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Animal Cloning: ...Old MacDonald's Farm Is Not What It Used To Be

Lauren Pecorino

articlehighlights

Cloning is seen by some in the same light as selective breeding of animals, with benefits that include:

  • food that is engineered to fight disease
  • preservation of endangered species
  • a good technology for biomedical research
  • enhancement of agricultural stock

September 2000

Although there has been limited success in cloning some animals, it’s still seen as a viable technology.
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The mule Idaho Gem (born May 4, 2003) was the first clone born in the horse family. Source: University of Idaho.

Ever since the announcement of the birth of Dolly three years ago, additional sheep, cows, goats, pigs and mice have been cloned. The desire to produce farm animals with outstanding and useful characteristics is ancient. One of the reasons that cloning is attractive is that it reduces the effort and time needed for farmers to do what they have been doing for years: selecting and propagating the best of the herd. Success with the technique, however, has not been easy in these animals (less than 2% efficiency) and barely achievable in other species such as chickens, monkeys and dogs.

The science behind the cloning

Dolly has the distinction of being not only the first cloned mammal but also the first to arrive by nuclear transfer.

The significance of the first cloned mammal, Dolly, was that for the first time cloning was achieved from an adult (differentiated) cell. To fully appreciate this point consider that normally, one cell, the fertilized egg, contains all of the information needed to multiply and give rise to all of the specialized cells in the body. It is important to remember that every cell in your body contains an identical set of genes. Cells turn on and off different genes as they become specialized (differentiated). For example, blood cells need the haemoglobin gene on while skins cells do not. In cloning, we are requiring that a differentiated cell (e.g. udder cell) reprograms or resets its genetic information so that it acts as a fertilized egg. Indeed, DNA-testing confirmed that Dolly originated from a differentiated udder cell. The technique used, nuclear transfer, involves removing the nucleus from an egg cell and replacing it with the nucleus from a differentiated cell. Although this procedure had been attempted for decades, Dr. Ian Wilmut and colleagues at the Roslin Institute in Scotland were able to create conditions that allowed the adult cell nucleus to reprogram its DNA, enabling their success with Dolly.

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Dolly was the first mammal to have been successfully cloned from an adult cell in 1996. Source: Wikimedia Commons.

Therefore Dolly answered a major biological question “Does the DNA of a cell become irreversibly modified as the cell becomes specialized and differentiates?” with a clear NO. The DNA of a cell that has developed to fulfill a specific function clearly can be reprogrammed to direct the development of a new individual. New questions of basic science are being posed: “How does the reprogramming occur?”, “What genes are involved in the control of this event?”, and “Can all adult cells be cloned?” (some evidence suggests not).

So far, most cloned animals die just before or after birth.

There are still obvious problems as evidenced from the numerous deaths of cloned animals that occur just before or after birth. The problems may be due to the experimental conditions under which the eggs are handled or may be an inherent problem that arises because these animals only have one parent. Normally, half the chromosomes of the new individual come from a sperm cell and half from an unfertilized egg but in a clone all of the genetic material (except mitochondrial DNA) comes from the donor nucleus.

What lies ahead

Cloning is a big first step. Genetic manipulation of cloned animals is the future direction of the cloning frontier. It is here that concerns are loudly voiced and take up headlines in the media. The public and the media’s views on the future of cloning often ignore some of its potential benefits:

Changing genetic traits is the next step in cloning - it can lead to medical benefits for animals as well as humans.
  • Agriculture and Drug Production: Not only can the best traits be perpetuated but farm animals could also be used as “machines” for large-scale production of medically important proteins. Polly, a transgenic cloned lamb, is an example. She is able to produce milk containing factor IX — the protein that is deficient in haemophiliacs.

  • Maintaining Biodiversity: Cloning may be an important tool for preserving endangered species if currently practiced methods fail.

  • Biomedical Research: Cloning can produce genetically identical laboratory animals which can be used as models for human disease. The most commonly used laboratory animal, the mouse, reproduces rapidly and its genetics have been well studied. Mice have been successfully cloned and will likely facilitate the discovery of new treatments for disease. Jean-Paul Renard, of the National Institute of Agricultural Research in France, is attempting to produce cloned transgenic rabbits to study cardiovascular disease in the hope of finding new treatments. In addition, it provides a model for studying the interaction of nuclear verses mitochondrial genes and for nuclear verses cytoplasmic factors.

  • Commercial Endeavours: Noting that no live dog clones have yet been reported, the company PerPETuate, Inc. (Connecticut) is freezing tissue from family pets for the future. Researchers have had little success in the steps required to make a dog clone, such as development after nuclear transfer and embryo implantation into the womb.

  • Treatment for Human Disease: Cells could be harvested from early embryos to provide cell and tissue replacement without the hazards of transplantation rejection. The U.K. government has recently accepted recommendations from its chief medical to permit research using embryos subject to controls, which include a 14-day limit (see the Department of Health website listed below in “learn more”).

Clones will not be carbon copies of the donor since environmental factors will influence their personalities.

To clone or not to clone humans

The cloning of human embryos for reproductive purposes is illegal at this time. Yet it is still important to examine the consequences and the likelihood of this scenario. The media may dream up and forecast robotic cloned armies of Hitler; however, identical twins illustrate that being genetically identical does not remove their humanness. Identical twins exhibit different personalities and behaviour because environment also plays a major role on who we become.

At any rate, there have been significant difficulties with cloning primates, including an extremely low success rate and a high number of abnormalities. These results make it unacceptable to attempt human cloning at this moment in time. The ethical and social issues that will arise in the future when more efficient methods are developed leave some time for a resolution. Some of the same issues that arose from in vitro fertilization will be revisited (e.g., infertile couples, “replacing” the death of an infant).

Conclusion

Cloning has opened many doors that could lead to remarkable medical advancements but, as with all new technologies, it will be accompanied by ethical and social dilemmas. Today’s successes will pave the road to improving efficiencies and help add to the basic understanding of our cells. Even Dolly’s creator, Ian Wilmut, is focusing less on sheep and more on understanding the mechanism of reprogramming our genetic material!

Dr. Lauren Pecorino received her Ph.D. in Cellular & Developmental Biology from the State University of New York at Stony Brook. She carried out a post-doctoral tenure as an EMBO Fellow at the Ludwig Institute for Cancer Research, London, England, working on limb regeneration. Currently, she is a Biochemistry Programme Leader at the University of Greenwich, U.K. Her most recent book is the student textbook Molecular Biology of Cancer Mechanisms, Targets, and Therapeutics (Oxford University Press, 2005).
http://www.gre.ac.uk/schools/science/staff/pecorino

Animal Cloning: ...Old MacDonald's Farm Is Not What It Used To Be

Primer on Ethics and Human Cloning

Dr. McGee offers ethical insights into human cloning on this web site.
http://www.actionbioscience.org/biotech/mcgee.html

The Cloning of Dolly

The site, Science Explained, provides an illustrated explanation of how Dolly was created. You can e-mail questions about Dolly to the author.
http://www.synapses.co.uk/science/clone.html

Cloning Ethics

Learn about some of the pros and cons of cloning.
http://www.allaboutpopularissues.org/cloning-ethics.htm

Department of Health, U.K.

Read about the U.K. (Dolly’s birthplace) view on cloning.
http://www.dh.gov.uk/Home/fs/en

“Cloning Noah’s Ark”

This article in Scientific American (11/00) is written by scientists who defend the use of cloning to save endangered species.
http://www.sciam.com/article.cfm?articleID=0002AB9E-F4AA-1C72-9B81809EC588EF21

Read a book

Cloning: For and Against (For and Against, V. 3) by M.L. Rantala and Arthur J. Milgram, Ph.D. (Editors), (Open Court Publishing Company; January 1999). This collection of 30 articles by scientists, ethicists, religious leaders, and legal experts explores the benefits and costs of cloning. Topics include: Playing God; Is Cloning the Salvation for Endangered Species?; No Need for Marriage; Can You Xerox a Soul?; and A Million Michael Jacksons. A lucid introduction offers readers an essential overview and understanding of the development and process of cloning, and the editors evenhandedly represent all sides of this controversial subject.

Do No Harm campaigns

Organized by The Coalition of Americans for Research Ethics, “a national coalition of researchers, health care professionals, bioethicists, legal professionals, and others dedicated to the promotion of scientific research and health care which does no harm to human life.”
http://www.stemcellresearch.org/

Medical Educators’ and Scientists’ Position

The American Society of Gene Therapy’s wants to keep cloning research legal in the U.S. Bottom of this petition page includes links to state-specific petitions.
http://www.asgt.org/

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Teaching Resources from the Northwest Association for Biomedical Research (NWABR)

The Northwest Association for Biomedical Research (NWABR) strengthens public trust in research through education and dialogue. Its diverse membership spans academic, industry, non-profit research institutes, health care, and voluntary health organizations. Through membership and extensive education programs, it fosters a shared commitment to the ethical conduct of research and ensures the vitality of the life sciences community.

Animals in Research
Through this curriculum, students are introduced to the complex topic of Animal Research using structured discussion, stakeholder activities, case studies, and the ethical frameworks used by those in support of, and in opposition to, this work. One of the goals of the curriculum is for students to support their own position on this issue through well-reasoned, fact-driven justifications in a classroom atmosphere of respectful dialogue.
http://www.nwabr.org/curriculum/animals-research
For the Greater Good
The “For the Greater Good” series is composed of five featured articles. Each article portrays one author’s personal stories of people and animals whose lives have been improved or saved by medical breakthroughs made possible by animal research. The Curriculum Guide includes a 5-lesson unit outlining the use of models in both science and ethics, and provides resources for exploring the use of animals in research.
http://www.nwabr.org/curriculum/greater-good

ActionBioscience.org original lesson

This lesson has been written by a science educator to specifically accompany the above article. It includes article content and extension questions, as well as activity handouts for different grade levels.

Lesson Title: Cloning Animals and Plants: Any Difference?
Levels: middle school, high school, undergraduate (year 1)
Summary: Depending on the grade level, students storyboard the history of famous animal clones, examine the differences between animal and plant cloning, experiment cloning a Coleus plant, design a controlled plant experiment … and more!

Download/view lesson.
(To open the lesson’s PDF file, you need Adobe Acrobat Reader free software.)

Useful links for educators

Useful links for student research

In addition to the links in the “learn more” section above:

  • » McLaren, A. 2000. “Cloning: Pathways to a pluripotent future,” Science 288:1775-1780.
  • » Roslin Institute’s transgenics and biotechnology page:
    http://www.roslin.ac.uk/research/animal.htm (accessed September 2000, URL no longer live) and its animal breeding page: http://www.roslin.ac.uk/research/transgenics.html . (accessed September 2000)**
  • » Wilmut, I., Schnieke, A.E., McWhir, J., Kind, A.J. and Campbell, K.H.S. 1997. “Viable offspring derived from fetal and adult mammalian cells,” Nature 385:810-813.
  • » __. “Can you clone your pet?” Lazaron BioTechnologies commercial information at http://store.yahoo.com/lazaronllc/cloningyourpet.html. (accessed September 2000)

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