|The Second Creation: Dolly and the Age of Biological Control|
|by Ian Wilmut, Keith Campbell, and Colin Tudge|
Posted: September 22, 2000
Dolly is the first mammal cloned from adult cellsappropriately enough, mammary gland cells, which is why her progenitors named her after the conspicuously curvaceous singer Dolly Parton. Her existence refutes conventional biological wisdom, which long insisted that once differentiated, a cell could never go back to its uncommitted beginnings and become a different kind of cell. Polly was also cloned from a differentiated cell, although one taken from a fetus rather than an adult sheep. But in addition, Polly was genetically engineered.
Dolly was a demonstration of principle and, despite the flap that greeted her, actually poses few real-world problems, except perhaps for the authors of existing textbooks, which must be revised.
Polly, on the other hand, is the wave of the future, and her implications are momentous. She is the herald of precision genetic engineering in mammals, including a species called H. sapiens. That isn't at all what Wilmut and Campbell had set out to do, and is a possibility of which they thoroughly disapprove. But they don't seem terribly hopeful that human genetic engineering can be prevented.
To clone an organism means to duplicate it without the help of sexual reproduction. We have been cloning plants for thousands of years, but animals, particularly mammals, are a different matter. As the authors observe, "Cloning is a very natural thing (meaning that it occurs throughout nature), but it is not, except in rare instances, a mammalian thing."
Identical twins are one of those rare instances. They are true clones, since they come about through division of a single cell, and thus share not only nuclear DNA but the very complex cell cytoplasm. Dolly is different, a genetic clone only. Her nuclear DNA came from one sheep, but it was transferred into an egg from a different sheep. Thus her cytoplasm is different from that of her genetic "mother." The authors believe that a cell's cytoplasm has enormous influence on the behavior of the genes in its nucleus and thus on an organism born of it. Four rams they cloned in different eggs are genetically identical, but they look different and have different personalities.
Wilmut had a foretaste of the media madness that would follow Dolly's arrival because he was the first scientist to coax a frozen embryo to become a live-born calf. He rather liked being famous for a moment. Which was just as well, given what was to come when Dolly appeared in 1997. Initially an embryologist at the Roslin Institute, a government lab near Edinburgh, he switched into molecular biology and genetic engineering early in the 1980s.
That was when Roslin moved into 'pharming,' the effort to create living pharmaceutical factories in the form of genetically engineered sheep that would produce therapeutic human proteins in their milk. Cloning was simply a means to that end. The idea was to transform cells from sheep embryos by adding human genes, such as the ones that make the blood clotting factors that are missing in hemophiliacs, and then to grow complete embryosand eventually live sheepfrom these altered cells.
But it was Campbell who made Dolly and Polly possible. He had taken an unconventional route into science and is himself somewhat unconventional, which may help explain why he rejected the dogma that differentiated cells could not be reprogrammed. He was also the first to realize that the key to this reprogramming was to pick the right moment in the cell cycle.
Wilmut and Campbell sat for many hours of taped interviews with Tudge, who attempts to recount events from the point of view of one researcher or the other. A top science journalist, Tudge did the writing, and is presumably responsible for the book's great strength: its detailed accounts of the centuries of biological investigations that led to that Scottish sheepfold. The Second Creation is not just a history of cloning, but also a lab manual that leads you painstakingly through the stepssome planned and some accidentalthat led to Dolly et al. In addition, it's a textbook and reference work on the biology of reproduction (both sexual and non-) and the mechanics of cell division, as well as a short-course in cell biology and the cell cycle. In addition, is provides a trek through theories about why sex evolved. These intricate topics have never been explained more clearly and gracefully.
The book concludes, of course, by exploring the ethical and social implications of cloning and human genetic engineering. The authors speculate wanly that perhaps public resistance to nuclear power and genetically modified crops indicates that people can eschew technologies they find troubling.
But what if people don't find them troubling? Selecting a child's sex has been the rage for years, especially in India and China. In vitro fertilization and its ilk are wildly popular in places where people can afford them, despite their sorry record of success. Whennot ifscientists find genes that boost intelligence, or athletic ability, or musicality, or even height, is it possible that prospective parents won't be storming the labs to demand them? Not bloody likely.
Freelance writer and editor Tabitha M. Powledge specializes in genetics, neuroscience, and science policy.