Portal de Periódicos da CAPES

Elizabeth C. Raff

2010; Elsevier BV; Volume: 20; Issue: 15 Linguagem: Inglês

10.1016/j.cub.2010.06.007

1879-0445

Elizabeth C. Raff,

Conservation, Ecology, Wildlife Education

Beth Raff grew up near Washington, D.C.; she got a B.S. in biochemistry from Penn State, and a Ph.D. in biochemistry from Duke. Following several postdocs, one stay-at-home-mother year, and some years as a research scientist, for the past 24 years she has been on the faculty of the Indiana University Department of Biology, where she is currently Professor of Biology. From 2002–2007, she was the first woman chair of Biology, during which time she had the immense satisfaction of hiring a third of the current 61 members of the department. She is married to evolutionary biologist Rudy Raff; they have two children and one grandchild. How did you get interested in science? Some people are more or less ‘born scientists’, biologists often starting as kid naturalists; others come to science through a later intellectual interest. I fall into the latter category, with a little flavoring from the first. Through most of my K-12 school career, I intended to be something ‘literary’, but in the end I was strongly influenced by my wonderful high school chemistry teacher, who held Saturday labs where we could do all kinds of — I now realise — not entirely safe chemistry experiments. I started college as a chemistry major, then switched to biochemistry when I hit upper-level analytical chemistry (too many decimal places). I loved biochemistry; it felt as natural to me as earlier organic chemistry had. But at first it was frustrating. When I walked into class a couple of days late after changing my major, the professor was talking about fascinating reactions, but it took me several days to figure out exactly where these reactions were happening — strangely, neither the professor nor the textbook mentioned cells. I have only ever taken two biology courses — one in high school, and the entry level course at Penn State, which I took in a class of thousands by remote access TV hook-up and remember only for the professor once standing on a tortoise. During my childhood, however, I was also strongly influenced by my experiences with real life biology as a farm girl in the summers I spent with my grandparents. I helped deliver many litters of piglets, rode horses, milked cows (we produced Grade C milk, but that's another, scarier, story). My cousin Ann, four years my senior, who eventually became a Professor of Spanish literature, first taught me some biology, starting with the marine fossils we found on our grandparents' farm. Ann also told me about genetics and evolution (the E-word was never mentioned during my public school education, nor indeed in my one undergrad Bio course or in any of the undergrad or graduate biochemistry courses I took). Her discussions of heredity left me feeling that ‘chromosome’ was a slightly dirty word that should not be spoken in front of grownups (she used it in the same sentence with the word ‘sperm’). And I gained the common erroneous conception that evolution is linear. For many of my primary school years I worried about what would happen if we humans didn't keep up with the pace of chimpanzee evolution and they became human before we turned into whatever was next. But although perhaps not perfectly accurate, Ann's science lessons did set me thinking about the ‘data’ and asking questions — that crucial first step. Women of your generation did not have as many role models as we fortunately have now: what was it like making a career in science at a time when there were far fewer women professors? I didn't have any women biochemistry professors as an undergraduate or graduate student. I vividly remember my first — and only — female science professor. She taught physics, giving lectures at 8am on Saturday mornings. I suspect that she was probably a graduate student and that was why she had to take this unpopular teaching slot, but she looked old to me at the time. One morning the door to the lecture hall burst open and two small children ran in, screaming with laughter at their feat in eluding their watcher, apparently my instructor's husband. She gave them a brief cuddle and then rounded them up and handed them back to the waiting baby minder. She actually said “there go my punkins” as she ushered them out the door. I was shocked. I had not known that a woman could be a professor and also have children. I wasn't even sure it was something that this woman should have admitted so casually. Didn't she know it might hold her back? At Duke, the biochemistry graduate admissions committee of six male professors admitted graduate classes that were approximately half women. However, only five of the six biochemistry admissions committee members interviewed me. The sixth never interviewed women applicants, always voted against their admission, and did not accept women into his lab. We took this as a matter of course. And I am sorry to say that of the 10–12 women in my class, only a few of us persisted in science. Earlier, as an undergraduate on my first trip to Manhattan, I had dropped by the biochemistry department of a famous university and asked for an application form to their graduate program. “No,” I was told, “we don't admit women to our program.” “Oh, ok.” All this was quite legal, though it wouldn't be for long. We never thought about it, or at least not much. I'm astonished now, looking back. Every woman of my generation or older had these kinds of experiences as a matter of course. The fact that these things didn't deflect me as I made my somewhat loop-the-loop way into a science career is something that much, much later I understood my mother had done for me, although quite subtly. She was typical of her time — a college graduate housewife. As a child and young girl, all the physicians she took me to were women. We lived in Chevy Chase, not far from NIH (which I had never heard of then) and there were many local doctors' offices. My parent's doctor was a man who lived in the neighborhood. I never thought about the often long bus and street car trips across D.C. that my sister and brother and I took with our mother to our various doctor or eye doctor appointments. You have worked on tubulin and microtubules for your whole career: how did you get interested in this topic? Basically it was love at first sight. Two seminars my first year in graduate school led me to want to know about cell structure in general and microtubules in particular. One was by J.D. Robertson, head of the Anatomy and Cell Biology department for many years, about his discovery of the unit membrane structure; the other was a seminar in Robertson's department by Shinya Inoué, about mitosis. Grad students then, as now, had to present yearly journal clubs; I wrote a timid letter to Inoué and he kindly loaned me a giant reel with a copy of his film of mitosis under polarizing light to show at my talk. Biochemistry then was in the era of Efraim Racker's admonishment, “don't waste clean thinking on a dirty enzyme.” But by this time I had attended enough seminars in the Anatomy and Biology departments to realize that life is a dirty system. I convinced Joe Blum in the Physiology department to let me study Tetrahymena cilia for my thesis research — the motile axoneme became my favorite flavor of microtubule. The other interest I found by straying out of the biochemistry department is human behavior. For my second journal club I talked about the neural mechanisms underlying the LSD experience. There were little data available about that in the mid-60s, and what there were, were wildly conflicting. That journal club wasn't very successful. However, I am currently teaching an upper-level non-majors course entitled “Heredity, Evolution, and Society” — this course is a great deal of fun and has allowed me to return to this long-term interest, while hopefully enticing non-science students to discover the delight of the world of biology, and, most importantly, to always ask questions and to think critically about all topics. Given the strong genetic focus of your work, do you still consider yourself a biochemist? Absolutely. To me, genetics is the best way to do biochemistry — the only way to get the ‘dirty enzyme’ conditions right. I lucked into Drosophila thanks to Thom Kaufman, who when he arrived at I.U. as a faculty member taught me how to tell the boys from the girls. Doing genetics on tubulins in flies has been enormously exciting. We were able to mix and match tubulins expressed in the fly's male germ line, allowing us for the first time to do definitive experiments in a complex eukaryotic tissue to test whether tubulins can be specialized or not. The answer is a resounding yes. It has been an amazing and satisfying surprise to discover the intricacy with which the sequence of the component tubulins can determine both microtubule structure and axoneme architecture and function. Using genetics to do our biochemistry, we made many exciting discoveries that could not have been predicted. Our first — key — test in this series of experiments was to ask whether another, slightly divergent fly β-tubulin could replace the normal testis β-tubulin. We discovered that the two tubulins were not functionally interchangeable. Even though the other isoform is a perfectly good tubulin in the tissues where it normally functions, it could not support axonemes or other testis-specific functions. We introduced a moth testis β-tubulin homolog into the fly testis and discovered that the moth tubulin brought with it the instructions for the moth's specialized 16 pf microtubules. We found that even an α-tubulin 98% like the normal testis α-tubulin was a dismal failure at making axonemes, although it could make spindles just fine. We discovered a carboxy-terminal sequence motif that specifies motile axoneme β-tubulins, conserved in all eukaryotes. We discovered that it matters how the ‘parts’ of the tubulins in a microtubule are put together: a heterologous β-tubulin can work in concert with the endogenous germ line β-tubulin, but if the tails and bodies of the molecules are swapped, the ‘trans’ configuration doesn't work — even though all the same tubulin sequences are present. We discovered that the identity of one internal amino acid in β-tubulin is crucial for the attachment of the outer dynein arms that power axoneme motility — this feature of axoneme β-tubulins is also conserved throughout phylogeny. Along with microtubule function, evolution of developmental mechanisms and the determination of body form has become half of your research efforts: how did that happen? The I.U. Biology department is a broad, unified department, a fantastic place to do science, with one of the best evolution groups in the country — making up for my life pre the E-word. I got into our now long-term evo-devo collaboration with my husband, Rudy Raff, through an experiment I urged him to do but ended up doing myself. In the 1980s, Rudy discovered an ideal system for experimentally accessing evolution of development, using two closely related species of Australian sea urchins that, although separated by only four million years, have completely different developmental pathways. One generates the typical long-lived planktonic pluteus larva and the other skips a feeding larval stage, going directly from a fertilized egg to a little sea urchin in just three to four days. Rudy, with his group, discovered the cellular and gene mechanisms involved in this reshaping of ontogeny. I wanted to try making hybrids between the two species, so in 1998 I took a mini-sabbatical to the University of Sydney. Adding to the lure of the questions I could ask about developmental pathways was the alluring location. The only negative I can think of for fly genetics is that no field studies are required. Evolutionary biologists always seem to have exotic field sites. At last I found my own ‘field’, the world's best city. I have always liked the fertilization literature, perhaps because of the featured role for sperm tail axonemes, and I figured out how to generate hybrids. As with tubulin genetics, I was hooked by spectacular and unexpected results. The cross in one direction generated viable hybrids — but with a novel ontogeny. Given this gift of biological revelation, we have pursued this system since then. Most recently, we discovered we can use the relatively giant (400 μm) direct-developing embryos to experimentally model how soft tissues can be fossilized, seeking insight into ancient animals represented by rare fossils. Another new avenue to explore has thus suddenly opened up. What's next — retirement? No way. Both doing and teaching science are still much too exciting — and fun, the key word.