The poetry of science

During the past year, I have taken part in an experiment in which I have been the experimental animal. I was awarded a fellowship that gave me the opportunity to take a sabbatical from science and spend a year in the School of Literature and Creative Writing at the University of East Anglia. The School of Literature and Creative Writing is internationally renowned, and past students include household names such as Ian McEwan, Kazuo Ishiguro, Trezza Azzopardi and Tracy Chevalier. I have a keen interest in creative writing and had written a few short stories. This was a formidable but thrilling challenge. During my adventure, I realized that, in many ways, I was coming home.     

Evolution and nature of science instruction

In this article, I provide an analysis of my work (1985–present) with non-major biology students and science teacher candidates in developing strategies for teaching and enhancing learning with respect to evolutionary science. This first-person account describes changes in evolution instruction over the course of a career based on personal experiences, research-informed practices, and a critical collaboration with colleague Mike U. Smith. I assert four insights concerning the influence and efficacy of teaching nature of science (NOS) prior to the introduction of evolution within college courses for science non-majors and science teacher candidates. These insights are: (a) teach explicit NOS principles first; (b) integrate evolution as a theme throughout a course in introductory biology (but after NOS principles have been introduced); (c) use active learning pedagogies; and (d) use non-threatening alternative assessments to enhance student learning and acceptance of evolutionary science. Together, these insights establish a pedagogy that I (and my colleagues) have found to be efficacious for supporting novice students as they engage in the study of evolutionary science.     

Looking back on a life of unacknowledged privilege and a call to action

The year 2020 provided a wake-up call about the role systemic racism plays in shaping our nation and shaping science. While hard work and great mentors helped bring me a long way from a farm in Minnesota, it’s become much clearer that the privilege of being white and male and the accumulated advantages that began there played powerful roles. It’s time for white scientists like me to listen, think, and take action.

We all have personal stories that we use to describe our trajectory in life and science. For the past five decades the narrative I told myself was a simple one of good luck, hard work, support from my community, and mentors at pivotal times. However, in many important ways, this was just a small part of the truth, ignoring the role unperceived privilege played. The many underlying injustices that were laid bare in our nation this past year began to open my eyes, prompting me to look back at the roles hidden privilege played in my career and the power that these have given me. This challenged me to use the power of that privilege to speak and act to try to change the system in which engrained advantages benefit some but not all. I am telling my story in hopes it will encourage my white colleagues to examine their own.     

The story of science: successes,failures, luck,privilege, and bias

I am incredibly honored to receive the 2021 WICB Junior Award for Excellence in Research in WICB’s golden jubilee year. In this essay, I traverse my scientific journey starting with my PhD, highlighting the highs and the lows and how these intersect with luck, privilege, and bias.

V. AnanthanarayananMy pursuit for a PhD started with a hiccup—I had applied to several places in the United States, but barely got any offers due to the economic upheaval that happened that year (2008). I had to forgo any dreams of a PhD in the United States and remained in Bangalore, India to complete a project I had started with William (Bill) Thies at Microsoft Research India on a programming language for expressing biology protocols. Applying to U.S. schools was an expensive task, one which I was unwilling to put my family through again. So, a year later, when I recommenced my search for a PhD position, I set my sights on Europe. I had heard about the PhD program at the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG ) at Dresden from a friend who had just joined the institute for her PhD. Fortunately, I received an interview call from MPI-CBG. At the end of a crucial interview week at Dresden, I “matched” with Iva Tolic´’s (now Institut Ruđer Boškovic´, Croatia) lab for my PhD. At the start of my PhD, I knew next to nothing about the cytoskeleton, motor proteins, or microscopy, but I found Iva and my lab members to be some of the warmest and most welcoming people. I made friends for life and graduated with a PhD in Biophysics, with a thesis focused on understanding the regulation of the motor protein cytoplasmic dynein. I was lucky to have been able to get a position at MPI-CBG and join Iva’s lab—of the other three places in Europe I had applied to for a PhD, only one other institute invited me for an interview, which also proved to be unsuccessful.On completing my PhD in 2014, I didn’t quite know what I wanted to do. Due to personal reasons, I had to return to India and was open to options in both industry and academia. But with my training in motor protein and cytoskeleton research, I had some ideas for exploring scientific questions related to dynein activation. However, most labs I approached for a postdoctoral position were not open to a project that was outside the realm of their research focus. Nonetheless, Iva, Nenad Pavin (University of Zagreb), and Jonathon (Joe) Howard (Yale University), who were members of my thesis advisory committee, gave me the courage to continue in academia. In my naïveté, I went ahead and applied for the INSPIRE Faculty Fellowship, which is targeted at fresh PhDs and junior postdoctoral fellows to establish their own independent group at an Indian institute. To my surprise, I ended up getting the fellowship. The next issue was finding a host institute that was preferably in Bangalore, where my partner was based. I applied at a few different places, but only after I attended IndiaBioscience’s Young Investigator Meeting in 2014 did I get the chance to meet representatives of potential host institutes, including the Indian Institute of Science (IISc). After a couple of research seminars at IISc, my application was assessed and I was offered the position of INSPIRE Faculty Fellow at the newly formed Centre for BioSystems Science and Engineering, IISc.While I did not have any additional start-up funding, I was given the infrastructure and the independence to pursue my research program. It was slow and frustrating at the start, not unlike most starting labs. I always wondered if it might have been easier if I had had a regular postdoctoral stint. During this time, I also started recognizing how hard it was to be a woman in Indian academia. As a woman principal investigator, one’s authority, expertise, and ability are constantly called into question. Justifying your presence in academia on a daily basis is an exhausting task. I had a great mentor in Sandhya Visweswariah (IISc) who helped me navigate the system. I also had an extremely supportive partner, who kept me going through some of the worst times. Eventually, my lab and I landed on our feet (more about this in “My INSPIRE’d Journey”). Our research has been recognized with grants and awards, but one of the most rewarding parts of the job is seeing other lab members discovering the joy of science (I wrote about my approach to mentorship recently [https://www.nature.com/articles/s41580-020-0256-6]).Three years into the faculty fellowship, I was able to transition to an Assistant Professor position in the same institute. However, this did not change my experience as a young woman in Indian science, and the implicit and explicit biases continued. In 2020, I accepted a fantastic opportunity to further my lab’s science as an EMBL Australia Group Leader at the Single Molecule Science Node at UNSW Sydney and made the move during a pandemic. My lab’s research focus is in understanding how stochastic and rare events pertaining to cytoskeleton and motor proteins give rise to complexity in intracellular organization. With this theme as the essence of our research, we ask specific questions about motor protein regulation to effect differential cellular trafficking, mitochondria-microtubule interactions, and their role in mitochondrial dynamics, and we aim to determine barcodes of global organelle positioning in health and disease.I have the privilege of being able-bodied, born in an upper middle-class family to college-educated parents who were extremely supportive of my choices. I have also inordinately benefitted from the fact that I was born to an Indian ‘upper caste’ family. I therefore had an undue head start in life. These were circumstances beyond my control and yet played a huge role in how my story turned out. I was embarrassingly ignorant of the rampant misogyny in academia until I had to contend with explicit and implicit gender-based biases myself when I started my independent research group in India. Women make up ∼40% of science PhDs awarded in India but represent only ∼13% of Indian academia (biaswatchindia.com), highlighting the stark gender biases at play in creating a leaky pipeline. While I tried my best to voice my discontent and affect changes to create an equitable environment within my department and institute, it was slow work. In 2020, when the pandemic hit and all conferences and meetings went virtual, conference posters advertised on social media made it immediately apparent just how much women were underrepresented in Indian STEM conferences. So, I teamed up with Shruti Muralidhar (now a scientist at Deep Genomics, Canada) to found BiasWatchIndia, an initiative to document women representation and combat gender-biased panels in Indian STEM conferences.BiasWatchIndia has been in existence for a little over a year now—we have achieved several milestones, but there’s still so much to do. “Manels” (conferences that feature only men) are still as rampant as they were when we first started—40% of all Indian STEM conferences are manels. And while we have just about started to tackle the underrepresentation of women in Indian STEM, we are conscious of the intersectionality of bias with gender, caste, ableism, and socioeconomic background and aim to understand how best we can advocate for all minorities.People who are in power in academia and who oppose equity, diversity, and inclusion initiatives and instead preach merit and equality as the gold standard need to introspect, because when options and opportunities are offered without consideration to the millennia of oppression based on gender, race, and background, it is not promoting equality but upholding values that will continue to oppress underrepresented groups. Still, I am optimistic and hope to see real changes that will result in equity in academia in my lifetime.     

A career at the interface of cell and developmental biology: a view from the crest

Just as neural crest cells migrate great distances through the embryo, my journey has taken me from a childhood in a distant land to a career as a biologist. My mentoring relationships have shaped not only the careers of my trainees, but also the trajectory of my own science. One of the most satisfying aspects of mentoring comes from helping to empower the next generation of scientists to do more tomorrow than is possible today. This, together with a passion for discovery and learning new things, motivates me and makes science such a rewarding career.First, let me say how honored I am to receive the Women in Cell Biology Senior Award. I am particularly thankful to my former postdoctoral fellows and students. I have learned as much, or more, from them as they have from me and take great pride and vicarious pleasure from their successes. My goal as a mentor has been to impart an enthusiasm for science and for the satisfaction it can bring at both a professional and personal level. It is the pleasure of discovery and the bonds of collegiality that make being a scientist not only a worthwhile and interesting but also a very fulfilling career.When looking back upon my life as a biologist, many of the “choices” made along my career path were more of a random walk than a premeditated trajectory. Perhaps the most important and constant influences come from my family background, wonderful friends and colleagues, and an inherent interest in the natural world. For me, these were mixed with a good deal of luck and the generous mentorship of valued colleagues.     

Work life balance?

There is no perfect recipe to balance work and life in academic research. Everyone has to find their own optimal balance to derive fulfilment from life and work. Subject Categories: S&S: Careers & Training

A few years ago, a colleague came into my office, looking a little irate, and said, “I just interviewed a prospective student, and the first question was, ‘how is work‐life balance here?’”. Said colleague then explained how this question was one of his triggers. Actually, this sentiment isn''t unusual among many PIs. And, yet, asking about one''s expected workload is a fair question. While some applicants are actually coached to ask it at interviews, I think that many younger scientists have genuine concerns about whether or not they will have enough time away from the bench in order to have a life outside of work.In a nutshell, I believe there is no one‐size‐fits‐all definition of work–life balance (WLB). I also think WLB takes different forms depending on one''s career stage. As a new graduate student, I didn''t exactly burn the midnight oil; it took me a couple of years to get my bench groove on, but once I did, I worked a lot and hard. I also worked on weekends and holidays, because I wanted answers to the questions I had, whether it was the outcome of a bacterial transformation or the result from a big animal experiment. As a post‐doc, I worked similarly hard although I may have actually spent fewer hours at the bench because I just got more efficient and because I read a lot at home and on the six train. But I also knew that I had to do as much as I could to get a job in NYC where my husband was already a faculty member. The pressure was high, and the stress was intense. If you ask people who knew me at the time, they can confirm I was also about 30 pounds lighter than I am now (for what it''s worth, I was far from emaciated!).As an assistant professor, I still worked a lot at the bench in addition to training students and writing grant applications (it took me three‐plus years and many tears to get my first grant). As science started to progress, work got even busier, but in a good way. By no means did I necessarily work harder than those around me—in fact, I know I could have worked even more. And I’m not going to lie, there can be a lot of guilt associated with not working as much as your neighbor.My example is only one of millions, and there is no general manual on how to handle WLB. Everyone has their own optimal balance they have to figure out. People with children or other dependents are particularly challenged; as someone without kids, I cannot even fathom how tough it must be. Even with some institutions providing child care or for those lucky enough to have family take care of children, juggling home life with “lab life” can create exceptional levels of stress. What I have observed over the years is that trainees and colleagues with children become ridiculously efficient; they are truly remarkable. One of my most accomplished trainees had two children, while she was a post‐doc and she is a force to be reckoned with—although no longer in my laboratory, she still is a tour de force at work, no less with child number three just delivered! I think recruiters should view candidates with families as well—if not better—equipped to multi‐task and get the job done.There are so many paths one can take in life, and there is no single, “correct” choice. If I had to define WLB, I would say it is whatever one needs to do in order to get the work done to one''s satisfaction. For some people, putting in long days and nights might be what is needed. Does someone who puts in more hours necessarily do better than one who doesn''t, or does a childless scientist produce more results than one with kids? Absolutely not. People also have different goals in life: Some are literally “wedded” to their work, while others put much more emphasis on spending time with their families and see their children grow up. Importantly, these goals are not set in stone and can fluctuate throughout one''s life. Someone recently said to me that there can be periods of intense vertical growth where “balance” is not called for, and other times in life where it is important and needed. I believe this sentiment eloquently sums up most of our lives.Now that I''m a graying, privileged professor, I have started to prioritize other areas of life, in particular, my health. I go running regularly (well, maybe jog very slowly), which takes a lot of time but it is important for me to stay healthy. Pre‐pandemic, I made plans to visit more people in person as life is too short not to see family and friends. In many ways, having acquired the skills to work more efficiently after many years in the laboratory and office, along with giving myself more time for my health, has freed up my mind to think of science differently, perhaps more creatively. It seems no matter how much I think I’m tipping the balance toward life, work still creeps in, and that’s perfectly OK. At the end of the day, my work is my life, gladly, so I no longer worry about how much I work, nor do I worry about how much time I spend away from it. If you, too, accomplish your goals and derive fulfillment from your work and your life, neither should you.     

Sociobiology and the Comparative Approach: One Way to Study Ourselves

This paper is based on my lecture in a macroevolution course I team-teach with Profs. Daniel Brooks and David Evans at the University of Toronto. The lecture has undergone many revisions over the years as I grappled with problems discussing certain areas (e.g., rape as an adaptive strategy, gender “roles”). Eventually, I realized that the problem areas said more about my personal conflicts than they did about the science. This was one of those epiphany moments, a time when I recognized that I was less likely to accept hypotheses that contradicted the way I wanted the world to be and more likely to uncritically accept hypotheses that confirmed my world view. That epiphany, in turn, led me to realize that science is never separate from the personal biases/demons of its practitioners, especially when we are asking questions about the evolution of human behavior. That realization was not novel within the vast literature of sociology and philosophy. But it was novel for me. I was aware of discussions about personal biases clouding scientific interpretation; I just didn’t think it applied to me (I absorbed the philosophical discussions without making the connection to “my world”). So, on the heels of that epiphany, the following is a very personal take on the question of teaching sociobiology, based on where my journey, aided by my experience as an ethologist and phylogeneticist and colored by my own history, has taken me.     

Seven transmembrane receptors—A brief personal retrospective

Receptors have fascinated biologists for more than a century and they have fascinated me for the entirety of my own research career. The seven transmembrane receptors, also known as G protein coupled receptors, represent the largest of the several families of plasma membrane receptors, comprising more than a thousand genes and regulating virtually all known physiological processes in mammals. Moreover, they represent one of the commonest targets of currently used drugs. I have spent the entirety of my research career working on these receptors. Here I set down some personal reflections on the evolution of the field during the past 35 years, hanging the thread of the story on some of the work from my own laboratory.     

A career pathway in protein folding: from model peptides to postreductionist protein science

This review discusses the inherent challenge of linking "reductionist" approaches to decipher the information encoded in protein sequences with burgeoning efforts to explore protein folding in native environments-"postreductionist" approaches. Because the invitation to write this article came as a result of my selection to receive the 2010 Dorothy Hodgkin Award of the Protein Society, I use examples from my own work to illustrate the evolution from the reductionist to the postreductionist perspective. I am incredibly honored to receive the Hodgkin Award, but I want to emphasize that it is the combined effort, creativity, and talent of many students, postdoctoral fellows, and collaborators over several years that has led to any accomplishments on which this selection is based. Moreover, I do not claim to have unique insight into the topics discussed here; but this writing opportunity allows me to illustrate some threads in the evolution of protein folding research with my own experiences and to point out to those embarking on careers how the twists and turns in anyone's scientific path are influenced and enriched by the scientific context of our research. The path my own career has taken thus far has been shaped by the timing of discoveries in the field of protein science; together with our contemporaries, we become part of a knowledge evolution. In my own case, this has been an epoch of great discovery in protein folding and I feel very fortunate to have participated in it.     

People's instinctive travels and the paths to science

To be the recipient of the E. E. Just Award for 2014 is one of my greatest honors, as this is a truly rarefied group. In this essay, I try to trace my path to becoming a scientist to illustrate that multiple paths can lead to science. I also highlight that I did not build my career alone. Rather, I had help from many and have tried to pay it forward. Finally, as the country marches toward a minority majority, I echo the comments of previous E. E. Just Award recipients on the state of underrepresented minorities in science.     

A preliminary report on my life in science

I describe my wanderings from the United States to East Germany and back. I hope this gives a glimpse of science in East Germany and encourages people who do science under less than favorable conditions. Although elements of my story are unique, the main points are general: don't be afraid to start something new; it pays to be persistent; and science is a passion--if it feels like fun, you've probably got it right.     

A different kind of quarterback

I am not big on celebrations, nor do I accept many invitations to receive awards. There is much work to be done, and the reward is in the doing. I learned this lesson early from my parents, Martha and Robert Guyden. However, I am humbled that anyone would even mention my name in association with E. E. Just. I, like he, was born into a segregated America, and somehow we both found biology. I think Just's life story instigates a discussion on diversity in science, as well it should. However, after reading Tyrone Hayes' (2010 E. E. Just Award recipient) essay from last year, "Diversifying the Biological Sciences: Past Efforts and Future Challenges" (Hayes, 2010), I have little to add on the subject. His words gave voice to my thoughts. That being said, I would like to use these pages to describe my journey into the "Cell" and the people who "hoed the row ahead of me."     

An unconventional route to becoming a cell biologist

I am honored to be the E. B. Wilson Award recipient for 2015. As we know, it was E. B. Wilson who popularized the concept of a “stem cell” in his book The Cell in Development and Inheritance (1896, London: Macmillan & Co.). Given that stem cell research is my field and that E. B. Wilson is so revered within the cell biology community, I am a bit humbled by how long it took me to truly grasp his vision and imaginative thinking. I appreciate it deeply now, and on this meaningful occasion, I will sketch my rather circuitous road to cell biology.I grew up in a suburb of Chicago. My father was a geochemist, and for everyone whose parents worked at Argonne National Laboratories, Downers Grove was the place to live. My father’s sister was a radiobiologist and my uncle was a nuclear chemist, both at Argonne; they lived in the house next door. Across the street from their house was the Schmidtke’s Popcorn Farm—a great door to knock on at Halloween. The cornfields were also super for playing hide-and-seek, particularly when you happened to be shorter than those Illinois cornstalks.Open in a separate windowElaine FuchsI remember when the first road in the area was paved. It made biking and roller-skating an absolute delight. Fields of butterflies were everywhere, and with development came swamps and ponds filled with pollywogs and local creeks with crayfish. It was natural to become a biologist. When coupled with a family of scientists and a mother active in the Girl Scouts, all the resources were there to make it a perfect path to becoming a scientist.I could hardly wait until I was in junior high school, when I could enter science fairs. You would think that my science-minded family might help me choose and develop a research project. True to their mentoring ethos, they left these decisions to me. My first project was on crayfish behavior. I recorded the response of the crayfish I had caught to “various external stimuli.” At the end of this assault, I dissected the crayfish and, using “comparative anatomy,” attempted to identify all the parts. The second project was no gentler. I focused on tadpole metamorphosis and the effects of thyroid hormone in accelerating development at low concentrations and death at elevated concentrations. Somehow, I ended up going all the way to the state fair, where it became clear that I had serious competition. That experience, however, whetted my appetite to gain more lab experience and to learn to read the literature more carefully.My experience with high school biology prompted me to gravitate toward chemistry, physics, and math. When it came to college, my father told me that if there was a $2000/year (translated in 2015 to be $30,000/year) reason why I should go anywhere besides the University of Chicago (where Argonne scientists received a 50% tuition cut for their children) or the University of Illinois (then $200/year tuition), we could “discuss” it further. Having a sister, father, aunt, and uncle who went to the University of Chicago, I chose the University of Illinois and saved my Dad a bundle of money. At Illinois, I thought I might revisit biology, but my choices for a major were “biology for teachers” or “honors biology.” The first did not interest me; the second seemed intimidating.I enrolled as a chemistry major. Four years went by, during which time I never took a biology class. I enjoyed quantum mechanics, physics, and differential equations, and problem solving became one of my strengths. In the midst of the Vietnam War era, however, Illinois was a hotbed of activity. I was inspired to apply to the Peace Corps, with a backup plan to pursue science that would be more biomedically relevant than quantum mechanics. I was accepted to go to Uganda with the Peace Corps, but with Idi Amin in office, my path to science was clear. Fortunately, the schools I applied to accepted me, even though, in lieu of GRE scores, I had submitted a three-page essay on why I did not think another exam was going to prove anything. I chose Princeton’s biochemistry program. This turned out to be a great, if naïve choice, as only after accepting their offer did I take a biochemistry class to find out what I was getting into. I chose to carry out my PhD with a terrific teacher of intermediary metabolism, Charles Gilvarg, who worked on bacterial cell walls. My thesis project was to tackle how spores break down one cell wall and build another as they transition from quiescence to vegetative growth.By my fourth year of graduate school, I was trained as a chemist and biochemist and was becoming increasingly hooked on biomedical science. I listened to a seminar given by Howard Green, who had developed a method to culture cells from healthy human skin under conditions in which they could be maintained and propagated for hundreds of generations without losing their ability to make tissue. At the time, Howard referred to them as epidermal keratinocytes, but in retrospect, these were the first stem cells ever to be successfully cultured. I was profoundly taken by the system, and Howard’s strength in cell biology inspired me. It was the perfect match for pursuing my postdoctoral research. The time happened to be at the cusp of DNA recombinant technology.At MIT, I learned how to culture these cells. I wanted to determine their program of gene expression and how this changed when epidermal progenitors embark on their terminal differentiation program. While the problem in essence was not so different from that of my graduate work at Princeton, I had miraculously managed to receive my PhD without ever having isolated protein, RNA, or DNA. Working in a quintessential cell biology lab and tackling a molecular biology question necessitated venturing outside the confines of the Green lab and beyond the boundaries of my expertise. Fortunately, this was easy at MIT. Richard Hynes, Bob Horvitz, Bob Weinberg, and Graham Walker were all assistant professors, and their labs were very helpful, as were those of David Baltimore and Phil Sharp, a mere walk across the street. On the floor of my building, Steve Farmer, Avri Ben Ze’ev, Gideon Dreyfuss, and Ihor Lemischka were in Sheldon Penman’s lab just down the hall, and they were equally interested in mRNA biology, providing daily fuel for discussions. Uttam Rhajbandary’s and Gobind Khorana’s labs were also on the same floor, making it easy to learn how to make oligo(dT)-Sepharose to purify my mRNAs. Vernon Ingram’s lab was also on the same floor, so learning to make rabbit reticulocyte lysates to translate my mRNAs was also possible. Howard bought a cryostat, so I could section human skin and separate the layers. And as he was already working with clinicians at Harvard to apply his ability to create sheets of epidermal cells for the treatment of burn patients, I had access to the leftover scraps of human tissue that were also being used in these operations.The three years of my postdoc were accompanied by three Fuchs and Green papers. The first showed that epidermal keratinocytes spend most of their time expressing a group of keratin proteins with distinct sequences. The second showed that these keratins were each encoded by distinct mRNAs. The third showed that, as epidermal keratinocytes commit to terminally differentiate, they switch off expression of basal keratins (K5 and K14) and switch on the expression of suprabasal keratins (K1 and K10). That paper also revealed that different stratified tissues express the same basal keratins but distinct sets of suprabasal keratins. I am still very proud of these accomplishments, and my MIT experience made me thirst to discover more about the epidermis and its stem cells.My first and only real job interview came during my second year of postdoc, at a time when I was not looking for a job. I viewed the opportunity, initiated by my graduate advisor, as a free trip home to visit my parents and my trial run to prepare me for future searching. I was thrilled when this interview materialized into an offer to join the faculty, for which the University of Chicago extended my start time to allow me to complete my three years with Howard.Times have clearly changed, and it is painful to see talented young scientists struggle so much more today. That said, I have never looked ahead very far, and having a lack of expectations or worry is likely to be as helpful today as it was then. I am sure it is easier said than done, but this has also been the same for my science. I have always enjoyed the experiments and the joy of discovery. There was no means to an end other than to contemplate what the data meant in a broader scope.I arrived at the University of Chicago with a well-charted route. My aim was to make a cDNA library and clone and characterize the sequences and genes for the differentially expressed keratins I had identified when I was at MIT. It was three months into my being at Chicago when my chair lined up some interviews for me to hire a technician. I was so immersed in my science that I did not want to take time to hire anyone. I hired the first technician I interviewed. Fortunately, it worked out. However, I turned graduate students away the first year, preferring to carry out the experiments with my technician and get results. After publishing two more papers—one on the existence of two types of keratins that were differentially expressed as pairs and the other on signals that impacted the differential expression of these keratin pairs, I decided to accept a student, who analyzed the human keratin genes. My first postdoc was a fellow grad student with me at Princeton; she studied signaling and keratin gene expression. My second postdoc was initiated by my father, who chatted with him at the elevator when I was moving into my apartment. He set up DNA sequencing and secondary-structure prediction methods, and the lab stayed small, focused, and productive.I was fascinated by keratins, how they assembled into a network of intermediate filaments (Ifs). When thalassemias and sickle cell anemia turned out to be due to defects in globin genes, I began to wonder whether there might be human skin disorders with defective keratin genes. I had no formal training in genetics, and there were no hints of what diseases to focus on. Thus, rather than using positional cloning to identify a gene mutation associated with a particular disease, we took a reverse approach: we first identified the key residues for keratin filament assembly. After discovering that mutations at these sites acted dominant negatively, we engineered transgenic mice harboring our mutant keratin genes and then diagnosed the mouse pathology. Our diagnoses, first for our K14 mutations and then for our K10 mutations, turned out to be correct: on sequencing the keratins from humans with epidermolysis bullosa simplex (EBS), we found K14 or K5 mutations; similarly, we found K1 or K10 mutations in affected, but not in unaffected, members of families with epidermolytic hyperkeratosis (EH). Both are autosomal-dominant disorders in which patients have skin blistering or degeneration upon mechanical stress. Without a proper keratin network, the basal (EBS) or suprabasal (EH) cells could not withstand pressure. Ironically, family sizes of all but the mildest forms of these disorders were small, meaning that the disorders were not amenable to positional cloning. But the beauty of this approach is that once we had made the connection to the diseases, we understood their underlying biology. In addition, the IF genes are a superfamily of more than 100 genes differentially expressed in nearly all tissues of the body. Once we had established EBS as the first IF gene disorder, the pathology and biology set a paradigm for a number of diseases of other tissues that turned out to be due to defects in other IF genes.Fortunately, I had students, Bob Vassar (professor, Northwestern University) and Tony Letai (associate professor, Harvard Medical School), and a postdoc, Pierre Coulombe (chair, Biochemistry and Molecular Biology, Johns Hopkins University), who jumped into this fearless venture with me. We had to go off campus to learn transgenic technology. I had never worked with mice before. When Bob returned to campus with transgenic expertise, we hired and trained Linda Degenstein, whose love for animal science was unparalleled. Pierre’s prior training in electron microscopy was instrumental in multiple ways. Additionally, I was not a dermatologist and had no access to human patients. Fortunately Amy Paller, MD, at Northwestern volunteered to work with us.The success of this project attests to an important recipe: 1) Pursue a question you are passionate about. 2) In carrying out rigorous, well-controlled experiments, each new finding should build upon the previous ones. 3) If you have learned to be comfortable with being uncomfortable, then you will not be afraid to chart new territory when the questions you are excited to answer take an unanticipated turn. 4) Science does not operate in a vacuum. Interact well with your lab mates and take an interest in their science as well as your own. And wherever you embark upon a pathway in which the lab’s expertise is limited, do not hesitate to reach out broadly to other labs and universities.I have followed this recipe now for more than three decades, and it seems to work pretty well. A lab works only when its students and postdocs are interactive, naturally inquisitive, and freely share their ideas and findings. I have been blessed to have a number of such individuals in my lab over the years. When push comes to shove, I am always inclined first to shave from the “brilliant” category and settle for smart, nice people who are passionate and interactive about science and original and unconventional in their thinking.So what questions have I been most passionate about? I have always been fascinated with how tissues form during development, how they are maintained in the adult, and how tissue biology goes awry in human disorders, particularly cancers. I first began to think about this problem during my days at Princeton. I also developed a dogma back then that I still hold: to understand malignancies, one must understand what is normal before one can appreciate what is abnormal. I think this is why I have spent so much of my life focusing on normal tissue morphogenesis, despite my passion for being at the interface with medicine. And because skin has so many amazingly interesting complexities, and because it is a great system to transition seamlessly between a culture dish and an animal, I have never found a reason to choose any other tissue over the one I chose many years back.I will not dwell on the various facets of skin biology we have tackled over the years. Our initial work on keratins was to obtain markers for progenitors and their differentiating lineages. This interest broadened to understanding how proliferative progenitors form cytoskeletal networks and how the cytoskeleton makes dynamic rearrangements during tissue morphogenesis.From the beginning, the lab has also been fascinated by how tissue remodeling occurs in response to environmental signals. Indeed, signals from the microenvironment trigger changes in chromatin dynamics and gene expression within tissue stem cells. Ultimately, this leads to changes in proteins and factors that impact on cell polarity, spindle orientation, asymmetric versus symmetric fate specifications, and ultimately, the balance between proliferation and differentiation.The overarching theme of my lab over these decades is clear, namely, to understand the signals that unspecified progenitors receive that instruct them to generate a stratified epidermis, make hair follicles, or make sweat and sebaceous glands. And if we can understand how this happens, then how are stem cells born, and how do they replace dying cells or regenerate tissue after injury? And, finally, how does this process change during malignant progression or in other aberrant skin conditions?In tackling tissue morphogenesis, I have had to forgo knowing the details of each tree and instead focus on the forest. There are many times when I stand back and can only admire those who are able to dissect beautiful cellular mechanisms with remarkable precision. But I crossed that bridge some years ago in tackling a problem that mandates an appreciation of nearly all the topics covered in Bruce Alberts’ textbook Molecular Biology of the Cell. I am now settled comfortably with the uncomfortable, and the problem of tissue morphogenesis in normal biology and disease continues to keep me more excited about each year’s research than I was the previous year. Perhaps the difference between my days as a student, postdoc, and assistant professor and now is that my joy and excitement is as strong for those I mentor and have mentored as it is for myself.     

Making restoration history: reconsidering Aldo Leopold's Arboretum dedication speeches

Scholarship surrounding Aldo Leopold's involvement in the University of Wisconsin Arboretum in Madison, Wisconsin, has often pointed to Leopold's 1934 dedication speech as a significant historical artifact. While reflecting both Arboretum history and the development of Leopold's thought and influence, the speech may also have been the first publically articulated rationale for ecological restoration in the modern era. This scholarly personal essay describes my 50‐year relationship with both Leopold and the Arboretum, and my recent research that offers a new historical interpretation of Leopold's speech. Two versions of the speech exist; tensions between them have been discussed in at least two professional journals. What I learned from examining the archival record indicates that we really don't know for sure what Leopold said that June morning of 1934. What we can be sure of, however, is that the dedication speech usually attributed to Leopold, by such able scholars as Curt Meine and Baird Callicott, was not the one Leopold actually delivered. What many historians continue to refer to as Aldo Leopold's 1934 Arboretum dedication speech was actually written for another Wisconsin audience. As I explored this mystery, I rediscovered Leopold's passion for ecological restoration and his commitment to educate a diverse, Depression‐era public about its goals and purposes. For Leopold, restoration involved not only the expression of social and ecological values, but also public critique of the destructive social forces that make restoration necessary. Embodying social critique and ecological science, Leopold continues to model for us personal and professional roles as public ecological citizens dedicated to land.     

Teaming up: from motors to people

When I reflect on how I became a cell biologist and why I love being one today, one thing that comes to mind is the many terrific collaborations I have had. The science I am most proud of from my graduate and postdoctoral training would not have been possible without working in teams with other scientists. Now, in my own group, much of our best work is being done collaboratively, both within the lab and with other labs. In this essay, I will highlight my experiences working in teams as a trainee, the role teamwork has played in my own research group, and how important I think collaborative science is for the future of biological research.     

The golden age of biochemical research in photosynthesis

The perspectives and enthusiasms recorded in this review describe the events I witnessed and, in small ways, contributed to. Two great rewards emerged from my experiences – the pleasure of doing experiments and the great wealth of friendships with students and colleagues. As a graduate student, phenomena appeared at the bench before me which clarified the coupling of electron transport to ATP synthesis. My first PhD graduate student measured concentrations of pyridine nucleotides in chloroplasts and his results have been often confirmed and well used. All of the many graduate students who followed contributed to our understanding of photosynthesis. I have taken much pleasure from documenting the details of photosynthetic phosphorylation and electron transport in cyanobacteria. Studies of the `c' type cytochromes in these organisms continue to fascinate me. My experiences in government in its efforts to promote research are unusual, perhaps unique. A rare event outside the laboratory – a natural bloom of cyanobacteria – stimulated new thoughts and special opportunities for laboratory science. Photosynthesis seems magisterial in its shaping of our planet and its biology and in the details of its cleverness that were revealed in the time of my witness. This revised version was published online in June 2006 with corrections to the Cover Date.     

Scientific approaches to science policy

The development of robust science policy depends on use of the best available data, rigorous analysis, and inclusion of a wide range of input. While director of the National Institute of General Medical Sciences (NIGMS), I took advantage of available data and emerging tools to analyze training time distribution by new NIGMS grantees, the distribution of the number of publications as a function of total annual National Institutes of Health support per investigator, and the predictive value of peer-review scores on subsequent scientific productivity. Rigorous data analysis should be used to develop new reforms and initiatives that will help build a more sustainable American biomedical research enterprise.Good scientists almost invariably insist on obtaining the best data potentially available and fostering open and direct communication and criticism to address scientific problems. Remarkably, this same approach is only sometimes used in the context of the development of science policy. In my opinion, several factors underlie the reluctance to apply scientific methods rigorously to inform science policy questions. First, obtaining the relevant data can be challenging and time-consuming. Tools relatively unfamiliar to many scientists may be required, and the data collected may have inherent limitations that make their use challenging. Second, reliance on data may require the abandonment of preconceived notions and a willingness to face potentially unwanted political consequences, depending on where the data analysis leads.One of my first experiences witnessing the application of a rigorous approach to a policy question involved previous American Society for Cell Biology Public Service awardee Tom Pollard when he and I were both at Johns Hopkins School of Medicine. Tom was leading an effort to reorganize the first-year medical school curriculum, trying to move toward an integrated plan and away from an entrenched departmentally based system (DeAngelis, 2000 ). He insisted that every lecture in the old curriculum be on the table for discussion, requiring frank discussions and defusing one of the most powerful arguments in academia: “But, we''ve always done it that way.” As the curriculum was being implemented, he recruited a set of a dozen or so students who were tasked with filling out questionnaires immediately after every lecture; this enabled evaluation and refinement of the curriculum and yielded a data set that changed the character of future discussions.After 13 years as a department director at Johns Hopkins (including a number of years as course director for the Molecules and Cells course in the first-year medical school curriculum), I had the opportunity to become director of the National Institute of General Medical Sciences (NIGMS) at the National Institutes of Health (NIH). NIH supports large data systems, as these are essential for NIH staff to perform their work in receiving, reviewing, funding, and monitoring research grants. While these rich data sources were available, the resources for analysis were not as sophisticated as they could have been. This became apparent when we tried to understand how long successful young scientists spent at various early-career stages (in graduate school, doing postdoctoral fellowships, and in faculty positions before funding). This was a relatively simple question to formulate, but it took considerable effort to collect the data because the relevant data were in free-text form. An intrepid staff member took on the challenge, and went through three years’ worth of biosketches by hand to find 360 individuals who had received their first R01 awards from NIGMS and then compiled data on the years those individuals had graduated from college, completed graduate school, started their faculty positions, and received their R01 awards. Analysis of these data revealed that the median time from BS/BA to R01 award was ∼15 years, including a median of 3.6 years between starting a faculty position and receiving the grant. These results were presented to the NIGMS Advisory Council but were not shared more widely, because of the absence of a good medium at the time for reporting such results. I did provide them subsequently through a blog in the context of a discussion of similar issues (DrugMonkey, 2012 ). To address the communications need, we had developed the NIGMS Feedback Loop, first as an electronic newsletter (NIGMS, 2005 ) and subsequently as a blog (NIGMS, 2009 ). This vehicle has been of great utility for bidirectional communication, particularly under unusual circumstances. For example, during the period prior to the implementation of the American Recovery and Reinvestment Act, that is, the “stimulus bill,” I shared our thoughts and solicited input from the community. I subsequently received and answered hundreds of emails that offered reactions and suggestions. Having these admittedly nonscientific survey data in hand was useful in subsequent NIH-wide policy-development discussions.At this point, staff members at several NIH institutes, including NIGMS, were developing tools for data analysis, including the ability to link results from different data systems. Many of the questions I was most eager to address involved the relationship between scientific productivity and other parameters, including the level of grant support and the results of peer review that led to funding in the first place. With an initial system that was capable of linking NIH-funded investigators to publications, I performed an analysis of the number of publications from 2007 to mid-2010 attributed to NIH funding as a function of the total amount of annual NIH direct-cost support for 2938 NIGMS-funded investigators from fiscal year 2006 (Berg, 2010 ). The results revealed that the number of publications did not increase monotonically but rather reached a plateau near an annual funding level near $700,000. This observation received considerable attention (Wadman, 2010 ) and provided support for a long-standing NIGMS policy of imposing an extra level of oversight for well-funded investigators. It is important to note that, not surprisingly, there was considerable variation in the number of publications at all funding levels and, in my opinion, this observation is as important as the plateau in moving policies away from automatic caps and toward case-by-case analysis by staff armed with the data.This analysis provoked considerable discussion on the Feedback Loop blog and elsewhere regarding whether the number of publications was an appropriate measure of productivity. With better tools, it was possible to extend such analyses to other measures, including the number of citations, the number of citations relative to other publications, and many other factors. This extended set of metrics was applied to an analysis of the ability of peer-review scores to predict subsequent productivity (Berg, 2012a , b ). Three conclusions were supported by this analysis. First, the various metrics were sufficiently correlated with one another that the choice of metric did not affect any major conclusions (although metrics such as number of citations performed slightly better than number of publications). Second, peer-review scores could predict subsequent productivity to some extent (compared with randomly assigned scores), but the level of prediction was modest. Importantly, this provided some of the first direct evidence that peer review is capable of identifying applications that are more likely to be productive. Finally, the results revealed no noticeable drop-off in productivity, even near the 20th percentile, supporting the view that a substantial amount of productive science is being left unfunded with pay lines below the 20th percentile, let alone the 10th percentile.In 2011, I moved to the University of Pittsburgh and also became president-elect of the American Society for Biochemistry and Molecular Biology (ASBMB). In my new positions, I have been able to gain a more direct perspective on the current state of the academic biomedical research enterprise. It is exciting to be back in the trenches again. On the other hand, my observations support a conclusion I had drawn while I was at NIH: the biomedical research enterprise is not sustainable in its present form due not only to the level of federal support, but also to the duration of training periods, the number of individuals being trained to support the research effort, the lack of appropriate pathways for individuals interested in careers as bench scientists, challenges in the interactions between the academic and private sectors, and other factors. Working with the Public Affair Advisory Committee at ASBMB, we have produced a white paper (ASBMB, 2013 ) that we hope will help initiate conversations about imagining and then moving toward more sustainable models for biomedical research. We can expect to arrive at effective policy changes and initiatives only through data-driven and thorough self-examination and candid discussions between different stakeholders. We look forward to working with leaders and members from other scientific societies as we tackle this crucial set of issues.Open in a separate windowJeremy M. Berg