Research Magazine > ARCHIVE > Summer
97 > Article
Cloning: Thoughts Evoked by the New Ewe
Possible uses of cloning*
by Dr. Ben Brackett, D.V.M., Ph.D.
Harvard, UGA College of Veterinary Medicine.
this year, the media were all aclamor over a lamb named "Dolly" and
the cloning experiment from whence she sprang. Dolly, born of an embryo whose
initial cell was the result of inserting the nucleus of a mammary cell from
an adult ewe into an egg cell, represented a scientific breakthrough:
This was the
first successful clone of a mammal from the cell of an adult of the species.
The media went wild. Not only did news reports and issues-oriented media
jump on the story, even comedians latched on. For weeks, you could hardly
the discussion: Now that science has cloned a sheep, they asked, would
be far behind?
All this hype generally ignored several important issues, not the least
of which is that the research that led to this development has been under
with little fanfare for decades. Not to understate Dolly's importance -
this is indeed a breakthrough - but scientists have long experimented with
of a nucleus from one biologic cell to another. This research may have
received less media attention than did Dolly, but its results have been
of great long-term
benefit and importance.
What is cloning?
Cloning has taken on airs of mystery in popular culture, but it is actually
a very simple concept. A clone is simply the progeny of an individual, produced
asexually. Biologists generally use the word cloning to refer to the production
of multiple genetically identical individuals, but the term is frequently
used in a more general sense, i.e., to refer to one or more such offspring.
Before Dolly, the state-of-the-art in cloning - in fact, the ultimate clone
in the sense of genetic identity - was identical twins (or triplets, etc.).
Identical twin cattle can result from splitting embryos under a microscope
and transferring them into recipient cows (usually two different cows) for
gestational development. This has been practiced extensively during the past
two decades. One of the major questions of developmental biology during the
past 50 years has been whether the genes of differentiated cells - such as
muscle, brain or mammary cells - can replace the nucleus of a fertilized egg
and lead to normal development. (While all differentiated cells contain the
entire complement of the organism's genetic code, some genes are suppressed
and others expressed during cell differentiation.)
To answer this, scientists have used a method known as "nuclear transplantation" or "nuclear
transfer. Because of the relatively large size of frog eggs, early experiments
dealt with amphibian cloning. Beginning in 1952, Robert Briggs and Thomas J.
King published a series of papers demonstrating that success as defined by
cloned frogs depends upon the proper transfer of nuclei obtained from very
young embryo donors. Similarly, mature nuclear transplant fish were reported,
and by 1981, Karl Illmensee and Peter C. Hoppe had produced live-born mice
following nuclear transplantation.
Nuclear transfer has been used in mammals as a valuable tool in embryological
studies and as a method for multiplication of "elite" bovine embryos.
About a decade ago, at least three biotechnology firms displayed serious interest
in offering embryo cloning commercially. This proved to be premature, since
procedures were unreliable, cumbersome and costly, and the resulting live calves
frequently have been larger than normal. Additionally, since the embryos cloned
were products of a dam and a sire, the calves were still a roll of the dice
Then, in 1996, the now famous Edinburgh team led by K.H.S. Campbell and Ian
Wilmut reported the birth of a lamb following nuclear transfer from an established
embryonic cell line. Scientists received this report with great excitement
since this approach should provide the same powerful opportunities for analyses
and modification of gene function in livestock that already were being accomplished
in mice. Thus, the stage was set for the ultimate experiment - the use of donor
nuclei from an adult for cloning.
At the annual meeting of the International Embryo Transfer Society in Nice,
France, in January, Campbell and Wilmut presented data on embryo-derived
cells and nuclear transfer. Although rumors were rampant, they did not openly
speak of the lamb "dolly" that had been born several months earlier
following transfer of the nucleus from a cell taken from a pregnant ewe's
mammary gland. The breakthrough involving the demonstration of cloning of
an adult was published in the Feb. 27, 1997, issue of Nature.
Scientists were excited upon hearing the good news of Dolly; the news media
and its consumers were overwhelmed. In spite of many obvious advantages for
cloning in research and animal production, the big question seemed to be, "When
will this be done with human beings?" Human cloning has become a subject
of major fascination. Public awareness of the new ewe has sparked creativity
around the planet as evidenced by a plethora of jokes, stories and speculations
regarding implementation of this new technology. Many countries already have
laws against artificial cloning of human beings and it seems likely that ours
will follow suit.
Most scientists would argue for maintaining the current system of regulation
involving institutional reviews of human experimentation. This system already
provides safeguards against abuse, and it also prevents inadvertent elimination
of potentially valuable research by excessive
Before fear of the new technology leads us to rattle legislative sabers, it's
important to understand that efforts to apply cloning technology to humans
is presently unthinkable. Remember that in the case of Dolly, 277 eggs were
fused with mammary epithelial nuclei and 29 recipient ewes were employed to
obtain one live lamb. The technology must be developed and procedures must
be improved to make feasible the application of cloning in animals.
Nevertheless, that technology can be - and should be - developed. In fact,
I believe that cloning of adult cattle can be anticipated sometime soon. The
progress with fetal cells recently announced by American Breeders Service illustrates
current efforts directed toward this goal. In this species it requires little
imagination to see benefits in elevating efficiency of milk and meat production
via transfer of reconstructed embryos known to be capable of expression of
the highest production traits.
At the same time, maintenance of genetic diversity, which is the normal result
of sexual reproduction, must remain of paramount importance. Without great
genetic diversity an entire species could easily be lost to a single devastating
disease. Rapid widespread use of cloning in the dairy industry could have severe
economic consequences. For instance, milk surpluses already plague the agricultural
economy. Through the years, farmers have suffered from successful innovations
in agriculture; this new technology holds the potential for exacerbation of
But these developments also should facilitate "gene targeting" in
livestock. This will enable the deletion of specific genes or alteration of
genetic traits in a controllable way involving selectivity of responding cells
prior to their use in cloning. Cloning now will allow multiplication of animals
for large-scale production of a variety of transgenic products, for example,
glycoprotein pharmaceuticals from milk, internal organs with altered antigenic
components and with complement inhibitor to fill the need for organ donation
for human patients.
Techniques of cloning offer an opportunity to study the possible persistence
and impact of epigenetic changes, which are external events that influence
genes. These include the duplication of genes during somatic cell development,
such as replacing skin cells, and the shortening of chromosome ends in aged
animals. Contributions of mitochondrial DNA can be better understood and used
to advantage. Additional uses and advantages include removal of genetic variation
in experiments, rapid production of inbred lines, copying small numbers of
animals with outstanding genetic composition for breeding and automatic sex
selection. If expense is no obstacle, it should even become possible to duplicate
the outward appearance of an aged pet.
Serious discussions of cloning have been initiated by the breakthrough published
by Wilmut and his colleagues at the Roslin Institute. With technological developments,
cloning should find valuable applications in animal industries and research.
Public awareness of developments in this, and other facets of science, is essential
for the appropriate handling of new technologies for the betterment of humankind.
For more information, e-mail Benjamin Brackett
Benjamin G. Brackett, D.V.M., Ph.D., is a professor
of physiology and pharmacology at the UGA College of Veterinary Medicine.
After his pioneering efforts with
rabbits and rhesus monkeys, Brackett was among the first researchers to work
with human in vitro fertilization. Essential to the development of test-tube
babies, in vitro fertilization involves removing eggs from a female, fertilizing
them in the laboratory, then returning the developed embryo to the female
for normal maturation and birth. Brackett's research led to the birth of
the first test-tube calf in 1981, and to the first test-tube billy goats,
Willy and Nilly, in 1993. This procedure could have major implications for
the development of therapeutic drugs and for animal breeding programs.
Possible Uses of Cloning
- increase milk and meat production in cattle
- remove genetic variation in experiments
- copy small numbers of animals with outstanding genetic traits for breeding
- produce theraputic drugs to treat cancer and other diseases
- make better formula for premature babies
- engineer animals to produce donor organs that would be less likely to
be rejected by human recipients
Return to Summer 1997 Index
Communications, Office of the VP for Research, UGA
For comments or for information please e-mail the editor: email@example.com
To contact the webmaster please email: firstname.lastname@example.org