Wednesday, March 21, 2007

Science Wins a Round

In a stunning reversal and departure from White House policy, the director of the National Institutes of Health, Dr. Elias Zerhouni, told the Senate health appropriations subcommittee that he backs an end to restrictions on federal funding for embryonic stem cell research (ESCR).

"We cannot, I would think, be second-best in this area," Zerhouni said. "I think it is important for us not to fight with one hand tied behind our back here, and NIH is key to that."

To date, Zerhouni’s support for ESCR had been less than full-throated. His response of unqualified support to the questioning by subcommittee chairman Senator Tom Harkin (D-IA) has energized proponents of the research and taken those opposed by surprise. Harkin called Zerhouni's comments "very profound and courageous.”

When Zerhouni was quizzed about the promise of ASCR and the promise that research might hold, he was blunt. “I think they are overstated," he said. "We do not know at this point where the breakthrough will come from…. All angles in stem cell research should be pursued."

Embryonic stem cells are so promising because they can develop into any kind of cell. Not only are these cells pluripotent (undifferentiated, able to become any type of cell in the body), they have a biological distinction from adult stem cells that underscores their promise.

Adult stem cells, like all mature cells, are subject to the Hayflick Limit. The Hayflick Limit was discovered in 1965 by researcher Leonard Hayflick, when he discovered that in vitro, cells replicate about 50 times, and then they die.

This cellular death after replication is due to chromosome shortening that occurs at the end of the DNA replication cycle. This shortening occurs when the primer at the 5’ (read 5-Prime) end of the lagging strand of the unwound DNA double helix is degraded because DNA polymerase can not ad nucleotides to the 5’ end of the lagging strand. This loss of nucleotides does not occur on the leading strand, or 3’ end, which can accept primers by DNA Polymerase.

In most replicating cells a small amount of telomerase is present, and this enzyme extends the ends of the chromosomes so that this problem does not occur. This extension occurs when the telomerase enzyme binds to a section of DNA on the 3' end and extends it using the normal replication machinery. This then allows for a primer to bind so that the complementary strand can be extended by normal lagging strand synthesis. Finally, telomeres must be capped by a protein to prevent chromosomal instability. This capping can not happen on the 5’ end, and after around 50 replications, the original cell dies because of the chromosomal instability that results from the loss of nucleotides on the 5’ end, or lagging strand, of the replicating DNA molecule.

Here is an analogy (the one I use for students every semester): Think of the telomere at the 5' end as the plastic aglet on a shoelace - it will wear out with repeated lacing and unlacing, and it will work perfectly fine for quite a while even after the plastic starts to chip away. But eventually, the aglet can't do it's job and the lace unravels. When the telomeres can't do their job any longer, the cell dies.

Supporters of ESCR have been fighting an uphill battle. The only veto the president has tendered in his entire six years in office was to veto federal funding for ESCR. Several states have enacted their own legislation to protect and fund the research. California and Massachusetts have passed laws and allocated funding for the research, and Missourians last November passed an amendment to the state Constitution that assured the state can not restrict research that is legal at the federal level.

In 2001, the president signed an executive order that limited federal funding for embryonic stem cell research to cell lines already in existence. 16 of those lines are still in use, but they have become genetically degraded and have been contaminated with mouse genes. Now they are ill-suited for such important research in an emerging field.

In 2006, the president vetoed legislation that would have allowed federal funding for research on new stem cell lines derived from embryos that would have otherwise been discarded by fertility clinics.

Prominent researchers rejoiced when they learned of Zerhouni's comments.

"I think it will certainly mobilize opinion up on [Capitol] Hill," said Jerome Zack, an embryonic stem cell researcher at the David Geffen School of Medicine at UCLA. With stem cell legislation moving again, Zack said, he was anticipating another Bush veto. But he hoped that it could be overridden.
"Convincing a handful of [lawmakers] of the opposing viewpoint could really sway things," he said.
Studies claiming that adult stem cells have as much potential as embryonic stem cells "do not hold scientific water," Zerhouni said Monday.

"When very prestigious physicians and scientists speak out, I think in the long run it will make a difference," said Renee A. Reijo Pera, director of the human embryonic stem cell program at Stanford University.
Fred H. Gage, a stem cell researcher at the Salk Institute in La Jolla, said Zerhouni may have taken a political risk by articulating a position so clearly at odds with that of the White House. "He's very careful about what he says, and fairly conservative in his policy statements," Gage said. "My guess is this was a very well-thought-out statement. "If it does put him at risk, all the more reason to respect his judgment," Gage added.
Predictably, religious conservatives expressed disappointment, and accused Dr. Zerhouni of not giving adequate consideration to treatments derived from ASCR.

I have a question for the religious conservatives – do you not understand the difference between ASC’s and ESC’s, or do you chose to ignore it? And if it’s the latter, is that really moral?

[cross-posted from Watching Those We Chose]

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