How nontraditional model systems can save us

In this essay I would like to highlight how work in nontraditional model systems is an imperative for our society to prepare for problems we do not even know exist. I present examples of how discovery in nontraditional systems has been critical for fundamental advancement in cell biology. I also discuss how as a collective we might harvest both new questions and new solutions to old problems from the underexplored reservoir of diversity in the biosphere. With advancements in genomics, proteomics, and genome editing, it is now technically feasible for even a single research group to introduce a new model system. I aim here to inspire people to think beyond their familiar model systems and to press funding agencies to support the establishment of new model systems.My career as a biologist began in the orange groves and lake waters of central Florida. An unstructured childhood was spent learning to observe and wonder. Without realizing it at the time, my training began with the mantra, “Study nature, not books,” the familiar entreaty of Louis Agassiz, a founder of what would become the Marine Biological Lab (MBL) in Woods Hole, Massachusetts. In that humid air, listening to cicadas click, I subconsciously practiced asking basic questions about the structure of the natural world. I suspect many of us began our careers this way, even though we ended up thinking about systems of molecules from behind the black curtains of the microscope room, immersed in the frosty air of the cold room, or bathed in the glow of a computer screen. Before the grown-up challenges of funding, publishing, and progressing in a career, we easily marveled at the complexity and surprises of the living world. How can we recapture the joy that comes from curiosity-driven inquiry? This being an essay for the midcareer award, it seems appropriate to blend material for a midlife with a plan for how we as a cell biology community can identify big new questions. So instead of a fancy car, a new microscope, or a dangerous (professional) liaison, try developing a new model system as an outlet for your midlife crisis!Open in a separate windowAmy S. Gladfelter     

The Chemical Synthesis of DNA/RNA: Our Gift to Science

It is a great privilege to contribute to the Reflections essays. In my particular case, this essay has allowed me to weave some of my major scientific contributions into a tapestry held together by what I have learned from three colleagues (Robert Letsinger, Gobind Khorana, and George Rathmann) who molded my career at every important junction. To these individuals, I remain eternally grateful, as they always led by example and showed many of us how to break new ground in both science and biotechnology. Relative to my scientific career, I have focused primarily on two related areas. The first is methodologies we developed for chemically synthesizing DNA and RNA. Synthetic DNA and RNA continue to be an essential research tool for biologists, biochemists, and molecular biologists. The second is developing new approaches for solving important biological problems using synthetic DNA, RNA, and their analogs.     

The wanderings of a free radical

In my career I have moved from chemistry to biochemistry to plant science to clinical chemistry and back again (in a partial way) to plants. This review presents a brief history of my research achievements (ascorbate–glutathione cycle, role of iron in oxidative damage and human disease, biomarkers of free radical damage, and studies on atherosclerosis and neurodegeneration) and how they relate to my research activities today. The field of free radicals/other reactive species/antioxidants underpins all of modern Biology. These agents helped to drive human evolution and the basic principles of the field are repeatedly found to be relevant in other research areas. It was an exciting field when I started some 40 years ago, and it still is today, but some major challenges must be faced.     

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.     

Gaia Pigino: Inside the cell

Gaia Pigino studies the molecular mechanisms and principles of self-organization in cilia using 3D cryo-EM.

Gaia Pigino was only 3 yr old when she became fascinated with nature in the beautiful countryside of Siena, Italy, where she grew up. The neighbor’s daughter showed her a hen in the chicken coop, and they caught it in the act of laying an egg. Gaia remembers, “This was for me almost a shock, as my experience about eggs was that they come directly out of paper boxes!” Her father was also an important part of awakening Gaia’s curiosity for the amazing things in nature. He used to bring home the award-winning magazine Airone, the Italian equivalent of National Geographic. Gaia never missed an issue; even before learning to read, she could spend hours looking at the captivating photos of the wildlife. She wanted to understand what she was seeing, and maybe because of that, she was determined to do science.Gaia Pigino. Photo courtesy of Human Technopole.Gaia took her first “scientific” steps with Professor Fabio Bernini and Professor Claudio Leonzio at the University of Siena, where she studied bioindicators of soil contamination and detoxification strategies of soil arthropods as part of her PhD project. But it was later, when she joined the laboratory of Professor Pietro Lupetti and met Professor Joel Rosenbaum, a pioneer of cilia research, that Gaia discovered the world of 3D EM and felt her place was “inside a single cell.” She solidified her interest in the structure of protein complexes of cilia and flagella and boosted her passion for cryo-electron tomography (ET) in the laboratory of Professor Takashi Ishikawa, first at the ETH Zurich and then at the Paul Scherrer Institut in Switzerland. In 2012, Gaia started her own laboratory at the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Germany, with the vision of creating a truly interdisciplinary laboratory. Her team combines techniques from different fields such as biophysics, cell biology, and structural biology to answer open questions in the cilia field. Gaia recently moved countries again—this time to take over the position of Associate Head of the Structural Biology Research Centre, at the Human Technopole, Milan, Italy.We reached out to Gaia to learn more about her scientific journey and future research directions.What interested you about cilia?The first thing that attracted me toward cilia and flagella were some EM micrographs, by Professor Romano Dallai in Siena, that showed the beautiful geometrical microtubular structures of sperm flagella. I was intrigued by the apparent perfection of these organelles that clearly showed me that a cell is a coordinated system of complex molecular machines, the mechanism of many of which we do not understand. Soon after, Professor Joel Rosenbaum introduced me to the bidirectional transport of components inside cilia, which, he explained to me, is required for both assembly and function of virtually all cilia and flagella, from the motile cilia in our lungs to the primary cilium in our kidneys. He called it intraflagellar transport (IFT) and compared it to a Paternoster elevator, where the individual cabins were what we now call IFT trains. I was completely fascinated by the IFT system, the structure, the function, the dynamics, and the mechanism of which were still largely unknown. Quickly, I realized that in addition to IFT, cilia represent a virtually infinite source of open biological questions waiting to be solved, from the mechanics and regulation of the beating to the sensory function of primary cilia, and their importance for human health.What are some of the scientific questions currently of interest in your laboratory?In the past few years, we have made substantial contributions to the current understanding of the structure and the mechanism of the IFT (1, 2, 3). Currently, we are investigating how the structure of IFT trains relates to their functions by looking, in cryo-electron tomography, at how anterograde trains transform into retrograde trains and at how different ciliary cargoes are loaded on the trains. Beside this more classical line of research, we are exploring other approaches to study IFT, for instance we have developed a method to reactivate IFT trains in vitro on reconstituted microtubules. We want to use this approach to investigate the behavior of IFT trains, and their motors, in experimentally controllable conditions, e.g., in the presence of only certain tubulin posttranslational modifications. We have also made interesting discoveries about the distribution of tubulin posttranslational modifications on the microtubule doublets of the axoneme and how this spatially defined tubulin code affects the function of different ciliary components. We hope we will be able to share these new “stories” with the structural and cell biology community very soon!What kind of approach do you bring to your work?I believe that the main reason for why science became an integral, and dominant, part of my life is because it provides infinite riddles and continuous challenges. I have always been curious about how things work in nature, but I quickly realized that learning from books didn’t satisfy me. My desire was to be at the frontline, to be among the ones that see things happening in front of their eyes, at the microscope, for the first time. I wanted to be among the ones that make the discoveries that students read about in textbooks. Thus, what I bring to my work is an endless desire of solving biological riddles, curiosity, creativity, determination, and energy, with which I hope to inspire the members of my team. My laboratory uses an interdisciplinary approach; we use whatever method, technique or technology is needed to reach our goal, from the most basic tool to the most sophisticated cryo-electron microscope. And if the method we need does not yet exist, we try to invent it.A young Gaia Pigino (3 yr old) the day she discovered how eggs are made. Photo courtesy of Giancarlo Pigino.Could you tell us a bit about the Structural Biology Research Centre at the Human Technopole (HT)?At the HT Structural Biology Centre, we are working to create a vibrant and interdisciplinary scientific environment that will attract molecular, structural, cell, and computational biologists from all over the world. We are creating fantastic facilities, including one of the most well equipped and advanced electron microscopy facilities in Europe—and likely the world—headed by Paolo Swuec. My team, together with the teams of my colleague Alessandro Vannini and the research group leaders Ana Casañal, Francesca Coscia, and Philipp Erdmann, already cover a vast range of competences and know-how from classical molecular and structural biology approaches, such as crystallography and protein biophysics, to cryo-CLEM, cryo-FIB SEM and cryo-ET, all of which allow us to address questions in cell biology. Our goal is to create a scientific infrastructure and culture that will enable biologists to obtain a continuum of structural and functional information across scales.What did you learn during your PhD and postdoc that helped prepare you for being a group leader? What were you unprepared for?I learned that everyday research is mostly made of failures, but that with the right amount of obsession, persistence, curiosity, and creativity, it is always possible to succeed and discover new things. Being given the freedom to develop your own ideas and your own project very early in your career is a treat; science is not only about having good ideas! One needs to follow up on these ideas with intense work and troubleshooting to make them reality. In addition, I realized that being fearless and attempting what is considered too difficult by others, despite challenges, can turn into a worthy learning experience. Also, how you present your work to the scientific community matters for swinging the odds of success in your favor. Different places might work in very different ways, and conducting good science does not only depend on you, but also on the possibilities given to you by your environment.What was I unprepared for?—I guess several things, but one comes immediately to mind: I underestimated how much being responsible not only for my own life and career, but also the career of students, postdocs, and others in the laboratory, would affect me personally.Structure of the 96-nm axonemal repeat reconstructed by cryo-ET and subtomogram averaging. Image courtesy of Gonzalo Alvarez Viar, Pigino Lab.What has been the biggest accomplishment in your career so far?This is a tricky question for me... I tend to look into the future more than celebrating the past. I fight to succeed in something, but as soon as I conquer it, I find it less of an achievement than the thing I could conquer next. Nevertheless, I am happy about the discoveries and the papers published together with my students and postdocs (1, 2, 3, 4, 5). I am extremely excited about the fact that after many years of work I am now leading an interdisciplinary laboratory, where we combine techniques from different fields. I am also happy that three times my husband and I were able to move from one world class academic institution to the another to start exciting and fitting jobs and could still live together in the same place. We worked hard for this, but we also got lucky.What has been the biggest challenge in your career so far?I studied French in school; I had almost no exposure to spoken English until the end of my PhD. To avoid having to show my English insufficiencies, I did hide beside the board of my poster at the first international conference I attended in 2004! It took me a while to overcome this barrier and feel confident to express my thoughts and ideas in English.What do you think you would be if you were not a scientist?I had been a good fencer during my youth. I was a member of the Italian National Team between ages 14 and 19 and saw quite a bit of the world, which was cool! When my sporting career failed, due to diabetes, I was torn between art and science. I guess that in a parallel universe, I am a wildlife photographer and a potter specialized in wood kiln firing. [Gaia confesses that she misses “the amazing and addictive adrenaline rush of a good fencing match!”]Any tips for a successful research career?Do not compare your performances to the ones of the people at your career stage; compare yourself with people that are already successful one level higher than you currently are at. For example, if you are a PhD student, ask yourself what in your current performance separates you from being a good postdoc—once a postdoc, what is missing to be a good PI.     

Why we need more basic biology research,not less

Much of the spectacular progress in biomedical science over the last half-century is the direct consequence of the work of thousands of basic scientists whose primary goal was understanding of the fundamental working of living things. Despite this, many politicians, funders, and even scientists have come to believe that the pace of successful applications to medical diagnosis and therapy is limited by our willingness to focus directly on human health, rather than a continuing deficit of understanding. By this theory, curiosity-driven research, aimed at understanding, is no longer important or even useful. What is advocated instead is “translational” research aimed directly at treating disease. I believe this idea to be deeply mistaken. Recent history suggests instead that what we have learned in the last 50 years is only the beginning. The way forward is to invest more in basic science, not less.     

How to succeed in science: a concise guide for young biomedical scientists. Part I: taking the plunge

Biomedical research has never been more intellectually exciting or practically important to society. Ironically, pursuing a career as a biomedical scientist has never been more difficult. Here I provide unvarnished advice for young biomedical scientists on the difficulties that lie ahead and on how to find the right laboratories for training in the skills that you will need to succeed. Although my advice is geared towards succeeding in the United States, many aspects apply to other countries.     

Wrongness,Responsibility, and Conscientious Refusals in Health Care

In this article, I address what kinds of claims are of the right kind to ground conscientious refusals. Specifically, I investigate what conceptions of moral responsibility and moral wrongness can be permissibly presumed by conscientious objectors. I argue that we must permit HCPs to come to their own subjective conclusions about what they take to be morally wrong and what they take themselves to be morally responsible for. However, these subjective assessments of wrongness and responsibility must be constrained in several important ways: they cannot involve empirical falsehoods, objectionably discriminatory attitudes, or unreasonable normative beliefs. I argue that the sources of these constraints are the basic epistemic, relational, and normative competencies needed to function as a minimally decent health‐care professional. Finally, I consider practical implications for my framework, and argue that it shows us that the objection raised by the plaintiffs in Zubik v. Burwell is of the wrong sort.     

Race Research and the Ethics of Belief

On most accounts, beliefs are supposed to fit the world rather than change it. But believing can have social consequences, since the beliefs we form underwrite our actions and impact our character. Because our beliefs affect how we live our lives and how we treat other people, it is surprising how little attention is usually given to the moral status of believing apart from its epistemic justification. In what follows, I develop a version of the harm principle that applies to beliefs as well as actions. In doing so, I challenge the often exaggerated distinction between forming beliefs and acting on them.¹ After developing this view, I consider what it might imply about controversial research the goal of which is to yield true beliefs but the outcome of which might include negative social consequences. In particular, I focus on the implications of research into biological differences between racial groups.     

Nickel hyperaccumulation in Thlaspi goesingense: A scientific travelogue

Summary During the past 6 years, my research group has been trying to unravel the molecular genetic basis of nickel hyperaccumulation in Thlaspi. Our long-term goal is to use the genes we identify to genetically engineer plants ideally suited for phytoremediation (Salt et al., 1998), This investigation has taken us on a journey with many twists, turns, dead ends, and through many types of terrains in the plant physiology landscape. In this short essay, I would like to retrace for you this journey, providing a glimpse of what we feel is now appearing as the essential components of how certain plants hyperaccumulate Ni.     

What is the matter with transcendence? On the place of religion in the new anthropology of ethics★

A focus on ordinary or everyday ethics has become perhaps the dominant concern in the rapidly developing anthropology of ethics. In this article, I argue that this focus tends to marginalize the study of the ways in which religion contributes to people's moral lives. After defining religion and transcendence in terms that make them less uncongenial to the study of ethics than many proponents of ordinary ethics suggest, I examine values as one sometimes transcendent cultural form that often informs ethical life. I draw on Victor Turner (along with Durkheim) to develop an account of how rituals often both present people with and allow them to perform transcendent versions of values. These encounters, in turn, shape people's ethical sensibilities, including those they bring to bear in everyday life, in ways we cannot understand unless we accord religion a more central role in the anthropology of ethics than it has played to this point. I illustrate my arguments with material drawn both from Turner's Ndembu ethnography and from my own research on Christianity in Papua New Guinea.     

After the year of the dumpster fire

2020 has been one of the craziest and strangest years we have lived through. Now that it’s over, it’s an opportunity to show gratitude for all the good things. Subject Categories: S&S: History & Philosophy of Science

I moved to New York City the year of the attacks on September 11, 2001, one of the bleakest moments in the history of the United States. I was also in New York City when Superstorm Sandy hit in 2012. Luckily, much fewer people died due to the storm, but it was incredibly disruptive to many scientists in the affected area—my laboratory had to move four times over a period of 6 years in the storm’s aftermath. These were awful, tragic events, but 2020 may go down in the record books as one of the most stressful and crazy years in modern times. Not to be outdone, 2021 has started terribly as well with COVID‐19 still ravaging the world and an attack on the US Capitol, something I thought I’d never see in my lifetime. The unnecessary deaths and the damage to America’s “House of the People” were heartbreaking.While these events were surely awful, nothing will be as crushing as the deaths of family members, close friends, and the children of friends; perhaps, it is these experiences—and the death of a beloved dog—that prepared me for this year and made me grateful, maybe even more than usual, for what I have. But in the age of a pandemic, what am I particularly grateful for?I''m ridiculously grateful to have a job, a roof over my head, and food security. The older I get, the more I see illness and injury affect my colleagues, family, and friends, I increasingly appreciate my good health. I am grateful for Zoom (no, I have no investment in Zoom)—not for the innumerable seminars or meetings I have attended, but for the happy hours that helped to keep me sane during the lockdown. Some of these were with my laboratory, others with friends or colleagues, sometimes spread over nine time zones. Speaking of which, I’m also grateful for getting a more powerful router for the home office.I''m immeasurably grateful to be a scientist, as it allows me to satisfy my curiosity. While not a year‐round activity, it is immensely gratifying to be able to go to my laboratory, set up experiments, and watch the results coming in. Teaching and learning from students is an incredible privilege and educating the next generation of scientists how to set up a PCR or run a protein gel can, as a well‐known lifestyle guru might say, spark serious joy. For this reason, I’m eternally grateful to my trainees; their endless curiosity, persistence, and energy makes showing up to the laboratory a pleasure. My dear friend Randy Hampton recently told me he received a student evaluation, thanking him for telling his virtually taught class that the opportunity to educate and to be educated is something worth being grateful for, a sentiment I passed onto a group of students I taught this past fall. I believe they, too, were grateful.While all of the above things focus on my own life, there are much broader things. For one, I am so grateful to all of those around the globe who wear masks and keep their distance and thereby keep themselves and others safe. I am grateful for the election of an American president who proudly wears a mask—often quite stylishly with his trademark Ray‐Ban Aviators—and has made fighting the COVID‐19 pandemic his top priority. President Biden''s decision to ramp up vaccine production and distribution, along with his federal mask mandate, will save lives, hopefully not just in the United States but worldwide.This Gen‐X‐er is also especially grateful to the citizens of Generations Y and Z around the world for fighting for social justice; I am hopeful that the Black Lives Matter movement has got traction and that we may finally see real change in how communities of color are treated. I have been heartened to see that in my adopted home state of New York, our local politicians ensure that communities that have been historically underserved are prioritized for COVID‐19 testing and vaccinations. Along these lines, I am also incredibly encouraged by the election of the first woman who also happens to be of African and Asian heritage to the office of vice president. Times are a changin''...While it is difficult to choose one, top thing to be grateful for, I would personally go for science. I am stoked that, faced with a global crisis, science came to the rescue, as it often has in the past. If I had to find a silver lining in COVID‐19—albeit it would be for the darkest of clouds—I am grateful for all of our colleagues, who despite their usual arguing, quickly and effectively developed tests, provided advice, epidemiological data and a better understanding of the virus and its mode of infection, and ultimately developed therapies and vaccines to save lives. The same can be said for the biotech and pharmaceutical industry that, notwithstanding its often‐noted faults, has been instrumental in developing, testing and mass‐producing efficient and safe vaccines in blistering, record time. Needless to say, I have also much gratitude to all of the scientists and regulators at the FDA and elsewhere who work hard to make life as we once knew it come back to us, hopefully in the near future.Once again, thank you for everything, Science.