Mammalian Cloning

Introduction

The power to clone a mammal, and therefore a human, has recently been placed in our hands. Not only does this discovery have the potential to revolutionize the raising of animals for labor and food consumption, but it also unleashes an entire realm of science fiction and hypothetical situations into our reality.

History

In 1997 the first mammal was successfully cloned at the Roslin Institute in Scotland. The cloned sheep, named Dolly, had the exact same DNA sequence as the adult somatic cells taken from the mammary gland of her genetic donor. Dolly exemplified her genetic fitness by naturally giving birth to a viable offspring in 1998.

The scientists appeared to have hurdled the task of making a cell of an adult mammal "forget" that it had become specialized to a certain task, such as transmitting nerve impulses or producing digestive enzymes. Cells specify themselves in this way to prevent every cell in the body from trying to form a new individual every time it divides.

Since Dolly's birth, the field of cloning has exploded. Cows, mice, and goats have all been successfully cloned. A cloned pig is due for birth by the year 2000. Even a human embryo has been successfully cloned through 12 days of growth before being terminated. Research has turned toward the production of transgenic clones and more efficient cloning methods.

Method

The initial step in the cloning process is the selection of somatic cells from the genetic donor. The cells chosen are typically those that still divide, unlike nerve cells of the CNS or red blood cells, and are exposed to the least number of mutagens, unlike the skin cells, given their exposure to ultraviolet light. The nuclear transfer process is then initiated. First, the cell of the genetic donor is starved in vitro. This starving drastically reduces the cell's production of proteins and places it in a resting state, known as Go in the life cycle of a cell. In this state the cell's nucleus becomes totipotent, although still lacking the cellular materials necessary to begin the production of a new individual. To provide the needed materials, an oocyte is enucleated. After the enucleated oocyte is placed next to the starved donor cell, an electric current causes the two cells to merge. The resulting chimeric cell possesses only one nucleus. This cell is kept in vitro for approximately seven days and is then implanted into the uterine wall of its surrogate mother.

Possibilities for Use

There are a multitude of uses for the cloning of animals. Entire herds of cattle could be produced from one extremely efficient milk producer. The average size of a beef cow could quickly become that of the largest in the herd. The best animals for studding could be cloned to fertilize a larger number of females than previously possible. With the advent of mammalian cloning, ideologically, no mammal need go extinct again.

Cloning, combined with transgenic techniques, provides even more possibilities. Producing a transgenic clone requires less time and fewer animals than using transgenic methods alone. A transgenic clone can also be produced of a specific sex to fit the herd's needs. It is now possible for mammals to be custom-tailored for milk and beef with specific properties and nutrients. The milk from transgenic cloned goats is currently being tested on patients with extremely low levels of antithrombin III (rhAT). The goats were engineered to produce rhAT in their milk. The milk should be able to prevent the patient's blood from clotting prematurely. Sheep have been cloned which, when they are old enough, should produce milk with blood-clotting factor IX. Presently in utero, cloned cows have been designed to produce human serum albumin in their milk. Designer clones open the possibility of procuring human therapeutic proteins and medicines in the same manner that milk is attained today.

The possibility of raising pigs with human organs for transplant, a process called xenotransplantation, is on a foreseeable horizon. Transplanted organs are often rejected due to the recognition of different specific protein combinations on their cell surfaces. These organs could be designed to match the individual requiring them, which would ensure the organ's acceptance by the immune system.

Barring ethical considerations, cloning opens a world of new human uses as well. Cloned totipotent cells could be used in the treatment of many disorders or injuries of the muscular and nervous systems, such as Parkinson's and Alzheimer's diseases. Many have even advocated the cloning of human individuals who are otherwise unable to have children. Others have noted the benefits of cloning people with remarkable talents in a given field.

Problems in Cloning

Scientific

Although cloning success rates have steadily increased with the use of new choices of donor cells and non-surgical nuclear transfer methods, there still remain a variety of flaws in the process. The first and foremost is that not all of the information used to form an individual is found in the DNA of the nucleus. Mitochondrial DNA (mtDNA) is contained in the mitochondria, which reside in the cytoplasm of the cell. This and all other organelles of the cloned embryo would be inherited from the provider of the egg donor — not the genetic donor. There is a large amount of maternal RNA found in the egg that largely controls the initial stages of mammalian development. Dolly is 20% larger than the individual from which she was cloned. This may denote the variation of weight possible for individuals, but most clones follow the trend of being significantly larger then their "identical" genetic donor. In order to insure the organelles and maternal RNA are the same for the cloned individual, the enucleated egg must also come from the genetic donor or the genetic donor's biological mother. This fact makes the exact cloning of a male a much harder task.

Another difference between the clone and the genetic donor is the amount of cytoplasm present in the first chimeric cell. The combining of the cells adds their cytoplasm and its contents to form the new cell. It is unknown how this difference could affect the growth of an individual at such an early stage.

Studies on Dolly's DNA have also shown that the telomeres of her chromosomes are shorter than those of the genetic donor's. Telomeres become gradually shorter with every somatic cell replication. This shortening may be what eventually causes cell death and aging. Some researchers have suggested the possibility of mtDNA being responsible for aging. In a few years, it may be found that Dolly and the other mammalian clones age prematurely.

There are even more problems with cloning humans. The development of the human brain depends heavily on the physical stimulants it receives early in life. Therefore, cloning a great musician could result in a tone-deaf scientist, if the same musical sounds are not heard before the brain cells lose their plasticity.

Legal/Ethical Considerations with Human Cloning

The Food and Drug Administration (FDA) currently claims jurisdiction over the regulation of cloning based on its being the regulatory body for somatic cell and gene therapy. Current legislation prevents the cloning of humans but is unspecific. The Biotechnology Industry Organization (BIOS) agrees with the FDA's stand against cloning humans but fears that further legislation may limit valuable research. An agreement between 19 European nations prohibits the cloning of humans. Several U.S. Federal and State Legislature bills are currently under discussion for the limiting of human cloning research. The cloned human embryo made in the U.S. was destroyed at 12 days, two days before the embryo would have naturally implanted into the uterine wall, to avoid legal repercussions.

The ethical considerations with human cloning appear to address the morality of manufacturing a human being. Twins are technically clones but they have no knowledge of what they are to be like as adults, nor do they have presupposed expectations to becoming someone else. Mammalian cloning has challenged society's concept of self. Once again, as with nuclear technology, the developments of science have forced humanity to decide how to bridle the powers it has grown to possess.

Mammalian Cloning Web Site Links

Biotech Laws - U.S. regulations on biotechnology.

Cloned Mice - Researchers have cloned more than 50 mice from adult cells.

Goat Clones Designed to Express Recombinant Human Antithrombin III (rhAT)

Human Embryo First Cloned - Human embryo revealed.

Reason Magazine Cloning and Other Discussions about Modern Science

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