Stem Cells: 5 Year Progress Report


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Stem cell:
A cell that can change into other types.

Embryonic stem (ES) cell:
Cell from embryo, can become any cell type.

Adult stem cell: Stem cell from mature animal, often from bone marrow.

Differentiation: Process of becoming more specialized.

A fertilized egg makes a blastocyst, which houses a group of undifferentiated cells. Offspring of these embryonic stem cells are the source of every cell in the body. Illustration by S.V. Medaris for the University of Wisconsin-Madison

The Bush compromise is probably slowing the research, but it could have been stopped altogether.


Epochal announcement
Five years ago today, scientists reported that, for the first time, they were growing do-it-all human cells. These embryonic stem cells form shortly after fertilization and their offspring eventually specialize into every cell in the body. Scientists had long known that blood stem cells could form other blood cells, but before there is a blood stem cell, there must be an embryonic stem (ES) cell.

 Reeve speaks from his wheelchair, two men in background.Actor Christopher Reeve, paralyzed from a riding accident, favors stem cell research as a key to regenerating spinal cord and other nervous system tissue. James Thomson and John Gearhart are two pioneers in stem cell research. Courtesy The American Society for Cell Biology

And that's why the announcement, from a group headed by developmental biologist James Thomson at the University of Wisconsin-Madison, sparked such excitement. "There is almost no realm in medicine that might not be touched by this innovation," gushed Harold Varmus, who was then running the National Institutes of Health.

In normal human development, ES cells are driven by a genetic program to automatically change, through a multi-step process, into the 220 human cell types. But even after 100 generations, Thomson's ES cells remained "totipotent" -- able to make any body cell.

 Diagram shows how stem cells are cultivated.

Much like a car-parts catalog on steroids, the offspring of ES cells include page after page of must-have items: Replacement cells? Just name the variety. Replacement tissues? Nothing more than a collection of similar cells. Replacement organs? Well, aren't they just a batch of tissues?

People with damaged cells took notice. Hoping that stem cells can be grown into neurons to repair his spinal cord, paralyzed actor Christopher Reeve, for example, just made a pitch for ES cell research.

In theory, at some point, after a lot more time and money is spent, the descendents of do-it-all cells may supplement or replace myriad diseased or dead cells:

Pancreatic cells might treat juvenile diabetes, a deadly scourge to 1 million Americans.

Replacement dopamine-producing cells in the brain might treat Parkinson's disease -- which robs half-a-million American adults of mobility.

Made-to-order heart-muscle cells might treat heart disease, the nation's largest killer.

Researcher creates research boon
Long before ES cells treat any disease (and we are talking five years minimum), they may help researchers understand:

How genes and chemical signals control development.

The function of specific genes

The structure and function of various cell types.

Drug effects and side-effects.

Research = murder?
Yet despite the long list of possible benefits, ES research quickly fell under a cloud. Human embryos die when the stem cells are removed, so if you think life begins at conception, this research amounts to murder.

Thus even though the embryos are left over by fertility-clinic clients, there was pressure to restrict or ban the research. (It didn't help that Thomson's 1998 report (see "Embryonic Stem Cell Lines Derived..." in the bibliography) appeared less than two years after a truly bizarre bit of scientific news: the cloning of Dolly the sheep.

In August, 2001, almost three years after Thomson's discovery, Pres. George W. Bush announced that the federal government would fund ES cell research -- but only on 60 or 70 existing lines of cells. These so-called "presidential stem cells," were deemed ethically acceptable because they would not require the destruction of more embryos.

If you wanted to work on other lineages, you could find your own money, or move to a country with less government regulation. (Speaking of which, Singapore is making a push to become a center of ES cell research, and many stem cell researchers we tried to reach were in Singapore for a meeting.)

Three round cells with blue-stained narrow cells
Microscopic view of colonies (rounded, dense masses of cells) of human embryonic stem cells in biologist James Thomson's research lab. The skinny cells are fibroblasts that help keep the ES cells in a primitive state. Copyright University of Wisconsin-Madison

Ifs, ands and buts
It seemed like a good compromise, but for a couple of "buts." First, more than two years later, nowhere near the 60-plus cell lines mentioned by Bush are available. Most estimates we saw were closer to one dozen.

Second, those cell lines were experimental, created to explore the culture of embryonic stem cells rather than treat disease. Because the cells were grown in contact with mouse cells, they could be a conduit for new infections. "Human therapy could be done on the existing cell lines," says Thomson, "but if I were a patient, I'd prefer it to be based on better lines." Any medical use, he stresses, is at least five years away. Beyond the infection problem, more must be learned about controlling differentiation and preventing runaway growth -- cancer.

Nonetheless, embryonic stem cell research is exploding. Globally, about 200 labs are working with the do-it-all cells. The Bush compromise, Thomson says, "is probably slowing the research [in the United States], but it could have been stopped altogether."

How close are embryonic stem cells to meeting those Texas-sized hopes?

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