects, and then observe the results.

Some variation of the Illmensee-Hoppe technique may one day be used to clone prize bulls or even human beings.

But other scientists question the ethics, as well as the scientific use, of trying to clone humans from undifferentiated cell masses. Whatever the original genetic imprint, the results would not be predictable, and mistakes would be stamped indelibly not on mice but on men. --By John S. DeMott.

Reported by Peter Stoler/New York

With reporting by Peter Stoler

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