A Test-Tube Baby Is Not a Clone

News of the impending birth of a baby conceived in a test tube caused scant surprise--or suspicion--among scientists and doctors. That was a far cry from their reaction last March, when they challenged as a "fraud" and a "hoax" a book called In His Image that claimed a baby boy had been cloned from a 67-year-old millionaire. The difference was that the test-tube fertilization had been performed by two respected scientists whose accomplishments and progress had been described in many published papers. But Image did not identify the clone or the cloner, and offered no evidence that the state of the art had advanced to the point at which mice, let alone human beings, could be cloned. While many of the technical problems involved in the test-tube conception of a human are being resolved, the cloning of Homo sapiens is still far beyond the current capability of medical science.

Unlike in vitro fertilization, which lets nature take its course (sperm from the father and an egg from the mother unite, albeit in a test tube), cloning is asexual, single-parent reproduction. Instead of being a mixture of genes from two parents, the clone (from the Greek word klon, meaning twig or slip) is a genetic copy of its single parent.

Cloning is based on a remarkable fact. Virtually every cell in an organism --be the life form a human being, a maple tree or a bacterium--carries all the genetic information needed to create the whole organism. The reason that a liver cell is different from, say, a skin cell is that different genes in each cell seem to be "turned on." In the language of biologists, the cells are differentiated. U.S. Biologists Robert W. Briggs and Thomas J. King confirmed this principle and pioneered the basic technique of animal cloning in the early 1950s. They removed the nuclei of unfertilized egg cells from female frogs. These nuclei were then replaced with nuclei taken from the cells of developing frog embryos, which at this early stage were merely clumps of cells that had not yet differentiated into specific organs. Some of the frog eggs, with their newly implanted nuclei, acted as if they had been fertilized; they started to divide and went on to develop into tadpoles.

In the early 1960s, British Biologist John B. Gurdon took the technique a step further by replacing the nuclei of unfertilized eggs with the nuclei of cells that had differentiated into intestinal cells of young tadpoles. Some of the resulting cloned tadpoles matured into adult frogs. There have since been reports of successful cloning with nuclei from adult frog cells, but researchers have found that the best results are obtained by using the nuclei from cells of frogs in the early stages of embryonic development. The nuclei of adult animal cells are generally considered poor cloning material, possibly because many of the genes have been irreversibly shut off.

The Gurdon experiments still represent the high-water mark of traditional cloning technique. Researchers find that cloning mammals is a much more complicated affair. For one thing, mammalian eggs are one-tenth to one-twentieth the size of frog eggs and thus difficult to manipulate. And while tadpoles grow into frogs in a pond (and therefore easily in a laboratory tank), mammalian embryos must develop in a womb.

Though cloning mammals by the classic method is a long way off, scientists are moving closer to cloning mice by an indirect route. In this technique, devised by Yale Biologist Clement Markert, eggs are removed from a female mouse shortly after fertilization. At this early stage, genetic material from egg and sperm have not yet mixed; the mother's and father's genes are still in two distinct sacs, called pronuclei. Using microsurgery, Markert removes either pronucleus. The egg is then exposed to a chemical that causes the remaining pronucleus to replicate, thus giving the cell a full complement of genes. Then the cell itself divides, and the resulting embryo is placed in the uterus of a female mouse to develop. Using this technique, Biologist Peter C. Hoppe of Jackson Laboratory in Bar Harbor, Me., and Swiss Microsurgeon Karl Illmensee have produced seven mice, all females. (Males cannot be produced by this method because the male and female pronuclei never merge, making it impossible for the male XY chromosome combination to form.)

Still, the mice are not clones. They each contain not a full set but two identical half sets of one parent's genes. But if the process is repeated with one of these mice, the new daughters would be clones of each other and the mother.

This technique has enormous implications for both laboratory research and animal husbandry. A particular strain of mouse needed for experiments could be duplicated in great numbers, as could prize dairy cows, horses, sheep and pigs. But cloning human beings by the same procedure is another story. Homo sapiens is a mongrel breed. Unlike domesticated or laboratory animals, man has not had harmful and even lethal genes bred out of him. These genes remain in humans, many as recessives, suppressed by dominant normal genes. If humans could be cloned by Markert's method, these recessive genes could come to the fore and express themselves, causing deformities and genetic illnesses, even death.

Thus while human cloning makes good cocktail-party chatter, it is not only very far off in the future, but also seems to be impractical and to present unsolvable ethical and social problems. Says Nobel Laureate James Watson, co-discoverer of DNA's double-helix structure: "What's to be gained? A carbon copy of yourself? Oh, if the Shah of Iran wanted to spend his oil millions on cloning himself, that's fine with me. But if either of my young sons wanted to become a scientist, I would suggest he stay away from research in cloning humans. There's no future in it."

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