Cloning: Copying DNA becomes a reality

by MattCoughlin assistantnews editor

The basic formula of life, DNA, can now be copied like a file from Napster.com, and there is no copyright. Cloning, once a denizen of sci-fi films and books is now being attempted in various parts of the world for various purposes.

Researchers provide three reasons for human cloning: to provide organs to be transplanted, to allow parents to clone a dead or dying child, or adults who want to clone themselves.

"It's unethical because then you lose the concept of identity between the original person and the clone,'' junior biology major Dana Cavalcanto said

As with identical twins, clones would be very different individuals. While the appearance of the clone and the original would be indistinguishable, on the molecular level, differentiation is possible. As with identical twins the fingerprints of a clone and an original will be different. For one, the clone's mitochondria (the energy-producing cell parts) would come from the egg donor, while the original's would be consistent with their DNA Clones are essentially younger identical twins.

You may remember "Dolly," the sheep cloned in Scotland in 1997. Scientists are unsure of whether all clones will be fertile, yet Dolly has successfully given birth to four lambs.

Dr. Louis Nudy, professor of chemistry, supports researchinto the benefits of human cloning. "It is something that needs to be studied considering the risks and benefits to the new offspring and society as well," Nudy said.

Human cloning is much more complicated than the cloning of animals because of the size of the human genome. Dolly required more than 276 attempts before success. Some scientists fear that before a human clone is successful, there will be many cases of malformations or diseased human clones. There also is the question of whether the age of the DNA used for the clone will affect its life span.

An international team of scientists at the University of Hawaii, led by Ryuzo Yanagimachi and Teruhiko Wakayama, has cloned adult mice more than 50 times, including some sixth generation animals - clones of clones of clones, etc. Yanagimachi's group has also produced the first male clones. While the production of Dolly resulted in 276 failures, the male mice resulted in 274 failures. Of the three live male mice produced, two died almost immediately after birth.

However, unlike previous attempts, the mice's telomeres are longer than expected. Telomeres are caps that protect the DNA of a chromosome and sustain cellular life (see below).

''Our results verify that telomere shortening is not a necessary outcome of the cloning process," Wakayama said.

Researchers at Advanced Cell Technology, based in Worchester, Mass., have cloned six heifers (female cows) from a 45-day-old fetus. The cows appear to be younger than their chronological age.

''We have shown that the clock gets reset," Dr. Michael West said, president and CEO of Advanced Cell. "It remains to be determined whether this would extend the life of the animal."

Dolly's chromosomes are showing signs of premature aging. Dolly's cells are the same age as those of the 6-year-old ewe from whom she was cloned. This is determined by looking at the telomeres, which wear with each cell division. Researchers from the Roslin Institute and PPL Therapeutics in F.dinburgh, Scotland report Dolly's telomeres are 20 percent shorter than those of sheep the same age.

Some scientists believe telomeres may hold the secret to aging.

The cells used by the Advanced Cell group were reaching senescence before the transplant because the process was slightly different from that used for Dolly. The original donor cells may make the difference - mammary cells for Dolly and connective fetal cells for the six heifers.

'The egg cell acts like a little time machine and can take [the DNA] back to the beginning of life,'' West said.

In an article written for "Scientific American,'' Ian Wtlmut, the man who cloned a sheep at Roslin Institute, claimed that "once techniques for the retrieval of egg cells in different species have been perfected, cloning will make it possible to introduce precise genetic changes into any mammal and to create multiple individuals bearing the alteration." This raises troubling questions. If we are able to alter the genes of an individual to create specified attributes where do we draw the line in designing humans.

Fuller-Espie feels it is unethical to use cloning to improve human stock. '1t is one thing for gene therapy of somatic cells - not germ cells - to correct a deficiency and another

Six heifers were cloned by Advanced Cell Technology in Worchester, Massachusetts. thing to use the whole genome for another purpose," Fuller-Espie said "I think it is not for humans to interfere in God's work." Fuller-Espie further explained that gene therapy on somatic cells is not inherited by the next generation.

According to Donum Vitae, a 1987 Vatican document, cloning violates "the dignity both of human procreation and of the conjugal union." Protestant theology often supports scientific ventures. This derives from the common Protestant belief that nature is "fallen:• However, cloning of humans goes too far, according to many Protestant theologians. Rabbi Richard Address, member of the Union of American Hebrew Congregations, said human cloning "violates the mystery of what it means to be human."

Cloning can benefit the research into animal transplant organs. There is a similarity between the organs of pigs and humans; however, the human immune system attacks the tissue of other species, particularly certain pig enzymes. Alexion Pharmaceuticals, a biotech company based in Connecticut, is attempt- ing to alter the pig genetic code to prevent transplant rejection. Wtlmut also points out that animals who have had their genome altered to resemble humans with diseases like cystic fibrosis and Parkinson's disease may permit more intensive studies of gene-based therapies. Yet, Wtlmut admits to a limited success rate. According to Wtlmut, laboratories report that 1 to 2 percent of embryos survive to become live offspring, and some of those clones die shortly after birth. The Scottish team produced one live lamb from 29 clones placed into 13 ewes.

While the benefits of cloning are many, the road to producing viable human clones, or even satisfactory healthy animal clones, stretches farther in front of us than behind; and many questions remain unanswered. ''We should be asking ourselves, 'why do we need to clone, who is it going to benefit?"' FullerEspie said Fuller-Espie believes that global guidelines and boundaries need to be placed on cloning, especially human cloning, by a "watchdog committee" of scientists and scientifically literate lay people.

The science behind the fiction of cloning

"What is so interesting about [Dolly] is that they used a somatic cell instead of a germ cell. They can reprogram the DNA to start all over again,'' Dr. Sheryl Fuller-Espie, professor of biology, said Cloning is based upon a somatic cell nuclear transfer technique. In this process, a somatic cell nucleusa mature cell nucleus taken from an adult organ - is transferred into an egg cell whose nucleus has been removed. This fused cell grows into an embryo that is implanted into a

"surrogate" mother's womb. The difficulty in duplicating this process in humans arises from the specialization of the human cell. Many genes are "turned off" when the cell becomes specialized. Currently scientists are unable to turn these genes back "on."

Somatic cells are the cells that make up the organs and all body parts; they are specialized cells. Somatic cells also are older and have replicated themselves many more times than germ cells or gametes.

Gametes are the cells used in reproduction; sperm and egg cells.

"Somatic cells include blood cells, cells of the tissues arid organs, neurons, and bone marrow stem cells, but do not include the sperm or ova which are referred to as germ cells or gametes," Fuller-Espie explained.

At the tips of chromosomes are telomeres, which are basically protective covers for the valuable DNA on the inside of the chromosome.

The telomeres in somatic cells degenerate with cell division, while the telomeres in gametes are repaired and maintained by an enzyme called telomerase. When the telomeres degenerate in somatic cells they get smaller and smaller until valuable strains of DNA are exposed and the cells dies.

'The telomeres are highly repetitive sequences - enough sequences for a normal life;' Fuller-Espie said.

In DNA replication, these telomeres get smaller and smaller, and over the course of a life the chromosome gets smaller. In humans, this cell division occurs about 70 times over an average life span. One risk in using these somatic cells for cloning is that the age of the cell is uncertain. When these telomeres are worn beyond repair the cells die. If the clone is made from an older cell, there may be less telomere to protect the DNA and as the clone grows it may be unable to produce vital proteins or develop defects based upon its genes, and its cell may begin to die prematurely. This process is known as senescence.