If Republicans lose the Senate, it could be because of the issue that George W. Bush put on the national agenda in his very first televised prime-time address to the nation, serving as yet another reminder of how the GOP’s chances in next week’s elections are inextricably linked to his presidency.

Although a Democratic takeover of the Senate is still less than likely, political oddsmakers point to the contest in Missouri as a must-win in any scenario that leads to such a changeover. And that race seems to be turning on stem cell research, the issue Bush introduced to most Americans during a speech in August 2001 in which he announced restrictions against federal funding of embryonic research.

Missouri presents the best Democratic opportunity of the three GOP-held Senate seats that are shaping up as the linchpins in deciding which party will control the Senate. If the dynamics in the other races around the country stay the way they are, Democrats will need to take either Virginia or Tennessee, along with Missouri, to win a majority.

That opportunity would not have presented itself to the Democrats without Missouri turning in their favor. And they have a state ballot initiative promoting stem cell research to thank for it. The measure, which has spawned $30 million in collective spending by the opposing sides, would engrave the right to conduct embryonic stem cell research into the state constitution.

Republican incumbent Jim Talent’s opposition to the measure appears to have put him at a disadvantage against his Democratic challenger, State Auditor Claire McCaskill, who is touting her support for the initiative. Recent polls show that nearly 60 percent of Missouri’s likely voters back the amendment.

As these ballot initiatives often do, this one is getting so much attention that it could boost turnout among voters who are motivated by the issue, if not by their Senate alternatives. And if the polls are correct in showing most voters aligned with the Democratic position, the net benefit of this ballot measure favors McCaskill and seems likely to be the deciding factor in this tight race.

A wave of television advertisements featuring celebrities for and against stem cell research ensured its high profile. The most prominent was actor Michael J. Fox, visibly shaking from the effects of Parkinson’s Disease, pleading with voters to back McCaskill.

Although the stem cell issue is not as pivotal outside Missouri, Democrats are running ads in other states where Republican incumbents have voted in support of Bush’s restrictions. In those places, the aim is mainly to suggest that the GOP stands against scientific progress. If this tactic makes a difference for the Democrats, they will have Bush to thank for making it possible.

Consider it a case of a wedge issue gone bad. When Bush unveiled his stem cell policy from his Texas ranch house, many were surprised that he chose what was then a little-known debate as the exclusive focus of his first big TV moment. But the use of embryonic stem cells to combat disease had long been a hot topic among anti-abortion conservatives who see it is a threat to the “sanctity of the unborn” and a step toward cloning. Giving such prominence to what most Americans saw as an arcane scientific dissertation was a politically motivated tactic to reward a bloc of voters crucial to his election.

The White House had always hoped that the issue would not resonate beyond those social conservatives. But over time the advocates of research, including former first lady Nancy Reagan, began mobilizing their side and putting Bush on the defensive.

The tipping point came last summer, when the Republican-controlled Congress sided against the president, voting in both chambers to lift his restrictions against federal funding. Although most GOP lawmakers in the House and Senate backed the president’s stand, enough Republicans opposed him to pass the measure in combination with an overwhelming majority of Democrats. Bush did not back down, casting the only veto so far in his presidency. GOP leaders, confident the president would win, immediately arranged a House vote on whether to override him — which came up 51 votes short of the two-thirds majority required.

Perhaps as an acknowledgment that Bush’s position had become a political loser, the White House banned news media coverage of the veto signing. Not even a photograph was permitted.

How ironic that, at least in the fight for control of the Senate, Republican lawmakers could lose their majority over a debate that moved so many, including the Senate majority leader, Bill Frist of Tennessee, to actually oppose the president.

Even Bush’s changing profile on this issue, from proudly announcing his stand in front of the cameras five years ago to going off camera last July to veto Congress’ rejection of it, suggests that he knows he did his party no favors in staking so much on an issue that would not be roiling Republicans had he never brought it up.

Contributing Editor Craig Crawford is a news analyst for MSNBC, CNBC and “The Early Show” on CBS. He can be reached at ccrawford@cq.com.