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John Harvard's Journal

Science and Politics and Stem Cells

7.1.01

Scientists became alarmed this spring when the National Institutes of Health (NIH) canceled a meeting to review applications for federally funded stem-cell research. Stem cells are considered the most promising area of research for treating many human diseases, from diabetes and cancer to heart disease. But because President George W. Bush reportedly opposes the use of human embryonic stem cells in research, politics will play a major role in stem-cell science, at least in the United States. "I'm a little surprised that the NIH, which is a scientific organization, said six months ago that it is okay to use federal funds for this sort of work, and now they're saying it is not," says Douglas Melton, a leading researcher. "What new information do they have?"

Melton before a slide showing an islet of the pancreas
Professor Douglas Melton, a leading figure in the field of stem-cell research, hopes to find a cure for diabetes using embryonic stem cells--and the federal government may be standing in the way.
Photograph by Stu Rosner
The fact that stem-cell research has become a political question clearly distresses Melton, Cabot professor of the natural sciences. Though his own work continues with private funding from the Howard Hughes Medical Institute and the Juvenile Diabetes Foundation, Melton wants to see a community of scholars studying stem cells. "There is not enough private money to effectively look into treating all these diseases--of the blood, heart, kidney, cartilage, muscle, pancreas, brain--there is not yet enough research done," he says, "to convince pharmaceutical companies that they should invest significant portions of their limited research budgets there. So the pace of research is going to be not slowed--it will essentially be shut down by the lack of public funding."

Stem cells hold tremendous promise because of two unusual characteristics that make them unlike any other cell in the body. They have, first, the ability to replicate themselves indefinitely. Second, they give rise to the specialized cells that make up distinct organs and tissues. A stem cell can create connective tissue like skin and muscle; bones; organs like the heart, the kidney, or the liver; blood; and brain. The human body creates all the various cells needed for life through a cascading process of cells begetting other cells, called differentiation. At the headwaters of this river of life are embryonic stem cells, an apparently inexhaustible source of renewal.

Although scientists have worked for decades with certain kinds of stem cells--such as the hematopoietic stem cell (HSC) that gives rise to blood--the evidence for their ubiquity as engines of cell renewal throughout the body in adults is partly deductive; scientists know the rate at which cells die, and so they know, for example, that when you look in the mirror, the face staring back at you is literally not the same one you would have seen two months ago. And since all the specialized cells in the body are post-mitotic--they are no longer dividing--stem cells must be the source of new cells to replace the ones that have died. But where in adults those stem cells reside is still a mystery.

For Melton, learning about these special cells is the next wave in biology--and an issue close to his heart. The mapping of the human genome is "a major achievement," he says, but "lost in the excitement is something we all know from high-school biology: that the unit of life is not the gene--the unit of life is the cell. The cell is what is alive and can grow; a gene you wouldn't say is alive." He believes, therefore, that stem cells hold more immediate promise than genetic techniques as a method for curing disease.

That's where the issue gets personal for Melton. A decade ago, his then six-month-old son Sam developed type 1 diabetes, an autoimmune disease that causes the body to attack and destroy its own insulin-producing pancreatic beta cells. Doctors believe the immune response was precipitated by a common cold virus. Ever since, a daily series of blood sugar tests and insulin shots has kept Sam alive. Melton's wife, Gail, has, he says, "become Sam's pancreas."

Melton, a molecular and cellular biologist, was studying early frog development at the time. "I knew nothing about diabetes," he says. But his life, like the lives of all parents of diabetics, is different now--and so is the focus of his research. He is attempting to harness the power of embryonic stem cells to create insulin-producing islets--organ-like structures within the pancreas, made up of beta cells--that could one day cure diabetes. Where the genetic approach to a cure is fraught with complexity--Melton points out that many interacting genes may contribute to diabetes, or each diabetic may have a slightly different genetic profile--the disease presents one simple problem at the cellular level: missing cells. (Melton notes that there are other diseases, such as Alzheimer's, Parkinson's, and osteoporosis, that are also caused by missing cells.)

Through a process called differentiation, human embryonic stem (ES) cells have the potential to become any tissue in the body, as illustrated at left. No other cell type in the body is known to have that capacity, or the ability to replicate itself forever, as ES cells do.
Through a process called differentiation, human embryonic stem (ES) cells have the potential to become any tissue in the body, as illustrated at left. No other cell type in the body is known to have that capacity, or the ability to replicate itself forever, as ES cells do.
Image courtesy Douglas Melton
Not all stem cells hold equal promise for regenerative medicine, however, and therein lies the controversy. Adult stem cells, such as the blood-making HSC, are not controversial, but they are not as plastic or long-lived as embryonic stem cells, which appear to be immortal and can give rise to any kind of specialized tissue. The problem for some people is that embryonic stem cells come from frozen blastocysts (an undifferentiated mass of four to 50 identical cells that forms in the first few days after a sperm fertilizes an egg). Although a blastocyst is "not a fetus," Melton explains, "it is a potential life"--and when stem cells are removed from frozen blastocysts (slated to be discarded by in-vitro fertilization [IVF] clinics), the blastocyst is no longer viable.

"It would be stupid, even misleading, for me to pretend that all of this is not connected to the politics of abortion," says Melton. "I'm not sure why or how, but I think that anything that has to do with fertilized eggs or embryos makes people think about abortion. That's clearly what has made this a difficult subject." But Melton believes that a hard look at the process shows that support for stem-cell research is the only defensible pro-life position and notes that historically "pro-life" politicians like U.S. Senator Strom Thurmond and former senator Connie Mack support stem-cell research.

Melton outlines four possible fates for the blastocysts frozen in IVF clinics nationwide. First, they could be discarded, "which if you're a practicing Catholic is killing." Second, they could remain frozen forever, "which is a cop-out that is essentially the equivalent of discarding them, because they are not alive." Third, they could be used for research, which means destroying the blastocysts but keeping the stem cells alive to help the living. Fourth, they could make a baby, "but not by the couple who donated them, because their fertility treatment is over."

An islet of the pancreas, seen in cross section thanks to the focused beams of a confocal microscope. Insulin-producing beta cells, which diabetics lack, are shown in blue. Scientists plan to use embryonic stem cells to grow islets and other tissues for transplantation, offering new treatments for numerous diseases.
An islet of the pancreas, seen in cross section thanks to the focused beams of a confocal microscope. Insulin-producing beta cells, which diabetics lack, are shown in blue. Scientists plan to use embryonic stem cells to grow islets and other tissues for transplantation, offering new treatments for numerous diseases.
Image courtesy Douglas Melton
"The pro-life position is actually number three," argues Melton, "because number four is never going to happen. There is no way that you are ever going to find enough women to have a baby" from the 50,000 to 1 million frozen blastocysts he estimates already exist. In any case, he says, only one or two in 20 can still produce a baby after being frozen. To critics he describes as "overly concerned about things that have the potential for life" he suggests more concern about "things that are alive": children suffering from disease, the thousands of children in orphanages in this country. Some people conclude that Melton is insensitive to their moral and ethical concerns. "I'm not insensitive," he answers. "I just think you need to consider all these issues and options and make a decision. It's not a simple decision."

Last year, a group of religious leaders, laymen, and medical doctors on the National Bioethics Advisory Commission recommended new guidelines for federal funding of stem-cell research. The policy encouraged the study of stem cells using public money, but concluded that creating stem cells with such funds was not appropriate: it would involve sacrificing blastocysts and possibly violating a law that bans federal funding for any research that destroys embryos. The guidelines were a palatable compromise to both advocates and opponents of stem-cell research. The "pro-life" concern that any federal funding for stem-cell research would fuel a secondary market for stem cells, thereby destroying additional embryos, turns out to be unfounded, Melton notes, because only a hundred to a thousand stem-cell lines would be sufficient for all future scientific research worldwide. Melton for his part regards the guidelines' denial of public funding for deriving stem cells as "troublesome"; he believes that it will hurt research in the field of early human development. But he, too, finds the guidelines palatable, because the process of creating stem-cell lines would be a one-time challenge for which he is confident that private money could be raised.

But now the present administration is considering eliminating all public funding for such research, instead of challenging the nation to harness stem cells for regenerative medicine, as President Kennedy challenged scientists to put a man on the moon. That is a blow Melton feels keenly, both as a scientist and as a father. Young doctors at Harvard Medical School, he says, are unlikely to pursue stem-cell research aggressively when public funding, and even private or University support, is "cloudy."

Late in April an NIH scientist, Dr. Ron McKay, announced that his laboratory had used embryonic mouse stem cells to create insulin-producing organs. Suddenly, the goal of achieving this feat in human beings seemed within reach. But McKay, as an employee of the NIH, can't work with the human cells. Melton, six other scientists, and the actor Christopher Reeve have filed a federal lawsuit accusing the Bush administration of illegally withholding funding for stem-cell research that they say will save lives. The new president asked for a review of funding guidelines for stem-cell research when he took office. As of late May, the review board had not met.