25 March 2009
The invention: Experimental technique for creating exact duplicates of living organisms by recreating their DNA. The people behind the invention: Ian Wilmut, an embryologist with the Roslin Institute Keith H. S. Campbell, an experiment supervisor with the Roslin Institute J. McWhir, a researcher with the Roslin Institute W. A. Ritchie, a researcher with the Roslin Institute Making Copies On February 22, 1997, officials of the Roslin Institute, a biological research institution near Edinburgh, Scotland, held a press conference to announce startling news: They had succeeded in creating a clone—a biologically identical copy—from cells taken from an adult sheep. Although cloning had been performed previously with simpler organisms, the Roslin Institute experiment marked the first time that a large, complex mammal had been successfully cloned. Cloning, or the production of genetically identical individuals, has long been a staple of science fiction and other popular literature. Clones do exist naturally, as in the example of identical twins. Scientists have long understood the process by which identical twins are created, and agricultural researchers have often dreamed of a method by which cheap identical copies of superior livestock could be created. The discovery of the double helix structure of deoxyribonucleic acid (DNA), or the genetic code, by JamesWatson and Francis Crick in the 1950’s led to extensive research into cloning and genetic engineering. Using the discoveries ofWatson and Crick, scientists were soon able to develop techniques to clone laboratory mice; however, the cloning of complex, valuable animals such as livestock proved to be hard going. Early versions of livestock cloning were technical attempts at duplicating the natural process of fertilized egg splitting that leads to the birth of identical twins. Artificially inseminated eggs were removed, split, and then reinserted into surrogate mothers. This method proved to be overly costly for commercial purposes, a situation aggravated by a low success rate. Nuclear Transfer Researchers at the Roslin Institute found these earlier attempts to be fundamentally flawed. Even if the success rate could be improved, the number of clones created (of sheep, in this case) would still be limited. The Scots, led by embryologist Ian Wilmut and experiment supervisor Keith Campbell, decided to take an entirely different approach. The result was the first live birth of a mammal produced through a process known as “nuclear transfer.” Nuclear transfer involves the replacement of the nucleus of an immature egg with a nucleus taken from another cell. Previous attempts at nuclear transfer had cells from a single embryo divided up and implanted into an egg. Because a sheep embryo has only about forty usable cells, this method also proved limiting. The Roslin team therefore decided to grow their own cells in a laboratory culture. They took more mature embryonic cells than those previously used, and they experimented with the use of a nutrient mixture. One of their breakthroughs occurred when they discovered that these “cell lines” grew much more quickly when certain nutrients were absent.Using this technique, the Scots were able to produce a theoretically unlimited number of genetically identical cell lines. The next step was to transfer the cell lines of the sheep into the nucleus of unfertilized sheep eggs. First, 277 nuclei with a full set of chromosomes were transferred to the unfertilized eggs. An electric shock was then used to cause the eggs to begin development, the shock performing the duty of fertilization. Of these eggs, twenty-nine developed enough to be inserted into surrogate mothers. All the embryos died before birth except one: a ewe the scientists named “Dolly.” Her birth on July 5, 1996, was witnessed by only a veterinarian and a few researchers. Not until the clone had survived the critical earliest stages of life was the success of the experiment disclosed; Dolly was more than seven months old by the time her birth was announced to a startled world.Impact The news that the cloning of sophisticated organisms had left the realm of science fiction and become a matter of accomplished scientific fact set off an immediate uproar. Ethicists and media commentators quickly began to debate the moral consequences of the use— and potential misuse—of the technology. Politicians in numerous countries responded to the news by calling for legal restrictions on cloning research. Scientists, meanwhile, speculated about the possible benefits and practical limitations of the process. The issue that stirred the imagination of the broader public and sparked the most spirited debate was the possibility that similar experiments might soon be performed using human embryos. Although most commentators seemed to agree that such efforts would be profoundly immoral, many experts observed that they would be virtually impossible to prevent. “Could someone do this tomorrow morning on a human embryo?” Arthur L. Caplan, the director of the University of Pennsylvania’s bioethics center, asked reporters. “Yes. It would not even take too much science. The embryos are out there.” Such observations conjured visions of a future that seemed marvelous to some, nightmarish to others. Optimists suggested that the best and brightest of humanity could be forever perpetuated, creating an endless supply of Albert Einsteins and Wolfgang Amadeus Mozarts. Pessimists warned of a world overrun by clones of selfserving narcissists and petty despots, or of the creation of a secondary class of humans to serve as organ donors for their progenitors. The Roslin Institute’s researchers steadfastly proclaimed their own opposition to human experimentation. Moreover, most scientists were quick to point out that such scenarios were far from realization, noting the extremely high failure rate involved in the creation of even a single sheep. In addition, most experts emphasized more practical possible uses of the technology: improving agricultural stock by cloning productive and disease-resistant animals, for example, or regenerating endangered or even extinct species. Even such apparently benign schemes had their detractors, however, as other observers remarked on the potential dangers of thus narrowing a species’ genetic pool. Even prior to the Roslin Institute’s announcement, most European nations had adopted a bioethics code that flatly prohibited genetic experiments on human subjects. Ten days after the announcement, U.S. president Bill Clinton issued an executive order that banned the use of federal money for human cloning research, and he called on researchers in the private sector to refrain from such experiments voluntarily. Nevertheless, few observers doubted that Dolly’s birth marked only the beginning of an intriguing—and possibly frightening—new chapter in the history of science.