On July 18, 2001, Sen. Bill Frist (R-Tenn.) stood on the Senate floor urging his colleagues to buck conservative orthodoxy and support federally funded research on embryonic stem cells. As the Senate's only physician, Frist made headlines -- and gave momentum to the controversial science -- with his endorsement.

The following month, however, President Bush announced a policy that was far more restrictive, limiting federal research to already existing embryonic stem cells, and Frist acquiesced.

A few weeks after Bush announced his policy, Frist said the differences between the two were minor because scientists at the National Institutes of Health had "informed the president that more than 60 cell lines exist and that this number is sufficient to provide ample opportunity to research the potential of embryonic stem cells."

Today, Frist is again at the center of the stem cell battle. Unlike four years ago, when he sought an influential role, the Senate majority leader has shied away from the issue, frustrating once-admiring researchers and patient advocates who now accuse him of exchanging sound medical thinking for with political calculations.

"We, as scientists, had great expectations for what he could do," said Mary Hendrix, president and scientific director of the Children's Memorial Research Center at Northwestern University. When she heard Frist's 2001 speech, Hendrix got "goose bumps" because the well-respected transplant surgeon had "put his credibility on the line."

Hendrix is puzzled and disappointed by what "appears to be a change in Senator Frist's position," she said in an interview. "I thought he was a staunch supporter."

As Congress begins its Fourth of July recess, activists on both sides of the stem cell divide are gearing up for what appears to be a fresh fight in the Senate, perhaps as early as the week lawmakers return.

On one side are scientists and patient groups who say the cells taken from days-old embryos hold enormous potential for treating a range of illnesses because they can grow into any type of cell or tissue in the body. Opponents object to the research because the process involves destroying the embryo.

When Bush announced his compromise in 2001, the White House said scientists would have more than 60 embryonic stem cell colonies, called "lines," to work on. But fewer than two dozen have materialized, reinvigorating the push to expand the policy.

In May, with 50 Republican votes, the House passed legislation that would permit federal research on tens of thousands of frozen embryos donated by couples at fertility clinics. Bush has threatened to veto the bill, placing additional pressure on Frist to stand by a policy that falls far short of the approach he envisioned four years ago.

"If he wants the Republican nomination, he may be worried that coming out for embryonic stem cell research funding would make conservatives angry, especially if it involves disagreeing with President Bush," said Harvard political scientist Michael J. Sandel. If stem cell legislation becomes Bush's first veto, "it would be a symbolic issue in the Republican primaries."

But if Frist is maneuvering to attract Republican primary voters in pursuit of the 2008 presidential nomination, he is doing so at the risk of angering loyal Tennessee supporters such as Anne Shockley.

"I thought he was for stem cell research, but ever since Bush got involved, [Frist has] gone all wishy-washy," said Shockley, a volunteer for the Tennessee Parkinson's Action Network. "It makes no sense. He's a physician; he knows what stem cell research can be. It seems to me it's become a political football, and it's frustrating."

Shockley, who described herself as a "pro-life" Republican, said she has stopped donating to Frist's campaigns, even as he considers a run for the presidency in 2008.

"He became [Senate Majority] Leader," said Sen. Arlen Specter (R-Pa.), one of the leading advocates of a broad research policy. "He has a little different responsibility now with respect to the party approach."

Over a period of three days, Frist aides did not respond to multiple interview requests. Spokesman Nick Smith left a voice message indicating only that the majority leader is trying to schedule a Senate vote this month.

Frist's 10-point stem cell proposal in the summer of 2001 was the result of extensive research, soul-searching and "20 years in the field of medicine and in science," he said. Describing himself as the "Senate's only physician and only medical researcher," he said he knew the promise and pitfalls of cutting-edge science.

His 11-page speech on the "promising and important line of inquiry" addressed in detail a host of scientific and ethical questions, displaying an impressive command of the complex science and a doctor's ease with life-and-death issues.

Drawing comparisons to his experience as a transplant surgeon, Frist stressed that the stem cells are taken only from "spare" embryos "that would otherwise be discarded."

"It is critically important that we understand, and in our moral and ethical framework ensure, that this tissue otherwise would not be used," he said. "It is similar to the fact that when I do a heart transplant, that heart otherwise would not be used for anything useful."

On the question of whether the days-old blastocyst is a life, Frist said: "There is a continuum from a sperm and an egg, to a blastocyst, to a fetus, to a child, to an adolescent, to an adult."

He acknowledged that other types of stem cells appear to offer some therapeutic benefits but said they were insufficient.

"It appears clear that research using adult stem cells does not hold the same potential for medical advances as does the use of the more versatile embryonic stem cells," he said.

Hendrix, who at the time was immediate past president of the Federation of American Societies for Experimental Biology, said she will never forget the excitement Frist's stance sparked in the research community. "The credibility he brought was something that was just profound," she said.

Conservative and religious activists were displeased, recalled Wendy Wright, senior policy director of Concerned Women for America.

"That was something we didn't care for," she said. "It wouldn't have comported with what the president came up with."

Frist added several caveats, including an outright ban on therapeutic cloning, a process for growing embryonic cells; a thorough consent process for embryo donors; and strict ethical oversight. He advocated limiting the number of cell lines to be used as a way to guard against abuses. But he also explicitly rejected what would become the central plank in the Bush policy.

"This does not mean limiting it to research using stem cells that have already been derived to date," he said, foreshadowing the difficulties scientists are now encountering with the older, federally approved stem cell lines. In a Senate hearing that day, Frist noted that some experts suggested 100 or 200 embryonic stem cell colonies might be enough for federal researchers to "jump-start" the burgeoning field.

When Frist generally accepted Bush's position, Wright praised the senator's change of heart, saying he had an "opportunity to be reeducated."

Last summer, with Bush campaigning for a second term, Frist said in an appearance at the National Press Club that it would be appropriate to reassess the president's stem cell policy after Election Day.

Peggy Willocks, Tennessee state coordinator of the Parkinson's Action Network, has tried unsuccessfully to discuss the issue with Frist. Now, she is resigned to sending him a message through staff, she said. "I want to tell him this is the time he is going to have to take himself up by his own bootstraps and make a decision that's not following Bush," she said.

Two weeks ago, however, Frist said he did not see a need to expand the Bush restrictions, as the House-passed bill does. As he put it: "I agree with the president's policy."