In 1966, J.B. Gurdon of Cambridge University succeeded in cloning frogs.1 Thirty years later, Ian Wilmut and colleagues of the Roslin Institute of Edinburgh, Scotland, succeeded in cloning sheep from fetal and embryonic cells,2 and in February of 1997, they made the sensational announcement that they had obtained a sheep, which they named Dolly, from a clone obtained from the cell of an adult female sheep.3 In January of 1998, it was publicly announced that two calves, produced by cloning, were born on a Texas ranch, and that others were soon to be born. In the case of Dolly, because the animal cloned was both an adult and a mammal (thus much closer physiologically to humans than the frog, an amphibian), this announcement created a great stir and controversy in scientific circles and among the public. There were immediate demands in the U.S. and in many other countries to prohibit such attempts. Presently there are laws in the United Kingdom and some other countries against the cloning of humans, but the U.S. has no such laws. President Clinton immediately issued orders prohibiting the use of federal funds to support research on human cloning and bills have been introduced in the U.S. Congress to prohibit the cloning of humans.
The goal of cloning is to produce offspring that are essentially genetically identical to the individual creature from which a cell nucleus has been obtained. The cell nucleus contains the genetic information, or DNA (deoxyribonucleic acid), which determines most of the features of the plant or animal (the mitochondria, the "energy factories" of the cell, contain DNA that is independent of the nuclear, or chromosomal DNA). In this procedure, an unfertilized egg cell is obtained from a fertile female, and the nucleus is removed from the egg. Having been deprived of the chromosomal DNA, the enucleated egg cell is rendered incapable of multiplying and developing. A cell is then removed from either a very young embryo, a developing fetus, or an adult animal, and the nucleus is removed from the cell. This nucleus is then inserted into the enucleated egg cell.
An unfertilized egg cell contains only one set of genes obtained from the female. A fertilized egg cell contains two sets of genes—those from the female and those from the sperm of the male. The nucleus of a cell obtained from an embryo, a fetus, or an adult, contains both sets of genes, those obtained from each of its parents. Thus, when the nucleus from a cell is inserted into the enucleated egg, the egg contains two sets of genes, just as if it had been fertilized. After culturing in an appropriate medium that permits development to the blastocyst or morala stage, the embryo is placed in the uterus of a recipient and allowed to develop to term.
Only certain genes are activated and all others are suppressed in the cells obtained from particular structures and organs of an adult animal. For example, in the cells making up the muscles of the heart, those genes that code for the proteins and other molecules that are required to construct heart muscle are activated, all others are repressed. In the cells of the tubules of the kidney, those genes required to code for the material making up the tubules are activated, all others are repressed (there is no need for heart tissue in a kidney). This is true of cells obtained from all of the various structures of an adult animal. Therefore, one cannot simply insert the nucleus obtained from a particular tissue of an adult into an enucleated egg and cause the egg to develop. The cells from which the nuclei are to be obtained must first be given special treatment in order to activate all the genes. Ordinarily, cells are cultured in a medium containing 10% fetal calf serum. It was found if the cells were "starved" by culturing them for five days in a medium containing only 0.5% fetal calf serum, all of the genes once again became activated (they are said to be totipotent).
In the case of Dolly, cells were obtained from the udder of a sheep and cultured in the medium containing 0.5% fetal calf serum. This caused the cells to leave the growth cycle and come to rest in what is called the GO stage. In these cells, all of the genes became activated—the cells became totipotent. Using electrical impulses, these cells were caused to fuse with enucleated unfertilized egg cells. After development to the appropriate stage by culturing in the proper medium, the embryos were implanted in the uterus of another sheep.
When the cells were obtained from the udder of an adult sheep, 277 fused cells were produced. Of these, 29 developed to the blastocyst or morala stage. These 29 embryos were implanted in the uteri of 13 sheep. One live lamb, Dolly, was obtained.3 Thus, it can be readily seen that when the cells were obtained from an adult, the rate of success was very low. The procedure is very time consuming, requiring culturing of donor cells in several media and culturing of the reconstituted recipient egg cell, in addition to the time required for the pregnancy to reach full term. While the success rate is slightly higher when the donor cells are obtained from embryos or fetuses, the desirability of an animal for donor purposes cannot be fully determined until the animal reaches the adult stage. The estimated cost of producing Dolly was about $50,000. Obviously, the success rate must be considerably improved before an economically feasible cost-to-benefit ratio is obtained.
What Are the Potential Benefits?
1. Animal Breeding
With a sufficiently high success rate, this procedure could be of great benefit to animal breeders. The clones possess essentially the same genetics as the animal, male or female, from which the cells providing the nuclei were obtained that are inserted into the enucleated eggs. In the case of sheep, the cells could be obtained from a disease-free animal producing a luxurious coat of wool or possessing an ideal quality of meat. In the case of cattle, the donor cells could be obtained from cows producing an abundant supply of milk or animals with high quality meat. Instead of breeding champion race horses, which dilutes the genes of the champion with the genes of the mate, clones of the champion race horse could be produced, resulting in offspring essentially genetically identical to the champion race horse. Such offspring should bring very high prices.
2. Human Reproduction
If sufficient research were performed and if the procedure is not prohibited by law, it is possible that some day humans will be cloned. At this point it is not possible to make a definite prediction as to success. What might be considered potential benefits? Human cloning would permit the production of a son or daughter for a non-fertile couple. Even if the wife had no ovaries and her husband could not produce healthy sperm, the nucleus obtained either from one of the wife's cells (thus producing a female offspring) or from one of the husband's cells (thus producing a son) could be inserted into an enucleated egg obtained from another woman. The reconstituted totipotent egg could then be implanted in her uterus or the uterus of another woman (a surrogate mother) and developed to term. The offspring would be essentially identical to either the husband or the wife. Many variations of this scheme can be imagined.
Legal and Moral Problems
There are no moral or legal problems with cloning of animals, but there are a multitude of serious moral and legal problems with the cloning of humans. During the cloning of animals, whether of frogs, sheep, or other creatures, there have been many cases of imperfect clones resulting in production of malformed fetuses and deaths. This is only an economic problem with animals, but would create very serious moral and ethical problems with human cloning. The idea of permitting research on human cloning for this reason alone is unacceptable. There are other serious moral problems with the cloning of humans. A large majority of Americans consider human cloning unacceptable. According to the Bible, the Christian family consists of husband, wife, and children. Cloning could and would result in all kinds of artificial, abnormal, and undesirable family units. For example, a single woman could have a clone. A nucleus from one of her cells could be fused into one of her enucleated eggs or one obtained from a donor, and this egg could then be implanted into her uterus or the uterus of a surrogate mother and developed in the usual manner. The female child produced would be essentially a genetic copy of the woman contributing the nucleus. A couple considerably beyond the normal reproductive age could have additional children by cloning either the husband or wife, placing children in family units in which one or both parents may be physically or financially unable to properly care for the child. Many other scenarios could be imagined.
The cloning of animals could result in considerable economic benefits. Every effort should be made, however, to preserve the original genetic diversity by maintaining at least small herds of the original donors. Cloning of humans, on the other hand, including research directed towards that end, is totally unacceptable and must be prohibited by law. Just recently nineteen countries from Europe, Scandinavia, and the Near East signed an agreement to prohibit human cloning. It has been announced that a proposal for an emergency prohibition on the cloning of humans will be introduced in the U.S. Congress in the session beginning in January 1998. In response to the claim by a physicist that he will soon initiate research on human cloning, the Federal Food and Drug Administration warned that this agency will shut down any such efforts that are without its permission. It should be clear that with human cloning vital interests rest not on any potential successes, but on its certain failures.
The as yet unsuccessful attempts to correct genetic diseases (such as hemophilia) through genetic manipulation will be discussed in a future article. Also to be covered are the successful production of human proteins in the milk of pigs, cows, and sheep, as well as the introduction of beneficial changes in plants by genetic manipulation. It must be borne in mind that all such genetic manipulations merely use what God has produced and are limited by the fact that genetic systems are incredibly complex and are difficult to manipulate without producing harmful and even lethal results. We can repair defective genetic systems, but we cannot improve a normal, healthy genetic system.
The question is often asked, would a human clone have a soul? Absolutely. Occasionally some people are troubled by the assumed possibility that human manipulation will present a problem too hard for God to solve. But with God nothing is impossible. He is always far ahead and above anything man may do. In fact, I am a clone, just as is true of all others who have identical twins. I am certain that both my twin brother and I have a God-given soul.
1 J.B. Gurdon, Nature 201:1240 (1966); Endeavor 25:97 (1966); Scientific American 219:24 (December 1968).
2 K.H.S. Campbell, J. McWhir, W.A. Ritchie, and I. Wilmut, Nature 380:64 (1996).
3 I. Wilmut, A.E. Schnieke, J. McWhir, A.J. Kind, and K.H.S. Campbell, Nature 385:810 (1997).
* Dr. Gish is Vice President ICR. He has a Ph.D. in biochemistry from the University of California at Berkeley and worked for many years in research at the Upjohn Company.