Reminiscences,collaborations and reflections

This is a personal account by a semi old-timer who completed his official term as a professor of plant biochemistry at Nagoya University in Japan in 1992. My university student life began soon after the World War II (1948). I shared the hardships of many in my age group, in that life was difficult during my college years. I was fortunate to have the opportunity of studying in the USA on a Fulbright scholarship first at Purdue University (1955–1956), and then at the University of California, Berkeley (1956–1957). My graduate study and postdoctoral training in the new world were vitally refreshing and stimulating, which gave me the impetus for becoming a natural scientist associated with academic institutions. Consciously and subconsciously I was impressed by the friendly and liberal atmosphere surrounding young students as well as senior scholars in the United States. But more importantly, I was inspired by the critical and competitive minds prevailing among these people.The appointment as a biochemist at the International Rice Research Institute (IRRI) in the Philippines (1962–1964) was the real start of my professional career. The work was continued upon my return to Nagoya to become a staff member of the Research Institute for Biochemical Regulation (1964–1992). Throughout the years, my major research interest has covered photosynthesis as a whole, involving photosynthetic CO₂-fixation (RuBisCO), carbohydrate metabolism, e.g. starch biosynthesis and breakdown (-amylase), and metabolic regulation, which are interrelated in the basic metabolism of plant cells.I shall briefly describe in this article highlights from my studies and discoveries made and I shall also discuss their possible significance in plant metabolism, with the hope that it does not contradict my sense of humility: They are (a) discovery of ADPG in plants and its role in starch biosynthesis; (b) structure-function relationship of RuBisCO proteins, in particular on heterologous recombination of their subunits of plant-type enzyme molecules derived from the prokaryotic photosynthetic bacteria; (c) molecular evolution of RuBisCO genes; (d) mode of actions (formation, intracellular transport and secretion) of rice seed -amylase and its structural characteristics (distinctive glycosylation), and (e) DNA methylation and regulatory mechanism of photosynthesis gene expression in plastids (amyloplasts). In each step of my research, I shared joy, excitement, disappointment, and agony with my colleagues, an experience that may be common to all researchers. Although it is now becoming well recognized among the scientific community in Japan, I want to point out that interaction of multinational scientific minds in the laboratory produces a vital and creative atmosphere for performance of successful research. I experienced and realized this important fact in my earlier days in the USA and the Philippines. Inasmuch as I believe that this is the most crucial element for any research laboratory to possess, I fondly remember the friendships gained with numerous overseas visitors and collaborators who have contributed immensely to our work.Written at the invitation of Govindjee.     

Astrocytes Provide Metabolic Support for Neuronal Synaptic Function in Response to Extracellular K<Superscript>+</Superscript>

It is an honour to have this opportunity write an article in recognition of the immense contributions of Bruce Ransom to the field of glial research. For me (BAM) personally there are many highlights both as a colleague and a friend that come to mind when I reflect on the many years that I have known Bruce. My own entry into the glial field was inspired by the early work by Ransom and his lab showing the sensitivity of astrocytes to neuronal activity. During my PhD and postdoctoral research I read these early papers and was inspired to ask the question when I first set up my independent lab in 1983: what if astrocytes also express some of the multitude of ion channels or transmitter receptors that were beginning to be described in neurons? Could they modify neuronal excitability during seizures or behaviour? As it turned out this was not only true but glial-neuronal interactions continues to be a growing and exciting field that I am still working in. I first met Bruce at the 1984 Society for Neuroscience meeting in Anaheim at my poster describing voltage gated calcium channels in astrocytes in cell culture. That was the start of a great friendship and years of discussions and collaborations. This review describes recent work from my lab led by Hyun Beom Choi that followed and was inspired by the groundbreaking studies by Bruce on electrophysiological and pH recordings from astrocytes and on glycogen mobilization in astrocytes to protect white matter axons.     

Experiments

In this article, I have provided a brief history of my life. After tracing my family background and my early interest in physical sciences, I discuss how I entered biology under the influence of Robert Emerson. I have always enjoyed doing experiments and this led to new measurements and analyses of chlorophyll unit, efficiency of photosynthesis, excitation energy transfer, delayed light emission, thermoluminescence and electroluminescence in photosynthetic organisms. It is my view that discoveries are made because we follow our scientific curiosities.This article was written at the invitation of Govindjee.     

Being at the right place at the right time

I am tremendously honored to receive the 2012 Women in Cell Biology Junior Award. In this essay, I recount my career path over the past 15 years. Although many details are specific to my own experiences, I hope that some generalizations can be made to encourage more women to pursue independent scientific careers. Mine is a story of choosing a captivating question, making the most of your opportunities, and finding a balance with life outside the lab.It is a great honor to have been awarded the 2012 Women in Cell Biology Junior Award from the ASCB. Looking back at the 15 years I have spent doing research in cell biology, my overwhelming feeling is that it has been and still is a lot of fun. I am extremely fortunate to have a job that I truly enjoy and that gives me complete intellectual freedom. My lab choices over the years were motivated by scientific curiosity and enthusiasm for new environments and topics, rather than by career building. It is thus truly amazing to be rewarded for (rather a lot of) work enjoyed.     

The Q-cycle – A Personal Perspective

In this Minireview, I provide an overview of the developments over the period 1970 to 1990 that led to the current view of the Q-cycle mechanism of the cytochrome bc (1) complex. The perspective is necessarily personal, and places some emphasis on research on the complex in the photosynthetic bacteria, where the kinetics could be studied in situ and with better time resolution than in mitochondria. Peter Mitchell's original Q-cycle underwent several early revisions. The version of the Q-cycle currently accepted in most labs owed much to a perceptive critique by Peter Garland, who proposed a modified Q-cycle that allowed the complex to act independently. This was among several variants discussed by Mitchell in a seminal review from 1976. Six years later, despite significant advances in both mitochondrial and bacterial work, discrimination between the half-dozen or so variants that remained in active contention had proved elusive, and the kinetic data from both mitochondrial and photosynthetic systems was refractory. This was the basis of my own opposition to the Q-cycle. While trying to explain this opposition to an undergraduate student in the lab I was led to a re-evaluation of the kinetic data in the light of the substantial advances in our understanding of the biochemistry and thermodynamic properties of the complex. From this it became apparent that one version of the Q-cycle could account with satisfactory economy for the data from the photosynthetic bacteria, and for most results from work with mitochondrial complexes. The resulting model was highly constrained, and, since it incorporated Garland's suggestions for an independent mechanism, was called the modified Q-cycle. The modified Q-cycle has stood the test of time well, and the recent structural information has both confirmed the general mechanism, and allowed extension to a more detailed understanding of the molecular architecture, and the relation between structure and function.     

Genome-enabled exploration of microbial ecology and evolution in the sea: a rising tide lifts all boats

As a young bacteriologist just launching my career during the early days of the ‘microbial revolution’ in the 1980s, I was fortunate to participate in some early discoveries, and collaborate in the development of cross-disciplinary methods now commonly referred to as "metagenomics". My early scientific career focused on applying phylogenetic and genomic approaches to characterize ‘wild’ bacteria, archaea and viruses in their natural habitats, with an emphasis on marine systems. These central interests have not changed very much for me over the past three decades, but knowledge, methodological advances and new theoretical perspectives about the microbial world certainly have. In this invited ‘How we did it’ perspective, I trace some of the trajectories of my lab's collective efforts over the years, including phylogenetic surveys of microbial assemblages in marine plankton and sediments, development of microbial community gene- and genome-enabled surveys, and application of genome-guided, cultivation-independent functional characterization of novel enzymes, pathways and their relationships to in situ biogeochemistry. Throughout this short review, I attempt to acknowledge, all the mentors, students, postdocs and collaborators who enabled this research. Inevitably, a brief autobiographical review like this cannot be fully comprehensive, so sincere apologies to any of my great colleagues who are not explicitly mentioned herein. I salute you all as well!     

My early days in photobiology with Philip Hanawalt

Phil and I started our careers on somewhat similar scientific paths. I had an undergraduate degree in physics from Swarthmore College and a Ph.D. degree in physics from Yale for research in the field for ultraviolet spectroscopy. Phil received an undergraduate degree in Physics from Oberlin College, joined the Yale Physics Department in 1954, and transferred to the new Biophysics Department in 1955. We began our interactions then by virtue of the fact that Phil had to take a Laboratory Course in Experimental Physics, one part of which was spectroscopy in which I was the instructor. One of my principal interests was in the effects of different wavelengths of ultraviolet (UV) radiation on proteins, viruses and bacterial cells. So what was more natural than for Phil to dream up a Ph.D. research project to investigate the effects of different wavelengths of UV on macromolecular synthesis in Escherichia coli. I became his mentor with expertise in UV, whereas he did most of the microbiological/biochemical work. Thus began a collaboration and a communicating friendship, the latter going on for 50 years. That communication was essential in elucidating some of the important steps in nucleotide excision repair-a field in which Phil is a pre-eminent scholar and investigator.     

Travels in a world of small science*

As a boy, I read Sinclair Lewis's Arrowsmithand dreamed of doing research of potential benefit to society. I describe the paths of my scientific career that followed. Several distinguished scientists served as my mentors and I present their profiles. Much of my career was in a small department at a small institution where independent researchers collaborated informally. I describe the unique method of carrying on research there. My curiosity about glycolate metabolism led to unraveling the enzymatic mechanism of the glycolate oxidase reaction and showing the importance of H₂O₂ as a byproduct. I discovered enzymes catalyzing the reduction of glyoxylate and hydroxypyruvate. I found α-hydroxysulfonates were useful competitive inhibitors of glycolate oxidase. In a moment of revelation, I realized that glycolate metabolism was an essential part of photorespiration, a process that lowers net photosynthesis in C₃ plants. I added inhibitors of glycolate oxidase to leaves and showed: (1) glycolate was synthesized only in light as an early product of photosynthetic CO₂ assimilation, (2) the rate of glycolate oxidation consumed a sizable fraction of net photosynthesis in C₃ but not in C₄ plants, and (3) that glycolate metabolism increased greatly at higher temperatures. For a while I studied the control of stomatal opening in leaves, and this led to the finding that potassium ions are a key solute in guard cells. I describe experiments that show that when photorespiration rates are high, as occurs at higher temperatures, genetically increasing leaf catalase activity reduces photorespiration and increases net photosythetic CO₂ assimilation. This revised version was published online in June 2006 with corrections to the Cover Date.     

A view from the NIH bridge: perspectives of a program officer

This essay is written from my perspective as a program officer for research and training activities at the National Institute of General Medical Sciences (NIGMS) for almost 27 yr. It gives a bird's-eye view of the job of a program officer, which includes providing advice to applicants and grantees, making funding recommendations, overseeing grantees' progress, facilitating scientific opportunities in specific areas of program responsibility, and shaping NIGMS and National Institutes of Health (NIH) policy. I have highlighted the numerous rewards of serving as a program officer, as well as some of the difficulties. For those who may be considering a position as an NIH program officer now or in the future, I've also described the qualities and qualifications that are important for such a career choice. Finally, this essay addresses some of the challenges for the NIH and the research community in the years ahead as we simultaneously face exciting scientific opportunities and tighter budgets.     

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.     

Research on Carbon Dioxide Fixation in Photosynthetic Microorganisms (1971–present)

This paper presents my personal account of research on CO(2) fixation from when I began these studies as a postdoctoral student in the early 1970s. It traces interests in microbial ribulose bisphosphate carboxylase/oxygenase (Rubisco) and considers early breakthroughs on the isolation, characterization, and significance of this enzyme from nonsulfur purple photosynthetic bacteria and other phototrophic organisms. This article also develops a historical perspective as to how recent efforts may lead to an understanding of molecular mechanisms by which the synthesis of this enzyme and other proteins of the pathway are regulated at the molecular level. In addition, how these studies impinge on the interactive control of CO(2) fixation, along with nitrogen fixation and hydrogen metabolism, is also considered. Finally, CO(2)-fixation studies in green sulfur photosynthetic bacteria and the discovery of the rather surprising Rubisco-like protein are described.     

Earlier researches on the mechanism of oxygen evolution: A personal account

A brief overview is given of the research which led to the discovery of the period-4 oscillations of the flash-induced oxygen production and which is the basis of the generally accepted Kok's model for water splitting and oxygen evolution.In this paper I discuss the earlier work of the groups of Robert Emerson, James Franck, C. P. Whittingham, and myself in relation to the development of new techniques for the detection of photosynthetic oxygen evolution. Also discussed are various hypotheses and speculations related to the concept of a priming photoreaction which is required for oxygen evolution. Finally, I discuss my long scientific collaboration with Bessel Kok which led to the elaboration by Kok of the classical model in which the formation of oxygen requires the sequential accumulation of four positive charges on the same photochemical center.Written at the invitation of Govindjee and Gernot Renger.     

Three decades of research in bacterial photosynthesis and the road leading to it: A personal account

In this minireview I present a very personal account of my life and research in bacterial photosynthesis. It is divided into two parts. The first part is autobiographical and narrates the events that led me to change fields from electrical engineering to physics and ultimately to biophysics. The second part describes the work on the primary processes in bacterial photosynthesis carried out with numerous collaborators in our laboratory over the past 30 years.     

A quest to understand molecular mechanisms for genetic stability

In the midst of the post-war turmoil in Japan, I fortunately followed a path to become a scientist. Sometime at an early stage of my career, I encountered the problem of the cellular response to DNA damage and had the chance to discover a DNA repair enzyme. This event greatly influenced the subsequent course of my research, and I extended my studies toward elucidating the molecular mechanisms of mutagenesis as well as of carcinogenesis. Through these studies I came to understand the importance of mechanisms for dealing with the actions of reactive oxygen species to the living systems. These recollections deal with these endeavors with emphasis on the early part of my scientific career.     

Fifty-eight years in science--a commentary

After 58 years in science, mostly in pharmacology, one gains perspective. Mine is that there have been important changes over this time, some good and some questionable. In this commentary, I try to reveal how I got to this stage, partially explaining my biases, and possibly helping others learn from my experiences including mistakes. Changing from seeking an M.D. to cellular biology and then to pharmacology early in my career were the best moves I made. The next best move was migration to Canada, away from the McCarthy-McCarran hysteria. Arriving at a time after the end of World War II when science in Canada was expanding was very good luck. I had an excellent opportunity to enjoy both the administration (as Chair of the first independent Department of Pharmacology at the University of Alberta) and the practice of pharmacology (as a practitioner of research on smooth muscle in health and disease). For me, the practice of research has always won over administration when a choice had to be made. Early on, I began to ask questions about educational practices and tried to evaluate them. This led me to initiate changes in laboratories and to seek nondidactic educational approaches such as problem-based learning. I also developed questions about the practice of anonymous peer review. After moving to McMaster in 1975, I was compelled to find a solution for a failed "Pharmacology Program" and eventually developed the first "Smooth Muscle Research Program". Although that was a good solution for the research component, it did not solve the educational needs. This led to the development of "therapeutic problems", which were used to help McMaster medical students educate themselves about applied pharmacology. Now these problems are being used to educate pharmacology honours and graduate students at the University of Alberta. The best part of all these activities is the colleagues and friends that I have interacted with and learned from over the years, and the realization that many of them have collaborated with me again in this volume.     

Inclusion: an individual pursuit requiring organization-level investment to sustain it

If this was not happening in the midst of the COVID-19 pandemic, I imagine that I would be speaking these words instead of writing them on my laptop. Even so, I am so jazzed for this opportunity! No word or phrase describes what I am feeling in this moment in receiving the 2021 American Society for Cell Biology Prize for Excellence in Inclusivity. It is certainly an honor to be recognized in this way. I am grateful to the Howard Hughes Medical Institute for awarding me additional resources to keep on keeping on. My approach to finding the connection between people and their science certainly could use the monetary support. Resources open doors. At the same time that I am grateful for the attention, I am not exactly sure what to do with the spotlight. Importantly, there are a host of other folks out there also doing amazing things who have never been recognized. Let’s work to ensure that their contributions are supported, appreciated, and recognized. Instead of focusing the spotlight on me, I would rather redirect it to recognize my foundational influences. I also hope to encourage the need for institutional approaches beyond celebrating individual accomplishment.

O. A. Quintero‐CarmonaJo Rae Wright was my graduate advisor and the model for how I have tried to work with my students and colleagues to support their opportunities while also “doing science.” I wanted to start graduate school as soon as I could after graduating college, so after letting the Cell and Molecular Biology Program at Duke University know that I was accepting their offer, I started thumbing through their program booklet looking for labs with interesting research projects (a web presence wasn’t even really a thing for departments in 1996). I worked alphabetically and contacted a handful of labs one at a time to see whether anyone was willing to take on an early-rotation student. It was an unusual request for the way that the program had operated previously, and Jo Rae was the only person to agree to it. I don’t remember exactly, but she said something like, “We accepted you into the program, so I would be happy to host your first rotation.” The sense that I got was that, within the limits of her time and resources, she was willing to become my mentor because I needed one. She trusted the admissions process, so why not bring an eager student into the lab. I spent the summer settling in to the life of a graduate student—sort of.At first, I was bad at graduate school. I am curious about all sorts of things, which means I am also easily pulled in too many directions. In that first year of school I spent way too much time simply visiting other students in my cohort to see what it was that they were up to each day. I cannot imagine how distracting I must have been to them and probably extremely irritating to their PIs as well. If you were in Cell Biology at Duke in 1996–97, I am sincerely grateful that you tolerated my shenanigans. Where others might have taken me to task, Jo Rae looked for opportunities to redirect my energies more productively. She and another professor, Dan Kiehart, guided me toward participating in the Physiology Course at the Marine Biological Laboratory, where I learned what I needed to do to be a scientist in a way that would not have been possible otherwise. While there, I saw PIs working with students chasing the joy of discovery, and it felt like it was purely for the sake of a deeper understanding of biology and preparing the next generation of scientists to do the same. Resources gave us the liberty to focus on scientific discovery with minimal concern for where would be the highest profile place to publish. Although I acknowledge that the summer course environments may not be the most representative of the daily life of a scientist at a home institution, such an opportunity left a mark—I wanted to come as close as I could to emulating that environment when I got back to Duke and (eventually) when I had the chance to run a research group and teach students.Along the way, Jo Rae made sure to include me and my fellow lab mates in all aspects of the science. At national meetings she included us at every step, introducing us to her contemporaries and putting us in spaces where we would rub elbows with luminaries in the field. When we were in those environments, she made sure that I felt like a junior colleague. I cannot recall ever feeling like a “trainee.” Back home at Duke, I had opportunities to do everything that a scientist might do in addition to “sciencing.” Sure, I would write papers, contribute to grants, and be part of her review of papers. I was also encouraged to mentor undergraduates, teach, advocate for federal funding at the time of the National Institutes of Health (NIH) doubling, and plan events for Duke’s summer undergraduate research program, if I so chose. Similarly, when I expressed an interest in focusing on science with undergraduates, she was 100% on board with finding ways to combine my graduate school commitments with teaching and mentoring opportunities. Importantly, at a time when expressing interest in an “alternative career” was not always supported by faculty mentors, Jo Rae encouraged me to seek out only those potential postdoctoral mentors who would actively support my goals. Not only that, she went out of her way to find out what options I might have, which led to her learning about the NIH-funded Institutional Research and Academic Career Development Award postdoctoral programs in their first year of existence.In a sentence, because Jo Rae was 100% invested in including me in science by finding the framework that best suited my interests and potential, I grew into my success. This was a form of success that wasn’t decided by someone else; I had defined it for myself with Jo Rae serving as a true advisor in every sense of the word—she was in it for me. She helped to build the crucial foundations that helped me find the opportunities that matched my goals. As a result of her influence, I have also had the strength to make some critical, nontraditional choices along the way. Her mentorship style was tailored to each individual’s needs. She invested the time to figure out our strengths, and also learned which levers would motivate us to meet our potential. The members of her lab became successes because she helped all of us to both define success and achieve our own version of it. Such a personal approach is extremely powerful. Jo Rae passed away in 2012, and with her passing I lost the most important influence in my professional life. Duke University and the pulmonary physiology community lost an example for inclusive mentorship and a significant amount of capacity for such an approach. Since her passing, multiple awards have been established to honor Jo Rae’s legacy as an outstanding woman in science. I would argue that mentoring of junior colleagues may be a more significant legacy than her scientific output. Jo Rae is deserving of this award.Recognitions such as this one are an important way to amplify examples of what we often say we hope to achieve as a department, an institution, or a scientific society. However, if our focus is solely on the efforts of individuals, we are missing an opportunity. While I am humbled to be considered in the same league as the previous award recipients, we are each in our own way scrambling to do what we can while we can do it. When individuals have some positive outcomes, our institutions and organizations will celebrate what these folks have done as they have played some role in supporting these opportunities. Although what we do is worthwhile, it is really hard to do it successfully and sustainably without proper institutional support. We each face hinderances that can undermine the work that we want to take on. Burnout is a real outcome of doing the work that we care about and that our organizations publicly state is important. This is especially true in environments where that work is undervalued and underresourced. You do not have to do a very extensive internet search to identify where the institutions that have supported my work also have exclusionary legacies and current negative influences that continue to hinder their potential for broader, more meaningful progress. In many instances inclusion has yet to be baked into institutional culture in a way that impacts how organizations operate. Although I have had some institutional support to develop a career modeled on what I experienced under Jo Rae’s mentorship, the students and faculty at these institutions know that what gets headlines can often be an exceptional situation, rather than a typical everyday experience. Rather than showcasing the good work of individuals in their ranks, an organization should devote itself to furthering the idea that it is willing to make significant institutional investments in that good work. By building the internal infrastructure and capacity to support inclusion efforts, organizations would demonstrate that inclusion is an essential component of the institutional standard practice. The positive outcomes that this award is intended to highlight would then be a shared characteristic of the community. A shared vision paired with shared effort and resource-support might cut down on burnout of those currently carrying more than their share of the load.I imagine that the idea for these awards is to celebrate good work while also demonstrating to other individuals what is possible. With that in mind, if institutions worked at using the example of those in the vanguard as a way to build structures that value and support inclusive approaches, they would increase their own ability to serve their constituents. They may also influence other institutions to do the same. My graduate institution benefited from Jo Rae’s work while she was present and was beginning to institutionalize her view of inclusion in the last years of her life. As Dean of the Graduate School, the model for how she ran her lab informed her vision for graduate education campus-wide. She wanted to build a structure that would identify, recruit, and retain talent. She wanted to provide that talent with opportunities to become expert in how they wanted to contribute to the world. By ensuring that they had access to the relevant experiences and skills, she hoped to support them as they set themselves up for success as they defined it.I accept this award in honor of Jo Rae Wright, and on behalf of the students who have trusted me. All I have ever wanted was to be able to recreate for my undergraduates what Jo Rae had done for the people under her wing. I am building a career around that goal as part of a department keenly supportive of these efforts. My hope is that other individuals will develop their own approaches to inclusion because they find themselves in supportive institutional environments. More importantly, I would like to see organizations begin to truly prioritize inclusive approaches through funding and through policy. Institutions could make sufficient resources available to support inclusive efforts and allow creativity in how faculty mobilize those resources. Just as Jo Rae had the flexibility to adjust to our needs, institutional efforts will benefit when limited resource access is not a hindrance to inclusive excellence. Additionally, it will be critical to acknowledge the time and effort that such endeavors require in evaluating faculty contributions. It can no longer be the icing on the cake of a portfolio—developing inclusive capacity has to be recognized as an essential component of our work. Until these changes take root at the institutional level, this kind of work may shine brightly, but will continue to be stochastic and short-lived. All those efforts “will be lost in time, like tears in rain.” It is on all of us to prevent such a tragic ending.     

Academic motherhood – what happens when you can't make it happen?

We need more openness about age‐related infertility as it is a particular risk for many female scientists in academia who feel that they have to delay having children. Subject Categories: S&S: Careers & Training, Genetics, Gene Therapy & Genetic Disease

Balancing motherhood and a career in academic research is a formidable challenge, and there is substantial literature available on the many difficulties that scientists and mothers face (Kamerlin, 2016). Unsurprisingly, these challenges are very off‐putting for many female scientists, causing us to keep delaying motherhood while pursuing our hypercompetitive academic careers with arguments “I’ll wait until I have a faculty position”, “I’ll wait until I have tenure”, and “I’ll wait until I’m a full professor”. The problem is that we frequently end up postponing getting children based on this logic until the choice is no longer ours: Fertility unfortunately does decline rapidly over the age of 35, notwithstanding other potential causes of infertility.This column is therefore not about the challenges of motherhood itself, but rather another situation frequently faced by women in academia, and one that is still not discussed openly: What if you want to have children and cannot, either because biology is not on your side, or because you waited too long, or both? My inspiration for writing this article is a combination of my own experiences battling infertility in my path to motherhood, and an excellent piece by Dr. Arghavan Salles for Time Magazine, outlining the difficulties she faced having spent her most fertile years training to be a surgeon, just to find out that it might be too late for motherhood when she came out the other side of her training (Salles, 2019). Unfortunately, as academic work models remain unsupportive of parenthood, despite significant improvements, this is not a problem faced only by physicians, but also one faced by both myself and many other women I have spoken to.I want to start by sharing my own story, because it is a bit more unusual. I have a very rare (~ 1 in 125,000 in women (Laitinen et al, 2011)) congenital endocrine disorder, Kallmann syndrome (KS) (Boehm et al, 2015); as a result, my body is unable to produce its own sex hormones and I don’t have a natural cycle. It doesn’t take much background in science to realize that this has a major negative impact on my fertility—individuals with KS can typically only conceive with the help of fertility treatment. It took me a long time to get a correct diagnosis, but even before that, in my twenties, I was being told that it is extremely unlikely I will ever have biological children. I didn’t realize back then that KS in women is a very treatable form of infertility, and that fertility treatments are progressing forward in leaps and bounds. As I was also adamant that I didn’t even want to be a mother but rather focus on my career, this was not something that caused me too much consternation at the time.In parallel, like Dr. Salles, I spent my most fertile years chasing the academic career path and kept finding—in my mind—good reasons to postpone even trying for a child. There is really never a good time to have a baby in academia (I tell any of my junior colleagues who ask to not plan their families around “if only X…” because there will always be a new X). Like many, I naïvely believed that in vitro fertilization (IVF) would be the magic bullet that can solve all my fertility problems. I accordingly thought it safe to pursue first a faculty position, then tenure, then a full professorship, as I will have to have fertility treatment anyhow. In my late twenties, my doctors suggested that I consider fertility preservation, for example, through egg freezing. At the time, however, the technology was both extravagantly expensive and unreliable and I brushed it off as unnecessary: when the time comes, I would just do IVF. In reality, the IVF success rates for women in their mid‐to‐late 30s are typically only ~ 40% per egg retrieval, and this only gets worse with age, something many women are not aware of when planning parenthood and careers. It is also an extremely strenuous process both physically and emotionally, as one is exposed to massive doses of hormones, multiple daily injections, tremendous financial cost, and general worries about whether it will work or not.Then reality hit. What I believed would be an easy journey turned out to be extremely challenging, and took almost three years, seven rounds of treatment, and two late pregnancy losses. While the driving factor for my infertility remained my endocrine disorder, my age played an increasing role in problems responding to treatment, and it was very nearly too late for me, despite being younger than 40. Despite these challenges, we are among the lucky ones and there are many others who are not.I am generally a very open person, and as I started the IVF process, I talked freely about this with female colleagues. Because I was open about my own predicament, colleagues from across the world, who had never mentioned it to me before, opened up and told me their own children were conceived through IVF. However, many colleagues also shared stories of trying, and how they are for various—not infrequently age‐related—reasons unable to have children, even after fertility treatment. These experiences are so common in academia, much more than you could ever imagine, but because of the societal taboos that still surround infertility and pregnancy and infant loss, they are not discussed openly. This means that many academic women are unprepared for the challenges surrounding infertility, particularly with advanced age. In addition, the silence surrounding this issue means that women lose out on what would have otherwise been a natural support network when facing a challenging situation, which can make you feel tremendously alone.There is no right or wrong in family planning decisions, and having children young, delaying having children or deciding to not have children at all are all equally valid choices. However, we do need more openness about the challenges of infertility, and we need to bring this discussion out of the shadows. My goal with this essay is to contribute to breaking the silence, so that academics of both genders can make informed choices, whether about the timing of when to build a family or about exploring fertility preservation—which in itself is not a guaranteed insurance policy—as relevant to their personal choices. Ultimately, we need an academic system that is supportive of all forms of family choices, and one that creates an environment compatible with parenthood so that so many academics do not feel pressured to delay parenthood until it might be too late.     

The Pollard lab at Salk: moving the leading edge forward

This essay will review the years that the Pollard lab was at the Salk Institute in the last half of the 1990s. It was a highly productive time both in research and in training. For me personally, it shaped my career for the better in ways I am still discovering.