The I in Scientist

Beyond the shared, and perhaps self-evident, characters of a scientist, such as an interminable child-like curiosity, a passion for understanding, and a quasi-obsessive single mindedness, each one of us has their own set of very personal drivers. Some less obvious, perhaps even weirder, than others.Bassem Hassan. Image courtesy of Einstein foundation.View Large Image | View Hi-Res Image | Download PowerPoint SlideAfter an almost idyllic childhood in what was back then West Germany, I grew up in the late seventies and eighties —between the ages of 6 and 22—in war-torn, and repeatedly occupied, Beirut, Lebanon. A city I adore and loathe in equal measure. It is impossible to describe to those who have not experienced it what it is like to spend your entire youth in a civil war. Aside from all the death and destruction, there is an absurdity to the notion of a society tearing itself apart, and inviting others to share in its destruction, that has left me with a disdain—to say the least—for all the ideas that separate people on the basis of manufactured identities or beliefs. At the same time, it engendered in me a desire for transcendence. A search for something bigger and more universal: more sharable, so to speak.“We grew up relatively privileged surrounded by all manner of books in a household that was a sort of a cultural oasis in the midst of war.”The culture of scientific research was essentially non-existent during the war. But I grew up in a family that (over)emphasized academic excellence and, more generally, high achievement, as almost the only meaningful reasons for being! My parents both came from poor backgrounds and climbed the social ladder through education and hard work. Growing up, my sisters and I would often be told that the only thing we will inherit is our education. Overall, we grew up relatively privileged surrounded by all manner of books in a household that was a sort of a cultural oasis in the midst of war. I quickly became an obsessive reader, mostly of poetry, novels, and the biographies of great historical figures (from which I developed my immense adoration for Beethoven). For as long as I can remember I wanted to be a poet and started writing poetry at the age of fourteen and still do to this day. There was a brief phase in fourth and fifth grades—in retrospect perhaps definitive—in which I found science the coolest subject in school, mainly thanks to our science teacher. Apart from that however, it was all about literature, especially Arabic poetry. There is a condensed beauty in poetry, and in the imagery and metaphor of great poems, that no other medium of expression parallels. There was no question in my mind that literature was my calling … until the last year of high school.Hassan with old lab colleagues at Hugo Bellen’s 60th birthday symposium.View Large Image | View Hi-Res Image | Download PowerPoint SlideIn 1986 another wonderful teacher, a gray-haired Lebanese of Greek background, taught us genetics, and I was smitten! The logic of Mendelian inheritance, the encoding of traits in DNA, the concept of a gene. All that revealed to me an esthetic elegance that life itself harbors. But this revelation came at a price: a sort of existential internal struggle. Poet or scientist? Scientist or poet? Looking back at it, I suppose the way I resolved the quandary is itself telling. I rationalized that as a scientist I could still write poetry, but that as a poet, I could not “do science.” Never mind that back then I had no clue what “doing science” actually entailed, and the only mechanism I could think about is to follow in my father’s footsteps and become a medical doctor. I started Pre-Med with a Biology major at the American University of Beirut but as soon as I was confronted with courses of animal anatomy and histology I realized that there was no way I would spend the next few years of my life memorizing names of muscles and bones. To me personally medicine was noble, but not beautiful, and I did not want to heal, I wanted to understand. I wanted to decipher the language in which nature writes her poems. I knew, however, of no way to change what seemed like a pre-set course. Once again an inspiring teacher—our microbiology instructor—changed my life. The microbiology course contained a healthy dose of molecular genetics of microorganisms and the basics of gene regulation. More importantly, our teacher had the answer to how to “do science” without getting an M.D. first! “Why don’t you do a Ph.D. in genetics in the US”? he suggested. My fate was sealed and the rest, as they say, is history!“The first time I saw these neurons and their axons and dendrites I was literally breathless. I just couldn’t stop looking down the microscope.”Fast forward more than 25 years and two amazingly generous scientific mentors and the drivers of my decisions, the hatred of war and the pursuit of beauty remain with me as major sources of inspiration. In the intellectual and experimental practice of science—if certainly not always in its institutions—I find a refuge from all the nonsense of identity politics. In science I have a pursuit that, like music, I find to be universal and timeless. Likewise, I find it extremely difficult to take on a project if I am not esthetically moved by it. I was driven to start working on two genes in my career as a Ph.D. student and then as a postdoc, simply because I found their expression patterns strikingly “beautiful.” I recall both moments as if they happened yesterday. The first occurred when I was looking for a new lab to do my Ph.D. I had started my Ph.D. working in a cancer research lab not because I was moved by it, but because I thought it would be “useful.” I suppose I was still under the influence of my pre-med days. Needless to say, without real motivation, things didn’t go very well, but thanks to a very supportive graduate program director, I had the opportunity to switch labs without losing financial support. I decided to do neuroscience because I thought neurons were amazingly cool cells and I wanted to work on Drosophila because of my lingering love for genetics. I visited the lab of Harald Vaessin, who had just started as a faculty member at Ohio State, and he showed me an in situ hybridization on a Drosophila embryo for the mRNA of a gene called prospero. The pattern of blue dots on white background in which you could see each cell that expressed the gene was simply stunning. How could I not work on that?! During my postdoc, I was again looking for a new project after publishing my first paper, when I walked into Hugo Bellen’s office to discuss some possibilities. On his desk was an image of a mouse embryo with blue dots (is there a theme developing here?) all over its skin. “What’s that? It’s very beautiful,” I asked holding the printout. “Take a guess,” he said smiling. “I’ll give you a hint: it’s a LacZ knock-in mouse from Huda’s [Zoghbi] lab.” “If there were such a thing,” I said, “I’d guess this is the mouse version of atonal,” I said sarcastically. “That’s exactly what it is!” Hugo exclaimed. That was the beginning of a long-lasting relationship between me and Atonal (a key neural transcription factor) that continues to this day and that has infected a few of my students and postdocs, I am afraid!Toward the end of my postdoc, again because of in situ hybridization for Atonal on Drosophila larval brains (yes, yes, blue dots …), I generated an enhancer-reporter line and ended up discovering an unknown neuronal circuit in the fruit fly brain. The first time I saw these neurons and their axons and dendrites I was literally breathless. I just couldn’t stop looking down the microscope. Their cell bodies formed two clusters located dorsally in the fly brain with their axons and dendrites arborizing exquisitely into the fly’s visual system. Based on their cell body position I named them the “dorsal cluster neurons” (DCNs), a name which I must admit I regret today because it is neither imaginative nor informative. Be that as it may, right there and then, I decided I would not stop until I figured out—some day—the rules of their development and function simply because I was—and still am—in awe of the “beauty” of their connectivity pattern. My lab still works on these neurons, and using them, my students and postdocs have contributed to our understanding of the probabilistic development of brain connectivity, leading to the formation of individualized neuronal circuits. A new generation of young scientists in my lab is taking these discoveries to new frontiers asking whether individualized neuronal circuit anatomy contributes to individualized innate behavioral tendencies.Dorsal cluster neurons (in green) in the fly brain.View Large Image | View Hi-Res Image | Download PowerPoint Slide“There is poetry in biology in both its form and content …”There is poetry in biology in both its form and content, and the pursuit of that beauty is both rigorously rational and emotionally uplifting. It is difficult for me to imagine a calling more satisfactory than this, and then sharing that passion for discovery with members of my team, in the hope that I give forward to them what my teachers and mentors have given me.In writing all this, I am keenly aware that this is a very personal story that may very well not resonate with or apply to many, perhaps most people. But that is the entire point of searching for, and being nourished by, our very personal drives. On that note, it is maybe a lucky coincidence—or perhaps not at all—that the twists and turns of my life and career have lead me today to study the neurodevelopmental basis of individuality … in flies! Perhaps somewhere in there lies another captivating line of nature’s magnificent poem that I will be lucky enough to read.