Bill Frist was in a small, shaky plane, racing toward a hospital across Tennessee. Someone was dead in Chattanooga, the heart available for transplant.

This time, an old college professor was aboard. Uwe E. Reinhardt, the noted Princeton health economist, had been in Nashville to talk to alumni; Frist, one of Reinhardt's brightest students from the early 1970s, was his escort. When the surgeon's beeper had gone off at dinner, he invited the teacher along.

By that night in late 1993, such interruptions had become routine for Frist. In a family of successful medical men, he had outdistanced them all, coming home to build from scratch a transplant program at Vanderbilt University Medical Center. There, he had replaced nearly 200 hearts and lungs.

As the plane flew southeast, Reinhardt was surprised to see Frist, amid all the jouncing, buried in a book. What, Reinhardt asked, was he reading?

Campaign literature, the surgeon replied.

On the return flight -- with the heart he had removed on ice in a Snoopy lunch bucket -- Frist told Reinhardt that this transplant would be his last: He was going to run for the U.S. Senate.

The decision to trade years of training and surgical stardom for a campaign against a powerful three-term Democrat at first stunned and disappointed Reinhardt and most of Frist's friends, colleagues and sprawling web of relatives in Nashville.

But by the rhythms of his life and the values of his family, the leap wasn't so peculiar: The man who just took over as Senate majority leader had been behaving in political ways since his youth. An examination of the influences and experiences that shaped Frist, 50, reveals an almost instinctive opportunism that belies his studious demeanor.

As a boy, he had accompanied his physician father on house calls to Tennessee's governors. As a teenager, he put "Mr. President" under his senior yearbook picture. As a young doctor, he promoted transplantation on a nationwide tour with country singer Barbara Mandrell.

His wife, Karyn, put it this way: "In the long hallway of his life, there is no door closed to him. If a door is cracked, he's in the room."

Medicine and a Motorcycle

In a city noted for its philanthropy, the Frist name stands out. There is a Frist Clinic and a Thomas F. Frist Centennial Sports Complex, and "Frist" hovers in silver lettering over each doorway of the new family-endowed art museum. But the family didn't achieve true wealth until William Harrison Frist was nearly grown.

He was the youngest of five children -- by far. As a boy, Billy had a thirst for books and a quiet manner but seemed to lead other boys with no effort; in the third grade, he prompted a dozen classmates to start collecting pennies and nickels by merely bringing a coin-card to school one day.

He was impish, though, and sought risk: When he was 14, he ended up in a coma for five days after he took off on a forbidden motorcycle ride and crashed down the road from his house. Growing up in an older family -- he was 16 years behind his eldest brother, seven behind his nearest sister -- he was surrounded by adult talk, and his parents seemed to him a little larger than life.

Frist's father, the Thomas for whom the sports complex is named, was the son of a railroad stationmaster in Meridian, Miss., who died from injuries suffered while rescuing a deaf woman and her child from an oncoming train. His widowed mother provided room and board to a doctor who apprenticed her son and helped him through college.

After medical school at Vanderbilt, Tom started out earning a few dollars apiece to treat local prisoners and built one of the most successful practices in middle Tennessee. He cared for governors, music celebrities and farm families. Later, he and his eldest son joined the man behind the Kentucky Fried Chicken Corp. to form the Hospital Corporation of America, which became the nation's largest for-profit hospital chain.

His mother, Dorothy, came from one of the most liberal families in Tennessee, one that made sure all its girls received a college education. A former elementary school teacher, she devoured newspapers, poured her prodigious energy into her family, and expressed her Presbyterian convictions through charitable acts, anonymously ordering appliances for other families that she heard were in need.

"I think Billy's intellectual horsepower comes from his mother," said H. Lee Barfield II, a Nashville attorney who is Frist's brother-in-law and a longtime confidant. Frist declined to comment for this article, but recommended Barfield and many other relatives, friends, mentors and family observers.

The family was prominent and prosperous, but not materialistic. The doctor bought suits from a seconds store; his wife carpooled Billy and his friends to school in an old Bel Air station wagon with a view of the pavement through a hole in the floorboard. They lived in a rambling, white-columned house, but vacationed in state park cabins.

However, Bill Frist "was exposed, at least within our family, to political discussions from the time he was old enough to understand what was being talked about," said a cousin, George Cate Jr., 74, who was Nashville vice mayor in the 1960s -- the only other family member to have held elective office.

In the '50s, an aunt was principal of the city's first elementary school to desegregate. In the early '60s, Frist's mother became one of the first Tennesseans to openly oppose the war in Vietnam.

His father, less political and more conservative, worked 16-hour days, recalled John Gibson, a friend since first grade. Six-foot-3 with red hair and horn-rimmed glasses, he had a reserve, a deep, melodious voice and "almost an evangelical tone . . . just a bit, so soft and subtle," said John Seigenthaler, former publisher of the Nashville Tennessean.

The youngest son sometimes went along on house calls, and it gave him an uncommon sense of the accessibility of the powerful. "I don't think he viewed the governor any different than the cotton farmer," Karyn Frist said. "It was planted there: 'We are impressed with people and not positions.' "

At the same time, "he was always a hyperachiever," said Tom Nesbitt, a local physician who has been a friend since first grade. In his 1989 book, "Transplant," Frist wrote of his teenage years: "Not surprisingly, with the family emphasis on self-worth, I longed to be first in everything, to be king of the hill . . . I imagine I was quite insufferable."

At age 14, Frist persuaded his mother to let him get a "limited license," intended to allow the children of families with hardships to drive to school, the grocery store and church. The day he turned 16 -- the first day he legally could -- he took his maiden solo flight, emulating his eldest brother, Tommy, a pilot who had been a flight surgeon.

Montgomery Bell Academy, Nashville's premier prep school, required its ninth-graders to write and deliver a speech to the entire school; Frist also traveled the state with the debate team. The school was all boys and, at the time, segregated. "Civil rights was a topic of conversation," Nesbitt recalled, "but we were more spectators in the change."

Frist was not a backslapper. But in his senior year, in addition to editing the yearbook, he was the quarterback, president of his fraternity and class president for the third year out of four. He also had begun to date a girl from a neighboring girls' school who was MBA's head cheerleader. Whenever guest speakers came to school, Frist made a point of introducing himself. "He knew how to network even then," Gibson recalled.

The summer after graduation, when the two boys took a three-week swing through the West, Gibson was astonished when Frist suggested that they look up a Stanford University physics professor who had spoken at MBA about taking troubled boys into his Palo Alto home. "The next thing I knew," Gibson said, Frist "calls him, and we are staying at his house."

By then Frist's brothers, Tommy and Bobby, were trained surgeons, but no one in the family had gone to an Ivy League school. At a time when southern parents were wary of student unrest up North, many of Frist's MBA classmates were aiming for Vanderbilt. He went to Princeton.

'You Have to Decide'

As Frist came of age, he remained detached from the prevailing passions of the day while immersing himself in his own. A "restless soul" is how Seigenthaler describes him.

At Princeton, he fulfilled pre-med requirements while pursuing one of the university's most difficult majors, a public policy program at the Woodrow Wilson School. He paid little mind to the biggest campus issues of his time, Vietnam (he had a student deferment from the draft). He would not vote until he was in his mid-thirties.

After medical school at Harvard, he entered one of the nation's top surgical residencies at Massachusetts General Hospital. He became engaged to his high school girlfriend -- but broke it off two days before the wedding.

Her house was piled with wedding gifts, he wrote in "Transplant," when he arrived to tell her "nothing was right with my life. With me. With me and her. I cried and she cried, and I stayed an hour." He flew back to Boston the next morning, not missing work.

He did not tell her that he had just met another woman, a former schoolteacher whose sprained wrist he had treated in the emergency room. Karyn Frist said that, with him working 24 hours on, 24 off, "we would fly a little bit during the day, and he would go back to work." They married after two years, in 1981.

After a decade of medical training, Frist became a cardiac surgeon -- like his brother Bobby -- but then specialized further, in the new field of transplantation, taking a residency at Stanford. Frist's closest friend there, fellow resident Vaughn A. Starnes, said they would arrive at the hospital by 6 a.m., usually perform two surgeries lasting three or four hours each, and leave around 9 p.m. -- if they weren't there all night.

Just before their training ended, the pair went to a surgical conference in Washington. While Starnes delivered a paper, Frist -- without an appointment -- went to Capitol Hill to try to talk about federal health reimbursements with then-Sen. Jim Sasser (D-Tenn.).

When he finished his training, in 1986, Frist returned to Nashville, not to the family business but to academic medicine. He would invest in the Hospital Corporation of America -- his 1995 financial disclosure listed HCA holdings valued at $5 million to $25 million. But the choice not to work there spared him from direct involvement in a Medicare fraud scandal -- a decade-long government investigation has brought civil and criminal fines totaling $840 million and the indictment of several officials, none of them Frists, who ran the company after a 1994 merger.

At the time, Frist saw his own opportunity: Vanderbilt University's medical school needed aggressive young faculty to develop new programs that would fill beds in its new hospital. The heart and lung transplant program could be his.

All of Frist's friends and relatives have stories like Uwe Reinhardt's, of the surgeon's beeper going off at dinners, at parties, in the dead of night, presaging another rush to harvest an organ and marathon surgery to stitch it into a Vanderbilt patient. But even amid that intensity, Frist seemed to be looking over the horizon.

He went to the state legislature to propose a law to allow Tennesseans to designate themselves as organ donors on their driver's licenses; it passed. He published "Transplant," which included a legally binding organ-donor card for readers to cut out. Then there was his media tour with Mandrell, a prelude to a 1988 celebrity softball game that attracted Oprah Winfrey, Bob Hope and Dick Clark and Meat Loaf to Nashville -- and raised $500,000 for the Vanderbilt transplant program.

Still, Frist had a broader goal in mind: a new model for a transplant center, one that would integrate his heart-and-lung specialty with transplants of other organs and related disciplines, such as psychiatry and ethics, that were relevant to all such cases. No program in the country was organized that way. "He was sort of the pied piper," said his Stanford mentor, Norman Shumway.

He also leapfrogged most of the medical school hierarchy and began trading memos with its top administrator, who made the surgeon, just two years out of training, head of the committee that would implement his ideas. "Many young, fresh assistant professors wouldn't be up there in the vice chancellor's office, but he was," said C. Wright Pinson, who has directed the Vanderbilt Transplant Center since Frist left.

In the early 1990s, Gov. Ned R. McWherter, a conservative Democrat, called his former doctor, Thomas F. Frist Sr., to ask whether his son might want to work on a plan to privatize the state's health care for the poor. Bill Frist would lead a commission that advised McWherter on the creation of TennCare, an early effort to import managed care into Medicaid.

Later, Frist called McWherter to seek his advice. The surgeon was considering entering politics, McWherter recalled, but his "goals for public life seemed unfocused."

Publicly, he told people that he was eager to save more than one life at a time, but some who knew him suspected there was more to his motives.

Like his father, Frist wasn't seeing much of his three sons. And even with his transplant center only partly built, said John A. Morris, a friend who is chief of Vanderbilt's trauma service, "I think he thought he had finished his work here. He saw the path, and the rest was a series of execution steps." Seigenthaler said, "I think the restless soul didn't want to cut chests open any more."

But his political identity was unformed. Karyn Frist remembers her husband debating whether he would find an elective or appointive position more satisfying.

In the end, McWherter advised him to do two things: "You have to decide whether you're a Democrat or a Republican, and you have to decide what office you want to run for."

Out of the 'Six-Pack'

From his father's and brother's business, and from his own disdain for high taxes and spending, Frist had developed a basic preference for limited government that made him a natural Republican. One of Frist's other advisers, former senator Howard Baker (R), recommended him to the state's party chairman, Randle Richardson.

In 1994, both of Tennessee's U.S. Senate seats were up for election, because Al Gore Jr. had become vice president two years before. Seasoned politicians were gravitating to the open seat, reluctant to challenge Sasser, who was chairman of the Senate Budget Committee and poised to become majority leader.

Richardson was recruiting fresh faces to run against him. He ended his first meeting with Frist by saying: "Bill, you may be one of the smartest people I have met . . . but my intern has more political experience than you."

Frist replied: "I will be the best student you will ever meet."

Frist's friends and family were less easily convinced. "The idea that this guy was going to bump off a senior senator -- that was pretty far out there," Pinson said.

According to Barfield, Frist's brother-in-law, his parents initially tried to dissuade him, saying politics was a "dirty business." Frist's brother, Tommy, had been host for a fundraiser for Sasser in 1988, but now predicted that Democrats would "throw mud at the company," Barfield said.

Sasser has always wondered whether Frist entered politics partly because the Budget Committee was starting to explore Medicare fraud, and HCA was vulnerable.

"I was almost incredulous the Frist family . . . that had supported me politically and I knew socially . . . would suddenly turn around and run against me in what was a vicious campaign," he said.

Frist emerged from a "six-pack" in the Republican primary -- a half-dozen men who had little or no political past. He hired a veteran campaign manager and with his "Frist Force" hustled around the state billing himself as a "citizen legislator" and promising not to serve more than two terms.

Democrats say his general campaign was tinged with racial allusions. At a debate just weeks before the election, Frist said: "While I've been transplanting lungs and hearts to heal Tennesseans, Jim Sasser has been transplanting Tennesseans' wallets to Washington, home of Marion Barry" -- a reference to the former Washington mayor, who had grown up in Memphis and is black.

Frist spent $9.8 million -- $6.2 million of it from his own funds, largely from HCA stock holdings -- compared with $4.4 million that Sasser spent that year. He won by 14 percentage points.

When he arrived in Washington in 1995, he was not immediately at ease with the rhythms of Capitol Hill.

He relished encounters with unfamiliar issues. Rather than merely checking the votes of senators down the hall, Frist directed his first chief of staff, J. Mark Tipps, a Nashville lawyer who was also a novice in politics, to find the best experts in the country.

But compared with the speed and choreography of transplant work, the legislative process struck the new senator as labored, meandering and focused on the short term, recalled Tipps, who routinely arrived at work to e-mail messages his boss had sent at midnight, 1:30 a.m., 5 a.m. When a legislative aide grumbled to Frist one day about a thwarted bill, Tipps said, the senator leaned back and said: "This isn't stressful. This is important, but not stressful. Stressful is when you see a 43-year-old mother of three die over several hours, and you've done everything you could."

But gradually, Frist again insinuated himself into his new environment, carving a reputation as the Senate GOP's health policy expert, becoming the public voice of reassurance on bioterrorism. When his first term was ending, in 2000, he became platform committee chairman for his party's presidential nominating convention and the Senate's liaison to George W. Bush's campaign.

Last month, when Sen. Trent Lott of Mississippi resigned as majority leader, Frist was well-positioned.

In 1993, Bill Frist, left, and colleague Doug Martin brought a heart to a Nashville hospital for a transplant. Frist once wrote he "longed to be first in everything."Sen. Bill Frist (R-Tenn.) talks to reporters in Nashville while his wife, Karyn, and sons, Jonathan and Bryan, right, watch, after Frist was elected Senate Republican leader.Sen. Bill Frist was the youngest of five children of a prominent Nashville doctor and a schoolteacher mother, center. The portrait that emerges of a young Frist is that of a quiet, bookish, ambitious leader.Bill Frist with his father, Thomas F. Sr., in 1981. Frist used to accompany his father on house calls, including those made to Tennessee's governors.Bill Frist, No. 14, was quarterback of the football team at Montgomery Bell Academy in Nashville in 1969. He also was president of his fraternity and class president.