ERIC ED467638: Cloning: Past, Present, and the Exciting Future. Breakthroughs in Bioscience.

14 Pages·1999·0.33 MB·English

by  ERIC

DOCUMENT RESUME
ED 467 638
SE 066 681
AUTHOR
Di Berardino, Marie A.
Cloning: Past, Present, and the Exciting Future.
TITLE
Breakthroughs in Bioscience.
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PUB DATE 1999-00-00
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DESCRIPTORS
Biology; *Biotechnology; Genetics; *Health; Science
Education; Technology
IDENTIFIERS *Cloning
ABSTRACT
This document explores the history of cloning by focusing on
Dolly the Sheep, one of the first large animal clonings. The disadvantages
and advantages of transgenic clones are discussed as well as the future
implications of cloning from the perspective of human health. (Contains 10
resources.)
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from the original document.
0,! Breakthroughs in Bioscience
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1
Cloning:
Past, Present,
and the
Exciting Future
by Marie A. Di Berardino, Ph.D.
BEST COPY AVAILABLE
2
This article is part of a series developed by the
Federation of American Societies for Experimental Biology (FASEB)
to educate the general public about the benefits of fundamental biomedical research
particularly how investment in such research leads to scientific progress,
improved health, and economic well-being.
©1999 by Federation of American Societies for Experimental Biology
COVER DESIGN BY ERIC J. PESANELLI
Breakthrough
Cloning: Past, Present, and the
Exciting Future
by Marie A. Di Berardino, Ph.D.
The not-too-distant
cessfully cloned from an adult cell,
the cell's nucleus and they carry the
one taken from a ewe's mammary
DNA, which is the genetic blueprint
future
gland.
for an individual.
The process that produced Dolly
Jimmy walks into the neighborhood
Nuclear transfer
differs from ordinary reproduction in
pharmacy to fill his prescription for a
two major ways. First, body (or
protein he was born without. He
Dolly was not created in the ordinary
somatic) cells from an adult ewe's
lacks the gene for blood clotting
way. Typically, a lamb is the product
udder (this is the donor) were placed
factor IX and relies on the local
of natural reproductiontwo germ
in a culture dish and allowed to grow.
drugstore for his medicine. Jimmy
cells, a sperm from an adult male and
The nutrients were then removed
pulls open the bag that contains his
an egg (oocyte) from an adult female,
from the culture, which stopped the
90-day supply of patches, removes
fuse at fertilization. Each of these
cells' growth. One of these non-
the old patch from his chest, and
germ cells (the sperm and the
growing cells was then fused (by
attaches a new one. He adjusts his
oocyte) contributes half the chromo-
electric jolts)' with another ewe's
jersey and heads out to meet his
somes needed to create a new indi-
oocyte from which the nucleus had
buddies for a game of touch football.
vidual. Chromosomes are found in
been previously removed (i.e.,
Even though he is hemophiliac, Jimmy
isn't worried about the bruises and
scrapes he is sure to get.
Similarly,
Sexual Reproduction (A) and Somatic Cell Nuclear Transfer (B) in Sheep
> Christine is scheduled to have her
A
B
Sheep Haploid Gametes
Body (somatic) cell
own genetically reprogrammed skin
Each cell with
cells transplanted to replace her
54 chromosomes
Oocyte
severely damaged heart cells.
(diploid)
> Margo, who has Parkinson's
Each haploid cell has
27 chromosomes
disease, receives special nerve cells.
She is not concerned about tissue
incompatibility and rejection,
because these cells are her own
Nuclear
genetically reprogrammed skin
transfer
Clone of
the body
cells.
cell
> Patients routinely buy anti-cancer
Enucleated oocyte. No
chromosomes, but a large
Fertilized egg has
or anti-viral drugs in large quanti-
amount of cytoplasm and
54 chromosomes
mitochondria
ties to treat their conditions.
(diploid)
Diploid = 52 autosomal chromosomes + 2 sex chromosomes
This is the future.
It is what Dolly so
Haploid = 26 autosomal chromosomes + 1 sex (Male Y or Female X) chromosome
wondrously has wrought. Born July
Chromosome = nuclear DNA molecule associated with proteins
1996, she is the first mammal suc-
Autosomal chromosome = a chromosome other than a sex chromosome
4
Federation of American Societies for Experimental Biology
Office of Public Affairs
enucleated, so it had no chromo-
somes). This procedure is known as
Dolly's Geneology and Offspring
`somatic cell nuclear transfer'.
Finn Dorset
yScottish Blackface
Within a day the fused cells began to
Dolly's Genetic y
Dolly's Mom
divide in the culture dish. After
.0,77
several divisions, the early embryo
Udder cell
was transferred to the uterus of a
Oocyte
donor
nucleus donor
surrogate mother and allowed to
develop.
Second, unlike the sperm and the
egg, each of which contributes half
the number of chromosomes at
Nuclear Transfer
fertilization, each body cell contains
twice the number of chromosomes in
each germ cell. So fusion of a sperm
and an egg forms an individual whose
full genetic composition is unique to
that individual. On the other hand, the
embryo cloned from somatic cell
nuclear transfer begins development
with the diploid (double) number of
chromosomes, all derived from one
somatic cell (adult udder) of a single
individual. This embryo has the same
Surrogate Mom
nuclear genetic composition as the
Scottish Blackface ewe
donor of the somatic cell.
David
Dolly
In the end, three sheep contributed
Welsh Mountain ram
Finn Dorset ewe
to the production of a single lamb
clone: a Finn Dorset sheep donated
her udder cells for culture; a Scottish
Blackface sheep donated the enucle-
Bonnie
ated oocyte (with its nucleus re-
from natural reproduction
moved, thus losing its own genetic
identity in the process); and a Scottish
Blackface sheep became the surrogate
Timeline
This illustrated timeline shows essential milestones in basic research that led to the cloning of Dolly and beyond, and some
benefits derived from that research. Some of the initial hypotheses have been refuted by later studies.
1 80s
1888
1901
Wilhelm Roux and August Weismann
Hans Spemann splits a 2-cell newt embryo
Wilhelm Roux performs the first test of the
independently propose the germ plasm
into two parts, successfully producing two
germ plasm theory: Destruction of one cell of
theory: The egg and sperm contribute
larvae.
the 2-cell frog embryo with a hot needle results
chromosomes equally to the zygote
in development of a half-embryo, supporting
(fertilized egg). The chromosomes are carriers
mistakenly the Roux-Weismann theory.
of the hereditary potentials, and the germ
2 Cell
1 Ceti
1894
cells (gametes) of the embryo are the only
Larvae
ones to carry the complete set of hereditary
Hans Dreisch isolates blastomeres of 2- and
potentials (nuclear determinants), whereas
4-cell embryos of sea urchins and observes
each somatic (body) cell type contains only
development of blastomeres into small but
part of these potentials required for the
complete larvae. These and other experi-
specific cell type.
ments disprove the Weismann-Roux theory.
2
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Breakthroughs in Bioscience
mother, carrying the embryo to birth.
ing `transgenic cells', or cells contain-
the sheep milk. Obviously, researchers
The clone (Dolly) was easily identified
ing a transferred gene.
still need to conduct controlled clinical
because she had the physical traits of
These transgenic cells were then
studies before this protein is available
the Finn Dorset sheep that donated the
separated from those without human
for hemophiliacs like Jimmy, but they
udder cells and differed from the traits
DNA and used to create Polly, the
have already made an astonishing
of the Scottish Blackface sheep used
transgenic sheep that today produces
breakthrough.
as the surrogate mother and the
the human clotting factor IX in her
oocyte donor.
milk. Purposely, scientists genetically
Traurusgenk cllones
And now Dolly herself is a
designed the transgenic sheep clones
The importance of the transgenic
motherthe old-fashioned wayby
so that the human gene would
clones is that biotechnology is now
mating with David, a Welsh mountain
function only in the mammary gland.
being extended to produce different
ram, and giving birth to Bonnie. In
It will soon be possible for the
human proteins like insulin (diabetes),
fact, Bonnie now has other siblings.
human clotting factor IX protein to be
interferon (viral infections), clotting
routinely harvested and purified from
Can Doll Ily hellp Ammy.
Christine, and Margo?
Making Transgenic Clones
Cell Culture
Imagine herds of female sheep, cattle,
Sheep Oocyte
Cells from
and goats producing large quantities
lamb fetus
of human proteins in their milk, an
ideal place for those proteins to be
harvested and used to treat patients
Transgenic cel
Some cells integrate
the human gene into
like Jimmy, the hemophiliac, whose
their chromosomes
blood cannot clot. We can realize
this dream todayone step at a time,
Enucleated
transgenic nucleus
Gene
call
added to oocyte without
for human
because the process that produced
nucleus
blood-clotting
factor IX added
Dolly also can be used to produce the
to culture plus
other regulatory
transgenic (one species carrying
DNA
another species' genes) clones.
Scottish scientists first removed
cells from a fetal lamb and grew them
Embryo develops
in a culture dish. Multiple copies of
fragments of DNA (deoxyribonucleic
acid, which holds genetic information)
containing the human gene for blood
clotting factor IX were added to the
glic:7 Implanted into
dish and coaxed into the cells. Some
sunogate mother
cells incorporated the human DNA
into their chromosomes, thus becom-
Polly: transgenic done
contains human gene for
doffing factor DC in her milk
19114
Spemann conducts early nuclear transfer. By using a strand of baby hair, he partially constricts a newly fertilized egg cell (zygote), forcing the
nucleus to one side and only cytoplasm to the other. As the nucleus side of the cell divides successively to the16-cell stage, a nucleus slips
over to the
cytoplasm on the other side. Cell division starts on this side also, and the hair knot is tightened, preventing further nuclear transfer. Twin larvae
develop, one slightly older (the side with the initial nucleus) than the other (the side with the initial cytoplasm). This proved that the nucleus from
a
16-cell stage could direct the growth of another larva.
a
o
3
Federation of American Societies for Experimental Biology
Office of Public Affairs
tural industry has intentionally
This cloning process simply acceler-
factor VIII (hemophilia), and tissue
propagatedby cloningbananas,
ates the older, slower, and less
plasminogen activator (dissolving
grapes, apples, sugar cane, pineapples,
predictable methods of crossbreeding
In other words, female
blood clots).
potatoes, asparagus, and many other
and hybridization.
clones of such animals as cattle,
plants. Identical twins and triplets
Strictly speaking, clones obtained
sheep, and goats are being genetically
that occur among many multicellular
from nuclear transfer are not exact
designed to be dairy/pharmaceutical
animal species including humans, are
copies of the donor. A clone like
producers, a virtual living bio-
derived by a cloning process. A cell,
Dolly produced by oocyte-somatic
pharmaceutical industry. Transgenic
cell fusion is a mosaica mixture of
isolated from other cells growing in a
clones of mammals are a major
culture dish, gives rise after cell
the oocyte and body cell. In addition
advance in biotechnology because
division to a clone. All these examples
to the nucleus, the donor cell contrib-
they can synthesize, in large quanti-
include the exact duplication of the
utes a tiny amount of cytoplasm and
ties, complex molecules critically
whole body cell, including the
nucleus, cytoplasm, and cell mem-
We are only beginning to understand the molecular
brane.
changes involved in nuclear reprogramming, yet this line
Why is this such a big
of basic research may result in some of the most beneficial
deal?
applications to humans. It might permit us to de-differenti-
ate mature cells and re-differentiate them into specific cell
Dolly has debunked a long-held,
generally accepted biological concept:
types required for tissue repair.
Adult cells have their fate sealed; put
another way, once an udder cell,
always an udder cell. This means that
cell membrane to the oocyte, but the
required for patient care. The current
the genetic status of the adult donor
egg cell contributes an enormous
recombinant DNA technology in
nucleus had to be reprogrammed, and
amount of cytoplasm and cell mem-
bacteria is capable of synthesizing
brane to the fused product. In fact,
that the oocyte cytoplasm seems to
only simple proteins, but not the
contain the appropriate molecules to
virtually all mitochondria (the or-
complex molecules that sheep can
trigger this reprogramming. The
ganelles in the cytoplasm that are the
produce in large quantities in their
value of cloning from an adult cell is
major source of cell energy and
milk. Indeed, Jimmy will be able to
that we can predict that the clone will
contain DNA of their own) are
wear his patch very soon.
be very much like the donor animal,
derived from the oocyte cytoplasm.
While these advances are on the
whereas we cannot do so when the
So cloning of multicellular organisms
horizon for us, beneficial applications
clone is derived from an embryonic or
is not equal to true cellular cloning
to agriculture are already being
fetal cell. Even when the parents of
that results from asexual reproduc-
implemented. Transgenic cloning can
embryos and fetuses are known, we
tion, when a one-celled organism like
be used for the genetic improvement
cannot yet foretell exactly the physical
the amoeba divides and clones itself.
of livestock related to milk produc-
traits of their offspring; they are a
Similarly, plants clone themselves
tion, quality of meat, growth rate,
combination of traits from both
when they reproduce by budding or
reproduction, nutrition, behavioral
parents. Additional variations occur
sprouting new shoots. The agricul-
traits, and/or resistance to diseases.
1962-65
1940s
1961-62
1950s
Robert G. McKinnell, Thomas J. King, and
John B. Gurdon and Robert G. McKinnell,
Various species of mammalian embryos are
Marie A. Di Berardino obtain swimming
by using the nuclear transfer method on
cloned by embryo splitting, but success is
larvae from enucleated oocytes injected with
different species of frog (Xenopus and Rana,
limited to splitting of embryos at stages prior to
adult frog kidney carcinoma cell nuclei. This
respectively), obtain adult frogs that
implantation to the uterus.
1952
demonstrates that some cancer cells can be
produced normal progeny. This demon-
controlled by the differentiation process, and
strates totipotency of embryonic nuclei.
Robert Briggs and Thomas J. King transplant a
that inducing cancer cells to differentiate may
nucleus from a frog embryo somatic cell into an
stop the cancer process.
unfertilized, enucleated oocyte. These injected
eggs developed into tadpoles and many metamor-
phosed into juvenile frogs. This technique,
nuclear transplantation (nuclear transfer)
becomes the prototype experiment for cloning
multicellular organisms.
4
7
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Breakthroughs In Biosdence
transplanted, the more likely it is that
organs of an adult. These studies
because, during the maturation of the
showed that frogs, salamanders,
the injected oocyte will develop
parents' sperm and egg before
abnormally. In fact, only a few
insects, fish, and mammals (mice,
fertilization, the genes are randomly
tadpole nuclei from frogs have been
rats, rabbits, pigs, goats, cattle, and
distributed to sperm and egg cells.
shown to be totipotent, and those may
sheep) could be produced by this
Thus, offspring cloned from adult
process. Furthermore, many of these
have come from immature cells.
cells are more similar to their donor
When fully differentiated cell types
species were fertile. (The only
than are offspring that result from
(pigment, skin, red and white blood
primates to have been cloned by
sexual reproduction, i.e., a combina-
cells) from adult frogs were used as
nuclear transfer thus far are two
tion of sperm and egg. There is,
donors, their nuclei gave rise to
Rhesus monkeys produced from the
however, no guarantee that an exact
tadpoles but not to fertile frogs. In
nuclei of an eight-cell stage embryo.)
copy will evolve, because variations in
mammals, very few fetal cell nuclei
the physical traits of the donor may
(approximately 0.3-2%) from sheep
result from environmental influences
IT1,777::.`71TS,.
and cattle led to the normal develop-
during pre- and postnatal development
ment of living newborn animals.
and, in some cases, from the mito-
Reprogramming Gene Function
Dolly, produced from an adult cell,
chondrial DNA of the oocyte.
Enucleated oocyte and
represents only a 0.2% cloning
cytoplasmic proteins
Totipotency
success. The inability to clone most
Body cell (somatic) -
nucleus donor and
nuclei from advanced stages probably
nuclear proteins
Animal cloning began more than a
results from protein changes that
century ago when scientists wondered
occurr in the chromosomes during
how an initially formless mass of
cell differentiation, changes that will
cells, the blastocyst, develops into a
have to be identified and controlled in
Chromosomes
structured organism composed of
the future.
separate skin cells, blood cells, muscle
cells, brain cells, stomach cells, and
Genetic repr gramming
so on. They specifically wanted to
know whether these many different
Scientists found that cloning actually
cell types were irreversible or whether
reprograms nuclear function and
these differentiated cells could reverse
returns some nuclei to an undifferenti-
and express again the totipotency of
ated state. This discovery followed a
the early embryo.
line of basic research that may result
Early Embryonic Cells Are Totipo-
in some of the most beneficial applica-
Nuclear transfer product
tentBy using an early version of the
tions to humans.
nuclear transfer technique in their
Soon after a nucleus is transferred
ninzafiftWii
MWstaligtifftegrinila
AU,
initial studies, scientists established
to an egg, there occurs a two-way
Few Nuclei Remain Totipotent
that nuclei from early embryonic cells
transfer of specific proteins between
throughout DevelopmentScientists
were indeed totipotent; that is, they
the nucleus and cytoplasm. This
now know that the older the donor
could develop into complete fertile
transfer causes modifications in
cell from which the nucleus is
organisms, with all the cell types and
chromosomal proteins, resulting in
1983
19154
James McGrath and Davor Solter develop
By using nuclear transfer, researchers obtain
F.C. Steward grows a complete carrot plant
nuclear transfer technology for mammalian
pre-feeding larvae from nuclei of differenti-
from fully differentiated carrot root cell.
embryos. Fertile mice were obtained when a
ated frog skin (J.B. Gurdon, R.A. Laskey,
This and the previous amphibian experi-
nucleus surrounded by minute amount of
O.R. Reeves) and lymphocytes (M.R.Wabl,
ments led some scientists to believe that
cytoplasm from a 1-stage fertilized egg was
R.B. Brun, and L. Du Pasquier).
cloning from differentiated animal cells was
fused with another enucleated fertilized egg.
possible.
1986
EXPERIMENT
RESULT
Tadpole
CNo division
Intestinal cell
nucleus insettec,
Intestinal
nucleus
John B. Gurdon and V. Uehlinger succeed in
into irradiated oocyte
Abnormal embryo
Oocyte
growing adult frogs from injection of tadpole
41:1)
.111.Tadpole (dies)
Jvv,
UV irradiation
intestinal cell nuclei into enucleated oocytes.
destroys oocyte
chromosomes Irradiated recipient
oocyte
5
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Federation of American Societies for Experimental Biology
nuclear DNA synthesis, and later in
In Hawaii, 17 months after the
muscle rigidity and tremors in
the expression of a new set of genes.
announcement of Dolly's birth, 31
parkinsonian rats were improved
These and other changes reflect
mice were cloned from cumulus cells
by transplanting cloned transgenic
reprogramming of nuclear function by
(i.e., cells that surround the develop-
bovine neurons into their brains.
chemicals in the oocyte cytoplasm.
ing oocytes in the ovaries), confirm-
This research, called
When investigators identify the role of
ing successful cloning from adult
xenotransplantation, is one of the
these proteins, we will understand
cells. Ten of these clones have
many avenues being pursued in an
how to convert,a nucleus from a
themselves produced normal progeny,
attempt to alleviate the desperate
differentiated adult cell type into one
and some of the 31 clones themselves
shortage of human tissues for
that is relatively immature. This might
came from clones, demonstrating the
transplantation.
permit us to actually reprogram
feasibility of augmenting the number
> Domestic animals can be geneti-
mature cells and turn them into
of clones. In December 1998, eight
cally designed to express a certain
specific cell types required for tissue
calves were cloned from a single adult
human disease and therefore serve
repair. By doing this, we could
cow's cumulus and oviductal cells
as models for the study and
potentially replace damaged heart or
(cells lining the tubes of the oviduct
treatment of human illnesses.
brain cells by reprogramming the
that transport oocytes to the uterus).
Although many mouse models of
patients' own skin cells into heart
These studies showed that not only
human diseases are available today,
muscle cells and nerve cells (for
adult cells could be reprogrammed,
such models in large domestic
people like Christine and Margo).
but also that some differentiated cells
animals physiologically more
(such as cumulus and oviductal cells)
similar to humans are sparse and
Dolly is
nily the firsti
had the same capability. Keep in mind
critically needed.
that not all adult cells are differenti-
Dolly is no longer unique, although
> Somatic cell nuclear transfer might
ated; for example, undifferentiated
she always will be the first animal
help preserve endangered species
cells are found in bone marrow, the
cloned from an adult cell. Being the
such as pandas that have low
intestinal lining, etc., of adults.
result of a nuclear transfer between an
reproductive rates.
adult ewe udder cell and an enucleated
Direct advantages
oocyte, she showed that an adult
[Indirect advantages
mammalian cell could be repro-
Transgenic clones can be directly
grammed genetically to be totipotent
Two other significant gains from
beneficial to humans, other animals,
and give rise to an entire individual
clones are worth mentioning.
and agriculture in additional ways.
that grew to maturity and gave birth
First, inducing cancer cells to
> They may be developed for tissue
to offspring of her own. Soon after
differentiate is a useful type of
and organ transplantation. Al-
Dolly was born, a set of triplet
therapy. We know that many types of
though not yet a reality, there is
transgenic calves bearing a foreign
cancer cells are less specialized than
promise that large animals can be
gene was cloned from fetal cells, all
their normal counterparts. For this
genetically designed and cloned so
sharing the same nuclear genes. This
reason investigators suspected that the
that their tissues and organs will
indicates the feasibility of producing
precursors of cancer cells could be
not trigger immunological re-
herds of sheep and cattle capable of
immature cells or stem cells that fail
sponses in the recipient and cause
producing the same protein.
to complete differentiation. If this is
them to be rejected. Recently,
19 3° 6
19 6
Marie A. Di Berardino, Nancy H. Orr, and Robert McKinnell obtain pre-feeding and feeding
Steen Willadsen clones lambs by fusing a
tadpoles from transplanting nuclei of adult frog erythrocytes (unlike humans, frog mature red
nucleus of an 8-cell embryo to enucleated
blood cells contain nuclei).
oocyte. An electrical impulse usually was
used for the oocyte fusion and activation
Rana
1st Meiotic
Activate + Enucleate
process. Other researchers subsequently
Erythrocytes
Metaphase
Matured Oocytes
Blastulae
Larva
succeeded in producing full-term cattle,
Oocytes
-DANN.
sheep, pigs, goats, and rats by using a similar
approach, as long as the blastomere nuclei
Enucleated
41
Dissociated
Egg
were obtained from embryos prior to
Blastula
Cells
4011110 -
implantation.
6
9
Breakthroughs in Bioscience
http://www.faseb.org/opar
chromosomes and others with
active ones. If we could isolate these
so, then by using information gained
abnormal ones. So far, the pros-
substances, we might be able to
from nuclear transfer technology, we
alleviateor reversesenescence.
pects for identifying an abnormal
may be able to induce the cells to
embryo prior to transfer to the
mature and stop making tumors.
Perlis
uterus are poor.
Previous studies have demonstrated
that we can control at least some
And there are other scientific con-
Although Dolly, mice, and calves have
cancer cells by using the differentia-
cerns:
been the first animals cloned from
tion process.
> the life span of the clone is un-
adult cells, the low efficiency in
Second, aged cell nuclei can be
known, as is
producing them negates attempts to
rejuvenated. People and other organ-
> the compatibility between the
clone humans. The Dolly experiment
isms change as they age. Environ-
genetic products in the cytoplasm
began with 434 attempts to fuse a
mental insults and diseases cause these
of the oocyte and the donor cell,
mammary gland cell to an oocyte, and
and
ended with only a 0.2% success rate;
If we could isolate these
the remaining attempts resulted in
> during the normal process of
substances, we might be
death either during fusion or in
sexual reproduction, there is a
various developmental stages. More-
able to alleviateor re-
natural selection of the fittest germ
over, the 1-2% success rate with
cells in fertilization. Although this
versesenescence.
mouse and 1-5% with calf cloning
process is not perfect (i.e., it fails
from adult cells are equally low. And
to eliminate some harmful muta-
high frequency of fetal (approximately
changes; others are intrinsic to the
tions), it does not exist in cloning.
60%) and neonatal (approximately
organism. Studies using cell culture
So we can see that it is unlikely that
50%) deaths are common. In a real
have shown that body cells grow and
cloning of a human being from any
sense, cloning is a roulette game.
divide normally in culture for awhile,
donor age will happen any time soon.
Even if cloning from adult cells did
but eventually stop dividing, become
Indeed, the scientific community was
become efficient, there still would be
senescent, and die. An exception was
so strongly opposed to the production
serious hazards.
seen in aged frog red blood cell nuclei
of a human being by cloning tech-
> Donor cells could suffer mutations
(human red blood cells lack nuclei):
niques that the Federation of Ameri-
from radiation, chemicals, aging,
After their transfer into enucleated
can Societies for Experimental Biology
and/or errors in DNA replication
oocytes, frog red blood cell nuclei
and other professional organizations
during the lifetime of the donor,
were rejuvenated. They carried out the
representing more than 67,000
which would be transferred to the
formation of tadpoles that survived
scientists have issued a voluntary
clone.
almost a third of the way to metamor-
moratorium against such an act. The
phosis. The oocyte cytoplasm contains
> Mutations could arise in donor cells
groups endorsing this position in-
an abundance of chemicals that
during cell culture, not an unusual
cluded those scientists most capable
promote DNA synthesis and cell
event, and there is no way of
of performing this type of work.
division after normal fertilization. We
distinguishing a normal donor cell
Although these scientists believe
believe that these substances also
from a mutant one.
that cloning a human being is unethi-
rejuvenate aged cell nuclei and turn
cal and reprehensible, they are still
> The embryo may be a mosaic of
non-cycling frog red blood cells into
concerned that some of the anti-
cells, some with apparently normal
1993
1998
1997
The Honolulu group, led by Teruhiko
M. Sims and N.L. First report for the first
Dolly, the first mammal cloned from an adult
Wakayama, reported the production of a
time production of calves by transfer of
cell, is produced in Scotland. Ian Wilmut and
large number of live mice from injecting
colleagues report the birth of a lamb derived
nuclei from cultured embryonic cells.
nuclei taken from adult ovarian cells into
from the transfer of a nucleus obtained from
enucleated oocytes. These investigators also
an adult ewe udder cell into an enucleated
report success in recloning efficiently the
oocyte that was then implanted into a
first clones.
surrogate mother.
The Japanese group, led by Yoko Kato,
Primate cloning: Two Rhesus monkeys
are the first and only primates thus far
produced eight calves from cumulus and
oviductal cells derived from one adult donor.
cloned by nuclear transfer from the 8-cell
stageDon Wolf's laboratory at Oregon
Regional Primate Research Center.
7
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