The cellular divide

Advocates and critics join scientists in debating the ethics and potential benefits of stem-cell research
Sunday, October 31, 2004 | 12:00 a.m. CDT; updated 2:19 p.m. CDT, Tuesday, July 22, 2008

For Kate Swearengen, 22, the political debate over embryonic stem cells is no mere theoretical exercise.

Swearengen, a Columbia native who is studying at Cambridge University in England, was diagnosed with Type 1 diabetes when she was 7. Her immune system killed the insulin-producing cells in her pancreas after mistaking them as foreign.

The lack of insulin in her body results in dangerously high blood-sugar levels, requiring Swearengen to constantly monitor those levels with repeated finger pricks and regular injections of insulin.

“When I was diagnosed with Type 1 diabetes in 1988, they told me there would be a cure by the time I graduated from high school, so I was very hopeful,” she said. “But then the enthusiasm petered out because no new discovery came up. Now, with embryonic stem-cell research, I am hopeful again.”

The science of embryonic stem-cell research is still relatively new, with such cells first isolated for potential research use only six years ago.

But as the Nov. 2 presidential election draws near, stem-cell research has emerged as one of the campaign’s most divisive issues, invoking passionate debates over the value of human life and inciting social, ethical and moral clashes pitting science against faith.

Closer to home, the debate over stem-cell research has infiltrated the 19th District state Senate race between Chuck Graham and Mike Ditmore as well as Missouri’s gubernatorial election.

In Jefferson City, a state senator is proposing a bill to ban therapeutic cloning, also known as somatic-cell nuclear transfer, in both private and publicly funded research institutes.

And at MU, two research groups at the Life Sciences Center are using one of only 22 viable embryonic stem-cell lines to examine how placental cells are formed in the embryo, which in the long run could lend a better understanding to why certain pregnancies fail.

Supporters cite the potential of embryonic stem cells to cure a range of ailments, from Parkinson’s disease and spinal cord injuries to multiple sclerosis and stroke-related injuries.

Opponents say the price of such progress — the destruction of human embryos — is too high.

The most common source of these cells are leftover embryos in fertility clinics that would otherwise remain frozen and unused. The embryo must be 4 to 6 days old before stem cells can be extracted and only then with parental consent.

Unlike nerve cells and other highly specialized cells found in the human body, embryonic stem cells are not sufficiently developed to perform specific functions. That gives these less-developed cells the capability of growing into any one of the more than 200 types of specialized cells in the human body.

For Mary Andersen, a biology researcher at the MU School of Medicine, the potential research benefit of embryonic stem-cell research doesn’t mitigate what she and other opponents consider the more fundamental problem: the destruction of human life in the pursuit of saving or enhancing human lives.

“Life begins when you have a cell that is genetically different from the mother,” said Andersen, a local activist for Missouri Right to Life and the Missouri Catholic Conference. “They are creating another human being and killing it to heal somebody else.”

Linda Swearengen, Kate’s mother, runs a local alert network for the Juvenile Diabetes Research Foundation. The Columbia resident said she has great respect for those whose strong religious beliefs guide their opposition to embryonic stem-cell research.

“But I don’t think that their religious beliefs should interfere with science, especially when there is potential benefit to millions of people around the world,” she said. “If they don’t believe in it, they don’t need to partake in it.”

Mahendra Rao, the lead investigator at the national Institute of Aging’s stem-cell biology unit, welcomes the public debate.

“It is important to remember that scientists don’t work in isolation from the society,” Rao said. “Decisions should be based upon consensus from open discussions.”

According to a July poll of 2,242 respondents by Harris Interactive, the majority of Americans — regardless of political affiliation or religion — support using embryos remaining from in vitro fertilization for stem-cell research.

Seventy-three percent of all respondents support such an initiative, the poll shows, including 80 percent of Democrats and 60 percent of Republicans surveyed.

Bill Temple, 71, has been suffering from Parkinson’s disease since 1981. A set of neurons in his brain that produces the chemical called dopamine began to die of unknown reasons, causing Temple to lose control of his muscles.

Unlike most Parkinson’s patients, he recently had deep brain stimulation surgery in which electrodes were implanted in his brain to help him recover most of the lost functions. He must rely on strong medicines with serious side effects, however, to maintain his dopamine levels.

Temple, a Columbia resident and retired minister, is optimistic that even if it is not during his lifetime, others like him will one day benefit from embryonic stem-cell research. He has little patience for the arguments of those opposed to embryonic stem-cell research.

“It’s ridiculous,” he said. “We are giving life to those who are alive and have diseases which interfere with their lives.”

Frozen embryos left over after in vitro fertilization procedures are the most common sources of embryonic stem cells. That treatment typically involves the implantation of numerous fertilized eggs at a time or over several times in hopes of finding just one viable embryo. This results in the production of more than one embryo per couple.

The extra embryos are stored in freezers but are destroyed by the in vitro fertilization clinics after a certain period of time. Storing the excess embryos for too long makes them unusable, not unlike the way food deteriorates if left too long in a freezer.

While there are no restrictions on private funding of embryonic stem-cell research, President George W. Bush in August 2001 decided to allow embryonic stem-cell research but also said that such cells derived after that date would not be eligible for federal funds.

Scientists have since found that only 22 of the 78 initial stem-cell lines — including the one that provided MU researchers with their cells — remain viable for research.

No easy answers

Like many ethical debates, the fight over embryonic stem-cell research defies easy answers, Linda Swearengen said.

“All the way through life, in many instances one has to make moral choices,” she said. “I have never thought of a fertilized egg stored in a freezer as more important than a live human being who is suffering from a disease.”

For scientists, the question is not just whether to allow the creation of more stem cells but also whether there is a need to increase the number of available stem-cell lines.

“We don’t know enough about the 22 cell lines we are working with right now,” said James Battey, the stem cell task force chairman at the National Institute of Health.

“Can I promise you though that there will never come a day when more stem-cell lines will be a limiting resource? No, I can’t promise you that.”

David Fleming, an MU internal medicine specialist who teaches medical ethics, said the debate boils down to the definition of a human being. He compared an organ donor and an embryo used to create stem cells as an example.

“The difference between these technologies and other situations where we use human tissue to heal others is that we don’t destroy the donor of an organ or of blood,” he said. “We do destroy the embryo when we remove the stem cells from it.”

Fleming said society awards the embryo and the organ donor different levels of respect. The donor is allowed to choose whether to donate the organs. The embryos aren’t given that choice.

“If the embryo is a human being, we have to justify using it as an implement of technology,” he said. “If we create another human life in order to kill it and use it to heal somebody else, it is slavery. We fought a civil war to prevent this.”

Even though some scientists support the research, they warn that sometimes the promises from this research are blown out of proportion.

One example is the prediction of curing Alzheimer’s disease through embryonic stem-cell research.

In fact, Alzheimer’s is a large-scale neurodegenerative disorder. Unlike Parkinson’s disease, where a localized set of neurons in the brain are lost, the loss of neurons in Alzheimer’s is more dispersed, and many different kinds of brain functions that scientists don’t understand fully are lost in Alzheimer’s patients.

Targeting such a large-scale disorder using embryonic stem cells in the near future is an unlikely possibility, said Michael Roberts, director of MU’s Life Sciences Center.

“There is very little hope for targeting Alzheimer’s through embryonic stem cell research in the immediate future,” said Roberts, who is working on the MU stem cell research project.

Battey agrees, noting that given the infant stages of embryonic stem cell research, it is inappropriate to make policy decisions based on an uncertain future.

“I think it’s dangerous to predict for what disease and when a treatment involving human embryonic stem research might be developed,” he said. “We are really at the basic science stage of this research and to extrapolate to when and if there will ever be clinical application, I think is a dangerous thing to do.”

Still, considerable progress has been made in transforming embryonic stem cells into specific cell types. Many researchers have succeeded in getting embryonic stem cells to develop into various cell types using mouse embryonic stem cells as well as human embryonic stem cells.

With human life at stake, though, that’s only the beginning. There are issues regarding successful transplantation, transplant rejection and transplant survival in the patient.

“We also need to understand how to make grafts of these cells, placed into a patient, function stably, avoid rejection and not continue to recycle such that a tumor may develop within the transplanted tissue,” Battey said.

Therapeutic Cloning

The most contentious source of embryonic stem cells are those created through therapeutic cloning, or somatic cell nuclear transfer. Often confused with reproductive cloning, the process involves taking an egg cell and replacing the egg’s nucleus with a nucleus taken from any other cell in the patient’s body.

This produces an egg cell capable of developing into an embryo without fertilization. The cell can then be grown in a laboratory to the blastocyst stage to obtain embryonic stem cells. It also allows the researcher to work with embryonic stem cells that are genetically identical to the patient’s, thereby avoiding immune rejection.

But most diseases, especially cancers and neurological disorders, have a narrow window during the disease’s onset during which treatment is most effective, which raises questions about the effectiveness of therapeutic cloning and its lengthy process.

Technical hurdles aside, therapeutic cloning has drawn more fire than embryonic stem-cell research. Across the country, state legislators are trying to ban the procedure on ethical grounds.

Sam Bartle, a Missouri state senator from Lee’s Summit, has introduced a bill to ban the therapeutic procedure in Missouri. Similar bills have been introduced and failed to pass twice before in the Missouri legislature. The ban would effectively prohibit any person or organization, private or public, to conduct therapeutic cloning in Missouri.

“We should not allow human embryos to be killed to help another human being,” he said.

Edmund Pellegrino, a professor emeritus of medicine and medical ethics, agrees with Bartle that there is no difference between a blastocyst created from therapeutic cloning and one created by traditional means.

“The totipotent blastocyst can become a baby if implanted into a woman’s womb,” said Pelligrino, who recently visited MU for a series of bioethics lectures. “Ethically there is no difference between the two embryos.”

Cynthia Kramer disagrees. She is a St. Louis resident with a rare form of lymphoma. Her cancer is in remission because she received therapy with stem cells produced by therapeutic cloning.

“This is a question of religious freedom,” she said. “They are trying to force their theology on me.”

Kramer, who is Jewish, said that the theological view on when life begins is a religious tenet and should not be the basis for state or national laws.

Locally, both the Democratic and Republican candidates for the District 19 state Senate seat said they would oppose the ban if elected.

“It will slow down medical research, and this is research that can help spinal-cord injury patients like me,” said Chuck Graham, the Democratic candidate. At 16, Graham was hurt in a car accident after he was thrown through the front windshield, breaking two vertebrae during the fall.

With excessive scar tissue in his bone marrow that would block any neurons from getting through, Graham does not have much hope of ever walking again. But stem-cell research has given him slight hope that he will be able to at least stand up, if stem cells could help regenerate neurons that can bypass the scar tissue altogether.

“I have been in this chair longer than I have been out of it,” he said. “But it would be great to just be able to stretch again.”

His Republican opponent, Mike Ditmore, said the legislature should be careful about making long-term decisions when its members don’t know where the research will lead. Ditmore is a MU professor in neurological surgery and believes in the fortuitous nature of medical research.

Unlike his opponent, Ditmore opposes using leftover embryos and aborted fetuses as a source of embryonic stem cells. Blastocysts created through therapeutic cloning could be used as long as they had not developed into embryonic cells before the stem cells where harvested, he said.

“Embryos should not be killed for their stem cells,” Ditmore said, adding he would oppose a ban on therapeutic cloning ban because private interests should be allowed to explore this type of research in the state.

Adult stem cells

One overlooked aspect of embryonic stem-cell research is in the field of drug discovery and drug testing. For years, adult cancer cell lines have been used to test cancer-fighting drugs.

Using embryonic stem cells and their derivatives to test newly discovered drugs or drugs under development provides an opportunity to determine the benefits as well as the side effects of drugs on specific cell types.

Since 22 cell lines mean 22 different genetic backgrounds, increasing the number of embryonic stem cell lines could increase accuracy of tests.

There are other examples of how cells cultured in the laboratory are used in medicine. While cancer cells have led to improved drug discovery, adult stem cells have long been used to treat many diseases.

Bone marrow transplants — in essence, the transplanting of blood stem cells — are a common treatment for lymphoma. Some children have been successfully treated with healthy adult stem cells to cure blood disorders such as thalassemia.

Adult stem cells have many restrictions, though. Unlike embryonic stem cells, they cannot be grown in cultures indefinitely. Also, adult stem cells are much less flexible in forming different cell types.

And because they are found in specific tissues, adult stem cells can form cells found only in their parent tissue. For example, a neural stem cell can form only cells in the nervous system.

Should research proceed?

Laura-Denise Maxwell is a student at Stephens College and has sickle cell beta thalassemia, a genetic disorder. Because her red blood cells are sickle shaped, they cannot travel through blood vessels as easily as normal oval-shaped blood cells, leading to tissue damage.

Because the thalassemia reduces her blood cells’ ability to transport oxygen around her body, her body is very sensitive to stress, and the slightest fluctuation in temperature throws her body into a serious oxygen crisis. She regularly takes painkillers and other medicines with at least two to three visits to the hospital per month.

Although Maxwell does not suffer from a form of the disease that is severe enough for a blood transfusion or bone marrow transplant, she hopes that those who suffer more than she does can one day benefit from anything that embryonic stem cells might offer.

“There was a time not 20 to 30 years ago when cancer research was in its infant stage,” she said. “Did we stop researching because we did not know what we would find? If 100 years from now scientists have been trying in vain without any therapy from embryonic stem-cell research, then you can ask me and I will agree that it can be stopped, but why should we give up without trying?”

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