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Medical milestone: South Korean scientists have cloned human cells to help treat disease. Find out how, and why it could change the future.

Since Dolly the sheep was born in 1996, scientists have produced a virtual zoo of cloned animals: pigs, cows, horses, goats, mice, cats, and even the cattlelike banteng--one of the first endangered species to be cloned. Now, researchers are closer than ever to a human. clone, or an exact genetic copy of a cell or an organism.

Scientists create clones for two very different reasons. Reproductive cloning produces a baby animal that's the genetic twin of an adult. So far, no scientist has pulled off human reproductive cloning--no cloned children have been born. Scientists did create cloned human embryos (unborn animals in the first eight weeks of growth) for the first time in 2001. But the embryos didn't live very long.

Then, this March, biologist Woo Suk Hwang and a research team from Seoul National University in South Korea announced that they had used a microscopic needle to create more than 200 cloned human embryos from adult cells. Hwang's research took the first steps in therapeutic cloning, a process in which stem cells (cells that can become any one of the 200 different cell types present in the human body) are taken from a cloned embryo. The cells are then used to grow replacement tissues that could help treat human ailments such as diabetes, Parkinson's disease (brain disease that impairs movement), and spinal cord injuries.

Thirty of the embryos Hwang created survived in petri dishes for longer than any cloned human embryos have survived before. For this reason, his research may be the closest science has come to producing a human clone. But that doesn't mean you can start planning for your clone. "We are opposed to any attempts toward human reproductive cloning," says Hwang--a view shared by many scientists.

Read on to learn how Hwang's team tweaked the process of sexual reproduction (creation of new life by combining genetic material from a male and a female) to clone human embryos, and how his research may eventually be used to treat deadly or debilitating diseases. Then have a class discussion: Is it right to clone humans?

BACK TO BASICS

You have two sets of chromosomes (DNA, structure that carries genetic information, and protein). One set came from your father's sperm (male sex cell) and one from your mother's oocyte (unfertilized egg). Before fertilization, the egg is stuck in a stage of growth called metaphase II. It still has two sets of DNA--one set too many. To produce a new person, the egg needs sperm. "The egg will just stay [in metaphase II] forever until the sperm comes in," says Jose Cibelli, a biotechnology scientist at Michigan State University.

When a sperm enters the egg, it releases a dose of calcium particles that kick-start the egg. The egg throws its extra set of DNA out in a speck of a cell called the polar body. And DNA from the egg and sperm are united. The fertilized egg cell begins to divide and grow to become a blastocyst (ball of about 100 cells), then an embryo, and finally a fetus (unborn animal eight weeks after fertilization).

WAY TO CLONE!

A clone's DNA comes from only one parent. Some female reptiles and insects can reproduce on their own by parthenogenesis, or when an unfertilized egg in metaphase II begins to divide without sperm. The embryo is identical to the mother--a natural clone. So why not just trigger parthenogenesis to clone a person? Only women could be cloned and as of today no mammals have ever been born this way, says Cibelli.

To clone an adult cell, Hwang and his colleagues used a process very similar to those used to clone other mammals. They first removed the nucleus (area that contains DNA) from an egg cell in metaphase II. Then they took a somatic cell (any cell in the body that is not a reproductive cell--sperm or egg) from a woman and inserted it into the enucleated (nucleus-free) egg (see diagram, p. 12). Every somatic cell holds two sets of DNA.

To trick the egg into "thinking" it was fertilized, the scientists spiked it with calcium. Then the egg began dividing on its own. But instead of letting the ball of cells grow into a fetus, the scientists kept it at the blastocyst stage. At this stage, "[the clone] is tiny, tiny, tiny," says Cibelli. "It's one tenth of a millimeter, or about one third [the size] of the period at the end of a sentence."

Hwang's team made history when they removed the inner cell mass (cells that become the embryo) from the blastocyst and grew the cells in a nutrient-rich petri dish. Most cells in the inner cell mass are stem cells. Hwang used the cells to create a stem cell line, or a group of cells genetically identical to each other that would continue to grow and divide forever. It's the first stem cell line ever created from a cloned human embryo.

MIRACLE CELLS

Stem cells were originally dubbed "miracle cells" by researchers, because of their potential to treat or cure many human diseases (for more on stem cells, see Science World, Nov. 12, 2001). Already, many treatments developed from embryonic and adult stem cells are in the works. Stem cells are, in a sense, unemployed. They have no specific job in the body, so scientists can use chemicals to force the cells to become a cell type that's missing or damaged. The cells are then injected into the diseased person's body.

Example: Scientist Don Wolf of the Oregon National Primate Center is working with stem cell lines to develop a treatment for human diabetes, a disease in which cells in the pancreas can no longer regulate blood sugar levels. "You can rescue the diabetic by injecting them with [new pancreatic] cells periodically as needed--similar to a flu shot," says Wolf.

But just like any other tissue or organ transplant, the body sometimes rejects tissues grown from stem cells. That's because the immune system is stoked to attack invaders--anything it doesn't recognize as its own tissue. Right now, all stem cell lines used to treat diseases have come from embryonic stem cells or adult stem cells donated by healthy people.

Hwang's new stem cell line could change that. Tissue grown from cloned stem cells would come from a person's own cells. That means the cells wouldn't be rejected by the body's immune system. So far, Hwang has coaxed cells from the stem cell line he created into becoming all three of the basic tissue types--endoderm, mesoderm, and ectoderm--present in a developing embryo. That's promising for stem-cell researchers. But despite its potential, many people are skeptical that Hwang's research brings science too close to a human clone (see sidebar, pp. 10 to 11).

What Do You Think? Is it right to clone humans?

Scientists aren't the only people who should consider the ethics of human cloning. The issue affects all of society. It's important for you to have your own opinion based on your morals and the science you've just learned, says Mark Frankel, an ethicist with the American Association for the Advancement of Science. "Talk with friends and family, and start thinking about what are the important questions to be answered in the context of cloning," says Frankel. Here are some questions and possible responses to get you started in your classroom discussion:

SHOULD CLONED EMBRYOS BE USED TO CREATE STEM CELL LINES?

Taking stem cells from a clone requires that scientists first create an embryo and then destroy it. Some scientists argue that it's wrong to destroy an embryo that could have grown into a healthy child. "Or should the lives of the people already here [and suffering from disease] carry more weight than those [embryos] who are 5 to 6 days old?" asks Frankel.

HOW SAFE IS THE REPRODUCTIVE CLONING PROCEDURE?

Reproductive cloning has so far proved to be a difficult procedure in other animals. "We get a number of pregnancies lost. Animals are born dead at high rates, they live for weeks and then drop dead, and even the mother can die," says Jose Cibelli. However, with more practice and future technology, cloning may become safer in the coming years.

HOW WOULD IT FEEL EMOTIONALLY TO BE A GENETIC CLONE?

A clone would be different from other children. For example, a clone would not have a biological mother and father. "This technology impacts the way we think about the relationships between parents and their children," says Frankel, "There are psychological issues involved."

IS IT POSSIBLE TO OUTLAW HUMAN REPRODUCTIVE CLONING BUT ALLOW THERAPEUTIC CLONING?

Right now, there is no U.S. law against cloning of any type. But U.S. law limits the amount of research that scientists can do with stem cells derived from human embryos. Many scientists insist that therapeutic cloning should be allowed to continue in the name of scientific progress. "But that it should be done under [strict] ethical guidelines and government regulations," says Frankel.

CLONING Zoo

SHEEP: Dolly, the first cloned mammal, was born in 1996. She suffered from arthritis and cancer, and died in 2003.

[ILLUSTRATION OMITTED]

PIGLETS: Five cloned pigs--named Millie, Christa, Alexis, Carrel, and Dotcom--were born on March 5, 2000.

[ILLUSTRATION OMITTED]

KITTY: Named CC (for Carbon Copy), the first cloned pet, was born in December 2001.

[ILLUSTRATION OMITTED]

MOUSE: Scientists have cloned 50 mice identical to the first mouse clone, named Cumulina, that was born in 1997.

[ILLUSTRATION OMITTED]

GOAT: The first cloned goat, named Yuanyuan, died 36 hours after its birth on June 16, 2000, in China.

[ILLUSTRATION OMITTED]

BANTENG: Once common throughout Asia, bantengs are now endangered. This cloned banteng was born in 2003.

[ILLUSTRATION OMITTED]

CREATING A CLONE

Recently, South Korean scientists became the first team to create a stem cell line from a cloned human embryo. Here's how they did it:

1 REMOVE NUCLEUS

Hwang cut a small hole in a woman's egg and gently squeezed out its nucleus, which holds a cell's DNA.

2 TRANSFER DNA

An adult cell, with its own nucleus and full set of DNA, was injected into the empty egg.

3 START DIVISION

A calcium injection tricked the egg to divide and grow. This early stage of embryo development took place in a nutrient-rich petri dish.

4 NURTURE CELL GROWTH

After a week, the egg grew into a blastocyst--a hollow ball of about 100 cells. No previously cloned embryos have grown larger than six or eight cells.

5 ISOLATE STEM CELLS

Scientists removed the outer cell layer and grew the inner cell mass in a petri dish to form a stem cell line, or group of continuously dividing cells.

6 FORM TISSUE

The stem cells could form the three basic tissue types present in a human embryo. Ectoderm: outer tissue, like skin. Mesoderm: middle tissue, like muscle. Endoderm: inner tissue, like organ linings.

[ILLUSTRATION OMITTED]

ONE OF A KIND

Cloning is difficult--Hwang's team created only one stem cell line from more than 200 eggs.

16 women donated ...

[ILLUSTRATION OMITTED]

242 eggs, which produced ...

[ILLUSTRATION OMITTED]

30 blastocysts, which yielded ...

[ILLUSTRATION OMITTED]

20 stem-cell clusters and ...

[ILLUSTRATION OMITTED]

1 stem-cell line

[ILLUSTRATION OMITTED]

Cross-Curricular Connection:

Language Arts: Write a creative story about what it would be like to be a clone of one of your parents. How might your life be the same or different?

Social Studies/Geography: The recent research in cloning human embryos was conducted in South Korea. Research that country and prepare a short presentation on one aspect of its culture (food, religion, etc.).

Did You Know?

* Not all stem cells are alike. Embryonic stem cells form about four days after fertilization and have the potential to become any cell type in the body. After a month, stem cells differentiate, or become a specialized cell type. But some cells in the skin, brain, bone marrow, and blood remain. stem cells through adulthood. These adult stem cells are also used in research, but they are already partially specialized and have limited ability to become other cell types.

* An endangered banteng was cloned in 2003 from a single skin cell taken from a captive banteng that died in 1980.

* In 2003, Clonaid--a private biotechnology firm--claimed to have created the first cloned human being. The group has provided no evidence to support its claims. And scientists don't take their claim seriously.

* A cloned animal is not an exact duplicate of the original. The cat CC, the first cloned pet, has a different coat color than Rainbow, the calico cat she was cloned from. The two cats also behave differently.

Resources

For a comprehensive look at the science of cloning, check out Principles of Cloning, by Jose B. Cibelli, Academic Press, 2002.

For more information on the history of therapeutic and reproductive cloning and related legislation, visit: www.genome.gov/10004765

This Web site is full of information and diagrams on cloning: http://science.howstuffworks.com/cloning.htm

CHECK FOR UNDERSTANDING

Directions: Answer the following questions in complete sentences.

1. What are two reasons for cloning as discussed in the article? Explain how they're different.

2. How is a clone's DNA different from the DNA of an embryo produced through sexual reproduction?

3. What is parthenogenesis?

4. What is the inner cell mass? What did Hwang's research team create from the inner cell mass?

5. How could Hwang's research help treat diseases such as diabetes?

ANSWERS

1. To produce a baby that is genetically identical to an adult, scientists engage in reproductive cloning. (No scientist has cloned a human.) The second reason is to use stem cells from a cloned embryo to grow replacement tissues. In humans with disease, these tissues can replace damaged tissues. This type of research is called therapeutic cloning.

2. A clone's DNA comes from one parent, whereas the DNA in embryos produced by sexual reproduction comes from two parents--one set of chromosomes comes from each parent.

3. Parthenogenesis occurs when an unfertilized egg--in its first eight weeks of development--begins to divide without sperm. That means the embryo is genetically identical to its mother.

4. The inner cell mass is the group of cells that becomes the embryo. Most cells in the inner cell mass are stem cells. Hwang's research team used these cells to create a stem cell line--a group of cells genetically identical to each other that will continue to grow and divide forever. A stem cell can become any one of the 200 different cells that make up the human body.

5. Hwang's research would enable someone suffering from a disease to receive new tissue without the probability of having the body reject it. That's because the new tissue would be grown from cloned stem cells that came from the individual's own body rather than from a foreign source.
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Title Annotation:Life: reproduction/cloning
Author:Tucker, Libby
Publication:Science World
Date:May 10, 2004
Words:2454
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