Dolly part one: the end of the beginning in mammalian cloning?
Reviewed by: Tony Perry
& Teru Wakayama
The Rockefeller University,
1230 York Avenue, New York, New York 10021
, USA.
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.
The Second Creation: The Age of Biological Control by the Scientists
Who Cloned Dolly
by Ian Wilmut
Keith CampbellColin Tudge
Headline Book
Publishing, £18.99 or
$27.00 (US), ISBN 0-7472-2135-9,
2000
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.
