How Scientific Progress Is Changing the Stem Cell Debate - Pacific Standard

How Scientific Progress Is Changing the Stem Cell Debate

The morality of human embryonic stem cell research has long been contentious, but new discoveries could end the controversy.
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Recent technological progress involving stem cells (green) may quiet the controversy surrounding their use. (Photo: ucirvine/Flickr)

Recent technological progress involving stem cells (green) may quiet the controversy surrounding their use. (Photo: ucirvine/Flickr)

"Embryonic stem cell research is at the leading edge of a series of moral hazards," declared George W. Bush in August 2001, as he announced his administration's new policy restricting federal funds for biomedical research involving human embryonic stem cells. The moral hazards Bush referred to defined a conflict between medical research and pro-life politics: Scientists and patients hoped that embryonic stem cells, with their unique capacity to develop into any type of cell in the body, would lead to radical new treatments for presently incurable diseases, while pro-life organizations opposed the destruction of human embryos necessary to obtain stem cells. As Bush put it, the issue "juxtapos[es] the need to protect life in all its phases with the prospect of saving and improving life in all its stages."

The conflict over stem cells soon became a high-profile political controversy with real consequences: It shifted political control of the United States Senate to the Democrats in 2006 and led California to create a new $3 billion stem cell research initiative, despite opposition from the Catholic Church and a coalition of pro-life organizations. Less than two months after Barack Obama took office, he eliminated Bush's restrictions with an executive order pointedly titled "Removing Barriers to Responsible Scientific Research Involving Human Stem Cells." In recent years, the controversy over stem cells has waned somewhat, but it hasn't gone fully away: In its current party platform, the GOP opposes any stem cell research that involves "the destruction of embryonic human life."

A big scientific question that has haunted the embryonic stem cell debate is this: Are these cells the only option? If therapeutic replacement cells could be obtained without using embryos, the controversy would end.

While the moral conflict over embryonic stem cells is unlikely to be resolved by compromise, recent technological progress may soon render the controversy largely moot. After a decade-long series of discoveries, two new studies describe developments that will likely enable medical researchers to skip the stem cells in medical treatments that were once thought to be impossible without them.

To see why avoiding embryonic stem cells is a big advance, it's important to understand why researchers and patients placed so much hope in them in the first place. In essence, embryonic stem cells seemed to offer a unique source of biological replacement parts, creating an opportunity to treat difficult diseases in a radically new way. Many chronic, incurable diseases are caused by the progressive loss of critical cells that are not re-generated in the sick person's body, such as dopamine-secreting neurons in Parkinson's or insulin-producing pancreatic cells in diabetes. Drugs can treat symptoms or slow the progression of such diseases, but they can’t restore lost or damaged cells—this is why these diseases are incurable.

In contrast to drugs, embryonic stem cells actually offer a cure. Because they have the capacity to become any cell type in the body, they can be used to derive replacements for a patient's lost or damaged cells. By transplanting these replacement cells into patients, medical researchers could reverse the otherwise irreversible symptoms of the disease. If successful, the results would be transformative: Parkinson's patients would regain control of their movements, diabetics could stop taking insulin, and patients suffering from macular degeneration would regain their vision. In 2001, embryonic stem cell-based therapies were completely hypothetical, though similar ones using more limited, non-embryonic stem cells—such as bone marrow transplants, which transfer specialized blood stem cells to treat leukemia—had existed for decades. Today, these embryonic stem cell treatments have been shown to work in laboratory mice but not much more; however, the first human clinical trials for a embryonic stem cell therapy for macular degeneration are now underway.

A big scientific question that has haunted the embryonic stem cell debate is this: Are these cells the only option? If therapeutic replacement cells could be obtained without using embryos, the controversy would end. And there has long been a good reason to believe that an alternative source of cells might be possible. Because nearly every cell in our bodies carries exactly the same genetic information, any cell—not just embryonic stem cells—could theoretically be converted into any other type of cell. A meter-long motor neuron that conducts electrical signals down the spine is physically and functionally very different from the micron-scale hepatocytes that metabolize carbs in the liver. Yet the neuron carries the same genes as the hepatocyte; the reason they differ is because the neuron has switched on a different set of genes. By finding a way to convert an ethically non-controversial source of cells—such as skin cells—into the cell types needed for therapies, we could end the debate.

But turning on genes to formulate a specialized cell is a complicated process involving a series of steps in which genes are switched on and off in a certain sequence. Embryonic stem cells lie at the beginning of this series; they are the crossroads from which one of many different paths can be chosen, leading to a final, specialized cell type. For a long time, researchers believed that cells travel these paths in only one direction: Once cells reach their final state, they almost never leave it. And though a neuron and a liver cell may have exactly the same genes, scientists believed they couldn’t change one into the other—as they say in Maine, you can't get there from here. There is no shortcut from a neuron to a liver cell; you have to start with a stem cell.

While this idea is true inside our bodies, researchers have now demonstrated that it is not this way in a test tube. In Nobel Prize-winning work published in 2006 and 2007, Japanese researcher Shinya Yamanaka and his colleagues managed to reset skin cells to a stem cell state, creating what are called "induced pluripotent stem cells,” and thus demonstrating how to get stem cells without using embryos. Induced stem cells have been an enormous boon to disease research, but they currently can't be used in stem cell transplant therapies because they usually contain mutations that would put patients at risk for developing tumors.

More recently, scientists discovered that there are, in fact, shortcuts between different types of cells. In 2010, a team at Stanford converted mouse skin cells directly into neurons, without creating stem cells first. And just last year, a team of Chinese scientists converted human skin cells into liver cells, which functioned normally when transplanted into mice. However, as with the creation of induced pluripotent stem cells, these studies relied on genetic manipulations that make the resulting cells inappropriate for therapies.

But in a pair of studies published earlier this month, two teams of Chinese researchers have demonstrated how to re-program skin cells into neurons without using genetic modifications, opening up a major new pathway for cell therapies that don't require human embryos. In each case, the researchers devised a drug cocktail that caused skin cells to shut off one set of genes and turn on another. Importantly, this process happens without any permanent changes to the cells' DNA—the drug cocktail simply prompts the skin cells to activate dormant neuronal genes, causing them to transform into neurons. In one study, researchers found that a combination of four drugs was enough to re-program mouse skin cells into functional neurons. In the second study, another research team achieved a similar result with human skin cells, using a different chemical cocktail. This latter team then went one step further: They took skin cells from an Alzheimer's patient and re-programmed those into neurons. The resulting neurons had some of the protein build-up that is characteristic of Alzheimer's disease, demonstrating that this method of re-programming cells—in addition to its possible therapeutic value for patients—is a potentially powerful way to study a disease in a petri dish.

Results like these have the potential to settle the debate over embryonic stem cells. The controversy isn't over quite yet though—while the newer techniques are immediately useful in research, they have yet to yield any therapies. And because embryonic stem cells are useful for studying how different types of cells develop naturally in the body, they still play an important role in ongoing biomedical research. However, viable alternatives to embryonic stem cells—which were only a hope in 2001—are now a reality. Technological progress has a well-known tendency to create moral controversies, something that was certainly true when scientists first learned how to derive stem cells from embryos. But in this case, technology will likely help us settle the controversy as well.

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