A Crucial Human Cell Isolated, Multiplied
By Rick Weiss
The long-awaited discovery of so-called human embryonic stem cells -- the primordial human cells that give rise to all the specialized tissues in a developing fetus -- was hailed by researchers as a landmark event with vast biomedical potential.
The cells multiply tirelessly in laboratory dishes, offering a self-replenishing supply from which scientists hope to grow replacement tissues for people with various diseases, including bone marrow for cancer patients, neurons for people with Alzheimer's disease, and pancreatic cells for people with diabetes.
Already, researchers have used the stem cells to grow human heart muscle cells that beat in unison in a laboratory dish, as well as blood cells, blood vessel cells, bone, cartilage, neurons and skeletal muscle.
But the cells are also giving rise to daunting legal and ethical concerns.
Stem cells are controversial because they offer embryologists a relatively simple method for creating "designer" babies bearing specific genetic traits that would become part of a child's permanent genetic lineage.
The discovery also threatens to reopen the debate over human cloning, since one of the simpler ways to grow transplantable replacement tissues from the new cells would call for a patient to be partially cloned.
And in the political arena, the new work has reignited a smoldering debate over a four-year-old congressional ban on the use of federal funds for human embryo research. With the therapeutic potential of embryonic cells suddenly very real, advocates are calling for a reexamination of that ban, saying the development of lifesaving applications will be hindered if federal dollars remain off-limits.
Such a reexamination would pit antiabortion forces and other strong proponents of the funding ban against a powerful biomedical research lobby that has in recent years become popular with Congress and the public.
Adding to tensions within the scientific community, it is unclear whether the ban's wording precludes federally funded researchers from studying laboratory-reared stem cells -- the progeny of cells taken from embryos by privately funded researchers -- which are generations removed from their embryonic source.
Lawyers at the National Institutes of Health were scrambling this week to settle that issue, even as Rep. Jay Dickey (R-Ark.), one of the authors of the congressional ban, reasserted his intention to keep the funding prohibition in place.
The new work was reported yesterday by two teams of scientists working independently. James A. Thomson, an embryologist at the University of Wisconsin, and his colleagues describe their success in today's issue of the journal Science. John D. Gearhart of the Johns Hopkins University School of Medicine in Baltimore led the other effort, results of which will appear in the Nov. 10 issue of the Proceedings of the National Academy of Sciences.
Both teams, along with a group at the University of California at San Francisco, had been racing for years to isolate the cells, viewed as a likely biotechnology gold mine. All three teams have licensed commercial rights to Geron Corp., a biotechnology company in Menlo Park, Calif., although the Wisconsin researchers said they would share their cells freely with academic researchers who want to conduct basic research on them.
In an unusual move applauded by ethicists and government officials, the university association holding patent rights to Thomson's cells said that anyone wishing to work with the cells will have to sign an agreement promising not to use them to clone an individual or to make a "human-animal chimera," a seamless cross-species hybrid that could, in theory, be make by injecting human stem cells into a developing embryo of another species.
Thomson said he did the work in a room in which not a single piece of equipment, not even an electrical extension cord, had been bought with federal funds, to ensure he did not violate the congressional ban. He used leftover embryos from fertility clinics, donated by parents.
He credited his success in part to the recent availability of new nutrient broths that have made it easier to grow human embryos up to about the five-day mark, when embryonic stem cells can be taken from the embryo's so-called inner cell mass.
Thomson then perfected a biochemical environment in which the stem cells would grow and divide but remain in their immature, "uncommitted" state. Only upon removing those biochemical controls do the cells begin to become specialized kinds of tissues. Although the cells can organize somewhat, researchers cannot grow them into organs and any possibility of doing so probably remains many years in the future.
Unlike Thomson, Gearhart retrieved his stem cells from the developing gonads of aborted fetuses. Human fetal research is eligible for federal support, but he too conducted the work in a privately funded lab to avoid controversy. His and Thomson's stem cells so far seem equivalent, Gearhart said.
Experts warned that significant work remains to be done before the findings can be translated into useful therapies. Scientists know little about how to get stem cells to become one kind of cell or another. They have had some success getting them to become neurons or heart cells by adding specific hormones. But for the most part they must simply watch for the desired kind of cells to erupt out of a mass of maturing stem cells, then tease them away to be grown on their own.
The ability to purify single cell types will be crucial. In one set of experiments done in another lab, batches of cardiac cells grown from mouse stem cells were injected into the hearts of living mice. A few contaminating stem cells must have been present, scientists said, because along with the new cardiac tissue, other tissues began to grow out of the hearts.
Thomson, Gearhart and others called for a renewed debate over the congressional funding ban. "I am convinced that in my lifetime there will be therapeutic applications, but exactly when that happens depends on whether there is federal funding," Thomson said. "Without public involvement it will take much longer." Floyd Bloom, editor in chief of Science, added that if stem cell work is done solely by private companies, then ethics and public accountability rules that apply to federally funded researchers may go unheeded.
Rep. Dickey said he was unmoved. "There are not any instances in which I feel the ban . . . should be lifted," he said in a written statement. "The language of this ban prevents taxpayer funding for bizarre experiments, such as cloning. Eventually, I could see the embryonic stem cell technology going in this direction."
In fact, researchers in Australia recently suggested that patients might someday want to clone themselves to take advantage of stem cell technology. The idea is not to make a full adult replica of oneself, but to clone a genetically identical embryo from which stem cells could be removed. Tissues made from those cells would be an exact immunological match and so would not be rejected.
But Gearhart and others said there are other ways to get around the problem of immune-system rejection, including genetic manipulations to make stem cells universally compatible or the establishment of "stem cell banks" like today's blood banks.
Scientists said stem cells could make it easier to engineer babies, because a single specially endowed stem cell injected into a developing embryo will divide and spread its endowment throughout the developing fetus. NIH rules preclude such experiments in people, but officials there are considering whether to loosen those restrictions.
Scientists said the first uses for human stem cells will probably be as a source of tissues upon which new pharmaceuticals can be tested and toxins assessed, and to study the earliest stages of embryo development -- an endeavor that could lead to treatments for infertility and a reduction in birth defects.
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