Robert Bittman (1942—2014) 

Robert Bittman

Robert Bittman, an organic lipid chemist and distinguished professor at the City University of New York and Queens College, died Oct. 1 of pancreatic cancer. He was 72.

Bittman won the Avanti Award from the American Society for Biochemistry and Molecular Biology in 2003 and served on the editorial board of ASBMB’s Journal of Lipid Research. One of the first recipients of the National Institutes of Health MERIT awards in 1986, Bittman “set new standards in the synthesis of bioactive lipids and their analogs with ingenuity and elegance,” said his longtime friend and collaborator Gabor Tigyi of University of Tennessee Health Science Center.

“His synthetic schemes benefited basic researchers and industrial chemists alike. Those of us who collaborated with him were beneficiaries of unique reagents, which provided new tools that led to many discoveries,” Tigyi said.

Bittman synthesized analogs of lysophosphatidic acid; phosphatidylinositol; sphingosine 1-phosphate; phosphatidylcholine; sphingomyelin; antitumor ether lipids; immunostimulatory and immunosuppressive derivatives of galactosylceramide and FTY720; photoactivatable cholesterol and phospholipids; cell-trafficking lipid tools; and chemopreventive sphingadienes. In 1992, Bittman was the first to prepare cell-permeable ceramide analogs. He also developed many methods for the enantioselective synthesis of sphingosine, ceramide and phospholipids.

“With these new reagents, he probed the roles of sphingolipids in the fusion of alpha viruses with cholesterol-containing viruses; sterol side-chain structure and sphingomyelin structure in lipid raft formation; and the effects of ceramide structure on ceramide’s dipole potential in monolayers,” Tigyi explained.

A meteoric rise, a prolific researcher

Bittman was born March 19, 1942, in New York City. A gifted student, he graduated from Jamaica High School in 1958 at age 16. He earned his undergraduate degree in chemistry in 1962 at age 20 from Queens College. He then earned his Ph.D. in chemistry in 1965 at age 23 at the University of California at Berkeley, where he worked under Andrew Streitwieser. That same year, he joined the lab of Manfred Eigen (who would win the Nobel prize in chemistry shortly thereafter) at the Max Planck Institute for Physical Chemistry in Germany. Bittman was recruited to the faculty at Queens in 1966 at age 25.

Over the next almost five decades, Bittman synthesized hundreds of molecules. His work was funded continuously by a National Institutes of Health grant that ran from 1973 through 2014.

By all measures, Bittman was prolific: He penned more than 300 scientific papers and 64 book chapters. Nineteen U.S. patents bearing his name were granted or are pending.

Tigyi, who met Bittman at a meeting in 1995 and went on to co-author 17 papers with him, said, “He was as much a sculptor of organic molecules as he was of sentences — who would not tolerate the smallest ambiguity in his manuscripts.”

Nigel Pyne of the University of Strathclyde in Glasgow, Scotland, agreed: “Although I have to say we always sent manuscripts to him with some apprehension, knowing they would come back with large numbers of mistakes corrected, he was really a line editor’s dream — but probably making them largely redundant.”

The “No. 1 go-to guy” for sphingolipids

Bittman’s collaborators all emphasized that he never met a stranger and never came across a problem not worth trying to solve.

Julie Saba, who met Bittman at an ASBMB meeting in 2005, said she was “struck with an immediate affinity for the man, who, within minutes of our introduction, began postulating structures and chemical hypotheses while leaning casually over the banister in the fifth-floor hallway and looking out into the empty space of the gallery as though he could see the chemical structures floating there.” Saba continued: “As we chatted during that first encounter, Bob’s scientific brilliance, curiosity, determination and utter unpretentiousness impressed me deeply.”

Richard Kolesnick of Memorial Sloan Kettering Cancer Center called Bittman “the No. 1 go-to guy when you wanted a sphingolipid synthesized, bar none.”

Kolesnick quipped that a quick call to Bittman was never quick at all. “After Bob would let you explain your needs for a few minutes, he would have 10 additional ideas as to how to generate new analogs that you never could have conceived of and that would further advance your idea. After his 45-minute tutorial on the structure of sphingolipids and their organic synthesis … you realized that you really didn’t know as much about your field as you thought, and you were thankful.”

Gilbert Arthur of the University of Manitoba echoed that sense of gratitude. Arthur published 23 papers and a book chapter with Bittman, and they shared three patents. Their relationship began in 1992. “Bob had synthesized a number of compounds that I was sure would be invaluable to the research I wanted to pursue, and after quickly realizing the futility of attempting to synthesize them myself, I decided to write to Bob and request some of his compounds,” Arthur said.

“The letter was written with the expectation that there would be no response,” Arthur said. “To my surprise and delight, Bob responded almost immediately.” Bittman sent the requested compounds, and a fruitful collaboration was born.

Elina Ikonen’s relationship with Bittman started in a similar way. “How many times have you sent an email to a stranger and hoped for a reply — in vain?” she asked. “I sent an email to a complete stranger almost 10 years ago and was not expecting any response. This time I was completely wrong. I had hit a gold mine! This gold mine was Bob Bittman.”

Ikonen continued: “My question was whether he might be willing to share one of the fluorescent lipid derivatives he had recently synthesized, BODIPY-cholesterol, with us. Not only did he reply promptly but more positively than I ever expected. This was the beginning of an active collaboration that, among other things, defined this compound as being suitable for assessing the behavior of cholesterol in cell membranes.”

Antonio GomezMunoz also came to know Bittman in the early 1990s, back when Gomez–Munoz was a postdoc at the University of Alberta in Canada. “I became interested in ceramide 1-phosphate, a phosphosphingolipid that had been observed by Rich Kolesnick in human leukemia cells a couple of years before. This molecule was not commercially available at the time, so I needed someone who could be capable of synthesizing it for me.”

He continued: “We contacted Bob, and he became even more enthusiastic than I on the project. Upon speaking with him, I could feel his energy and enthusiasm through my skin. Not only did he provide us with the compound, but he taught me excellent organic chemistry and gave me suggestions that turned out to be crucial for our studies.” Gomez–Munoz went on to publish six studies with Bittman on caged ceramide 1-phosphate and has three more in the pipeline.

A problem-solver to the end

Pyne, who met Bittman in 2009, underscored that Bittman was “able to discard the periphery and to go straight to the central question.” He said: “Bob was rather good at spotting these central questions, primarily because his mind was one that was unburdened and constantly searching for biology problems to solve with his compounds. His publication record is a testament to how good he was at that.”

Throughout his career, Bittman dedicated himself to service to the scientific community. He served in NIH study sections, lectured across the globe, trained 20 postdoctoral researchers and 23 graduate students, served as a member and later as chairman of the Biophysics Section of the New York Academy of Sciences, won election as vice-president of the Queens College chapter of Phi Beta Kappa, and sat on the editorial boards of the JLR, Subcellular Biochemistry, Chemistry and Physics of Lipids, and the Journal of Liposome Research. In addition, he served as secretary and co-secretary ofOrganic Reactions from 1968 to the end of his life. He was inducted as a fellow of the American Association for the Advancement of Science in 2004.

Walter Shaw, founder of Avanti Lipids, the sponsor of ASBMB’s Avanti Award that Bittman won a decade ago, met Bittman in the early 1970s. “I have seen him work his synthetic sorcery with organic molecules to produce numerous compounds that were thought to be beyond our field’s current synthetic capabilities,” Shaw recalled. “Our field has lost a great chemist, but more importantly, the world has lost a truly great man.”

Bittman’s friends say that he was reluctant to tell many people about his illness. But, Tigyi said, when Bittman did break the news to him, “he was calm and told me about his plan how to fight the disease against all odds.” Tigyi continued: “He survived the diagnosis by many, many more months than projected. In a way, it was his triumph over an unbeatable disease.”

To learn more about Bittman’s life and contributions to science, please read this full-length Retrospective article contributed by Gabor Tigyi, Julie Saba, Nigel J. Pyne, Richard N. Kolesnick, Gilbert Arthur, Elina Ikonen, Antonio Gomez-Munoz and Walter Shaw. This report is a composite of their tributes compiled by ASBMB Today’s editor, Angela Hopp.