William M. Gelbart was a Professor of Molecular and Cellular Biology, a fly researcher extraordinaire, a prime mover of FlyBase, an early advisor to the Human Genome Project (HGP), a promoter of scientific community and common resources, a dedicated mentor to students and colleagues, a devoted family man, a doting grandfather sometimes called Apa, a squash player, a soccer coach and referee, and, overall, a humanitarian. He loved research and teaching equally, and cared deeply about students and their equal opportunities. He joyously broke into songs from musicals, quipped from Mel Brooks movies and Seinfeld episodes, discussed obscure films with art critics, and delved into other cultures. He enjoyed eating at the Aegean restaurant, holding rambunctious barbecues full of family and friends in his backyard and, generally, making work fun.
“Bill and I were graduate students together at the University of Wisconsin and became friends for life,” said Dr. Daniel Hartl, a faculty member in Harvard’s Organismic and Evolutionary Biology department. “It was a pleasure to see his career develop so successfully year on year, going from one important discovery to another, including his international leadership in creating and maintaining genetic databases for which every user owes Bill a debt of gratitude. He was also a superb and committed teacher. Bill enjoyed travel and was an accomplished sportsman, and he never really got over the baseball Dodgers leaving his native Brooklyn.”
In the words of his sister-in-law, “Bill was a rock star in science and just a regular guy from Brooklyn.” His untimely death has left a gap in the department and the many other organizations he was energetically engaged in until the very end.
“Bill Gelbart was a superb teacher and a devoted mentor, a wise and collegial member of our Department and a constant friend to many,” said Dr. Matthew Meselson, the Thomas Dudley Cabot Professor of the Natural Sciences. “He made important contributions to understanding the genetics of development — discovering and characterizing the TGF-beta signaling system in non-mammalian animals — and to bioinformatics and the building of vital community resources, including FlyBase, the core database of genetic and genomic data for the insect family Drosophilidae, of which Bill was principal investigator ever since its inception in 1992. Bill served on important national science policy panels, including years of service as Chair of the National Human Genome Institute Committee for Prioritization of Large-Scale Sequencing Projects. He devoted much time to bringing science education to underprivileged young people, developing and regularly teaching a course ‘Frontiers in Genomics’ at the University of New Mexico. In all of this, Bill was motivated by the best interests of students, science and the public interest and by his own humanity.”
“Bill was a most gentle and thoughtful colleague and friend to many of us,” summarized Dr. Alexander Schier, the chair of MCB. “His dedication to the wider community, from FlyBase to his mentorship of under-represented minority students, was remarkable and inspiring.”
Career
Dr. Gelbart was born on September 11, 1945, in Brooklyn, NY. He received a BS in biology from Brooklyn College in 1966 and a PhD in genetics from the University of Wisconsin in 1971. He conducted postdoctoral work with Ed Lewis at Caltech and Art Chovnick at the University of Connecticut. During that time, he met Dr. Thom Kaufman, now at Indiana University, Bloomington who shared an academic mentor and had mutual interests in the fruit fly (Drosophila melanogaster) and in transvection, a pairing-sensitive gene regulation phenomenon that few other people worked on. “We were in competition for a professorship at Indiana,” Dr. Kaufman recalled. “When I was offered the position, Bill had to take a lesser job at Harvard in 1976. Our paths crossed continuously. Bill became the brother I never had.”
At Harvard, Dr. Gelbart became full Professor of Molecular and Cellular Biology in 1983. He served as the Head Tutor for the undergraduate concentration in biology, program director for an interdepartmental predoctoral training program in genetics and genomics, a freshman student advisor, and chair of the faculty advisory committee for the Harvard Foundation for Intercultural and Race Relations. “The students are deeply saddened by the loss of a teacher who cared so genuinely about them,” said Dr. Allen Counter, the foundation’s director. “He was a very fine person, an outstanding scholar, and a compassionate man, with a commitment to the highest ideals. He cared exceedingly about interracial and interreligious relations on our campus, and he dedicated himself to the Harvard Foundation’s mission of diversity, equity and inclusion.” Days before his death, he was helping Dr. Counter plan the visit of a humanitarian speaker from Greece.
Research
Professor Gelbart’s long-term research interest was in understanding how the products of genes interact to guide the spatial patterning of cells in the development of organisms. His laboratory work focused on understanding the molecular basis of pattern formation in higher animals, using the fly as a model system. “You can learn so much about humans from flies,” Dr. Gelbart once said: basic biology, molecular pathways, cell-cell signaling, the networks involved in the development of an entire organism, and the structure and organization of the genome.
“Bill’s pioneering research on a key gene in fruit-fly development gave insight into human bone growth. He devised ingenious genetic trickery with a DNA sequence that can change position in the genome, and he carried out diverse research in genomics,” Dr. Hartl said.
Among Dr. Gelbart’s major discoveries was a mutant gene in drosophila that results in multiple abnormalities owing to defective development of small clusters of cells that form the adult integument. He called this gene decapentaplegic (dpp), which he named after a mutant fly missing all its limbs. The fly gene that is mutated in this disorder is an ortholog of human bone morphogenetic proteins (BMPs) that are intensely studied for their role in embryonic development and later cellular functions.
The dpp gene’s protein product, DPP, proved to be the first member of a type of transforming growth factor beta (TGF-beta) proteins that are important in cell growth, cell proliferation, cell differentiation and other morphogenetic processes. In elucidating the decapentaplegic pathway, his group also identified the genes for DPP receptors and discovered the intracellular proteins that transduce extracellular signals from TGF-beta ligands to the nucleus where they activate downstream gene transcription.
Related to his interest in development, Dr. Gelbart’s research helped clarify an epigenetic phenomenon known as transvection, in which the expression of specific genes is affected by chromosome pairing in the nucleus. He characterized transvection interactions and effects in Drosophila eye color genes, which provided key insights into the functional role of nuclear architecture in gene expression.
In his studies of transposable elements (mobile pieces of DNA that jump around and can leave behind or move DNA segments), he established the transposon hobo as a vector for making genetic transformations in flies, a technique now accomplished with gene editing tools like CRISPR.
A master in methods for genetic manipulation, Professor Gelbart devised a method using two distinct transposable elements, which can change position in the genome, to create nested sets of genomic deletions ranging in size from tens to thousands of base pairs starting from any point in the genome. This method has been important in functional analysis of the fruit fly genome including identification of protein-coding genes, noncoding RNA molecules, and dissecting large regulatory regions of DNA into their component parts.
FlyBase
Beyond his own laboratory, Dr. Gelbart’s research interests encompassed the vast international Drosophila community. Throughout the 20th century, fly researchers relied on the Red Book, a thousand-page compendium of information about fly genetics updated once every decade or two. To keep abreast of the data streaming in from new DNA sequencing machines by the early 1990s, Dan Lindsley, the keeper of the paper repository, recommended shifting it to an electronic database that could be updated many times a year. “This was before the Internet, when we retrieved files by gopher downloads,” recalled Dr. Kaufman. Drs. Kaufman, Gelbart and collaborators at Cambridge University, UK and the University of California, Los Angeles initiated the FlyBase Consortium in 1991 with the goal of connecting genetic and molecular data with fly genome sequences, and making the information freely available and easily accessible worldwide.
“Today it is an indispensible resource that thousands of researchers use on a daily basis. It’s the quintessential common global good,” said Dr. Brian Oliver, a Drosophila researcher in the National Institutes of Health (NIH) Intramural Research Program who called his relationship with Dr. Gelbart a “profoundly rewarding professional experience that evolved into a fond friendship”
The National Human Genome Research Institute (NHGRI) grant for the entire program was based at the MCB Biolabs at Harvard, and Bill served as overall principle investigator since its inception, cheerfully shouldering a huge volume of the work. “Bill was instrumental in making the complicated process at FlyBase work as well as it does,” said Dr. Oliver. “In professional settings, he was always interested in hearing what people had to say, even it were it critical. He cared about other people and listened to them. It’s a competitive world, and many of us have felt anxiety, anger and worry. He disarmed all those negative feelings. He was always positive and optimistic even when bad things happened. He’d say, ‘The world won’t come to a screeching halt.’”
In recognition of his work with FlyBase, Dr. Gelbart received the 2010 Genetics Society of America George Beadle Medal for outstanding contributions to the community of genetics researchers. At a plenary session of the recent European Drosophila meeting held a month after his death in Heidelberg, Dr. Norbert Perrimon, fly geneticist at Harvard Medical School, presented a 15-minute slideshow and about Dr. Gelbart’s career and life. A senior member of FlyBase, Dr. Gillian Millburn, Cambridge University, gave an update of the program and closed with Dr. Gelbart’s photo and said, “Bill made FlyBase fun.”
Bioinformatics and Susan Russo Gelbart
From the beginning, Dr. Gelbart realized that making this valuable database accessible required organizing and presenting data so researchers can know what is available and how they can use it in their own diverse studies. In 1992, Nobel Laureate Dr. Walter Gilbert’s Human Genome Lab at the MCB BioLabs was ending a project on a gene sequencing technique for which Susan Russo had contributed her then rare expertise in computational biology (a specialty now called bioinformatics). In 1993, Dr. Gelbart asked her to help organize and manage the FlyBase data, and she joined his lab. She has been working with the FlyBase consortium since then, and now leads the Harvard group under Norbert Perrimon.
Her early impressions of her future husband were as a down-to-earth and grounded person with a great sense of humor. “He was intelligent, kind and congenial, and could speak with anyone. He loved the students, the community and family. Many who spent time with him as a colleague became his friend.” In her case, they became what French colleague Dr. Anne Ephrussi, of the European Molecular Biology Laboratory in Heidelberg, called “un couple fusionnel,” two intensely close individual identities moving in complete harmony “like ballet dancers evolving with perfect grace and mutual respect on the stage of life.”
Level Playing Field
With NHGRI funding came the mandate to increase the participation of minorities and underrepresented groups in genetic sciences. “Bill did not just give lip service to making science more inclusive,” said Dr. Oliver, who served with Dr. Gelbart on the NHGRI’s Scientific Advisory Committee. “He developed a solid project that is effective. He showed a rare commitment to enlarging the circle of scientists.” Said Susan, “It wasn’t just that he cared about minorities. He inherently cared about people in general.”
Dr. Gelbart was already involved in Harvard’s efforts to increase minority participation in science. But he also wanted to make a difference beyond Harvard, particularly among Hispanics and Native Americans of the South West. He worked closely with Dr. Francis Collins, former director of the HGP who now directs the NIH. (They were together in Washington, DC on 9/11 – Bill’s birthday.) Dr. Gelbart told him, “We can’t just pluck up promising Native American students to enter our programs because they have such strong ties to family and community. We should take the program to them.”
Dr. Gelbart proposed enhancing a program that FlyBase colleague Dr. Maggie Werner-Washburn had established at the University of New Mexico (UNM), Albuquerque, where more than half of the students are Hispanic or Native American. Dr. Collins agreed to fund this initiative, and in a condolence note to Susan wrote that he always valued Dr. Gelbart’s good science advice and also the human element he brought into the work.
Genomics Frontiers in New Mexico
In collaboration with colleagues at UNM, Dr. Gelbart created a course, Frontiers in Genomics, designed to inform and mentor under-represented minority students in the fields of genetics and genomics. For six years each fall, he flew back and forth between New Mexico and Massachusetts to teach the seven-week Friday afternoon course. Said Dr. Kaufman, “Bill used to take great joy in baffling the New Mexico students with Yiddish – such as “chazzerai” to describe some particularly sloppy work.” He usually flew out earlier, on Wednesday, to meet with students or invite them to lunch with renowned leaders in genomics prior. “People thought it must be exhausting,” Susan said. “It energized Bill, and gave him such gratification. The students were so interested and passionate. There’s a lot of love there for him.”
Dr. Washburn said, “Bill came to UNM because he fell in love with our students. He worked to engage our students and faculty in the work and ideas of genomics.” His ongoing care for the students inspired many to go to Harvard, the Broad Institute, Stanford, University of Washington, University of Chicago, and elsewhere.
A Model Database
FlyBase was one of the first biological databases on the World Wide Web, and it became the model for many others. Dr. Gelbart served on the Scientific Advisory Boards of WormBase, Zebrafish Information Network (ZFIN), The Arabidopsis Information Resource (TAIR) and Germplasm Resource Information (GRIN)-Global, the National Human Genome Research Institute (NHGRI) Large-Scale Genome Sequencing Network Advisory Committee, and the NHGRI National Advisory Council. He chaired the NHGRI Coordinating Committee for Selection of Large-Scale Sequencing Projects.
He also helped shape the genomic landscape in Canada, wrote Dr. Cindy Bell, executive vice president of corporate development for Genome Canada, where Dr. Gelbart served on the Board of Directors (2007-2011) and on its international review committees. He participated regularly in scientific meetings and events to educate the lay community and politicians about the importance of genomics.
Family Man
Dr. Gelbart did not rest when not working. He was active in club leadership at the Newton Squash and Tennis Club, coached for Newton Girls Soccer and later Wayland BAYS soccer, and became a licensed FIFA soccer referee. “Bill didn’t need a lot of sleep – luckily,” said Susan. They enjoyed extensive traveling and were often joined with close friends or their daughters in Maui and in Crete, where Dr. Gelbart regularly attended scientific meetings and they found not just a vacation home, but a village that warmly welcomed them.
Dr. Gelbart kept his cancer diagnosis private because he did not want to be treated as a sick person but as a one embracing work and enamored with life. He is deeply mourned by his beloved Susan; his loving daughters, whom he was exceptionally proud of, Marnie Carey, Courtney Phelon, and Jennifer Walsh; his adoring grandchildren Delilah, Theodore, and Amelia (there is now a new grandson named William); sons-in-law James Carey and Scott Phelon; his brother Herb; and many in-laws, nieces, nephews, and dear friends.
The MCB treasured Dr. Gelbart’s contribution to the department and our students, and shares in the widespread grief at his passing.
A memorial service honoring Bill will take place on Saturday, October 24 at 1 p.m. in The Memorial Church of Harvard University. The service will be followed by a reception at the café in the Northwest Building, 52 Oxford Street. All are welcome.
In lieu of flowers, contributions may be made to The Greater Boston Food Bank or WGBH (Boston’s PBS).
Nature Genetics Obituary or download PDF
Harvard FAS Memorial Minute or download PDF
GSA: In Memoriam William Martin Gelbart (1945–2015) or download PDF
