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Stem cell battle resumes
POSTED 16 SEPTEMBER 2010

No cures yet, but...

Circular multicolored mass in center, surrounded by blue fibroblasts.
Microscopic view of human embryonic stems cells in the lab of developmental biologist James Thomson. The ES cells in the circular mass are being fed by the flat, elongated cells, called fibroblasts.

Critics correctly note that no cures have emerged from human embryonic stem cells. But Stephen Duncan, of the Medical College of Wisconsin, observes that these complex cells have only been under study for 12 years, and with limited funding, "we have not been able to do the research that would be required to take them to the clinic. If the federal government continues the funding blockade, of course we will never be in a position to use them therapeutically."

Cutting ES research now because it has yet to pan out would be "akin to saying in 1965 that we should scrap the Apollo program because there has never been a man on the moon," Duncan insists.

Lawrence Goldstein, of the University of California, concurs. "It's a ridiculous argument. The point about research is that you start a line of investigation that may take many years to develop into a therapy."

Fifty years after the discovery of adult stem cells, Goldstein says they have not produced a treatment for neural diseases like ALS or Parkinson's -- key targets of ES researchers. "We need to expand our approach. If you worked on an automobile engine with just a screwdriver for 30 years, you would have reached the limit of what you can do; it's time to invent the wrench. You could say, 'Nobody has used a wrench to work on an auto engine,' but that's an absurd argument."

A promising alternative?

Opponents of ES research also point to a newer type of non-ES stem cell, the induced pluripotent stem (iPS) cell. These hybrids originate from adult cells, but revert to a primitive form with many of the same talents as ES cells.

Although iPS cells require no embryo, experts say they are different from ES cells, which remain the standard for evaluating iPS cells. Anita Bhattacharyya, who studies Down Syndrome at the Waisman Center at UW-Madison, says. "I study early brain development, what mistakes lead to chromosomal abnormalities, and I mostly work with iPS cells. But I need ES cells to tell me what is different about the iPS cells."

Bhattacharyya says two of her approved grants have been put in limbo by the temporary injunction. "When the funding stopped, I was a little panicked about how to pay my technicians."

iPS cells do have a lot of promise, but they differentiate rather erratically, says Su-Chun Zhang, a professor at the UW-Madison School of Medicine and Public Health. "Embryonic stem cells can pretty much be predicted, but induced cells cannot. That means there is still some work to be done to generate ideal induced pluripotent stem cells for application."

And iPS cells, like ES cells, have no proven utility in treating human disease.

The promise of embryonic stem cell research

Diagram shows that stem cells can be used to study drugs, cell differentiation and birth defects
Embryonic stem cell research could lead to treatments and perhaps cures for many incurable illnesses.

What does it mean?

As Washington politicians ponder whether to try to overturn the Dickey-Wicker amendment, scientists are wondering what will happen to their research programs.

The vast majority of basic medical research in the country is funded by the federal government, and shutting down programs gives highly trained scientists the willies. "There is a quick-death portion to this decision: You have to let people go because money is not there," says David Gamm of UW-Madison.

Interpreted literally, the Lamberth decision could require scientists to halt projects and stop feeding cells and animals that they have been developing for years. It could return us to the situation during the Bush Administration, when lab equipment had to be duplicated and federal funds could not pay for so much as a paperclip in ES labs.

 Room with empty cabinets, 2 long bare tables with drawers, 3 chairs and 2 cardboard boxes
Embryonic stem cell research could lead to treatments and perhaps cures for many incurable illnesses.

Even California scientists, who are eligible for state funding, are threatened, because their many out-of-state collaborators are reliant on federal funding.

ES work cannot stop and start like a streetcar, says Bhattacharyya. "Humans develop slowly, the human ES and iPS cells grow slowly. Every step takes weeks rather than days. If we had to stop, and start all over again, it would take several months to get back to where we were."

Longer gaps carry further risks, as research teams disband or investigators go to other countries where ES research is more accepted, says Gamm of UW-Madison. "When a thing shuts down, it will take years, if not decades, to recover. People will go away, go to other countries or to different forms of research, and not return."

Israel, Singapore and the United Kingdom are all actively promoting stem-cell research, and are interested in attracting skilled researchers. This international competition could add to pressure on Congress to reject the Dickey-Wicker amendment, says Buddy Ratner, a biomaterials expert and professor of bioengineering and chemical engineering at the University of Washington. "The biotechnology industry in the U.S., including big pharma, wants stem cell research and will use their influence to shift legislation," he told us by email.

Ratner expects other pressure to come from patient advocacy groups and major U.S. universities. "The voices against stem cell research are actually a small minority of Americans (but very loud and politically effective)," he says. "I think their voice will be drowned out when the groups advocating stem cell research get organized."

Middle-aged man in lab coat and younger man in purple shirt standing and looking into a book on a desk
Losing the next generation of stem cell researchers could result from the funding restrictions.

Unwanted interruption

The funding shutdown could affect the entire research enterprise, says Gamm. "Who would want to train in a lab and learn techniques that have no chance of obtaining federal funding? A university does not want to hire people who won't get federal grants. The threat is that we'll lose a generation of researchers."

"We spend a lot time training the next generation of students," agrees Duncan. "These are the guys who will be making many of the new breakthroughs that you will be seeing in the hospital in the next 10 or 20 or 30 years. This is the long-term impact of impairing our ability to conduct research with human ES cells."

The ultimate impact of the ES funding dispute concerns desperate patients, who will continue dying with the hope that science and biology can come to their rescue. "In normal times, we get two to five calls a day from patients, and we can always offer them some hope, we are working on this," says Jan Nolta, head of a large stem cell program at the University of California at Davis. The recent injunction "was such a shock, so depressing. It was hard to keep giving hope to these patients."

Nolta says in her specialty, the always fatal Huntington's disease, "we hope to make medium spiny neurons, the kind that slowly die out in Huntington's, and do replacement therapy. It's a horrific disease, heartbreaking. Patients and families are living every day, hoping we can start trials to move the science forward. This injunction is like a slap across the face, telling them their government does not care about them."

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