The mammal copiers – advances in cloningThe cloning of Dolly the sheep has stimulated discussion on the benefits and risks of the development of cloning techniques.
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Back to basics You will get more from this topic if you have mastered the basics of DNA and genes – this link will take you to an annotated list of sites with helpful background information. Key textIn nature, cloning is common among plants and is used extensively in plant propagation. The offspring produced by cloning (and other methods of asexual reproduction) simply develop from cells produced by the parent. Because the offspring have genetic information identical to the parent, they develop very similar characteristics to their parent (and to one another) as they mature. This means that an agriculturalist who grows new plants from pieces of an older plant ensures that the new crop will be a fairly uniform one (Box 1: Propagating plants). In contrast, an individual formed by sexual reproduction develops from a cell produced by the union of two cells, usually from different parents. Offspring produced in this way are not genetically identical to each other or to their parents, unlike offspring formed by asexual methods of reproduction.The only clones produced naturally in vertebrate animals are identical twins. These are formed when cells produced by the early divisions of the fertilised egg separate and independently develop into new individuals. They are therefore genetically identical to each other but not identical to their parents. Cloning mammals Since the 1970s scientists have been able to clone mammals such as sheep and monkeys, using cells taken from embryos. What made the cloning of Dolly the sheep so remarkable was that she was cloned from the cell of an adult sheep – something that scientists thought couldn't be done. To understand the reason that scientists thought it couldn't be done, you need to know a bit about animal cell differentiation. Animal cell differentiation As an embryo grows, it produces new cells that all contain the same DNA. At a certain point the cells start to differentiate – or become specialised. Some cells, for example, become nerve cells while others become muscle cells. Scientists thought that this differentiation was irreversible and that once a cell had differentiated to become, say, a skin cell, it could not change into anything else. It was thought that somehow the DNA inside any particular cell had been chemically 'programmed' to produce only the range of proteins required for it to perform its specific tasks, and that 'reprogramming' was impossible. The scientists that produced Dolly laid this notion to rest. They found a way to 'reprogram' the DNA of an adult cell so that it could start again from scratch – producing embryonic cells that eventually grew into a living, breathing animal (Box 2: How Dolly the sheep was cloned). Whole animal cloning While the cloning of Dolly was greeted with excitement, whole animal cloning (reproductive cloning) is unlikely to be used routinely until the success rate increases substantially – Dolly was the only successful clone from 277 attempts. Recent genetic engineering successes in sheep and cattle suggest that efficient gene transfer systems may soon be available to livestock breeders, without the need to clone from adult tissue.
Cloning techniques may one day enable the production of 'spare parts' such as tissues and organs. These spare parts could then be used for the treatment of damaged or diseased tissue and organs. This is known as therapeutic cloning and involves using stem cells to grow new cell types. One human organ, skin, is already grown in the laboratory. Healthy skin cells taken from a patient who has suffered severe burns can be grown to provide a self-compatible skin graft – this means that the risk of rejection by the patient's immune system is reduced to virtually zero. Scientists are able to grow skin more readily than other organs or tissues because mature, differentiated skin cells retain the ability to divide and produce more cells. Most other types of adult cells need to be 'reprogrammed' before they are able to divide. Researchers are now attempting to 'reprogram' and grow other self-compatible cells, such as nerve cells for patients with spinal injuries or muscle cells for heart attack victims.
Horticulturalists use a technique called tissue culturing to propagate plants. They cut off a small piece of tissue (called an explant), wash it in sodium hypochlorite bleach to kill any micro-organisms on the surface, and place it on nutrient agar in a culture tube to grow. Sterile conditions are maintained throughout the procedure otherwise the explant would be swamped by micro-organisms growing on the nutrient medium. The explant, usually a bud, is cultured first on a medium containing a fairly high concentration of a cytokinin. Cytokinins are substances that stimulate cell division, and the one used in this procedure induces the outgrowth of shoots. When the explant has produced many shoots it is dissected into more explants, each of which is placed in a new tube of culture medium. This subculturing can be carried on indefinitely to produce large numbers of clones. To obtain plants, the subcultured shoots are transferred to a culture medium containing a moderately high concentration of an auxin to promote root growth. After the roots develop, the plants are transferred to soil to grow. Species propagated commercially by tissue culture in Australia include Australian natives, indoor foliage plants, crop plants and ornamentals. A commercial laboratory starts with hundreds of explants and produces thousands of new plants in a year.
Before the nucleus was transferred from the donor cell to the recipient cell, the scientists used a high-powered microscope and a very fine micropipette to suck out the recipient cell's nucleus. (Inside the nucleus are chromosomes, the packages that contain the cell's DNA.) Each donor cell was then forced into a state of 'quiescence' – where the DNA stops dividing – and placed alongside a recipient cell. The two cells were then encouraged to fuse by way of an electric pulse. The recipient egg cell now had 'new' DNA – that of the donor cell – with which to begin the process of cell division and growth. It was implanted in the uterus of yet another sheep and its progress monitored. Of the 277 original donor cells, only 29 made it to the stage of being implanted, and of those only one – Dolly – went full term. In 1998, several laboratories announced the successful cloning of other species, although the rate of success remained low in all cases. A University of Hawaii lab has produced dozens of cloned mice, using a variation of the nuclear replacement technique used with Dolly. Instead of fusing the donor and recipient cells, the researchers inserted the nucleus of the donar cell directly into the recipient cell. The cells from which the donor nucleus was extracted are naturally quiescent cells found in the ovary. According to Ian Wilmut, the leader of the team that produced Dolly, getting donor cells (or donor DNA) into a quiescent state is essential because it allows the reprogramming of the adult DNA. Nevertheless, scientists in a US lab claim they have produced cloned calves without establishing quiescence beforehand. Related sites
Here is the executive summary of the statement We define cloning as production of a cell or organism with the same nuclear genome as another cell or organism. We have chosen this simple definition to reduce ambiguity in public discussion, to guard against legislative misinterpretation and to underpin any regulatory or licensing guidelines. In this Statement we distinguish between reproductive cloning to produce a human fetus and therapeutic cloning to produce human stem cells, tissues and organs. It had been widely accepted that cell differentiation (or increasing cell specialisation) in the developing mammal is irreversible, until the recent successful reproductive cloning of sheep, cattle and mice from adult cells. These experiments suggest that it may also be possible to reprogram human adult cells to revert to earlier stages of development. Speculation in the popular press about selfish or compassionate reproductive cloning of humans has tended to obscure the real scientific challenges in capturing this advance in knowledge for therapeutic cloning, for the benefit of mankind. Cloning techniques may one day revolutionise medical treatment of damaged tissues and organs, should it become possible to use human adult cells as the starting material for growth of new tissues. At present, one human organ, skin, can be grown in the laboratory to provide self-compatible skin grafts for burns victims. The possibility of growing other self-compatible cells, such as nerve cells for patients with spinal injuries or muscle cells for heart attack victims, could one day be a reality, albeit within an unknown time-frame. That such a possibility could become a reality is suggested by the combined application of knowledge arising from three recent and significant advances in biomedical research. These advances are (a) the cloning of mammals from adult cells; (b) the establishment of cultures of 'all-purpose' cells, human embryonic stem (ES) cells with the potential to grow into many different cell types; and (c) the demonstration that human fetal nerve stem cells can develop into multiple and appropriate nerve cell types following transplantation (into experimental animals). These findings provide new opportunities for research in cellular and developmental biology and, taken together, suggest that future possibilities may exist for self-compatible tissue and organ repair. The Council, in accord with international opinion, considers that reproductive cloning to produce human fetuses is unethical and unsafe and should be prohibited. However, human cells, whether derived from cloning techniques or from ES cell lines, should not be precluded from use in approved research activities in cellular and developmental biology. In Australia at present, production of human ES cells would be approved only in exceptional circumstances under National Health and Medical Research Council (NHMRC) Ethical guidelines, originally prepared to ensure ethical practices in in vitro fertilisation (IVF) clinics. For Australia to participate fully and capture benefits from recent progress in cloning research, it is necessary to revise the 1996 NHMRC Ethical Guidelines on Assisted Reproductive Technology and repeal restrictive legislation in some States. This could be done in the context of establishing a national regulatory arrangement, taking into account recent advances in biomedical research and advocated best practice elsewhere. The regulations should be binding on both publicly and privately-funded research activities. Noting that the Australian Health Ethics Committee (AHEC) has recommended (December, 1998) that the Minister for Health and Aged Care should urge States and Territories to introduce legislation to limit research on human embryos according to the principles set out in the NHMRC Ethical Guidelines on assisted reproductive technology, the Council of the Australian Academy of Science makes the following recommendations with respect to existing and any proposed regulatory and legislative arrangements regarding human reproductive and therapeutic cloning. Recommendations
Related sites
Australasian Science October 2006, pages 26-28 Cloning goes to the movies (by Craig Cormick) Analyses the effects that Hollywood is having on public perceptions of cloning.
Cosmos 6 December 2006 Back from the dead (by Jacqui Hayes) Discusses the possibility of cloning extinct animals.
Nature 22 February 2007, pages 800-801 Dolly: A decade on (by Meredith Wadman) Covers the changes that have occurred in the ten years since Dolly was cloned.
New Scientist A collection of New Scientist articles on cloning is available.
26 April 2008, pages 40-43 Struggling to find an appetite for cloned meat (by Sharon Oosthoek) Discusses the production of food from cloned animals.
18 April 2007, pages 24-25 Perfect clones, to the last computer-generated wrinkle (by Celeste Biever) Provides a glimpse into the future, where the real and the virtual lookalike are undistinguishable.
1 July 2006, pages 8-10 Ten years on, has the cloning dream died? (by Peter Aldhous and Andy Coghlan) Reviews the 10 years since Dolly was first cloned.
1 July 2006, page 11 Therapeutic cloning set by hype and fraud (by Peter Aldhous and Andy Coghlan) Discusses some of the issues about using cloned embryonic stem cells for therapeutic cloning.
1 April 2006, page 10 Champion horse is daddy of the clones (by Henry Nicholls) Covers a highly efficient method to clone a stallion.
22 November 2003, page 23 A crime against humanity (by Alan Trounson) A leading stem cell scientist presents his views on why reproductive cloning should be condemned.
Scientific American February 2002, pages 10-11 What clones? (by Gary Stix) Covers the scientific doubt that greeted the announcement of the first human embryo clones.
January 2002, pages 42-49 The first human cloned (by Jose B. Cibelli, Robert P. Lanza and Michael D. West, with Carol Ezzell) An article written by the scientists who have cloned human embryos.
November 2000, pages 66-71 Cloning Noah's ark (by Robert P. Lanza, Betsy L. Dresser and Philip Damiani) Explains that cloning might help save endangered species.
The cloning of Dolly (Science Explained, UK)
Explains how Dolly the sheep was cloned.
Stem cells: A special report (New Scientist)
A collection of New Scientist articles relating to cloning and stem cell technology.
Scientific American (USA) Explorations
Ask the experts
Public interest – Cloning (Roslin Institute, UK) Defines different types of cloning and provides information on cloning technology, limitations of nuclear transfer and applications for cloning.
National Institutes of Health (USA)
Cloning animals (Biotechnology Australia)
Describes the some of the methods used to clone animals.
Australian Broadcasting Corporation (transcripts)
Cloning clash (Insight, 10 October 2006, Special Broadcasting Service, Australia
The transcript of a television debate on therapeutic cloning.
Human stem cell research (Australian Academy of Science)
This report reviews scientific and regulatory developments up until April 2001.
Human cloning: scientific, ethical and regulatory aspects of human cloning and stem cell research (House of Representatives, Parliament of Australia)
This report was tabled on 17 September 2001. Each of the ten chapters of the report is available as a pdf file. For example, click on 'Chapter two' for an introduction to the science of cloning.
DNA (deoxyribonucleic acid). The nucleic acid forming the genetic material of all organisms with the exception of some viruses which have RNA. DNA is present in the nucleus and other organelles such as mitochondria and chloroplasts. genetic engineering. A set of procedures whereby a specific piece of DNA can be excised from a chromosome and inserted into the DNA of a chromosome of a different organism. immune system. The cells, tissues and organs that assist the body to resist infection and disease by producing antibodies and/or altered cells that inhibit the multiplication of the infectious agent. organ. A specialised structural unit which serves a particular function in a body. Examples of animal organs are kidneys and hearts. Different tissues are organised into organs. sexual reproduction. A type of reproduction that involves the union of two cells. The offspring from this type of reproduction have a unique combination of genes stem cell. An undifferentiated cell which is a precursor to a number of differentiated (specialised) cell types. therapeutic cloning. Medical and scientific applications of cloning technology that do not result in the production of genetically identical fetuses or babies. For more information see Therapeutic cloning for tissue repair (Australian Academy of Science). tissue. A group of specialised cells with a common structure and function. Examples of animal tissues include nervous tissue and muscle tissue. Illustrations of different tissue types can be found at Mammalian differentiated cell types, part 1 and Mammalian differentiated cell types, part 2 (Access Excellence, USA).
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