HUMAN CLONING : ETHICAL ISSUES

ETHICAL ISSUES
UNITED NATIONS EDUCATIONAL, SCIENTIFIC AND
H
C UMAN
UL
CLONING
TURAL ORGANIZATION

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HUMAN
CLONING
ETHICAL ISSUES
UNITED NATIONS EDUCATIONAL, SCIENTIFIC AND CULTURAL ORGANIZATION

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Graphic design (brochure): Jérôme Lo Monaco
Graphic design (cover): Marion Lo Monaco
Photo credits:
Page 8
Image of Nuclear Transfer, Roslin Institute
Page 9
Cloned Sheep “Dolly” and its Surrogate Mother, Roslin Institute
Page 10
Cloned Cat “CC”, Texas A&M University, College of Veterinary medicine
Cloned Mice, University of Hawaii
Cloned Mule “Idaho Gem”, Phil Schofield/University of Idaho
Cloned Calves, University of Tennessee
Cloned Pigs, Revivicor, Inc. (formerly PPL Therapeutics, Inc.), Blacksburg, Virginia
Cloned Rabbits by Jean-Paul Renard research team, INRA/Bertrand Nicolas
Illustrations: Jérôme Lo Monaco
Further information:
Secretariat of the Bioethics Section
Division of Ethics of Science and Technology
Social and Human Sciences Sector
United Nations Educational, Scientific and Cultural Organization (UNESCO)
1, rue Miollis, 75732 Paris Cedex 15, France
Tel. 33 (0)1 45 68 37 81
Fax. 33 (0)1 45 68 55 15
http://www.unesco.org/bioethics
First published in 2004 by the United Nations Educational, Scientific and Cultural Organization
Second edition, updated, 2005
7, place de Fontenoy F-75352 Paris 07 SP
© UNESCO 2005
Printed in France
HUMAN CLONING

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C
O
N
T
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N
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S
Preface by the Director-General
5
A Brief History of Cloning
7
Recent Development of Cloning Research on Animals
10
What are the Ethical Issues regarding Human Cloning?
11
Is Research Cloning different from Reproductive Cloning?
12
Can Adult Stem Cells replace Embryonic Stem Cells?
15
Cloning and the International Community
17
Ongoing Discussion on Ethical Issues
19
Further Reading and Useful Resources
19
HUMAN CLONING

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P
R
E
F
A
C
E
In this new century, there has been no slackening of the pace of scientific research and discovery.
Academic publications and the mass media inform us, virtually on a daily basis, of new and
profound discoveries that seem to probe further than was ever believed possible, penetrating
to the very core of the universe and unveiling the essence of what constitutes human beings.
Few discoveries exemplify these sweeping developments more than cloning – the laboratory-aided
replication of a strand of DNA that is used to produce an identical being. Suddenly, concepts and
practices that just a generation or two ago would have been relegated to the realms of science
fiction are fast becoming reality.
However, with such rapid scientific progress come reflection and often concern about its proper
use. The question constantly arises as to how far the practice of cloning should be allowed to
proceed.
Some ethical guidelines have been successfully established by the international community through
the Universal Declaration on the Human Genome and Human Rights, adopted by UNESCO’s
General Conference in 1997 and endorsed by the United Nations General Assembly the following
year. This document delves into the heart of the matter when it asserts that human life has
an intrinsic value. It further states that “practices which are contrary to human dignity, such
as reproductive cloning of human beings, shall not be permitted”.
While each nation must determine for its society the proper limits to set on cloning, much can be
gained from discussion and reflection at the international level. Understandably, it has been
decision-makers, scientists and bioethicists who have assumed a leading role in the discussions
relating to cloning and the profound ethical questions that it poses for humanity. However,
other bodies of opinion, including the public at large, also have a major stake in a wider ethical
debate and they often wish to know more.
It is up to UNESCO, custodian of an ethical mandate that remains unique within the United
Nations system, to continue being vigilant on this matter, to monitor the direction in which
research is going and to provide governments, policy-makers, the scientific community and the
general public with the accurate, reliable information they require when making decisions about
cloning. It is also the role of the Organization to work with all the relevant stakeholders and assist
them in reconciling rapid developments in science with the ethical values we all cherish.
This is why I am pleased to present this explanatory brochure, which outlines the main phases of
development of the cloning sciences and describes the efforts that have been made to make sense
of what may be a vast new frontier for the biological sciences.
Koïchiro Matsuura
Director-General of UNESCO
HUMAN CLONING
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A BRIEF HISTORY OF CLONING
Cloning may seem to be a relatively recent laboratory phenomenon, but the word itself derives
from antiquity: the Greek word klwn for “twig”. Initial use of the term applied to early 20th
century botany, designating plant grafts. “Clone” eventually came to be used for micro-organisms
as well. Then, by the 1970s, the word came to designate a viable human or animal generated from
a single parent. Over the last few years, cloning has come to mean any artificial, identical genetic
copy of an existing life form. How is cloning different from natural reproduction? Many organisms
including human beings result from sexual reproduction. That is, the female egg is fertilized by
the male sperm, and an embryo forms (fig.1). The embryo’s genetic structure, those pairs of
chemicals, which determine human characteristics, is located in the chromosomes1 found in the
nucleus of every embryonic cell. The new organism obtains one half of its genes from the mother’s
egg and the other half from the father’s sperm.
In cloning by nuclear transfer, on the other hand, the egg nucleus is removed through a microscopic
1 chromosome – A threadlike
laboratory procedure and replaced with a donor’s nucleus, containing the unique genes of that individual.
structure several to many
of which are found in the
nucleus of plant and animal
(eukaryotic) cells.
Chromosomes are composed
of chromatin and carry the
genes in a linear sequence;
A sperm
these determine the individual
enters an egg
characteristics of an organism.
A Dictionary of Biology.
Oxford University Press, 2000.
Oxford Reference Online.
Oxford University Press.
10 October 2003
Fertilization :
<http://www.oxfordreference.co
The nucleus
m/views/ENTRY.html?subview=
of the sperm
Main&entry=t6.000855>
The embryo starts
and the egg fuse
to develop
Blastocyst
into many cells
Fetus
FIG.1 : DEVELOPMENT OF AN EMBRYO
HUMAN CLONING
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Photo 1. Image of Nuclear Transfer:
The egg, which grows into an embryo, therefore contains only
The nucleus of the egg is removed
the donor's genes (photo 1). The cloned organism is a near
through a microscopic laboratory
genetic copy of its sole “parent”, (0.05% to 0.1% of genes are
procedure and replaced
carried by cytoplasmic2 components such as mitochondria3)
with the nucleus of a donor cell
rather than a random genetic combination of two parents.
The pioneer era of cloning dates to 1952 with the work of
biologists Robert Briggs and Thomas King in Philadelphia.
2 cytoplasm – the jelly-like
Scientists already knew about natural cloning in some forms
substance that surrounds
of invertebrates (organisms without a spinal structure). For
the nucleus of a cell.
example, an earthworm divided in two could regenerate into a complete individual. But cloning
Concise Medical Dictionary.
Oxford University Press, 2002. Oxford
vertebrates through human intervention seemed far more complex. Briggs and King decided to
Reference Online.
experiment on the frog species. They approached their task by using “somatic cell nuclear transfer”, a
Oxford University Press.
method first theorized in its rudiments in the 1930s by German embryologist Hans Spemann, who had
10 October 2003
done laboratory work on salamanders. This procedure involves removing the nucleus of a somatic cell4
<http://www.oxfordreference.com/
views/ENTRY.html?subview=
and inserting it into an “enucleated”5 unfertilized egg cell (fig. 2).
Main&entry=t60.002431>
3 mitochondrion – (chondriosome) n. (pl.
mitochondria) a structure,
occurring in varying numbers in the
cytoplasm of every cell, that is the site of
the cell's energy
production. Mitochondria contain ATP
and the enzymes involved
Unfertilized egg
Somatic
in the cell's metabolic activities,
cell
and also their own DNA;
mitochondrial genes (which in
humans encode 13 proteins) are inhe-
rited through the female line. Each
mitochondrion is
bounded by a double membrane,
the inner being folded inwards
to form projections (cristae).
Concise Medical Dictionary.
Oxford University Press, 2002.
Oxford Reference Online.
Oxford University Press.
10 October 2003
<http://www.oxfordreference.com/view
The nucleus
s/ENTRY.html?subview=
The nucleus
of the egg
Main&entry=t60.006317>
of a somatic cell
is removed
is taken out
4 somatic cell – any cell of an
organism other than
the reproductive cells.
The Concise Oxford Dictionary. Oxford
University Press, 2001. Oxford
The nucleus
Reference Online.
of the somatic cell
Oxford University Press.
is inserted into the
11 October 2003
enucleated egg
<http://www.oxfordreference.com/view
s/ENTRY.html?subview=
Main&entry=t23.053122>
5enucleate – remove
the nucleus from (a cell).
Clone
The Concise Oxford Dictionary. Oxford
embryo
University Press, 2001. Oxford
Reference Online.
Oxford University Press.
10 October 2003
<http://www.oxfordreference.com/
views/ENTRY.html?
subview=Main&entry=t23.018458>
Fig.2 :CLONING BY SOMATIC CELL NUCLEAR TRANSFER (SCNT)
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HUMAN CLONING

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The transplanted nucleus then begins to divide and multiply, as in a normal cell, while retaining its
unique genetic identity. When Briggs and King first succeeded in cloning tadpoles, they transferred
embryo cell nuclei into enucleated eggs. However, when they used nuclei derived from more advanced
cells, the survival rate of the nuclear transplant embryos decreased. It suggested that as embryos
develop to differentiated cells, an irreversible change would occur in genes and they could not be
reactivated. If so, it would be impossible to create a clone, a genetic copy of an adult animal, using
its somatic cell. It was in the 1970s that this theory was reversed when British biologist John Gurdon
successfully cloned a tadpole from a somatic cell proving that a
Photo 2. The world’s first cloned
developed embryo or differentiated cells can be reactivated and
mammal; Dolly the sheep (left)
can produce a new life.
and its surrogate mother (right)
To accomplish the same feat on mammals, however, appeared a
quantum leap since cloning a mammal involves technically more
complicated procedures than with amphibians. In particular,
collecting mammalian eggs is harder than frog eggs since they are
much fewer and require invasive procedures to remove. Cloned
embryos must then be transplanted into a womb and result in a
pregnancy in order to reproduce a mammal clone. Thus, for
many years, cloning in more complex species, such as mammals,
appeared a remote possibility and remained largely of interest
only to the scientific community.
But that situation changed abruptly in early 1997 when a Scottish team announced the birth in the
previous year of Dolly, a lamb cloned from an adult sheep (photo 2). This biological breakthrough earned
Unfertilized egg
Somatic cell
Enucleated
egg
The nucleus
The nucleus from
of the egg is removed
the somatic cell
A clone embryo is created by fusing
is taken out
the nucleus of the somatic cell
with the enucleated egg
The embryo is
implanted into
the womb of
a surrogate
mother
A lamb carrying the same genes as
the donor of the somatic cell
nucleus is born
FIG.3 : REPRODUCTIVE CLONING OF SHEEP
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front-page attention around the globe and seemed to open the perspective of a new biomedical world,
fraught with consequences. Dolly’s birth was engineered by veterinary researcher Dr Ian Wilmut and
his colleagues at the Roslin Institute, and their achievement shattered the belief that adult mammal cells
could not be used to re-create a genetic copy. Wilmut’s group in Edinburgh employed an updated
version of the Briggs-King technology, subsequently refined by British biologist John Gurdon.
To create Dolly, Wilmut’s group used the nucleus of a “quiescent” mammary cell from a white Finn
Dorset sheep, that is, a cell that had stopped dividing when it was previously deprived of nutrients.
Next, the nucleus was implanted through the protective zona pellucida into an enucleated oocyte
(unfertilized egg) from a Scottish Blackface ewe, and a minute electric charge helped it fuse with the
oocyte’s cytoplasm. After many failed attempts, the researchers managed to obtain an egg cell that
began dividing normally, and this was implanted into the surrogate Scottish Blackface mother. After
a normal gestation period of about five months, Dolly was born (fig.3). Genetic tests proved her to
be a clone, and Dolly became an international icon.
RECENT DEVELOPMENT
OF CLONING RESEARCH ON ANIMALS
Since Dolly, the cloning of several mammal species has resulted in many live births. Pigs, sheep,
cows, cats, rodents and, most recently, a mule have been successfully cloned (but not yet dogs or
Photo 3 :
monkeys) (photo 3). The cloned mule gained some special attention since
Cloned cat CC:
that species — a hybrid of a horse and a donkey — is normally sterile.
The first cloned cat CC has quite
Interestingly, cloning does not always result in a visual lookalike, as in
a different character and fur
colouring from its gene donor
the case of a common house cat cloned in 2001 with fur colour different from
its gene donor. Several genes situated in the X chromosome are involved in cat
fur colouring, and some of these genes are randomly inactivated during
embryo development for female cats, since they have two X chromosomes.
Cloned mule:
Therefore, even derived from a same donor, some cells will produce a black
“Idaho Gem”, first cloned animal
coat if the other colouring genes are suppressed, and others will result in an
in the horse family
orange coat when inserted into an enucleated egg and developed to a kitten.
The main purpose behind developing animal cloning techniques is to facilitate
the genetic engineering of animals. Traditionally, new DNA for modifying animal
genes can be inserted only into very young embryos, usually at the 1- or 2-cell
stage. But whether these genes are incorporated into the embryos is determined
Cloned pigs:
purely by chance. Thus, the success rate is very low and the procedure time-
Some research focuses on pig
consuming. With cloning techniques, the DNA is added to dish-cultured cells
clones as organ suppliers for
by the thousands or millions. It then becomes feasible to detect which cells
human transplants
have incorporated the inserted DNA. Then, technicians can transfer the
nucleus of such cells to enucleated egg cells to produce embryos, which
Three generations
of mice created by cloning
contain modified DNA.
Therefore, animal cloning would also interest some food and drug industries
if it could result in consistently high-quality, marketable products such as milk or
meat or, with genetic engineering, if it could generate therapeutic proteins from
Cloned calves:
goat or cow milk or chicken egg whites (commonly called “pharming”), or even
Ten cloned calves of a single adult
pig organs transplantable to humans without immune rejections. One biotech
Jersey cow were born alive
company, PPL Therapeutics, Inc., working with the Roslin Institute, cloned
“Polly” in 1997, a sheep produced from an embryonic cell that had been
genetically transformed. Polly secretes a human blood-clotting protein in
Cloned rabbit:
her milk, useful for treating haemophilia. International standards for regulating
Cloned rabbits and other cloned
such a technique have not been established, and various non-human cloning efforts
animals may be useful
have sprouted here and there.
to investigate the causes
of human diseases
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HUMAN CLONING

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News of successfully cloned animals has caught public attention, but scientists are far from perfectly
controlling the results. Success rates for producing cloned embryos depend on the species and types of
cells used, but they remain generally very low. Even with a successful birth, a wide range of
abnormalities and defects are observed in cloned animals, among them, one known as Large
Offspring Syndrome (LOS). Cloned animals are often too large for normal delivery, and the placenta has
grown abnormally.
Such defects are not yet fully explained, but one possibility is that a nucleus removed from a somatic
cell may not be properly reprogrammed to develop into a normal offspring. According to some, such
cloning technique flaws will be resolved as research progresses. Others argue that cloning a perfectly
healthy offspring is ultimately impossible and that even apparently healthy cloned animals may contain
genetic defects.
WHAT ARE THE ETHICAL ISSUES
REGARDING HUMAN CLONING?
The possibility of human cloning has long fired the popular imagination, including in the world of
popular entertainment. For example, a thriller novel, The Boys from Brazil, subsequently made into
a 1978 Hollywood film, depicted a Nazi war criminal who raises a colony of young Hitler “clones”. For
many others, cloning implied overtones of human immortality or of assembly-line eugenics. Hoaxes,
wild claims and media speculation have inevitably intruded into the cloning discussion, sometimes
originating more in pure science fiction than actual scientific experiments. Dolly gave added impetus
to talk — and concern — about human cloning.
The cloning debate involves scientists, legislators, religious leaders, philosophers and international
organizations, but not always harmoniously. General agreement, if not absolute unanimity, evolved
that human “reproductive” cloning — for the purposes of producing a human genetic-copy baby —
is unethical. Wilmut himself explained to the United States Congress that cloning a mammal involved a
high failure rate, since of his 277 “reconstructed” embryos, only 29 were implanted in ewes and only
one developed successfully. “Similar experiments with humans
would be totally unacceptable”, Wilmut concluded.
Box 1: Ethical Issues
regarding Human
The high failure rates (more than 90 per cent) and high morbidity of
Reproductive Cloning
•Technical and medical safety
animal cloning strongly suggests its inapplicability to humans.
• Undermining the concept
Furthermore, cloned animals seem to suffer high deformity and
of reproduction and family
disability rates. Dolly herself was finally put down in 2003, at
• Ambiguous relations of
the age of just six and a half years, even though many sheep live
a cloned child with the
more than 10 years. She had developed a progressive lung disease,
progenitor
which is usually found in older sheep, as well as premature
• Confusing personal identity
arthritis. Some cloning experts have consequently hypothesized
and harming the psychological
that cloned humans might need hip replacement surgery while
development of a clone
still adolescents and might suffer from senility by the age of 20.
• Concerns about eugenics
• Contrary to Human Dignity
The ethical ramifications of cloning, especially with regard to
• Promoting trends towards
humans, seem to defy easy limitation. Even if cloning technique
designer babies and human
problems are resolved with time, many questions remain. On
enhancement
what grounds could reproducing children by cloning be allowed
or prohibited? Should cloning be used for sterile couples or for
homosexual couples who want biological offspring? How would a child born by asexual reproduction
experience life, as a unique individual or as a genetic “prisoner”? Is a cloned child simply a twin of its
genetic donor, with a certain time lag? Should parents choose the traits of a future child, as is possible
with cloning? Those and other such issues now preoccupy scientists and bioethicists who see in cloning
procedures the potential to endanger human identity (Box 1).
HUMAN CLONING
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