TALLAHASSEE - With the possible exception of football coach Bobby Bowden, few employees have done more to build Florida State University's reputation than Robert Holton.

In the early 1990s, Holton developed the semisynthetic version of Taxol, a drug that fought ovarian and breast cancer. It was to FSU what Gatorade was to the University of Florida -- only better. It saved lives.

But the university that named a medal for Holton and featured the chemistry professor in an ad campaign now complains he's too controlling. FSU is returning Holton's $5 million gift meant for a state-of-the-art chemistry building, a move that may also force the school to return a $5 million state matching grant plus another $6 million from an account Holton controls.

Holton, meanwhile, filed a lawsuit demanding FSU honor an agreement to accept the gift. He has since dropped the suit and hired a public-relations firm, making a last-ditch effort to lobby the school's board of trustees.

Holton's tale began as a $350 million example that universities and their professors could make money, help society and absorb the lessons of the business world. It has evolved into a more complicated chronicle of a passionate researcher's vision clashing with university leaders who say his demands would tie FSU too closely to a costly and specific field of research.

And it's now among a small handful of instances in philanthropy in which a multimillion-dollar gift is being returned over accusations of too much meddling. Of course, few donors would have the expertise to make requests like Holton's.

''He's a very opinionated and forceful guy, and that rubs some people the wrong way,'' said Marty Schwartz, Holton's doctorate supervisor in 1971 who now keeps an office down the hall from him. ``My only experience is that he's been right more than he's been wrong.''

Holton, a multimillionaire who still gets to his lab at 4 a.m., declined numerous requests to comment for this report. FSU officials say they are building a $50 million building without him, though they continue to rely on an earlier $6 million gift -- which is separate from the money now in dispute.

Holton's Taxol story is told often at FSU -- highlighted in an advertisement and a glossy in-house magazine. Taxol was discovered by government researchers in the 1960s, a compound found in the bark of rare yew trees of the Pacific Northwest. Scientists learned the chemical could reduce the size of tumors. But it took the bark of three Pacific yews and thousands of dollars to treat a single patient.

PROLONGED LIVES

Holton's team won a race to develop a cheaper semisynthetic version, and, in 1993, Bristol Myers Squibb began marketing it. Like other chemotherapy drugs, it had side effects. But it also prolonged lives and, in some cases, defeated cancer.

''It made a major impact on lung cancer, ovarian cancer, breast cancer and also to head and neck cancer,'' said Dr. Stefan Glück, clinical co-director of the breast cancer institute at the University of Miami's cancer center.

Glück, who does not know Holton, calls Taxol one of the five most important cancer drugs ever, used at some point by nearly every American breast cancer patient.

Before the drug company's exclusive license expired, FSU made $350 million in royalties, vaulting the school into the company of Columbia University and California's state universities in research profits. UF, by comparison, has made $118 million since its scientists created Gatorade more than three decades ago.

By agreement with FSU, Holton got about $140 million and control of a $50 million lab account.

Talbot ''Sandy'' D'Alemberte, president of FSU from 1994 to 2003, said coach Bowden once noted how much money he was bringing to FSU. D'Alemberte told Bowden he was valuable, but didn't account for a fraction of the dollars FSU's researchers delivered. And Holton, 62, topped the list of researchers by a large margin.

''It wasn't just the money. It was having the ability to develop discretionary funds'' to enhance the university, D'Alemberte said.

FSU used its share to lure renowned professors in diverse fields -- dance, oceanography, creative writing among them -- and dole out research grants. About 80 percent of FSU's $90 million research foundation comes from Taxol royalties, according to Kirby Kemper, vice president for research.

Holton donated half his money to create his own research foundation and started a company called Taxolog, both designed to find more cures for cancer. Holton owns no shares of the company and collects no salary, said Lewis Metts, a longtime friend who runs Taxolog. Metts said Taxolog has three new cancer drugs in clinical trials.

In 1999, Holton began talking with D'Alemberte and other university officials about a new chemistry building. Holton started with a $6 million donation that, with matching grants, would go toward a $24 million project. One of five floors would be devoted to Holton and his colleagues in synthetic organic chemistry.

Negotiations continued for years. D'Alemberte said Holton was tough and not much of a diplomat, but he respected and admired the scientist's focus.

In 2002, Holton made another deal that increased the cost of the building by $22 million and added another $20 million for four endowed research professors in Holton's specialty. Most of the money would come from Holton, the state and FSU's Taxol royalties, but FSU would be committed to high salaries and a long-term focus on Holton's specialty, synthetic organic chemistry. It now occupied three or four floors of a five-story building.

Lawrence Abele, FSU's provost then and now, signed the deal but said he never liked it. He said the gift was too expensive to accept. He was overruled by D'Alemberte, who thought the school should ``bet on your winners.''

QUESTIONS RAISED

But after the deal was signed, costs continued to escalate above $60 million and relations between Holton and the administration soured this summer. There were attempts to work out new deals, but Kemper said the university was getting worried about the extent of its commitment to Holton's specialty, one of five branches of chemistry. FSU's priorities may change down the line, he said.

''It's one of control. Who controls the destiny of a university? Does a donor or does the university?'' Kemper said.

But that has not always been FSU's attitude when the money comes from politicians. FSU President T.K. Wetherell, a former Florida House speaker, eagerly accepted money from the Florida Legislature last year for a chiropractic school that was derided by some faculty members as quack science and ultimately killed by a state board.

Wetherell called Holton's proposal, on the other hand, a ``take it or leave it.''

On June 29, Holton wrote a letter threatening to take back his donation if the sides couldn't come to terms. Holton later apologized. But it was too late.

Wetherell called his bluff.

''I believe Bob realizes he screwed up,'' Wetherell wrote in a July 11 e-mail to administrators about the apology. ``I don't think we need to rub his nose in it, but I think it's time we split sheets and move on.''

The dispute grew more personal when Holton went over Wetherell's head, pleading his case to FSU's board of trustees.

''When someone starts going to the BOT, then we play the card differently,'' Wetherell wrote in another June 29 e-mail to an administrator. ``The building we are looking at will be a lot better for the Chemistry dept. and the students vs a tribute to Bob Holton.''

Holton, in court papers and letters, argued that FSU was rejecting his money at the 11th hour, harming a project to develop cancer drugs and diminishing an area that was putting FSU on a plane with elite universities.

''Without question, the public's interest would not be served if FSU independently used taxpayer dollars to build the new FSU chemistry building rather than gift monies,'' he argued in a court briefing.

Despite Holton's last-minute attempts to salvage the deal, Wetherell says he's finished negotiating with Holton and plans to start construction on a scaled-back chemistry building in November.

The groundbreaking date was chosen so it won't interfere with parking for athletic department boosters at this year's home football games. The building will sit on a parking lot not far from buildings named for John Thrasher and the parents of Jim King, former leaders of the Legislature who knew how to twist arms and stroke egos to persuade their friends to spend taxpayer money on FSU.

Holton isn't a politician; he's an ''outrageous genius,'' said his friend Metts. That kind of man, Metts said, isn't ``going to be a slap-you-on-the-back, congenial and politically astute fellow.''

BY NOAH BIERMAN
nbierman@herald.com