The autophagy community

There are various definitions of community. A definition that I found in one of my dictionaries is the following: “A social, religious, occupational, or other group sharing common characteristics or interests and perceived or perceiving itself as distinct in some respect from the larger society within which it exists.” Thus, I think it is fair to say that there is a worldwide autophagy community. That is, there is a group of researchers (our occupation), whose members share an interest in autophagy (our common characteristic), and that group is distinct from the larger society (I do not want to begin describing the many ways this applies). But do we feel like a community, and do we need a community? I suggest that a community is indeed beneficial, and I propose one mechanism for enhancing the development of the autophagy community.     

Dr. Manners

Good manners make a difference—in science and elsewhere. This includes our social media etiquette as researchers. Subject Categories: S&S: History & Philosophy of Science, Methods & Resources, S&S: Ethics

Elbows off the table, please. Don’t chew with your mouth open. Don’t blow your nose at the table. Don’t put your feet up on the chair or table. And please, do not yuck my yum. These are basic table manners that have come up at some of our lab meals, and I have often wondered if it was my job to teach my trainees social graces. A good fellow scientist and friend of mine once told me it was absolutely our place as mentors to teach our trainees not only how to do science well, but also how to be well‐mannered humans. While these Emily Post‐approved table manners might seem old‐fashioned (I’m guessing some readers will have to look up Emily Post), I strongly believe they still hold a place in modern society; being in good company never goes out of style.Speaking of modern society: upon encouragement by several of my scientist friends, I joined Twitter in 2016. My motivation was mainly to hear about pre‐prints and publications, conference announcements and relevant news, science or otherwise. I also follow people who just make me laugh (I highly recommend @ConanOBrien or @dog_rates). I (re)tweet job openings, conference announcements, and interesting new data. Occasionally, I post photos from conferences, or random science‐related art. I also appreciate the sense of community that social media brings to the table. However, social media is a venue where I have also seen manners go to die. Rapidly.It is really shocking to read what some people feel perfectly comfortable tweeting. While most of us can agree that foul language and highly offensive opinions are generally considered distasteful, there are other, subtler but nonetheless equally—if not more—cringe‐worthy offenses online when I am fairly certain these people would never utter such words in real life. In the era of pandemic, the existence of people tweeting about not being able to eat at their favorite restaurant or travel to some destination holiday because of lockdown shows an egregious lack of self‐awareness. Sure it sucks to cancel a wedding due to COVID‐19, but do you need to moan to your followers—most of whom are likely total strangers—about it while other people have lost their jobs? If I had a nickel for every first‐world complaint I have seen on Twitter, I’d have retired a long time ago; although to be honest, I would do science for free. However, these examples pale in comparison with another type of tweeter: Reader, I submit to you, “the Humblebragger.”From the MacMillan Buzzword dictionary (via Google): a humblebrag is “a statement in which you pretend to be modest but which you are really using as a way of telling people about your success or achievements.” I would further translate this definition to indicate that humblebraggers are starved for attention. After joining Twitter, I quickly found many people using social media to announce how “humble and honored” they are for receiving grant or prize X, Y, or Z. In general, these are junior faculty who have perhaps not acquired the self‐awareness more senior scientists have. Perhaps the most off‐putting posts I have seen are from people who post photos of their NIH application priority scores right after study section, or their Notice of Awards (NOA). When did we ever, before social media, send little notes to each other—let alone to complete strangers—announcing our priority scores or NOAs? (Spoiler: NEVER)Some of you reading this opinion piece might have humblebragged at one or time or another, and might not understand why it is distasteful. Please let me explain. For every person who gets a fundable score, there are dozens more people who do not, and they are sad (I speak from many years of experience). While said fundable‐score person might be by someone we like—and I absolutely, positively wish them well—there are many more people who will feel lousy because they did not get funding from the same review round. When has anyone ever felt good about other people getting something that they, too, desire? I think as children, none of us liked the kid on the playground who ran around with the best new Toy of the Season. As adults, do we feel differently? Along these lines, I have never been a fan of “best poster/talk/abstract” prizes. Trainees should not be striving for these fleeting recognitions and should focus on doing the best science for Science’s sake; I really believe this competition process sets people up for life in a negative way—there, I’ve said it.Can your friends and colleagues tweet about your honors? Sure, why not, and by all means please let your well‐wishers honor you, and do thank them and graciously congratulate your trainees or colleagues for helping you to get there. But to post things yourself? Please. Don’t be surprised if you have been muted by many of your followers.It is notable that many of our most decorated scientists are not on Twitter, or at least never tweet about their accomplishments. I do not recall ever seeing a single Nobel laureate announce how humbled and honored they are about their prize. Of course, I might be wrong, but I am willing to bet the numbers are much lower than what I have observed for junior faculty. True humility will never be demonstrated by announcing your achievements to your social media followers, and I believe humblebragging reveals insecurity more than anything. I hope that many more of us can follow the lead of our top scientists both in creativity, rigor, and social media politeness.     

Finding autophagy: It’s a question of how you look at it

To tell the truth, I find it difficult to work when flying, or even when sitting in an airport for an extended period of time. So, typically I take along a book to read. And when I truly cannot concentrate, for example when a flight is considerably delayed, I have even been known to resort to word puzzles. Depending on the type, they do not require much attention (that is, you can pick up right where you left off after you glance at the flight status screen for the twentieth or so time, even though you know nothing has changed), or effort (although you need to use a pen or pencil, not a keyboard), but nonetheless they can keep your mind somewhat occupied. I even rationalize doing them based on the assumption that they are sharpening my observational/pattern-finding skills. One type of word puzzle that is particularly mindless, but for that very reason I still enjoy in the above circumstances, is a word search; you are given a grid with letters and/or numbers, and a list of “hidden” terms, and you circle them within the grid, crossing them off the list as you go along. I do admit that the categories of terms used in the typical word searches can become rather mundane (breeds of dog, types of food, words that are followed by “stone,” words associated with a famous movie star, words from a particular television show, etc.). Therefore, on one of my last seminar trips I decided to generate my own word search, using the category of autophagy.     

Genetic structure of chimpanzee populations

Little is known about the history and population structure of our closest living relatives, the chimpanzees, in part because of an extremely poor fossil record. To address this, we report the largest genetic study of the chimpanzees to date, examining 310 microsatellites in 84 common chimpanzees and bonobos. We infer three common chimpanzee populations, which correspond to the previously defined labels of “western,” “central,” and “eastern,” and find little evidence of gene flow between them. There is tentative evidence for structure within western chimpanzees, but we do not detect distinct additional populations. The data also provide historical insights, demonstrating that the western chimpanzee population diverged first, and that the eastern and central populations are more closely related in time.     

Sphingolipids: regulators of crosstalk between apoptosis and autophagy

Apoptosis and autophagy are two evolutionarily conserved processes that maintain homeostasis during stress. Although the two pathways utilize fundamentally distinct machinery, apoptosis and autophagy are highly interconnected and share many key regulators. The crosstalk between apoptosis and autophagy is complex, as autophagy can function to promote cell survival or cell death under various cellular conditions. The molecular mechanisms of crosstalk are beginning to be elucidated and have critical implications for the treatment of various diseases, such as cancer. Sphingolipids are a class of bioactive lipids that mediate many key cellular processes, including apoptosis and autophagy. By targeting several of the shared regulators, sphingolipid metabolites differentially regulate the induction of apoptosis and autophagy. Importantly, individual sphingolipid species appear to “switch” autophagy toward cell survival (e.g., sphingosine-1-phosphate) or cell death (e.g., ceramide, gangliosides). This review assesses the current understanding of sphingolipid-induced apoptosis and autophagy to address how sphingolipids mediate the “switch” between the cell survival and cell death. As sphingolipid metabolism is frequently dysregulated in cancer, sphingolipid-modulating agents, or sphingomimetics, have emerged as a novel chemotherapeutic strategy. Ultimately, a greater understanding of sphingolipid-mediated crosstalk between apoptosis and autophagy may be critical for enhancing the chemotherapeutic efficacy of these agents.     

Autophagosomes,phagosomes, autolysosomes,phagolysosomes, autophagolysosomes… Wait,I’m confused

When an autophagosome or an amphisome fuse with a lysosome, the resulting compartment is referred to as an autolysosome. Some people writing papers on the topic of autophagy use the terms “autolysosome” and “autophagolysosome” interchangeably. We contend that these words should be used to denote 2 different compartments, and that it is worthwhile maintaining this distinction—the autophagolysosome has a particular origin in the process of xenophagy that makes it distinct from an autolysosome.     

Developing a set of guidelines for your research field: a practical approach

Since 2008, the autophagy community has periodically published a set of guidelines, currently titled “Guidelines for the Use and Interpretation of Assays for Monitoring Autophagy.” The newest version of the guidelines was published in 2016. There are many reasons for establishing a set of guidelines in a given research field. This Perspective explores some of these reasons, including standardizing nomenclature for better communication, improving reproducibility, and making it easier for newcomers to enter the field. It also includes the approach I have used to generate and update the guidelines that are now widely used in the autophagy field. The suggestions are not meant to be formulaic, and the method is certainly not perfect. Instead, this should be viewed as a starting set of, well, guidelines.     

The autophagic tumor stroma model of cancer or “battery-operated tumor growth”: A simple solution to the autophagy paradox

The role of autophagy in tumorigenesis is controversial. Both autophagy inhibitors (chloroquine) and autophagy promoters (rapamycin) block tumorigenesis by unknown mechanism(s). This is called the “Autophagy Paradox.” We have recently reported a simple solution to this paradox. We demonstrated that epithelial cancer cells use oxidative stress to induce autophagy in the tumor microenvironment. As a consequence, the autophagic tumor stroma generates recycled nutrients that can then be used as chemical building blocks by anabolic epithelial cancer cells. This model results in a net energy transfer from the tumor stroma to epithelial cancer cells (an energy imbalance), thereby promoting tumor growth. This net energy transfer is both unilateral and vectorial, from the tumor stroma to the epithelial cancer cells, representing a true host-parasite relationship. We have termed this new paradigm “The Autophagic Tumor Stroma Model of Cancer Cell Metabolism” or “Battery-Operated Tumor Growth.” In this sense, autophagy in the tumor stroma serves as a “battery” to fuel tumor growth, progression and metastasis, independently of angiogenesis. Using this model, the systemic induction of autophagy will prevent epithelial cancer cells from using recycled nutrients, while the systemic inhibiton of autophagy will prevent stromal cells from producing recycled nutrients—both effectively “starving” cancer cells. We discuss the idea that tumor cells could become resistant to the systemic induction of autophagy by the upregulation of natural, endogenous autophagy inhibitors in cancer cells. Alternatively, tumor cells could also become resistant to the systemic induction of autophagy by the genetic silencing/deletion of pro-autophagic molecules, such as Beclin1. If autophagy resistance develops in cancer cells, then the systemic inhibition of autophagy would provide a therapeutic solution to this type of drug resistance, as it would still target autophagy in the tumor stroma. As such, an anti-cancer therapy that combines the alternating use of both autophagy promoters and autophagy inhibitors would be expected to prevent the onset of drug resistance. We also discuss why anti-angiogenic therapy has been found to promote tumor recurrence, progression and metastasis. More specifically, anti-angiogenic therapy would induce autophagy in the tumor stroma via the induction of stromal hypoxia, thereby converting a non-aggressive tumor type to a “lethal” aggressive tumor phenotype. Thus, uncoupling the metabolic parasitic relationship between cancer cells and an autophagic tumor stroma may hold great promise for anti-cancer therapy. Finally, we believe that autophagy in the tumor stroma is the local microscopic counterpart of systemic wasting (cancer-associated cachexia), which is associated with advanced and metastatic cancers. Cachexia in cancer patients is not due to decreased energy intake, but instead involves an increased basal metabolic rate and increased energy expenditures, resulting in a negative energy balance. Importantly, when tumors were surgically excised, this increased metabolic rate returned to normal levels. This view of cachexia, resulting in energy transfer to the tumor, is consistent with our hypothesis. So, cancer-associated cachexia may start locally as stromal autophagy and then spread systemically. As such, stromal autophagy may be the requisite precursor of systemic cancer-associated cachexia.Key words: caveolin-1, autophagy, cancer associated fibroblasts, hypoxia, mitophagy, oxidative stress, DNA damage, genomic instability, tumor stroma, wasting (cancer cachexia), Warburg effect     

Freelancer

What long‐term changes can we expect, in how academic work is conducted and remunerated, in the post‐pandemic world? Subject Categories: S&S: Economics & Business, S&S: History & Philosophy of Science, S&S: Ethics

Although still two years away, my looming “retirement” from university employment is inevitably going to herald a major change of life. “Of course, you''ll become ‘Emeritus’”, most colleagues have opined. My answer to all of them has been a firm “No. I''ll become a freelancer”. The concept of a freelance scientist is obviously so alien to most of them that they invariably change the subject immediately. However, my gut feeling is that in 20 years or less, almost all of us will be freelancers of some kind.The COVID‐19 pandemic has altered the world of work in very obvious ways. There has been much talk of how the changes are likely to carry over to the future, even if more traditional patterns will probably reassert themselves in the short to medium term. Working from home, conducting meetings remotely, not wasting days travelling between continents for a few precious hours of face‐time and being free to structure workdays around our own priorities: these are the most obvious novelties that many believe will continue long after the effects of the pandemic on health and wealth have faded. But I have a slightly different take.Major disruptive events of worldwide import—world wars, global economic slumps, cataclysmic volcanic eruptions and pandemics—have often been harbingers of profound social change. This is not only due to their direct and immediate effects, but more so because the disruption accelerates and facilitates changes that were already happening. In the case of COVID‐19, one may place in this category the demise of cash, the rise of streaming services in place of live entertainment, online grocery shopping and even virtual dating. Another is paying people to stay home and do nothing, otherwise known as the universal basic income (or, in the USA, “stimulus cheques”).Inefficient practices in academia are equally ripe for change. Why bother with classes for 500 first‐year students when a much better edition of the lecture by an expert communicator is available on the internet? What’s the use of an ageing PhD advisor 20 years away from bench science, who struggles to guide the next generation of experimentalists in the lab, when the expertise of a plethora of specialists can easily be accessed online? What’s the value in published papers that are read by fewer people than wrote them? Or in seminars delivered to a roomful of attentive postdocs and PhD students who lack the courage or the time to address even a single question to the speaker?Yes, there is still great value in small‐group teaching and mentorship, in the creative verve of a close‐knit laboratory team, and in good writing and oratory: but the required skills are already different from those in which we were schooled. Thus, even if I do not hold in my palm the crystal ball to predict exactly which changes will happen and how fast, I believe that our traditional jobs are going to melt away very fast in the post‐pandemic world. Universities and research institutes may still exist, but I expect that their practices will be different, reshaped by rational need more than by tradition. Today’s academic science is already quite unlike that of 1920, but it has evolved so slowly during that century—spanning a much longer time period than the lifetime of a scientific career—that we barely perceive the changes that have occurred. In contrast, the changes now afoot will certainly happen much faster, especially since the funds to support the current “inefficient” model are likely to diminish rapidly.So, I predict that university teaching and science communication in general will be the first to evolve into freelance activities, where universities will invite bids from individuals or their agents and award commissions on a fee‐paying basis rather than using salaried employees. But these are not the only component parts of academia facing such a shake‐up. The practices of laboratory science are also likely to be rebuilt. When discussing with colleagues how research might be undertaken on a freelance basis, they usually raise issues such as bricks and mortar and the complex infrastructure that is needed to sustain cutting‐edge research, especially in the life sciences: how, they ask, could a freelancer access state‐of‐the‐art imaging, mass spectrometry or DNA sequencing? How could their acquisition of such expensive hardware possibly be financed, especially if they had to somehow acquire it personally and set it up in the garage or carry it around with them?But the answers to these questions are already evident in the practices of some major research agencies, most notably in Europe’s pioneering funder of single‐investigator grants for blue‐skies science, the European Research Council (ERC). The ERC already treats its awardees as freelancers, in the sense that it encourages them to shop around for the most attractive venue in which to embed and implement their research project. The quest for the best host institution takes place not only at the preparatory step of an ERC application: it also happens after the grant is awarded, since the grant money is considered inherently portable and can even be moved later on from one institution to another. This encourages potential host universities to compete for providing the best research environment, in which many factors come into play, not just but not least, the quality of its research infrastructure. How well it supports, rather than burdens its staff with administrative tasks, the nature of its recruitment and personnel policies, how it handles relocation issues for incoming researchers and their families, what opportunities it provides for further training in relevant skills and career development: these are just some of the factors in play.In recent years, universities have seen their primary role in this process as encouraging their own tenured or tenure‐track staff to apply for ERC grants. But I foresee the emphasis shifting increasingly to investigators who seek out universities that can make the most appealing offer, whilst universities and government agencies standing behind them will shape their policies so as to remain competitive. Moreover, in such a landscape there is no reason why a scientist cannot operate research projects on multiple sites if this offers the most convenient arrangement. The tools for remote meetings and cloud computing to which we have all become accustomed mean that there is no longer any need for a research group to be located in one building or even in one country, to operate efficiently as a team.At the same time, many of the tasks involved in running a research institute or department can be efficiently outsourced to the most competitive bidder—to be assessed on the basis of value‐for‐money, not just minimum cost. As a society, we should be asking ourselves why we continue to waste the talents of highly specialized scientists on performing admin tasks for which they are neither properly trained nor motivated, instead of just engaging a smart‐software developer. Why should we fund creative thinkers to undertake laboratory projects in host institutions that do not have the required state‐of‐the‐art facilities to perform them? Or allocate budgets that are so pared down that grantholders cannot even afford to purchase such services elsewhere? Why should we expect them to make do with poorly paid trainees instead of a team of professionals? And why should we continue to organize research in pyramid structures where everything depends on commands from the top, where all findings are announced using an institutional slide template, where colleagues elsewhere are considered as untrustworthy “competitors”, and where credit for individual creativity is usurped by seniors who barely know the contents of the papers they “write”?In the “old system”, we have all gotten used to making do with sub‐optimal working arrangements and grumbling about them, whilst considering them an immutable fact of life. But I envisage a time coming soon where we scientists will have the edge in reshaping the market for teaching and research in a way that is much more to our liking and properly aligned with our skills. At the same time, our individual success in accomplishing our professional goals will have a direct effect on our income and job satisfaction, and steer us towards activities where our talents are most effectively deployed. In short, I believe that we, as freelance scientists, will be much more firmly in control of science in the future and that time is not far off.     

A 20-year encounter with the imposter syndrome

Both in their formative years and later careers, some scientists suffer from something more than occasional self-doubts. There is a more severe affliction that strikes many more than was once realized. Here I reflect on my encounter, in the hope that sharing it can be of some value.

A landmark study 42 years ago presented the results of a survey of 150 highly successful women professionals as regards their self-assessment of confidence. The results were stunning. Many subjects gave responses revealing moderate to intense emotional stress and anxiety as to their qualifications. To characterize this revealed broad experience, the authors coined the term “the imposter syndrome” (Clance and Imes, 1978). It was apt indeed, the first word conveying the haunting sense of being an intruder in the guild, unqualified, and in the game only by some fluke; the second term meaning that the condition was encountered as a constellation of effects, from heart to mind to gut, with fear the signal transduction onto all those centers. This study was a turning point, inter alia, in the broadening field of scholarship examining the barriers to women in the workplace.At the time of the Clance and Imes publication it was not known if this same affliction occurs in men and, if so, with what prevalence, or whether it occurs in some professions more than others. In at least the sciences, it now appears that both females and males encounter it, both as students and as young trainees, although the prevalence is less well known for males. I have no expertise in this field beyond my one experience, which I share here in the hope that it may have some nugget of value for all those who doubt their talent.Science was not my first love academically. I had no butterfly collection, nor did I conduct explosion-seeking chemistry experiments in the cellar. My favorite subject in high school was Latin, my least favorite was biology. I remember a lecture on vitamins in the latter course, where we had to memorize what happens when each one is missing or limiting in the diet. We asked the teacher for an explanation for pellagra, scurvy, and so forth (meaning: what do these vitamins do?). He replied, “They are essential.” QED. (But in fairness, this teacher could be better sometimes—for example, he told us why the mouthwash “Listerine” was so named.)After studying English and Latin in college, I came to biology for a second try and it felt better. I applied to medical school but declined my acceptances and went for a Ph.D. During this time, I do not recall feeling particularly anxious about my abilities, although I had not yet really done anything to reveal their presence or absence. I do recall a few times when I was nervous, but that is not uncommon for graduate students. But one day, I got the first sensation of perhaps something more. It was my Ph.D. qualifying exam in the Department of Zoology at Syracuse University, in 1961. One part was a four-hour written exam in one’s field, the other was a free-for-all with the whole faculty asking about anything under the sun in biology. At one point I was asked to derive the Nernst equation (describing a cell’s membrane resting potential). I replied “OK, but from what?” The faculty member thought I was being evasive, but I was just looking for a little guidance (as when the Scripps–Howard Spelling Bee contestant asks the moderator: “Can you please use that in a sentence?”) I knew one cannot get the Nernst equation from f = ma, there is an electrical component (duly named for Michael Faraday). I managed to get through this question and all the others, but it was then I began to wonder if I was playing some charade. Maybe I had been clever but not really grounded. That I had gotten through the oral exam didn’t quiet my sense that I might have “pulled something off” and maybe hadn’t deserved to have passed. That was the moment when a visitor first arrived in my consciousness. It whispered, “You know, Thoru, it’s just possible that you might be a phony.”During my postdoc this nagging feeling got stronger. I had moved from a very good zoology program at Syracuse to an elite department of cell biology at the Albert Einstein College of Medicine. My work was going well, but all the people around me seemed so much smarter and their research seemed more significant. On one side of the lab I was in, Phillip Coffino, an M.D./Ph.D. student, was measuring the somatic mutation rate of immunoglobulin genes with Matthew Scharff, and on the other side, Ellie Ehrenfeld was isolating the poliovirus RNA replicase in the laboratory of Donald Summers. These were pioneering projects and I was in awe of both them and their science. By the time I left Einstein my case of the imposter syndrome had reached the point where I felt lucky to get an independent position.Today, I reflect on all this. First, and as conveyed in the original study, was the certitude in my assessment of myself. At the time this affliction had me in its maw, no one could have convinced me otherwise. As other victims of this condition have attested, the sense that it is totally true is overwhelming. The second feature of the imposter syndrome, as was also revealed in the study, was that the day was just around the corner when I would be found out. This evokes a pattern of paranoia where, on each and every day, one is just waiting for “the truth” to come out.But then, when I was 40, I got over this thing. It was quite sudden. I was on my way to Caltech to give a seminar and looked out the window over Kansas at the puffed popcorn of white clouds and got a simple idea, a question that should always be asked by any scientist. What if I were wrong? What if I were misinterpreting the data? For the first time, looking out that airplane window, it came to me that the obsession that I was totally incompetent was not supported by the facts, and that a hypothesis that I was at least competent in a “guild-average” sense seemed to be at hand.How the imposter syndrome affects females vs. males is still being studied. I do think that when it hits males, we compensate in ways that are different from females. One of the most compelling books in this field describes an intrepid group of women who provided powerful anchors for each other (Daniell, 2008). They were not all suffering from the imposter syndrome, but rather receiving the totality of slings and arrows that professional women face on many fronts. This landscape of inquiry and scholarship is worthy of further investigation as we seek to understand the degrees to which gender differentially influences the aspirations of all those coming up, and to which the imposter syndrome is an infection that may have no host restriction as to gender or ethnicity. The key question now, more than four decades after the landmark study, is whether the imposter syndrome has afflicted all genders and ethnicities to similar or differing degrees, and not only in America and not just in the sciences. This is the total perspective in which this career-inhibitory/destructive phenomenon must be understood, to elevate our ability to mentor, and if possible “vaccinate,” all students and emerging young professionals who suffer from it. Only when we all understand the roots of the phenomenon’s existence in the first place can we do our best to stamp it out.     

Challenges in the Care of Clients with Established Cardiovascular Disease: Lessons Learned from Australian Community Pharmacists

Background

As primary healthcare professionals, community pharmacists have both opportunity and potential to contribute to the prevention and progression of chronic diseases. Using cardiovascular disease (CVD) as a case study, we explored factors that influence community pharmacists’ everyday practice in this area. We also propose a model to best illustrate relationships between influencing factors and the scope of community pharmacy practice in the care of clients with established CVD.

Methods

In-depth, semi-structured interviews were conducted with 21 community pharmacists in New South Wales, Australia. All interviews were audio-recorded, transcribed ad verbatim, and analysed using a “grounded-theory” approach.

Results

Our model shows that community pharmacists work within a complex system and their practice is influenced by interactions between three main domains: the “people” factors, including their own attitudes and beliefs as well as those of clients and doctors; the “environment” within and beyond the control of community pharmacy; and outcomes of their professional care. Despite the complexity of factors and interactions, our findings shed some light on the interrelationships between these various influences. The overarching obstacle to maximizing the community pharmacists’ contribution is the lack of integration within health systems. However, achieving better integration of community pharmacists in primary care is a challenge since the systems of remuneration for healthcare professional services do not currently support this integration.

Conclusion

Tackling chronic diseases such as CVD requires mobilization of all sources of support in the community through innovative policies which facilitate inter-professional collaboration and team care to achieve the best possible healthcare outcomes for society.     

Prenatal genetic screening and the evolving quest for “perfect babies”: at what cost for genetic diversity?

Commercial screening services for inheritable diseases raise concerns about pressure on parents to terminate “imperfect babies”. Subject Categories: S&S: Economics & Business, Molecular Biology of Disease

Nearly two decades have passed since the first draft sequences of the human genome were published at the eyewatering cost of nearly US$3 billion for the publicly funded project. Sequencing costs have dropped drastically since, and a range of direct‐to‐consumer genetics companies now offer partial sequencing of your individual genome in the US$100 price range, and whole‐genome sequencing for less than US$1,000.While such tests are mainly for personal peruse, there have also been substantial drops in price in clinical genome sequencing, which has greatly enabled the study of and screening for inheritable disorders. This has both advanced our understanding of these diseases in general, and benefitted early diagnosis of many genetic disorders, which is crucial for early and efficient treatment. Such detection can, in fact, now occur long before birth: from cell‐free DNA testing during the first trimester of pregnancy, to genetic testing of embryos generated by in vitro fertilization, to preconception carrier screening of parents to find out if both are carriers of an autosomal recessive condition. While such prenatal testing of foetuses or embryos primarily focuses on diseases caused by chromosomal abnormalities, technological advances allow also for the testing of an increasing number of heritable monogenic conditions in cases where the disease‐causing variants are known.The medical benefits of such screening are obvious: I personally have lost two pregnancies, one to Turner''s syndrome and the other to an extremely rare and lethal autosomal recessive skeletal dysplasia, and I know first‐hand the heartbreak and devastation involved in finding out that you will lose the child you already love so much. It should be noted though that, very rarely, Turner syndrome is survivable and the long‐term outlook is typically good in those cases (GARD, 2021). In addition, I have Kallmann syndrome, a highly genetically complex dominant endocrine disorder (Maoine et al, 2018), and early detection and treatment make a difference in outcome. Being able to screen early during pregnancy or childhood therefore has significant benefits for affected children. Many other genetic disorders similarly benefit from prenatal screening and detection.But there is also obvious cause for concern: the concept of “designer babies” selected for sex, physical features, or other apparent benefits is well entrenched in our society – and indeed culture – as a product from a dystopian future. Just as a recent example, Philipp Ball, writing for the Guardian in 2017, described designer babies as “an ethical horror waiting to happen” (Ball, 2017). In addition, various commercial enterprises hope to capitalize on these screening technologies. Orchid Inc claims that their preconception screening allows you to “… safely and naturally, protect your baby from diseases that run in your family”. The fact that this is hugely problematic if not impossible from a technological perspective has already been extensively clarified by Lior Pachter, a computational biologist at Caltech (Pachter, 2021). George Church at Harvard University suggested creating a DNA‐based dating app that would effectively prevent people who are both carriers for certain genetic conditions from matching (Flynn, 2019). Richard Dawkins at Oxford University recently commented that “…the decision to deliberately give birth to a Down [syndrome] baby, when you have the choice to abort it early in the pregnancy, might actually be immoral from the point of view of the child’s own welfare” (Dawkins, 2021).These are just a few examples, and as screening technology becomes cheaper, more companies will jump on the bandwagon of perfect “healthy” babies. Conversely, this creates a risk that parents come under pressure to terminate pregnancies with “imperfect babies” as I have experienced myself. What does this mean for people with rare diseases? From my personal moral perspective, the ethics are clear in cases where the pregnancy is clearly not viable. Yet, there are literally thousands of monogenic conditions and even chromosomal abnormalities, not all of which are lethal, and we are making constant strides in treating conditions that were previously considered untreatable. In addition, there is still societal prejudice against people with genetic disorders, and ignorance about how it is to live with a rare disease. In reality, however, all rare disease patients I have encountered are happy to be alive and here, even those whose conditions have significant impact on their quality of life. Many of us also don''t like the term “disorder” or “syndrome”, as we are so much more than merely a disorder or a syndrome.Unfortunately, I also see many parents panic about the results of prenatal testing. Without adequate genetic counselling, they do not understand that their baby’s condition may have actually a quite good prognosis without major impact on the quality of life. Following from this, a mere diagnosis of a rare disease – many of which would not even necessarily have been detectable until later in life, if at all – can be enough to make parents consider termination, due to social stigma.This of course raises the thorny issue of regulation, which range from the USA where there is little to no regulation of such screening technologies (ACOG, 2020), to Sweden where such screening technologies are banned with the exception of specific high‐risk/lethal medical conditions both parents are known carriers for (SMER, 2021). As countries come to grips with both the potential and the risks involved in new screening technologies, medical ethics board have approached this issue. And as screening technologies advance, we will need to ask ourselves difficult questions as a society. I know that in the world of “perfect babies” that some of these companies and individuals are trying to promote, I would not exist, nor would my daughter. I have never before had to find myself so often explaining to people that our lives have value, and I do not want to continue having to do so. Like other forms of diversity, genetic diversity is important and makes us richer as a society. As these screening technologies quickly advance and become more widely available, regulation should at least guarantee that screening must involve proper genetic counselling from a trained clinical geneticist so that parents actually understand the implications of the test results. More urgently, we need to address the problem of societal attitudes towards rare diseases, face the prejudice and fear towards patients, and understand that abolishing genetic diversity in a quest for perfect babies would impoverish humanity and make the world a much poorer place.     

The traits of “trait ecologists”: An analysis of the use of trait and functional trait terminology

Trait and functional trait approaches have revolutionized ecology improving our understanding of community assembly, species coexistence, and biodiversity loss. Focusing on traits promotes comparability across spatial and organizational scales, but terms must be used consistently. While several papers have offered definitions, it remains unclear how ecologists operationalize “trait” and “functional trait” terms. Here, we evaluate how researchers and the published literatures use these terms and explore differences among subdisciplines and study systems (taxa and biome). By conducting both a survey and a literature review, we test the hypothesis that ecologists’ working definition of “trait” is adapted or altered when confronting the realities of collecting, analyzing and presenting data. From 486 survey responses and 712 reviewed papers, we identified inconsistencies in the understanding and use of terminology among researchers, but also limited inclusion of definitions within the published literature. Discrepancies were not explained by subdiscipline, system of study, or respondent characteristics, suggesting there could be an inconsistent understanding even among those working in related topics. Consistencies among survey responses included the use of morphological, phonological, and physiological traits. Previous studies have called for unification of terminology; yet, our study shows that proposed definitions are not consistently used or accepted. Sources of disagreement include trait heritability, defining and interpreting function, and dealing with organisms in which individuals are not clearly recognizable. We discuss and offer guidelines for overcoming these disagreements. The diversity of life on Earth means traits can represent different features that can be measured and reported in different ways, and thus, narrow definitions that work for one system will fail in others. We recommend ecologists embrace the breadth of biodiversity using a simplified definition of “trait” more consistent with its common use. Trait‐based approaches will be most powerful if we accept that traits are at least as diverse as trait ecologists.     

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.     

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.