Clone: The road to Dolly,
and the path ahead
Remaking Eden: Cloning and beyond in a brave new world
By Gina Kolata. 276 pp. New York, William Morrow, 1998. $23. ISBN 0-688-15692-4.
By Lee M. Silver. 317 pp. New York, Avon Books, 1997. $25. ISBN 0-380-97494-0.
On February 27, 1997,
Ian Wilmut and his colleagues at an animal-husbandry research center near Edinburgh, Scotland,
announced in Nature the birth of Dolly. This was no mere birth notice: Dolly was produced
by fusing the nucleus of a cell from the udder of a six-year-old sheep with an unfertilized,
nucleus-free egg from another sheep. For the first time, the restricted genetic information in
the nucleus of a differentiated mammalian cell was reprogrammed to reveal everything it
knew about forming all the other cells of the body. In effect, cellular time was reversed a terminally
differentiated cell reverted to its primordial ancestor. Moreover, Dolly also showed that
chemical messages in the cytoplasm of an unfertilized egg can awaken the genes that differentiation puts
to sleep. The identification of the ovular messages that repeal the genetic injunctions
imposed by differentiation could yield immense benefits to medicine.
is an identical twin of the anonymous animal that donated the nucleus, but at her
birth she was six years younger than her sister. Therein lies the rub. Dolly is a
clone, and because, imprisoned in her surrogate womb, Dolly nevertheless had escaped the
iron grip of sexual reproduction, she ignited an immediate worldwide reaction. Within
weeks of the publication of the paper by Wilmut and his colleagues, politicians in
Washington began drawing up prohibitive legislation, and in some European countries and
China the cloning of humans was declared illegal. Well-known ethicists decried the
experiment on talk shows Dolly reminded several commentators of Aldous Huxley's Brave
New World, The Boys from Brazil, which involved a plot to produce clones of
Adolf Hitler, or Woody Allen's Sleeper, in which the cloning of a dictator
was attempted from his nose. Meanwhile, Clonaid, a company based in the Bahamas, was
proposing to clone humans for a mere $200,000 a copy.
Through all the
uproar and self-righteous posturing, the science that created Dolly and the potential
benefits of cloning mammals were neglected or seriously misunderstood. Few who
spoke out publicly recognized the possible practical applications of the technique
and how cloning from an adult nucleus could advance our understanding of normal
and abnormal differentiation, aging, and cancer. Wilmut's motivation had nothing
to do with cloning humans. He wanted to improve livestock and make genetically engineered
animal factories that would produce medically useful proteins, such as clotting
factors. Indeed, 10 months after Wilmut's paper was published, Schnieke et al.
(Science 1997;278:2130-3) reported that they had fused enucleated ovine
oocytes with fetal fibroblasts not with adult cells, as Wilmut had done that
had been transfected with the gene for factor IX linked to the promoter for the -lactoglobulin
gene for the purpose of producing sheep that would secrete the scarce human clotting factor
in their milk.
The two books under review deal with these fascinating matters in
different ways. In Clone, Gina Kolata, a well-known science writer
for the New York Times, takes us on a breezy, journalistic tour of
cloning. The writing is vivid and clear. Anyone who reads her book will come
away with an appreciation of the main scientific and ethical issues. She will
engage you with the historical background and sharply etched portraits of
the leading figures in the drama. As a journalist, Kolata has an ear for chitchat
and scandal. For example, she gives us an extended account of David Rorvik's
book In His Image: The Cloning of a Man (Philadelphia: J.P. Lippincott,
1978), which was advertised as a true chronicle of the cloning of a mysterious,
unnamed millionaire; the publisher ultimately admitted that it was a hoax.
And she tells in detail the story of Karl Illmensee, who fooled the scientific
community for years with his claim to have cloned mice by nuclear transfer.
The relevance of these lengthy asides to the main issues is dubious, but Clone is
worthwhile as an entertaining summary of the biology of the new millennium.
Eden Lee Silver, a professor in the Department of Molecular Biology
at Princeton University, gives us a panoramic view of molecular genetics,
sexual reproduction, in vitro fertilization, and cloning. His book
is an outstanding achievement. Silver addresses the uninitiated with
clear writing and straightforward explanations of complex phenomena,
but experts, especially ethicists and policy makers, will also profit
from reading this book. Any physician should find this book remarkable.
Silver analyzes the issues soberly, often with provocative examples.
Some of his cases are hypothetical; others are drawn from real life.
high point of the book is Silver's analysis of the treatment of
Anissa Ayala, a girl with acute myelogenous leukemia who received
a bone marrow transplant from her sister; the sister had been
deliberately conceived in the hope that her marrow would be histocompatible
with Anissa's. The new sister's marrow was indeed a match, and
five years later Anissa, now a hematopoietic chimera, appeared
to be cured. Silver's answer to prominent ethicists who strongly
objected to this procedure is simple: what's wrong with it when
the motive is love and affection? Who had the right to say that
Marissa, the new sister, would not be loved for herself as much
as Anissa? Silver's approach to ethical issues related to cloning
and in vitro fertilization is refreshing: no nonsense, no pontificating,
just the facts, just common sense. He makes his position clear
with the question, "Why is it that so many politicians seem to
care so much about cloning but so little about the welfare of
children in general?"
According to legend, 1000 years ago
King Canute tried to hold back the tides. Those who believe
that they can limit the progress of science or any
other branch of human knowledge will repeat Canute's
error. Barbara Tuchman's classic A Distant Mirror (New
York: Alfred A. Knopf, 1978) and a recent translation of Johan
Huizinga's magisterial The Autumn of the Middle Ages (Chicago:
University of Chicago Press, 1996) give us an extraordinary picture
of the superstition, ignorance, folly, and pestilence that
ruled Western Europe 500 years ago. Five hundred years later
we have arrived at Dolly, and there is no way of turning back.
Instead, the imperative is to use our knowledge with the compassion
advocated by Lee Silver. Gina Kolata is wrong when she emphasizes
that by producing Dolly, Wilmut was "breaking the laws of
nature." Nature's laws cannot be broken. What we must understand
is that Wilmut's feat revealed, rather than broke, the laws
of nature. The remarkable potential of this revelation is
a cause for hope, not despair.
Robert S. Schwartz, M.D.
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