Book Review | Published:

Dolly part one: the end of the beginning in mammalian cloning?

Nature Genetics volume 24, page 347 (2000) | Download Citation

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The Second Creation: The Age of Biological Control by the Scientists Who Cloned Dolly

By ,  &

 Headline Book Publishing, £18.99 or $27.00 (US), ISBN 0-7472-2135-9, 2000

The Second Creation describes the cloning of sheep, among them Dolly, whose arrival heralds “the age of biological control”. Its cover resembles a Leonardo da Vinci manuscript and as such, the tome beckons with the allure of the profound and arcane: the biology of cloning made accessible by its authors.

Dolly was generated at Roslin Institute, Edinburgh in the mid-1990s, and The Second Creation provides a synopsis of the underlying language, history and ideas. Many readers will be intrigued by descriptions of the research environments that fostered the work. Anecdotes of the book's authors and protagonists appear throughout; establishing a human angle is evidently a key feature in the marketing of science, as if there is some magic in the revelation that scientists are what Colin Tudge describes as “ordinary blokes”. We learn that Keith Campbell “plays the drums, and races at high speed over the hills” and why it was that Ian Wilmut had to quit his first love, farming. Leitmotifs include the cause of openness in scientific discourse and the non-desirability of human cloning. This latter viewpoint is expounded in its own chapter at the end of the book and is one illustration of the sensitivity of the scientists to the societal impact of their research.

Any summary of cloning is an ambitious undertaking, and The Second Creation tackles this with a logical progression of its subject matter, although it perhaps suffers from an absence of illustrations; of the 13 black-and-white plates, only 3 are technical. Whereas illustrations may furnish an unwanted textbook image, their absence makes the book, well, prosaic, and one wonders for whom it was written. The introductory first half of The Second Creation is a mixture of material not germane to the description of cloning that ensues, blended with much that is. We learn, for example, that nine-banded armadillo embryos naturally split to produce quadruplets that are clones of each other; the programmed cloning of mammals is not a human invention after all. Unfortunately, such nuggets are unevenly scattered across a landscape of terminological inexactitudes. For example, entry of the sperm at fertilization does not allow “calcium to rush in”; “Genetic engineers” can transfer more than one gene at a time; and “In truth, a DNA molecule should not simply be called a ‘molecule’ since it consists of many different molecules…” is misleading.

The text becomes increasingly authoritative the nearer its focus gets to cloning. The history of cell biology and the first cloning experiments are described with clarity and erudition, and they are a pleasure to read. Yet The Second Creation is at odds with itself in apportioning credit for the more recent techniques employed to generate Dolly and her forerunners, Megan and Morag. Whereas it is acknowledged that these techniques had been conceived and reduced to practice by others, including Steen Willadsen, about ten years before Dolly, this seems to have been overlooked elsewhere: “… we developed a technique to reprogramme cells that were already differentiated …” The precise technical contribution made at Roslin Institute is one of several issues that, although not explicitly flagged by The Second Creation, are collectively critical to it, as if the book is partly defined by its negative space. How prescriptive were the commercial participants? Why is there not a more detailed history of Dolly's progenitor cell culture than has been permissible so far? What is scientifically contentious in cloning today?

The sensational arrival of Dolly, cloned from a mammary-derived cell, was met with both public and professional acclamation as well as skepticism. For some biologists, any report of an animal cloned from an adult-derived cell required incontrovertible supporting evidence, although with poetic licence, Dolly could be said to have arisen from an unidentifiably fertilized ooplast (UFO). Yet this was not UFOlogy; a single event—however remarkable—is not evidence of reproducibility but a case report, and as the authors themselves generalize, “The essence of science is reproducibility.” The Second Creation does little to assuage critics on this cardinal point or suggest why there was no Third Creation; after all, given that Dolly was so named to reflect a mammary association with Ms Parton, they might at least have cloned a pair.

The Second Creation adumbrates an age that may or may not have begun: that of biological control. The veracity of this depends on what is meant by ‘control’. Today, nuclear-transfer cloning methods, or those that work by cell fusion like the one used to generate Dolly, fail to generate offspring in at least 98% (or so) of attempts. Even ‘successes’ are beleaguered by increases in rates of perinatal death, birth weight, adult weight and possibly hypoplasia compared with their non-cloned counterparts. In short, no one knows why mammalian cloning succeeds some of the time—or why it fails most of it. This is a systemic problem with The Second Creation : it tells a story still unfolding as if it were unfurled. Even the central experimental credo, that the cell cycle of the nuclear donor is critical in cloning (held to be “one of the most significant insights of modern biotechnology”), is seriously challenged by recent findings.

Dolly has triggered a resurgence of interest in cloning, which is celebrated in The Second Creation as a renaissance, and in this spirit we should be optimistic that today's cloning headaches are not insuperable. But not until their disappearance can Dolly take her rightful place in the story of cloning.

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Affiliations

  1. The Rockefeller University, 1230 York Avenue, New York, New York 10021 , USA.

    • Tony Perry
    •  & Teru Wakayama

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DOI

https://doi.org/10.1038/74163

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