|MadSci Network: Genetics|
As you may know from the news, cloning of mammals was first achieved in 1997 when Dolly the sheep was cloned by Dr. Ian Wilmut and his collaborators in Edinburgh, Scotland. Since then, a number of different species of mammals have been cloned, including mice and cattle. When we say that an animal has been cloned, we mean that another animal having exactly the same collection of genes has been produced. All animals of a particular species have essentially the same genes, but there are variants of each individual gene in a particular species. These variants are called alleles. For example, mammals with dark hair have a gene that produces an enzyme (a kind of protein that catalyzes chemical reactions) called tyrosinase. The enzyme tyrosinase produces a dark pigment called melanin that is present in hair and skin. In mice, cats, humans, and other mammals, there are alleles of this gene that produce an enzyme that has very little activity, so very melanin is produced. Mammals have two copies of most of their genes. If both of the copies of the tyrosinase gene are the allele with little or no enzyme activity, the animal is an albino, with white hair or fur, pink skin, and pink eyes, and looks very different from other members of its species. In a similar way, there are different alleles (often many different alleles) of each of the tens of thousands of genes that all mammals have. In addition, an individual can have two different alleles of most genes, because mammals have two copies of most genes. What this means is that most individuals in a population of a species are genetically unique. No two individuals in the population have exactly the same collection of all of the alleles of all of their genes. One exception to this is identical twins. You might know some brothers or sisters who are identical twins. Identical twins are born when for some reason the early embryo (made up of two or four cells) splits into two embryos. Because the embryo started out as a single cell, all of the cells derived from that embryo are genetically identical, so the two embryos develop into a pair of genetically identical individuals. You could say that one member of a set of identical twins is the clone of the other. When sheep, mice, cattle or other mammals are cloned, a nucleus (the part of the cell that contains the genes) is transferred from some kind of cell from a completely developed individual into a egg cell from which the pronucleus (the unfertilized nucleus) has been removed. The egg is then activated (caused to start development) by some sort of experimental treatment. The embryo is allowed to develop for a few cell divisions in a culture dish before being implanted into a 'foster mother' who will give birth to the clone. The success rate on cloning mammals is not very high. One of the problems is that cells from a fully developed individual are differentiated into specialized cell types, such as skin cells, muscle cells, liver cells, and so on. These cell types are different because a different collection of genes is active in each cell type. Once a cell has differentiated, it has a very limited ability (or even no ability at all) to turn into a cell that is able to form other cell types. The cells of an early embryo are special because they are able to form all of the different cell types that make an individual. In cloning experiments, it is not uncommon for only a few embryos out of a hundred to make it to live birth. In addition, some of the animals are born with birth defects that appear to result from an incomplete reprogramming of the differentiated nucleus back into a nucleus that can form all cell types. Biologists don't think that people are very different from other mammals in terms of their basic genetics and development, so if you ask a biologist whether it would be possible to clone a human, they would answer that, yes, it is. So far it has not been done. There are two sorts of reasons fro this. The first sort of reason is technical. In order to clone a human, scientists would have to obtain a supply of hundreds of unfertilized human eggs. This is technically possible. Unfertilized human eggs are collected at fertility clinics from women who very much want to have children but who, for some reason, are not able to have them normally. This involves treating a woman with hormones to cause an unusually large number of eggs to be released at the same time (instead of the one or two a month that are normally released). The eggs are then collected surgically, which involves some risk to the woman's health. It is possible to collect up to about twenty unfertilized eggs from a woman undergoing this procedure. Normally, these are fertilized with her husband's sperm, some are implanted, and others are usually frozen for later attempts. Suppose that we could get twenty or thirty women to agree to undergo this procedure not to have children of their own, but to provide eggs for a human cloning experiment. We would then use hundreds of these eggs to accept nuclei from cells from a person that we wanted to clone. Most of these embryos would fail to develop normally, and there is a very good chance that even if we got to a live birth, the clone would have birth defects resulting from a failure to completely reprogram the nucleus. This brings us to the second reason why this has not been done, which is that it would be unethical. We would have to ask dozens of perfectly healthy women to undergo a procedure involving some risk to their health to provide the raw material for an experiment that might produce a few children who have an excellent chance (much higher than for normal births) of being born with birth defects. The purpose of this experiment would be to produce a cloned human. There isn't any good reason to do this. We can learn all we need about genetics, biology and development in humans from doing ethical experiments, including the cloning of experimental animals. As for using a newborn baby as the donor for the nuclei, there isn't any substantial difference between a newborn baby and an adult with regard to the significant processes of development. A newborn is far less different from a adult than it is from a fertilized egg. This is an excellent web site on cloning: http:// www.ri.bbsrc.ac.uk/library/research/cloning/ The site above includes this Glossary: http://www.ri.bbsrc.ac.uk/library/research/cloning/glossary.html You might also find this Glossary useful: http:// www.informatics.jax.org//userdocs/glossary.shtml This is a Scientific American article on cloning: http://www.sciam.com/explorations/030397clone/030397beards.html This is a good cloning site also: http:// library.thinkquest.org/24355/ This is a site on the ethical issues of cloning: http:// www.religioustolerance.org/cloning.htm Thank you for your interesting question. I hope that you find this answer useful, and that it helps you learn more about all the exciting work in biology and genetics that is going on right now. Yours, Paul Szauter Mouse Genome Informatics
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