In 2003, the Nobel Prize winner David Baltimore, then president of the California Institute of Technology, paused to reflect on his role as one of the world’s most decorated scientists.
“People keep e-mailing me to ask, ‘What is the meaning of life?’” Baltimore told an interviewer, with amusement. “And they want me to e-mail them back quickly with an answer!”
Baltimore was then 65, an age when many people are retired from public life, yet he was still actively leading one of the world’s top research universities. Others, he said, found their meaning “in friends, in dogs, in religion, in the self-reflectiveness of writing, etc. But Caltech people largely find it in the continual contest with nature.”
It was a contest that Baltimore waged right to the end of his life, as scientist, businessman, and internationally respected conscience of the new world of biological engineering. He died Saturday at his home in Woods Hole, Mass., according to his wife, as reported by the New York Times. Baltimore was 87.
His death concludes one of the most illustrious careers in 20th century science. The bearded scientist with the penetrating blue eyes played a role, usually a leading one, in virtually every important national debate over the use and potential misuse of the science of genetic engineering, whether it was gene-splicing and the search for an AIDS vaccine, or the dangers of tinkering with the human genome.
But it was as a working scientist that he made his most enduring contributions, the role he was most proud of. “When you are a scientist, and you are trying to prove or disprove a notion, you work at the bench doing the dullest, most routine things over and over and over again,” Baltimore once explained.
“I can’t tell you how many ways things go wrong. All the time you are doing this because there is an idea behind it.”
“David Baltimore’s contributions as a virologist, discerning fundamental mechanisms and applying those insights to immunology, to cancer, to AIDS, have transformed biology and medicine,’’ Caltech President Thomas Rosenbaum said in a statement.
“David’s profound influence as a mentor to generations of students
and postdocs, his generosity as a colleague, his leadership of great scientific
institutions, and his deep involvement in international efforts to define
ethical boundaries for biological advances, fill out an extraordinary
intellectual life,” he added.
David Baltimore was born March 7, 1938, in New York City, the son of a garment industry merchant, Richard Baltimore, and Gertrude Lipschitz-Baltimore. Richard’s family was Orthodox Jewish, from Lithuania, and though the Baltimores in America were not overtly religious, the family communicated a moral code that influenced their son’s concern for the underprivileged. This led him to take public stands on social issues, such as the AIDS epidemic and nuclear proliferation, that other scientists shunned. In 1970, while performing experiments that would win him the Nobel Prize, he shut down his lab for a week and joined demonstrators in Boston against the Vietnam War-era invasion of Cambodia.
In high school, Baltimore enrolled in a summer program at the prestigious Jackson Laboratory at Bar Harbor, Maine, where he made a discovery that altered his life and set him on the path to science.
“It was the process of research. I discovered that I could investigate the unknown as a high school student, that the frontier of knowledge was actually very close and very accessible,” he said, many years later.
After graduating from Swarthmore College, Baltimore earned his doctorate from the Rockefeller Institute (now University), before doing three years of research at the Salk Institute in La Jolla, where he met his future wife, Alice Shih Huang. His postdoctoral student, Huang collaborated in his research on animal viruses, later becoming a full professor at Harvard Medical School. At this time, Baltimore was particularly interested in the poliovirus, which attacks the RNA (ribonucleic acid) in cells.
“He was on the cutting edge of molecular biology,” said his friend and colleague the science historian Daniel Kevles. “There was no molecular biology to speak of and very little virology. … It was a brave field of work.”
At the time, it was an ironclad rule in molecular biology that genetic information was a one-way street, flowing from the double-helix structure of DNA to the single-stranded RNA, which the cell’s machinery uses to make proteins. But some biologists were beginning to question that assumption, and Baltimore joined the hunt for evidence that genetic information might flow in both directions, which, if true, held enormous potential for understanding the spread of viruses.
After leaving the Salk, Baltimore returned to Boston and became an associate professor of microbiology at MIT. As it became apparent that not all viruses behaved alike, Baltimore launched a new classification system, one that is still in use, grouping them by families according to their genomes and replication systems.
It was during this work that he discovered an enzyme that enabled a virus made of RNA to be copied into DNA, a process known as reverse transcription. The discovery of reverse transcriptase was greeted with overheated predictions that science had at last found a cure for cancer. The thinking went, if one could use RNA to code DNA, scientists could seize control of the body’s defenses.
Baltimore knew his work did not augur a cure for cancer, but the discovery of reverse transcriptase was nonetheless important because it led to an understanding of how genes can modify cells, turning normal cells into cancer cells. Reverse transcriptase is also used by a unique family of viruses, known as retroviruses, to replicate themselves. This finding would be critical to understanding the AIDS virus, HIV, which is a retrovirus, and devising anti-HIV treatments.
Baltimore’s discovery was attended by great fanfare and led to his promotion to full professor at MIT. In 1973, he was awarded a lifetime research professorship by the American Cancer Society, and a year later was elected to the National Academy of Sciences and the American Academy of Arts and Sciences. Finally, in 1975, with Howard Temin, a friend and colleague who had discovered reverse transcriptase around the same time, Baltimore was awarded the Nobel Prize for physiology or medicine.
With the prize came fame; people began referring to Baltimore as the most influential biologist of his generation. To the general public, who did not necessarily understand what he had done, only that it was important, he became, at the age of 37, a full-fledged savant.
The prize had a profound effect on colleagues. “I don’t see it as a burden, but you can’t get away from it,” Baltimore said later on. “I know that when I talk to young scientists, they are looking at me and saying, ‘God, I am talking to a Nobel Prize winner.’ I try to break that down. It gets harder every year.”
His new celebrity status gave him a platform to address issues of broad cultural and scientific importance, a role Baltimore embraced.
In the 1970s, when people became concerned that gene-splicing techniques could lead to the production of super viruses, Baltimore organized a conference at Asilomar near Monterey to design a self-regulating system to monitor those experiments. In the early 1980s, he led the fight against a crash program to map all human genes, fearing, once again, unknown consequences. In each case, when it was shown the dangers had been overestimated, he then led the effort to relax federal restrictions. He became an early champion of federal AIDS research and chaired a national commission that concluded the federal government’s response to the epidemic was dangerously inadequate.
As his reputation grew, he took leadership roles on political issues. When Pope John Paul II wanted to warn President Ronald Reagan of the danger of nuclear weapons, Baltimore was one of four scientists the pontiff appointed to carry his message.
In 1984, Baltimore was chosen founding director of the new Whitehead Institute for Biomedical Research, molding it into one of the world’s leading institutions of its kind. Following that success, he was appointed president of the Rockefeller University.
Along the way, he became not only a respected link between the government and scientists but also a key player in the burgeoning biotechnology industry. His early involvement in the industry made him a “relatively wealthy man,” according to a 1997 Times magazine profile.
The profile described a man in the fullness of middle age, harvesting the benefits he had earned, drinking the best wines and single malt scotch, driving appropriately luxurious but not ostentatious vehicles. “With his wife, Dr. Alice Huang, he shares a luxury duplex condominium on Union Wharf, which has a commanding view of Boston Harbor,” it said.
In person, “Baltimore’s practiced elegance frames a fierce pride and a sometimes brutal intellect, softened only by his insistence that professional criticism be leavened by personal respect.”
And then, the entire edifice crumbled as Baltimore became the focus and fall guy for one of the more infamous investigations of scientific misconduct in the last half of the 20th century. A colleague wrote a paper claiming sensational results. When others could not reproduce those results, allegations of fraud were aired, causing Congress to get involved. With the decline of the space program, biology had emerged as the preeminent science, and Congress was becoming skeptical about how millions of dollars in federal research grants were being spent.
The whiff of scandal was attached to Baltimore himself, even though his work was never questioned. Still, his refusal to admit error, or to abandon his problematic colleague, came to symbolize for many the arrogance of the new mandarins of the biological sciences.
“The Baltimore case is reminiscent of the Watergate scandal,” fumed the New York Times.
Four federal investigations and a grand jury probe later, Baltimore’s colleague, and Baltimore himself, were exonerated. The ordeal had consumed a decade of his life. Then, within months, everything changed. He was chosen to coordinate the federal effort to develop an AIDS vaccine and then appointed president of the California Institute of Technology. It was a breathtaking reversal of fortune.
“It is even more breathtaking,” Baltimore said in 1997, shortly after taking the Caltech job, “to live through it.”
Kevles, a professor at Caltech at the time, recalled that when Baltimore’s name was announced to the assembled faculty, “the room erupted in cheers. I had never seen the biologists look so ecstatic. It legitimized their field.”
In his eight years as president, Baltimore raised the university’s profile, both as a place where cutting-edge biology is done and as a respected voice on pressing national scientific debates. Under his leadership, Caltech raised more than $1.1 billion. He cited the gift of $600 million to the school by Intel Corp. co-founder Gordon Moore and his wife, Betty, as the “decisive moment” of his presidency.
“Caltech is a wonderful place, the best place to do science I have ever seen,” Baltimore said in 2005, when he announced his resignation. “I will have done what I can do [as president], and it is time for somebody else to be thinking about it.”
As for what would come next, Baltimore said, “I have a fairly extensive life in science and in business that I will pursue.”
If he thought his return to the laboratory would be a placid coda to his career, he was soon proved wrong, by yet another advance in genetic engineering, this one called CRISPR. “I’ve seen revolution after revolution in biology,” Baltimore said in 2016. “This one is a big deal.”
As one writer noted, if the gene-splicing technology of the 1970s spurred images of laboratory-hatched plagues from the “Andromeda Strain” novel and movie, CRISPR inspired comparisons to “Brave New World.” MIT’s Technology Review wrote of labs in which “man rebuilds creation to suit himself” and warned of “a path toward a dystopia of superpeople.”
Just as he did decades earlier, Baltimore took a leadership role in starting a public discussion about how to manage the powerful new tool. “At Asilomar, we had identified the genetic modification of humans as the biggest coming issue,” Baltimore said. “We just didn’t know when it would come.”
A statement drafted by participants at a meeting in Napa in early 2015 spoke of the promise of “curing genetic disease” but also warned of “unknown risks to human health and well-being.”
The statement listed 18 authors, with Baltimore at the top. Though he wrote an op-ed for the Wall Street Journal entitled, “Let’s Hit ‘Pause’ Before Altering Humankind,” Baltimore admitted later that genome-editing would in all probability take place sooner rather than later.
After retiring as president of Caltech, he remained on staff in an emeritus capacity, and was appointed the Robert Andrews Millikan professor of biology. He finally shuttered his lab in 2019 but remained active in business. He helped found a number of companies, including Calimmune and Immune Design, which carried on the work he began in immunology and virology. Though he was most visible for his public advocacy of cancer and AIDS research, it was his work as a “lab-based, working biologist” that gave him the most pleasure, and for which he hoped to be remembered.
Besides the Nobel Prize, he received the National Medal of Science in 1999, and the Warren Alpert Foundation Prize in 2000. He was the 1999 recipient of the National Medal of Science and published more than 700 peer-reviewed articles.
He was also a member of numerous scientific advisory boards, including Amgen, the Broad Institute, Ragon Institute, and Regulus. Baltimore was past-president and chair of the American Assn. of the Advancement of Science.
He is survived by his wife, Alice, and daughter, T.K. Baltimore.
Johnson is a former Times staff writer. City News Service contributed to this report.
