Dr. Baltimore was only 37 when he made his Nobel-earning discovery, upending what was called the central dogma, which stated that information in cells flowed in only one direction -- from DNA to RNA to the synthesis of proteins. He showed that information can also flow in the reverse direction, from RNA to DNA. The key was finding a viral enzyme, called a transcriptase, that reversed the process.
The discovery led to an understanding of retroviruses and viruses, including HIV, that use this enzyme. Today, gene therapies with disabled retroviruses are used to insert good genes into patients' DNA to correct genetic diseases.
Admired and envied, lionized and attacked, Dr. Baltimore spent most of his life in the scientific limelight, a towering figure of modern biology. He was president of two leading universities and an early proponent of AIDS research; he also fought what turned out to be trumped-up charges of fraud in a highly publicized decade-long case, beginning in the 1980s, involving accusations that a researcher in his lab had misreported data.
In 1968, Dr. Baltimore joined the faculty of the Massachusetts Institute of Technology. Two years later, he began the work that would earn him the Nobel Prize.
It was a time when a group of Young Turks ruled the MIT biology department. Dr. Baltimore was most definitely one of them, with a coterie of graduate student aspirants who vied to work in his lab.
"Most of us young faulty at MIT were thought of as arrogant," said his friend David Botstein, now a Princeton professor, in an interview for this obituary. "David fit into that culture of competitive smartness. He was the smartest of all."
Dr. Baltimore first presented his data overthrowing the central dogma at an evening seminar in an MIT classroom, inviting just faculty and friends. Botstein was there.
"I remember it like it was yesterday," Botstein said. "It was in room 16-310. He gave this talk and I remember walking out of it and saying to Maurie Fox" -- another faculty member -- "'He is going to get the Nobel Prize for that.'"
A few years later, it happened.
Huang, an accomplished biologist who was working with Dr. Baltimore in his lab when he made the discovery, was among the first to know. In 1975 she was at a conference in Copenhagen where George Klein, a scientist who was scheduled to give a talk, suddenly announced that he had been with a committee that decided on Nobel Prizes. In half an hour, Klein said, the committee would announce that Dr. Baltimore had won the Nobel Prize for Physiology or Medicine, along with two others: Howard Temin, who had independently made the same discovery, and Renato Dulbecco, for his work on tumor viruses.
Huang "immediately got on the phone and called me," Dr. Baltimore said in an interview for this obituary. He speculated that he was probably "the only person who ever was told he had won a Nobel Prize by his wife."
David Baltimore was born on March 7, 1938, in Manhattan to Richard and Gertrude (Lipschitz) Baltimore. His parents moved to Great Neck on Long Island when he was in second grade so he and his younger brother, Robert, could attend better schools.
His father, who worked in the garment industry selling women's clothes, never went to college. His mother studied psychology at the New School and became a faculty member there before moving to Sarah Lawrence, where she got tenure at age 62.
From the start, David was an academic star -- and perhaps a bit of a showoff. When he was in high school, he once turned in only the answers for his math homework, written in the upper corners of pieces of paper, because he could solve everything in his head. "I simply wrote down all the answers, without having to do any calculations," he said in an oral history interview for the California Institute of Technology, where he was president for many years. "It all came very easily to me."
His passion for science was spurred after his junior year in high school. His mother had arranged for him to spend a summer at the Jackson Laboratory in Maine, a center for the study of mouse genetics.
"I made the discovery that a person with only the education I have could work at the forefront of science," Dr. Baltimore said. "I came back and said, 'This is what my life is going to be.'"
When he finished high school, he had his choice of colleges. He chose Swarthmore and discovered his vocation. It was the dawn of the age of molecular biology, and he wanted in.
"I realized I was living through a revolution that I could become part of," he said in the interview for this obituary. Researchers at the time were discovering the genetic code and how genes provide the instructions for making proteins.
He joined the doctorate program at Rockefeller University in New York City, where his work attracted immediate attention. His thesis for his doctorate in 1964 was considered a major breakthrough, establishing ways to study viruses in animal cells. During his thesis defense, Igor Tamm, a professor of virology and medicine, said that Dr. Baltimore's work was one of the times "in the development of a field of knowledge when the ground for the next major development is laid."
A year later, lured by Dulbecco, Baltimore joined the Salk Institute for Biological Studies in San Diego to continue his research. That year Huang, who had gotten her doctorate at Johns Hopkins, came to the Salk Institute as a postdoctoral fellow. They married three years later. Their daughter, TK (pronounced "teak") Baltimore, was born in 1975. In addition to his wife and daughter, he leaves a granddaughter.
His next position was as a professor at the Massachusetts Institute of Technology. That was where he disproved the central dogma, but it was also where in 1985, a decade after his Nobel, he found himself ensnared in a scandal and the subject of attacks that tested his resolve and resilience.
It began when a postdoctoral fellow, Margot O'Toole, accused a researcher, Thereza Imanishi-Kari, of misreporting data in a paper that was published in the journal Cell. Dr. Baltimore was an author of that paper, although the work was not done in his lab.
The case escalated, with investigations by the National Institutes of Health and the Secret Service, which conducted a forensic study of Imanishi-Kari's notebooks. There were also contentious hearings led by the Michigan Democrat John Dingell Jr., who was chair of the House Energy and Commerce Committee. As a Nobel laureate, Dr. Baltimore became fodder for the case; he held his ground, standing up to Dingell in hearings and insisting that there had been no fraud.
As the investigation continued, Dr. Baltimore, who had left MIT during the episode to become president of the Rockefeller University, was forced to resign. He left in 1990, just 18 months after taking up the position. MIT immediately invited him back as a professor.
"It was MIT's finest hour," Botstein said.
Dr. Baltimore and Imanishi-Kari were finally vindicated in 1996, when an appeals panel found the accusations of fraud unfounded. But, Dr. Baltimore said, the case had taken its toll.
"I will never be able to forget it," he said in an interview at the time. He said he had kept all the front-page New York Times articles about the accusations in his basement, unread, hoping someday to have the stomach to look at them.
He later said that he did eventually read one piece in The Times, an editorial that vindicated him. "That," he added, "is one of the things I remember most fondly" from that nightmarish period of his life.
His exoneration was complete in 1997, when he was appointed president of the California Institute of Technology. Dr. Baltimore, who published more than 600 scientific papers over the course of his career, stepped down in 2006 but remained at the institute as a professor of biology and returned to his lab there. He and Huang lived mainly in Pasadena but spent summers in Woods Hole.
During his time at Caltech, Dr. Baltimore never ceased his research into AIDS, which he began in 1986. He also headed a national committee on AIDS policy. And he discovered a cancer-causing gene in the Abelson leukemia virus, which opened the door to the creation of the cancer drug Gleevec.
He pleaded with other virologists to study AIDS -- but, he said, his pleas were to little avail.