Tuesday, August 4, 2009

'Hedging bets' on embryo research; ethical stem cells the way to go

I recently stumbled upon a stem cell research story in the August issue of U.S. News & World Report (titled "Stem cell diversification: Even as embryonic cells get a lift, experts hedge bets" in the print edition), available online here. I was encouraged to see that the article, written by Katherine Hobson, is frank about the scientific difficulties with embryonic stem cells and the recent breakthroughs in non-embryonic research. Some excerpts:
While the attention of the public and ethicists has been focused on embryonic stem cells, research into other kinds of stem cells ... has been advancing and, in some cases, exploding. "I have never been in a field that is moving at this pace," says Jonathan Chernoff, deputy scientific director at the Fox Chase Cancer Center in Philadelphia. Adult stem cells have been used in bone marrow transplants for 40 years, and trials ... are expected to expand their use. Meanwhile, many scientists predict that induced pluripotent stem cells, or iPS cells, created by turning back the biological clock of normal adult cells, will one day supplant embryonic stem cells.

But scientists still call embryonic cells the "gold standard" for stem cells, which is why they've been the subject of privately- and state-funded research while federal funds were restricted. It's also why researchers are excited about Obama's move to allow the government to fund research using lines of embryo-derived cells, as long as the embryos are left over from fertility treatments, not created solely for research purposes.
It makes sense that those with absolutely no ethical qualms about killing human embryos would see no harm in continuing with embryonic research even as alternatives advance. Why not? Something good could come of it. Still, the superiority of iPSCs over embryonic stem cells -- the same pluripotency (and thus the same potential benefits), but cheaper, easier to obtain and without the risk of immune rejection -- threatens to make advocating for more funding into embryo research irresponsible (apart from ethical concerns), it seems to me.

The story continues by explaining the benefits of adult stem cell research:
The earliest therapeutic breakthroughs are likely to arise from adult stem cells ... "In the short term -- say, the next five years -- most of the therapeutic applications from stem cells will be from adult stem cells," says Steven Stice, director of the Regenerative Bioscience Center at the University of Georgia. Their most likely uses: disorders of the blood and blood vessels, bone, and immune systems, he says.

A host of ongoing projects are testing adult stem cells. In one, researchers at the University of California-San Diego are studying whether stem cells derived from a patient's own fat cells might help treat multiple sclerosis. At UCLA, scientists are looking at using blood stem cells from melanoma patients to create immune cells that recognize and attack their disease. The cells may work in other ways than simply creating new cells to replace diseased ones. In the heart, for example, research suggests they increase blood vessel growth rather than create new heart muscle.

Or, they may lead to new drugs.

"The way stem cells [used as therapy] exert much of their power is to provide the chemical signal to turn on [existing but dormant] stem cells in the body," says Robert Hariri, chief executive officer of Celgene Cellular Therapeutics, which is studying possible treatments based on placental stem cells. So treatments could be derived from those cells, then used to turn on the body's existing stem cells.
... and the problems with embryonic stem cell research:
"[Embryonic stem cells are] the teenagers of stem cells; they have great potential, but we can't always get them to do what we want them to do," says Michael Reardon, chief of cardiac surgery at Methodist.

Guiding their differentiation -- their journey to becoming a specialized cell or tissue -- with a lab-made brew of growth factors and other chemicals is a big scientific challenge, and it's not the only one. "You want to be sure you can differentiate [the stem cell] into the therapeutic cells," says Judith Gasson, codirector of the Broad Stem Cell Research Center at UCLA. "Once it's differentiated, you have to get it to go to the right physical location in the patient -- the nervous system, pancreas, whatever. That's not necessarily going to be trivial." The new cell also has to be integrated into a diseased or damaged tissue, says Martin Pera, director of the Institute for Stem Cell and Regenerative Medicine at the University of Southern California. And how to do that, he says, "is an enormous black box at the moment." Even if scientists can accomplish that, there's no guarantee of a lasting therapeutic effect.
Moving on to induced pluripotent stem cells:
There are reasons for caution [about embryonic stem cells]. For one, embryonic stem cells can form tumors. And because the cells are biologically foreign -- like a transplanted organ -- recipients will need to take powerful immunity-suppressing drugs, which have a host of side effects, to prevent rejection.

It's that latter problem that makes scientists particularly excited about iPS cells, which would have the clinical potential of embryonic cells but can be created from a patient's own cells. Reprogramming an adult cell into an embryolike, more malleable state sidesteps the issue of immune rejection, not to mention the moral debate. It's also simple in concept -- adding just four genes to an adult cell can do the trick. But the virus needed to transport the genes into adult cells poses a cancer risk. In late April, scientists reported a breakthrough in mice: They induced pluripotency by inserting proteins, which don't require a virus to carry them, instead of genes, which do. In June, researchers said they'd accomplished the same thing with human cells.

Some scientists, including Geron founder Michael West, who's now CEO of the stem cell technology company BioTime, are betting iPS cells will eventually supplant embryonic stem cells. "But right now," he says, "iPS cells are less than perfect, and they're enough less than perfect that I don't know any scientist who feels they would be safe in humans as of today." For that reason, this is no time to scrap research on embryonic cells, he says.

It will be years, if not decades, before iPS cells can be refined enough to use in patients. But even if treatments are years off, Chernoff says iPS cells have another, more immediate use: to study the progression of a disease. Researchers could take normal and malignant cells from a pancreatic cancer patient, for example, turn back the clock on both, and then reprogram the cells to form pancreatic tissue. They could then monitor the cancer-derived cells to see what, exactly, goes wrong.
One conclusion doesn't make sense: "this is no time to scrap research on embryonic cells," says one scientist, because iPSCs are "less than perfect." But iPSCs are "less than perfect" only because they suffer the same problems as all pluripotent stem cells, including embryonic stem cells: differentiation problems and the formation of tumors. iPSCs are not "safe in humans as of today" for exactly the same reason embryonic stem cells are not safe in humans.

Currently, only adult stem cells are successfully treating patients. And the speculative potential benefits of embryonic stem cells are all available through iPSCs. I think the therapeutic justification for research with human embryos is now obsolete.