Posttranscriptional regulation of colonic epithelial repair by RNA binding protein IMP1/IGF2BP1

Correction to: EMBO Reports (2019) 20: e47074. DOI 10.15252/embr.201847074 | Published online 6 May 2019The authors noticed that the control and disease labels had been inverted in their data analysis resulting in publication of incorrect data in Figure 1C. The corrected figure is displayed below. This change affects the conclusions as detailed below. The authors apologize for this error and any confusion it may have caused.In the legend of 1C, change from, “Differential gene expression analysis of pediatric ileal CD patient samples (n = 180) shows increased (> 4‐fold) IMP1 expression as compared to non‐inflammatory bowel disease (IBD) pediatric samples (n = 43)”.Open in a separate windowFigure 1CCorrected Open in a separate windowFigure 1COriginal To, "Differential gene expression analysis of pediatric ileal CD patient samples (n = 180) shows decreased (> 4‐fold) IMP1 expression as compared to non‐inflammatory bowel disease (IBD) pediatric samples (n = 43)”.In abstract, change from, “Here, we report increased IMP1 expression in patients with Crohn''s disease and ulcerative colitis”.To, “Here, we report increased IMP1 expression in adult patients with Crohn''s disease and ulcerative colitis”.In results, change from, “Consistent with these findings, analysis of published the Pediatric RISK Stratification Study (RISK) cohort of RNA‐sequencing data 38 from pediatric patients with Crohn''s disease (CD) patients revealed that IMP1 is upregulated significantly compared to control patients and that this effect is specific to IMP1 (i.e., other distinct isoforms, IMP2 and IMP3, are not changed; Fig 1C)”.To, “Contrary to our findings in colon tissue from adults, analysis of published RNA‐sequencing data from the Pediatric RISK Stratification Study (RISK) cohort of ileal tissue from children with Crohn’s disease (CD) 38 revealed that IMP1 is downregulated significantly compared to control patients in the RISK cohort and that this effect is specific to IMP1 (i.e., other distinct isoforms, IMP2 and IMP3, are not changed; Fig 1C)”.In discussion, change from, “Indeed, we report that IMP1 is upregulated in patients with Crohn''s disease and ulcerative colitis and that mice with Imp1 loss exhibit enhanced repair following DSS‐mediated damage”.To “Indeed, we report that IMP1 is upregulated in adult patients with Crohn''s disease and ulcerative colitis and that mice with Imp1 loss exhibit enhanced repair following DSS‐mediated damage”.     

Experts in science communication: A shift from neutral encyclopedia to equal participant in dialogue

Even if the predominant model of science communication with the public is now based on dialogue, many experts still adhere to the outdated deficit model of informing the public. Subject Categories: Genetics, Gene Therapy & Genetic Disease, S&S: History & Philosophy of Science, S&S: Ethics

During the past decades, public communication of science has undergone profound changes: from policy‐driven to policy‐informing, from promoting science to interpreting science, and from dissemination to interaction (Burgess, 2014). These shifts in communication paradigms have an impact on what is expected from scientists who engage in public communication: they should be seen as fellow citizens rather than experts whose task is to increase scientific literacy of the lay public. Many scientists engage in science communication, because they see this as their responsibility toward society (Loroño‐Leturiondo & Davies, 2018). Yet, a significant proportion of researchers still “view public engagement as an activity of talking to rather than with the public” (Hamlyn et al, 2015). The highly criticized “deficit model” that sees the role of experts as educating the public to mitigate skepticism still persists (Simis et al, 2016; Suldovsky, 2016).Indeed, a survey we conducted among experts in training seems to corroborate the persistence of the deficit model even among younger scientists. Based on these results and our own experience with organizing public dialogues about human germline gene editing (Box 1), we discuss the implications of this outdated science communication model and an alternative model of public engagement, that aims to align science with the needs and values of the public.Box 1

The DNA‐dialogue project

The Dutch DNA‐dialogue project invited citizens to discuss and form opinions about human germline gene editing. During 2019 and 2020, this project organized twenty‐seven dialogues with professionals, such as embryologists and midwives, and various lay audiences. Different scenarios of a world in 2039 (https://www.rathenau.nl/en/making‐perfect‐lives/discussing‐modification‐heritable‐dna‐embryos) served as the starting point. Participants expressed their initial reactions to these scenarios with emotion‐cards and thereby explored the values they themselves and other participants deemed important as they elaborated further. Starting each dialogue in this way provides a context that enables everyone to participate in dialogue about complex topics such as human germline gene editing and demonstrates that scientific knowledge should not be a prerequisite to participate.An important example of “different” relevant knowledge surfaced during a dialogue with children between 8 and 12 years in the Sophia Children’s Hospital in Rotterdam (Fig 1). Most adults in the DNA‐dialogues accepted human germline gene modification for severe genetic diseases, as they wished the best possible care and outcome for their children. The children at Sophia, however, stated that they would find it terrible if their parents had altered something about them before they had been born; their parents would not even have known them. Some children went so far to say they would no longer be themselves without their genetic condition, and that their condition had also given them experiences they would rather not have missed.Open in a separate windowFigure 1 Children participating in a DNA‐dialogue meeting. Photographed by Levien Willemse.     

A short history of beer brewing: Alcoholic fermentation and yeast technology over time

The history of beer: from a staple food to a consumer product with an enormous variety of styles and tastes. Subject Categories: Biotechnology & Synthetic Biology, History & Philosophy of Science

As far back as we can retrace history, beer has always been an important part of human life: it was and still is a valuable food staple that has been constantly improved and adapted to human needs. For most of the time, intoxication was not the main purpose and could only be achieved to a limited extent, if at all, given that beer had a low alcohol content for most of human history. Instead, beer, owing to its specific ingredients and characteristics—alcohol, carbon dioxide and a low pH value—was often the only safe liquid to drink when clean water was rare.

For most of the time, intoxication was not the main purpose and could only be achieved to a limited extent, if at all, given that beer had a low alcohol content for most of human history.

In addition, beer and other fermented foods are an important source of essential vitamins, such as vitamin B or riboflavin, trace elements and other health‐promoting ingredients. Especially for poorer people who mainly lived on bread or porridge, supplementing their diet with beer was beneficial to their health. Beer was also an important staple for certain professions, such as seafarers, who had to live of vitamin‐poor foodstuffs for longer times. Not surprisingly, many seafaring nations contributed to the spread and improvement of beer brewing (Fig 1).Open in a separate windowFigure 1Beer brewing over timeThe most important discoveries and developments during a history of 10,000 years of brewing beer.     

Structural basis of transport and inhibition of the Plasmodium falciparum transporter PfFNT

Subject Categories: Membranes & Trafficking, Microbiology, Virology & Host Pathogen Interaction, Structural Biology

We recently reported the first structures of the Plasmodium falciparum transporter PfFNT, both in the absence and presence of the inhibitor MMV007839 (Lyu et al, 2021). These structures indicated that PfFNT assembles as a pentamer. The bound MMV007839 was found in the middle of the elongated channel formed by each PfFNT protomer, adjacent to residue G107. MMV007839 exists in two tautomeric forms and can adopt either a cyclic hemiketal‐like structure or a linear vinylogous acid conformation (Fig ​(Fig3A).3A). Unfortunately, these two tautomeric forms could not be clearly distinguished based on the existing cryo‐EM data at 2.78 Å resolution. The bound MMV007839 inhibitor was reported as the cyclic hemiketal‐like form in the structure in Figs ​Figs3A3A and ​andF,F, and ​and4C,4C, Appendix Figs S10A and B, and S13 and in the online synopsis image.Open in a separate windowFigure 3Cryo‐EM structure of the PfFNT‐MMV007839 complex

1. Chemical structure of MMV007839. The compound can either be in cyclic hemiketal‐like or linear vinylogous acid tautomeric forms.
2. Cryo‐EM density map of pentameric PfFNT viewed from the parasite’s cytoplasm. Densities of the five bound MMV007839 within the pentamer are colored red. The five protomers of pentameric PfFNT are colored yellow, slate, orange, purple, and gray.
3. Ribbon diagram of the 2.18‐Å resolution structure of pentameric PfFNT‐MMV007839 viewed from the parasite’s cytoplasm. The five protomers of pentameric PfFNT are colored yellow, slate, orange, purple, and gray.
4. Ribbon diagram of pentameric PfFNT‐MMV007839 viewed from the extracellular side of the parasite. The five protomers of pentameric PfFNT are colored yellow, slate, orange, purple, and gray.
5. Ribbon diagram of pentameric PfFNT‐MMV007839 viewed from the parasite’s membrane plane. The five protomers of pentameric PfFNT are colored yellow, slate, orange, purple, and gray. Densities of the five bound MMV007839 are depicted as red meshes.
6. The MMV007839‐binding site of PfFNT. The bound MMV007839 is colored green. Density of the bound MMV007839 is depicted as black mesh. Residues involved in forming the inhibitor binding site are colored yellow. The hydrogen bonds are highlighted with black dotted lines.

Open in a separate windowFigure 4Structure of the central channel in the PfFNT‐MMV007839 protomer

• CA cartoon of the central channel formed within a PfFNT protomer. The channel contains one constriction site in this conformational state. Residues forming the constriction and the K35‐D103‐N108 and K177‐E229‐N234 triads are illustrated as sticks. Residues F94, I97, and L104, which form the first constriction site in the apo‐PfFNT structure, are also included in the figure.

Eric Beitz alerted us to the findings reported by his group that the linear vinylogous acid tautomer of MMV007839 constitutes the binding and inhibitory entity of PfFNT (Golldack et al, 2017).     

From the freezer to the clinic: Antifreeze proteins in the preservation of cells,tissues, and organs

Understanding the mechanisms by which natural anti‐freeze proteins protect cells and tissues from cold could help to improve the availability of donor organs for transplantation.

The first successful organ transplant in humans was performed in 1954 by Joseph Murray, who used a patient’s twin as a kidney donor. Murrays’ breakthrough paved the way for organ transplantation and the number of transplanted organs has grown ever since. For example, in 2017, a total of 139.024 solid organs—mostly kidney, liver, heart, lung, pancreas, and small bowel—were transplanted (Fig 1A). But this number only reflects 10% of the worldwide need; many patients still die of end‐stage organ failure while on a waiting list. The limited number of donor organs contributes only partially to this shortage. Many donor organs are not transplanted eventually owing to inefficient preservation techniques that shorten their extracorporeal lifetime. In fact, the percentage of donor organs that are unused is estimated to range from around 25% for kidneys and livers up to 70–80% for hearts and lungs (Giwa et al, 2017); Fig 1B).Open in a separate windowFigure 1Organ transplantation and preservability statusStatistics show a positive correlation between the duration of ex vivo preservation and the number of organ transplants. Number of solid organs transplanted in 2017 (A). Percentage of organs failed to be transplanted (B). Duration of solid organ ex vivo preservation in static cold storage (C). Sources: Data from the Global Observatory on Donation and Transplantation and (Parsons et al, 2014), (Guibert et al, 2011) and (Editorial: Buying time for transplants (2017))

Many donor organs are not transplanted eventually owing to inefficient preservation techniques that shorten their extracorporeal lifetime.

To address the shortage of donor organs and decrease the number of organs that go to waste, biobanks could efficiently store viable tissues and organs until transplantation. Yet, the current standard for ex vivo preservation of donor organs is static cold storage (4–8°C) which, depending on the organ, ensures viable conservation for only some hours; hearts are typically viable for a maximum of only 4 h (Fig 1C). In addition, this approach leads to hypothermic damage and to ischemia/reperfusion injury.Hence, there is an urgent need for strategies that prolong the viable preservation of donor organs. Two main strategies have emerged for cryopreservation and subzero storage, both of which cool tissues below the freezing point. While subzero storage just below 0°C may suffice for short‐term preservation, cryopreservation at −80°C or even lower temperatures is required for long‐term storage in biobanks. A proof‐of‐principle study already demonstrated that subzero preservation extended the preservation of rat hearts up to 24 h after collection (Amir et al, 2004); cryopreservation of whole hearts is currently not possible. The main reason is that lowering the temperature below the freezing point of water leads to ice formation, which causes cell damage and destroys tissues. One of the main challenges in biomedical research for organ transplantation is therefore finding non‐toxic and biocompatible antifreeze compounds that enable subzero storage and cryopreservation without causing tissue damage. An additional benefit is a larger time window to perform evaluation in terms of organ size and human leukocyte antigens matching and preparing the recipient patient to increase the chance of a successful transplantation.     

The COVID‐19 pandemic: agile versus blundering communication during a worldwide crisis: Important lessons for efficient communication to maintain public trust and ensure public safety

Governments’ measures to control the COVID‐19 pandemic and public reaction hold important lessons for science and risk communication in times of crisis.

The world is in the grips of a global pandemic, the end of which is not yet in sight. Nations struggle to deal with the severe health, economic and social impacts of COVID‐19 with varying success. Their ability to handle this crisis depends on many factors, some of which, such as the availability of vaccines, are variable, while others – geographical location or population density – are determined. More importantly though, public health infrastructures, political will and action, and clear communication have so far proved to be the most successful levers for coping with the pandemic. This article examines how political will and communication in particular have helped to alleviate the impact of the virus in some countries.

… public health infrastructures, political will and action, and clear communication have so far proved to be the most successful levers for coping with the pandemic.

News that a new virus had emerged in Wuhan, China, was just of fleeting interest for most people in December 2019. This changed rapidly: by March 2020, large parts of the world had gone into lockdown to curtail the rapid spread of SARS‐CoV‐2. Many governments issued more or less harsh restrictions on private contacts, travel and other freedoms, followed by easing these regulations during the summer, which precipitated new outbreaks in the fall along with mutations of the virus that triggered new restrictions; it is likely that this pattern will continue until a sufficient number of people are vaccinated to achieve herd immunity.COVID‐19 came “out of the blue”, hit a largely unprepared human population and has therefore affected human civilisation in an unprecedented manner (Fig 1). People are not only concerned about their health: as the pandemic continues, citizens also worry about the social, economic and psychological impacts. Even though vaccination programmes are under way, only a few countries will be able to achieve herd immunity by the summer; in the meantime, public acceptance for the ongoing restrictions of freedom are waning as the negative social and economic effects become more urgent. Thus, political action and planning along with efficient communication in particular are crucially important to ensure the public’s understanding of the situation and maintain acceptance for restrictive measure until enough vaccines become available. The antipodes in communication strategies were a mixture of evidence‐based messages, transparency, building confidence and open discussion of scientific uncertainty to gain and maintain public trust versus the unfettered spread of alternative facts, targeted disinformation and omission of important information that eventually eroded said trust.Open in a separate windowFigure 1Fear in times of COVID‐19An elderly pedestrian wearing a face mask due to the COVID‐19 pandemic, walks past graffiti depicting the subjects within famous artworks, in Glasgow on 2 September 2020 after the Scottish government imposed fresh restrictions on the city after a rise in cases of the novel coronavirus (© Andy Buchanan/AFP via Getty Images)

… political action and planning along with efficient communication in particular are crucially important to ensure the public’s understanding of the situation and maintain acceptance for restrictive measure…

     

Creativity as an antidote to research becoming too predictable

In this commentary, Sonne‐Hansen and colleagues argue that research leaders and organizations should encourage more “theory‐guessing” by budding young scientists, rather than incentivizing safe mainstream research. Subject Categories: History & Philosophy of Science, Science Policy & Publishing

Most living things do not like extreme heat. Case in point—in 2021, French winemakers recorded the smallest harvest since 1957 due to rising temperatures. Unlike the grapes that give birth to dry whites and luscious reds, some organisms flourish in extremely hot environments, however. In the late 1960s, Thomas Brock, a microbiologist from Cleveland, and his undergraduate student Hudson Freeze conducted research in Yellowstone National Park. What drew their interest was that some organisms seem to thrive in the hot springs sprinkled throughout the park. From a sample of pink bacteria collected from Mushroom Spring, Brock and his student isolated a prokaryotic organism thriving at 70°C, which they named Thermus aquaticus—after the Greek word for “hot” and the Latin for “water.” The ability of an enzyme (DNA polymerase) from Thermus aquaticus to tolerate high temperatures would later spur the invention of the polymerase chain reaction or PCR, which won biochemist Kary Mullis a share of the 1993 Nobel Prize in Chemistry and revolutionized biomedicine.When it was published in the Journal of Bacteriology, the work by Brock and Freeze went largely undetected. It generated a few citations but did not manage to attract the attention of the wider community of biologists (Bhattacharya & Packalen, 2020). Of course, this is not uncommon for novel findings—their true value may remain unknown for a while, even if the work later spurs new ideas and scientific breakthroughs. Precisely, because it constitutes a venture into the unknown, pursuing novel ideas requires a special set of circumstances. Without the National Science Foundation''s financial support and without Brock being able to spend a decade exploring the hot springs of Yellowstone National Park, satisfying his curiosity about things that thrive in extreme heat (but undoubtedly offending his nose in the process—those thermal pools can be quite pungent), the world likely would have had to wait longer for the advent of PCR.Our core argument is that the conditions that allow and encourage scientists to engage in the relentless, creative exploration of the unknown are becoming harder and harder to find. There are several reasons for this. For one, finding new ideas appears increasingly difficult. Data from the United States, for instance, suggest that research productivity (defined as ratio of the output of ideas to the inputs used to make them) in a number of fields, including medical research, is declining over time. To offset the difficulty in finding new ideas, the United States would have to double its research effort every 13 years (Bloom et al, 2020).One of the consequences of this increase in research activity is that the number of papers published each year has increased over time (Chu & Evans, 2021). This growth has some undesirable side effects. Scientists focus their attention on work that is already well‐cited rather than on new ideas or on ideas on the fringes of the scientific mainstream (Chu & Evans, 2021). Sifting through a deluge of ideas—published in an actual Mount Kilimanjaro of papers (Van Noorden et al, 2014)—to find a nugget of wisdom is hard. This leads to a calcification of the intellectual structure of a field, slowing down progress over time.Funding agencies further exacerbate this trend. There is a tendency to minimize risk—it has become the norm that grant proposals have to already provide substantial amounts of data supporting the proposed theories/hypotheses (incidentally, something that Thomas Brock would not have been able to do)—and to reward work on topics that are more established. As recently as the 1990s, however, research that explored more current ideas was not at a disadvantage when it came to funding (Packalen & Bhattacharya, 2020). Going back to these “old ways” of maintaining a balance between funding work that builds on more established ideas and work that builds on more recent advances may be something that the biomedical sciences could aspire to. Small steps are being undertaken. For instance, some foundations in Denmark are now providing opportunities for (modest) funding of applicants whose ideas would likely get shunned by the traditional funding schemes.As obtaining external funding is the lifeblood for many research programs, investigators are responding to these pressures by “playing it safe,” pursuing ideas that, from the outset, are likely to be publishable to ensure a constant stream of papers. Long gone are the days that biologists could explore the hot springs of Yellowstone National Park without knowing what all that exploring would amount to (other than a nice tan). A journey into the exploration of the unknown has been replaced with a ticket on the Shinkansen “bullet train”—“destination: known” and always on time.Contemporary academic training practices have not been able to fight back these developments. Quite the contrary—one of the consequences of the “pressure to produce” is that budding researchers are often recruited onto preexisting projects with already defined milestones and deliverables, all the while having to develop a range of other skills. Naturally, this leaves little room and time for engaging in more exploratory aspects of the scientific process. The result is that we are turning the next generation of scientists into excellent experimentalists and “research managers,” rather than into bold scientific thinkers.We are at a point at which a systematic focus on training and injecting creativity into the research process in the life sciences is imperative. When hearing the word “creativity,” many people think of the tortured artist, toiling away in isolation in a village in the south of France (but who would not want a sip of a French Cabernet Sauvignon at the end of a hard day''s work—before it runs out). As enticing as this image of radiant colors and crystalline light might be, it is by no means the sole context in which creativity can flourish. Creativity is defined as the generation of ideas that are new and have potential value by addressing a problem or capitalizing on an opportunity. There is no mention of artistic endeavors in this definition! In fact, creativity is fundamental to the human condition and, as such, can be found anywhere, anytime, given the right circumstances.Creativity may be most pressingly needed during the early stages of the knowledge production process—when we have to make what physicist Richard Feynman has called “educated guesses” as to how the world may work. This is the opaquer part of the scientific process; the part that benefits from the use of intuition and of a language that is permissible of it—what Itai Yanai and Martin Lercher refer to as night science language (Yanai & Lercher, 2020; check out also their podcast series entitled, “Night Science”). While the part of the process that deals with testing existing ideas is highly visible and more easily describable, the guessing, theory‐generating part often gets far less systematic attention. Yet, it is the part of the scientific process that is becoming ever more important. We are not so much in need of more data, but of educated guesses (i.e., a theory) about what to look for in the first place. This call for ideas is echoed by Paul Nurse, quoting the famous words of the late biologist Sydney Brenner, “we are drowning in a sea of data and starving for knowledge” (Nurse, 2021).To understand the value of creativity for making educated guesses, it is helpful to dissect it into its components. According to Teresa Amabile, one of the pioneers of the study of creativity, there are three components to creativity—domain expertise, intrinsic motivation, and creativity‐relevant skills (Amabile, 1996). To put it simply: creativity flourishes when people have the wit (knowledge of the domain), the will (intrinsic motivation), and the necessary creative tools to tackle interesting and challenging problems (Fig 1).Open in a separate windowFigure 1Three components of creativityDomain expertise refers to a high level of domain‐specific knowledge acquired though experience. Without expertise, it is impossible to know where on the scientific frontier to look for new and interesting problems. However, there is a downside to becoming an expert. The more we know about a domain and the longer we have studied it, the more we lose flexibility in seeing new problems and devising novel solutions to them (Dane, 2010). Edward Tufte, for instance, describes how experts are likely to glance past unexpected findings in their datasets, whereas outsiders are more likely to pay attention to these surprises, as they see the world through what he calls “vacation eyes” (Tufte, 2020). While the loss of flexibility may not be of immediate concern to budding scientists, the benefits of learning ever more about the very same domain start to evaporate rather quickly over one''s career. Luckily, there is an antidote—investing in becoming well‐versed in new and different domains, that is, developing knowledge breadth rather than (further) depth. Research suggests that there are immediate benefits from knowledge breadth for creativity—even scientists just at the beginning of their academic journey should benefit from developing expertise in additional domains (Mannucci & Yong, 2018).How can we accomplish this? One strategy is to allow and encourage early‐stage scientists to immerse themselves in analogous problems domains and the solutions they may inspire. An example might serve to illustrate this principle: Some years ago, the already mentioned Shinkansen “bullet train” needed redesign. The train''s speed created a sonic boom that was heard for hundreds of meters when exiting tunnels. So, a group of engineers was charged with making the train quieter. One of the lead engineers, Eiji Nakatsu, was a bird watcher. He realized that birds diving into water to catch pray face the same challenge as the train trying to cut through air while going through a tunnel. The new design of the train''s front was based on the shape of the Kingfisher''s beak—a bird diving at high speed from one medium (air) into another (water) with barely a splash. To emulate Eiji Nakatsu, it will be necessary to allow scientists to not only spend time studying topics other than the ones they are actively investigating, but also to allow them to join research collaborations with scientists from other domains and even disciplines investigating analogous problems.Creativity requires a certain type of motivation—intrinsic motivation. People are intrinsically motivated to the extent that they derive pleasure from the work itself and from the opportunity to acquire new skills. Extrinsic motivation is just the opposite—it is the drive that comes from incentives, such as financial compensation and recognition. The reason why intrinsic motivation is so important to the creative process is that it provides perseverance—in the face of setbacks, obstacles, and naysayers. Intrinsic motivation is largely a function of the nature of the work—how challenging it is and how much autonomy it affords. Whenever we have the freedom to explore new lines of inquiry, to satisfy our curiosity, and, perhaps most importantly, to make mistakes, intrinsic motivation ensues. However, the knowledge production process that has become dominant in the life sciences is antithetical to budding scientists experiencing autonomy. Predefined (externally funded) research projects that are too rigidly managed (be it by funders or by principal investigators) with their milestones and deliverables offer little room to exercise autonomy.If we want research to flourish, it will be imperative for us to take responsibility and rethink the knowledge production process in our laboratories to allow for the occasional detours, setbacks, and dead ends. Case in point—Richard Feynman, who won the Nobel Prize in Physics for his contributions to quantum electrodynamics, developed his ideas based on an observation that many would consider a major intellectual detour—a cafeteria worker throwing a plate into the air. Feynman observed that the “Cornell” logo on the plate was going around much faster than the plate''s wobble. Armed with this observation and allowed the freedom to explore the dynamics of the motion of the plate, he developed the basis for the Feynman diagrams (Feynman et al, 1985). Naturally, this more autonomous and playful approach may decrease the efficiency of the knowledge production process. However, efficiency is not the primary criterion by which to evaluate research quality. The novelty and utility of our ideas should be the primary criteria. Research leaders may thus want to embrace the values of autonomy and novelty more courageously and embolden early‐stage researchers to do just the same. Similarly, academic institutions need to take a good, hard look at themselves, increasing the “breathing space and time” for scientist to engage in exploration of new ideas and research avenues.The final component contributing to our creativity is a set of creative skills that allow people to take greater advantage of their drive and of what they know. One skill that is imperative here is the ability to tolerate uncertainty. The uncertainty of not knowing, of taking guesses in the absence of a firmly established knowledge base, and of trying out things without knowing exactly what the outcome will be. The systems biologist Uri Alon refers to this as staying in the “research cloud,” highlighting the value of transitioning from the “known” to the “unknown” (i.e., the research cloud) and temporarily residing in this state of uncertainty despite the discomfort and frustration that are bound to arise (Alon, 2013). The notion of the “research cloud” may seem to conflict with the prevailing scientific culture, in which there is little room for speculations or intuitions. To combat this, we need to re‐imagine the ways in which research leaders interact with their teams, so as to encourage budding scientists to become more comfortable stepping outside the scientific path they learned as students. Case in point—critical thinking is highly priced in the training of university students. However, the inquisitive and evaluative processes that critical analysis relies upon can be antithetical to the generative processes required for creativity—it is difficult to develop new insights while at the same time having to defend them from others'' critical examination. This calls for supervisors and mentors to create what we call “creative oases”—spaces in which critical analysis is dispensed with and risk‐taking and speculation are encouraged.Another lesson from creativity research is that it is impacted heavily by the work environment in which people operate. Creative teams thrive in high‐trust environments, and whenever their members practice a “yes and” rather than a “no because” approach that encourages young researchers to engage and contribute toward new solutions to long‐standing scientific questions. Thus, it is crucial that administrative and research leaders are engaged in building a supportive and inclusive culture. To illustrate—at four biomedical research centers at the University of Copenhagen, we held in autumn 2021 a four‐session workshop for research group leaders on how to nurture a culture that fosters creativity. The sessions focused on how to guide teams through the different phases of the creative process, and introduced tools for divergent and convergent thinking. The underlying principle was that creativity thrives when leaders build an environment that allows the team to capitalize on the collective knowledge of individual members—an environment built on the principles of diversity of thought, autonomy, and a high degree of psychological safety (e.g., deferring judgment in order to promote idea sharing and interpersonal risk‐taking).In conclusion, we believe that research organizations should not dwell too much on the structural barriers to creativity (funding agencies and politicians need to dismantle these barriers) but rather take action to encourage more “theory‐guessing” and nurture the ability for budding scientist to find delight in staying in the “research cloud”—at least for some time. Also, research communities and academic institutions should take greater responsibility for embracing a truly team‐based approach to creativity (rather than the “lone genius” model), in which scientists are granted the freedom to take the occasional intellectual detour or flight of fancy—without repercussions or fear of failure. These efforts will be needed if we are to make lasting changes to the way in which we engage the scientific process and venture into the unknown in the pursuit of transformational research.     

Standing on the shoulders of microbes: How cancer biologists are expanding their view of hard‐to‐kill persister cells

Similar to persister bacterial cells that survive antibiotic treatments, some cancer cells can evade drug treatments. This Commentary discusses the different classes of persister cells and their implications for developing more efficient cancer treatments. Subject Categories: Cancer

Similar to persister bacterial cells that survive antibiotic treatments, small populations of cancer cells can evade drug treatments and cause recurrent disease. This Commentary discusses the different classes of persister cells and their implications for developing more efficient cancer treatments.In 1944, Joseph Bigger, a lieutenant‐colonel in the British Royal Army Medical Corps, reported a peculiar population of bacteria that could survive very high concentrations of penicillin (Bigger, 1944). He termed these hard‐to‐kill cells “persisters” and argued they might explain the limited success of penicillin in curing infections. At the time, 16 years after antibiotics revolutionized bacterial infection treatment, this was a groundbreaking hypothesis as it was largely believed that partial killing was mostly due to inadequate blood supply or tissue barriers. Later on, the understanding that cell‐intrinsic properties may contribute to transient drug tolerance sparked research aimed at targeting microbial persister cells. In a seminal paper, Sherma and colleagues (Sharma et al, 2010) showed that reversible cell‐intrinsic resistance can also be observed in cancer cells in response to therapy. Similar to bacterial persisters, these cancer persister cells gave rise to a drug‐sensitive cell progeny following a short “drug‐holiday” and did not harbor any known resistance‐mediating alteration mutation. However, in contrast to microbial persisters that are largely dormant, a small fraction of cancer persister cells were able to resume proliferation even under continued drug treatment. Understanding the similarities and differences between cancer and microbial persister cells is pivotal to devise approaches to eliminate them (Fig 1).Open in a separate windowFigure 1Different persister classes(A) Classic persisters, (B) targeted‐persisters, and (C) immune‐persisters. The mechanism of escape is dependent on the mode of action of the drug. While classical persisters are common to both bacteria and cancer cells, other persister classes are cancer‐specific and are associated with the ability of cancer cells to probe a wide range of cells states and lineage trajectories.So why can some bacteria persist in the face of therapy? The answer largely lays in the mode of action of antimicrobial drugs. Penicillin and newer generation antibiotics target bacterial cell division. As such, if the bacteria are dormant or reside in a low metabolic state, they are unafflicted by the drug. Dormant bacteria are frequently resistant to multiple stressors and drugs making them difficult to eradicate even with a very aggressive treatment. Unsurprisingly, similar phenomena are observed in the context of chemotherapy treatments in cancer. Like antibiotics, early cancer therapies were largely based on drugs that target highly proliferative cells. Sustained proliferation in the absence of external stimuli is one of the hallmarks of cancer. Because cancer cells divide more frequently than most normal cells, they are more likely to be killed by chemotherapy treatment. As both antibiotics and chemotherapy treatments target proliferating cells, it is not surprising that cell dormancy was linked to cell persistence in both cases. “Classical” nondividing persister cells have been implicated in treatment failure both in cancer and in microbial infections and are thought to provide a reservoir for subsequent relapse events.In the last 20 years, a new class of cancer drugs, called targeted therapies, have emerged and revolutionized patient care. Unlike chemotherapies or antibiotics, these drugs do not target proliferating cell per se but rather act on specific molecular targets associated with cancer. For example, some targeted therapies target proteins that are more abundant on the surface of cancer cells compared with that of normal cells. While slow proliferation has also been implicated in tolerance in the context of targeted therapy, multiple additional mechanisms are at play, which are not characteristic of microbial persister cells. For instance, oncogene‐targeted therapies are taking advantage of the acquired dependence of a cancer cell on the activity of a single oncogenic gene product. As many oncogenes control cell metabolism (Levine & Puzio‐Kuter, 2010), for example by regulating glucose uptake, drugs that target oncogene addiction can have profound effects on metabolism. In line with this, oncogenic‐persisters, for example, persisters that escape killing by oncogene‐targeted therapies show higher levels of fatty acid oxidation (Oren et al, 2021). This shift away from the “Warburg” glycolytic state into a more mitochondrially active energy production state, which resembles non‐transformed cells, might indicate the release from oncogenic addiction. Importantly, this shift does not lead to overall lower metabolic activity and in some cases might even allow persisters that were arrested to resume cell cycle in the presence of a drug. This high modularity is possible in cancer cells as they can, under certain conditions, tap into a vast space of cellular states that reflect different tissues and developmental trajectories. Cancer persister cell plasticity is perhaps best exemplified by phenotypic transformation from non‐small‐cell lung adenocarcinoma to small‐cell lung cancer upon prolonged treatment with EGFR inhibitors (Shaurova et al, 2020). Such lineage switching accounts for up to 14% of acquired resistance to EGFR‐targeted therapy. Clinical data of relapsed patients strongly support the hypothesis that this transformation happens via persister cells that were able to withstand EGFR therapy. Taken together, these observations show that cancer persister cells can circumvent oncogenic withdrawal by adopting alternative cell states. Notably, these changes do not necessarily require any genetic alteration and in theory can be reversible and potentially mediated by microenvironment signaling.The most recent addition to the cancer‐fighting arsenal are immunotherapies designed to boost immune responses. Immune‐persisters, cells that can evade immune response, have been reported in multiple cancer types and are thought to underlie the late relapse frequently observed in patients (Shen et al, 2020). While tumor dormancy might play a role in this context as well, it is interesting to note that immune evasion can be achieved by modulating immune checkpoint molecules without any need to suppress cell proliferation. Furthermore, in the case of CAR T‐cell therapy, a class of immunotherapy that is based on revamped T cells, persistence might be viewed as a dynamic cell‐to‐cell communication process. It was shown that to elicit killing a cancer cell has to have multiple interactions with a T cell (Weigelin et al, 2021). This multihit sequential process that can take more than an hour in vivo may allow cancer cells to modulate the cytotoxic T cell in a way that would favor their persistence. Hence, understanding what underlies T‐cell phenotypes might as be as important as studying the cancer persister cells they are targeting.The holy grail of the persister filed is finding ways to target these drug‐tolerant cells in a manner that would prevent disease recurrence. However, given at least three classes of persisters have been already reported, and more are expected to arise as we continue to expand our therapeutic toolbox, would it even be possible to implement a single approach to eliminate them? Studies that searched for a magic bullet that could eliminate persister cells were largely based on the hope that persister cells would be less heterogenous than the drug‐naïve cell population they were derived from (Cabanos & Hata, 2021; Hangauer et al, 2017). If such convergence on similar cell states exists upon treatment, it simplifies the need to combine multiple drugs to eliminate the entire cell population. Unfortunately, it seems that persister cells can come in multiple forms and that distinct persister phenotypes may coexist in a single tumor. The major drivers of this heterogeneity currently remain unclear and may include tumor lineage, treatment type, or a combination of both. Moreover, it is unknown if the heterogeneity in persister phenotypes can be predicated based on the drug‐naïve population and how these diverse persister fates are associated with clinical outcomes. Understanding persister heterogeneity is critical as the simplistic approach of trying to eliminate as many persister cells as possible, assumes that all cells are equally pathogenic, which might not be the case if only a subset of them are able to contribute to relapse. Furthermore, persister cells might differ in their aptitude to give rise to cells that harbor a resistance‐mediating mutation. Such differences in evolvability must be considered when weighing possible treatments. Answering these questions would be key to devising effective therapeutic approaches to eliminate persister cells. In the last century, the study of microbial persistence had provided important insights into how to fight infections. Hopefully, in the years to come, we will build upon this valuable knowledge foundation and expend it to devise better ways to fight cancer.     

Lamin A‐mediated nuclear lamina integrity is required for proper ciliogenesis

The authors were alerted to the fact that the statistical analysis of cilia measurements lacked important information regarding sample size and pooling of datapoints. The authors therefore wish to add the following information to the Materials and Methods section to clarify the method used for the statistical analysis of cilia counts.Open in a separate windowFigure 2Lmna null mice display defective primary cilia in the skeletal muscle, kidney, uterus, and ovary.

• E(E) The statistical analysis of cilia counts from mouse tissues was based on a comparison of the pooled counts across 3 pairs of the control and Lmna^−/− mice.

Source data are available online for this figure.     

Structural basis of transport and inhibition of the Plasmodium falciparum transporter PfFNT

In “Structural basis of transport and inhibition of the Plasmodium falciparum transporter PfFNT” by Lyu et al (2021), the authors depict the inhibitor MMV007839 in its hemiketal form in Fig 3A and F, Fig 4C, and Appendix Figs S10A, B and S13. We note that Golldack et al (2017) reported that the linear vinylogous acid tautomer of MMV007839 constitutes the binding and inhibitory entity of PfFNT. The authors are currently obtaining higher resolution cryo‐EM structural data of MMV007839‐bound PfFNT to ascertain which of the interconvertible isoforms is bound and the paper will be updated accordingly.     

Biodiversity 2030: a road paved with good intentions: The new EU Commission's biodiversity Strategy risks to remain an empty husk without proper implementation

The EU''s Biodiversity Strategy for 2030 makes great promises about halting the decline of biodiversity but it offers little in terms of implementation. Subject Categories: S&S: Economics & Business, Ecology, S&S: Ethics

Earth is teeming with a stunning variety of life forms. Despite hundreds of years of exploration and taxonomic research, and with 1.2 million species classified, we still have no clear picture of the real extent of global biodiversity, with estimates ranging from 3 to 100 million species. A highly quoted—although not universally accepted—study predicted some 8.7 million species, of which about 2.2 million are marine (Mora et al, 2011). Although nearly any niche on the surface of Earth has been colonized by life, species richness is all but evenly distributed. A large share of the known species is concentrated in relatively small areas, especially in the tropics (Fig 1). Ultimately, it is the network of the interactions among life forms and the physical environment that make up the global ecosystem we call biosphere and that supports life itself.Open in a separate windowFigure 1Biological hotspots of the worldA total of 36 currently recognized hotspots make up < 3% of the planet''s land area but harbor half of the world''s endemic plant species and 42% of all terrestrial vertebrates. Overall, hotspots have lost more than 80% of their original extension. Credit: Richard J. Weller, Claire Hoch, and Chieh Huang, 2017, Atlas for the End of the World, http://atlas‐for‐the‐end‐of‐the‐world.com/. Reproduced with permission.Driven by a range of complex and interwoven causes–such as changes in land and sea use, habitat destruction, overexploitation of organisms, climate change, pollution, and invasive species–biodiversity is declining at an alarming pace. A report by the Intergovernmental Science‐Policy Platform on Biodiversity and Ecosystem Services (IPBES) issued a clear warning: “An average of around 25 per cent of species in assessed animal and plant groups are threatened, suggesting that around 1 million species already face extinction, many within decades, unless action is taken to reduce the intensity of drivers of biodiversity loss. Without such action, there will be a further acceleration in the global rate of species extinction, which is already at least tens to hundreds of times higher than it has averaged over the past 10 million years” (IPBES, 2019) (Fig 2). Although focused on a smaller set of organisms, a more recent assessment by WWF has reached similar conclusions. Their Living Planet Index, that tracks the abundance of thousands of populations of mammals, birds, fish, reptiles, and amphibians around the world, shows a stark decline in monitored populations (WWF, 2020). As expected, the trend of biodiversity decline is not homogeneous with tropical areas paying a disproportionately high price, mostly because of unrestrained deforestation and exploitation of natural resources.Open in a separate windowFigure 2The global, rapid decline of biodiversity(A) Percentage of species threatened with extinction in taxonomic groups that have been assessed comprehensively, or through a “sampled” approach, or for which selected subsets have been assessed by the IUCN Red List of Threatened Species. Groups are ordered according to the best estimate, assuming that data‐deficient species are as threatened as non‐data deficient species. (B) Extinctions since 1500 for vertebrate groups. (C) Red List Index of species survival for taxonomic groups that have been assessed for the IUCN Red List at least twice. A value of 1 is equivalent to all species being categorized as Least Concern; a value of zero is equivalent to all species being classified as Extinct. Data for all panels from www.iucnredlist.org. Reproduced from (IPBES, 2019), with permission.

Driven by a range of complex and interwoven causes […] biodiversity is declining at an alarming pace.

Against this dire background, the EU has drafted a Biodiversity Strategy 2030, an ambitious framework aimed to tackling the key reasons behind biodiversity loss. The plan hinges around a few main elements, such as the establishment of protected areas for at least 30% of Europe''s lands and seas (Fig 3); a significant increase of biodiversity‐rich landscape features on agricultural land by establishing buffer zones like hedges and fallow fields; halting and reversing the decline of pollinators; and planting 3 billion trees by 2030 (https://ec.europa.eu/info/strategy/priorities‐2019‐2024/european‐green‐deal/actions‐being‐taken‐eu/eu‐biodiversity‐strategy‐2030_en). The budget for implementing these measures was set at €20 billion per year.Open in a separate windowFigure 3Natura 2000, the EU''s network of protected areasIn 2019, 18% of land in the EU was protected as Natura 2000, with the lowest share of protected land in Denmark (8%) and the highest in Slovenia (38%). In 2019, the largest national network of terrestrial Natura 2000 sites was located in Spain, covering 138,111 km², followed by France (70,875 km²) and Poland (61,168 km²). Reproduced from Eurostat: https://ec.europa.eu/eurostat/statistics‐explained/index.php?title=Main_Page “Nature is vital for our physical and mental wellbeing, it filters our air and water, it regulates the climate and it pollinates our crops. But we are acting as if it didn''t matter, and losing it at an unprecedented rate”, said Virginijus Sinkevičius, Commissioner for the Environment, Oceans and Fisheries, at the press launch of the new EU action (https://ec.europa.eu/commission/presscorner/detail/en/ip_20_884). “This new Biodiversity Strategy builds on what has worked in the past, and adds new tools that will set us on a path to true sustainability, with benefits for all. The EU''s aim is to protect and restore nature, to contribute to economic recovery from the current crisis, and to lead the way for an ambitious global framework to protect biodiversity around the planet”.Environmental groups and other stakeholders have welcomed the EU''s pledge in principle. “This is a unique opportunity to shape a new society in harmony with nature”, applauded Wetlands International. “We must not forget that the biodiversity and climate crisis is a much bigger and persistent challenge for humanity than COVID‐19”, (https://europe.wetlands.org/news/welcoming‐the‐eu‐biodiversity‐strategy‐for‐2030/). EuroNatur, a foundation focused on conservation, stated that the goals set out by the new strategy provide a strong basis for improving the state of nature in the EU (www.euronatur.org).Alongside the voices of praise, however, many have expressed concerns that the strategy could turn into a little more than a wish list. “The big issue of the strategy is that while setting a goal for financial funds, the EU does not specify where the money is supposed to come from. It only says it should include ‘EU funds and national and private funding’”, commented the European Wilderness Society, an environmental advocacy non‐profit organization headquartered in Tamsweg, Austria. “Goals are important, but do not create change without an organized and sustainable implementation. It''s a good and ambitious document, but what is also obvious is the lack of strategy of how to implement it, and a lack of discussion of why previous documents of this type failed” (https://wilderness‐society.org/ambitious‐eu‐biodiversity‐strategy‐2030/).

Alongside the voices of praise, however, many have expressed concerns that the strategy could turn into a little more than a wish list.

The Institute for European Environmental Policy (IEEP) is on the same page. The sustainability think‐tank based in Brussels and London noted that the outgoing EU 2020 biodiversity strategy showed major implementation problems, especially because of lack of engagement at national level and of ad hoc legislation supporting the meeting of key targets. Therefore, “[it] can be argued that a legally binding approach to the biodiversity governance framework is urgently needed unless Member States and other key stakeholders can show greater intrinsic ownership to deliver on agreed objectives”, (https://ieep.eu/news/first‐impressions‐of‐the‐eu‐biodiversity‐strategy‐to‐2030). In addition, IEEP remarked that money is an issue, since the €20 billion figure appears more as an estimate than a certified obligation.“The intentions of the Commission are good and the strategy contains a number of measures and targets that can really make a difference. However, implementation depends critically on the member states and experiences with the Common Agricultural Policy the past decade or so have taught us that many of them are more interested in short‐term economic objectives than in safeguarding the natural wealth of their country for future generations”, commented David Kleijn, an ecologist and nature conservation expert at the Wageningen University, the Netherlands. “I think it is important that we now have an ambitious Biodiversity Strategy but at the same time I have little hope that we will be able to achieve its objectives”.

I think it is important that we now have an ambitious Biodiversity Strategy but at the same time I have little hope that we will be able to achieve its objectives.

There is further criticism against specific measures, such as the proposal of planting 3 billion trees. “To have lots of trees planted in an area does not necessarily translate into an increase of biodiversity. Biodiverse ecosystems are the result of million years of complex multi‐species interactions and evolutionary processes, which are not as easy to restore”, explained plant ecologist Susana Gómez‐González, from the University of Cádiz, Spain. Planting a large number of trees is a too simplistic approach for saving European forests from the combined effects of excessive anthropic pressure and climate change, and could even have detrimental effects (see Box 1). More emphasis should be placed instead in reducing tree harvesting in sensitive areas and in promoting natural forest renewal processes (Gómez‐González et al, 2020). “For a biodiversity strategy, increasing the number of trees, or even increasing the forest area, should not be an objective; priority should be given to the conservation and restoration of natural ecosystems, forests and non‐forests”, Gómez‐González said.In other cases, it could be difficult, if not impossible, to reach some of the goals because of lack of information. For example, one of the roadmap''s targets is to restore at least 25,000 km of Europe''s rivers back to free‐flowing state. However, the number of barriers dispersed along European rivers will probably prevent even getting close to the mark. An international research team has collected detailed information on existing instream barriers for 147 rivers in 36 European countries, coming up with the impressive figure of over 1.2 million obstacles that inevitably impact on river ecosystems, affecting the transport and dispersion of aquatic organisms, nutrients, and sediments (Belletti et al, 2020). Existing inventories mainly focused on dams and other large barriers, while, in fact, a large number of artificial structures are much smaller, such like weirs, locks, ramps, and fords. As a result, river fragmentation has been largely underestimated, and the models used to plan flow restoration might be seriously flawed. “To avoid ‘death by a thousand cuts’, a paradigm shift is necessary: to recognize that although large dams may draw most of the attention, it is the small barriers that collectively do most of the damage. Small is not beautiful”, concluded the authors (Belletti et al, 2020).

Box 1: Why many trees don''t (always) make a forestForests are cathedrals of biodiversity. They host by far the largest number of species on land, which provide food and essential resources for hundreds of millions of people worldwide. However, forests are disappearing and degrading at an alarming pace. The loss of these crucial ecosystems has given new impulses to a variety of projects aimed at stopping this devastation and possibly reversing the trend.Once it is gone, can you rebuild a forest? Many believe the answer is yes, and the obvious solution is to plant trees. Several countries have thus launched massive tree‐planting programs, notably India and Ethiopia, where 350 million trees have been planted in single day (https://www.unenvironment.org/news‐and‐stories/story/ethiopia‐plants‐over‐350‐million‐trees‐day‐setting‐new‐world‐record). The World Economic Forum has set up its own One Trillion Tree initiative (https://www.1t.org/) “to conserve, restore, and grow one trillion trees by 2030”. Launched in January last year at Davos, 1t.org was conceived as a platform for governments, companies and NGOs/civil society groups to support the UN Decade on Ecosystem Restoration (2021–2030). The initiative has been christened by renowned naturalist Jane Goodall, who commented: “1t.org offers innovative technologies which will serve to connect tens of thousands of small and large groups around the world that are engaged in tree planting and forest restoration”, (https://www.weforum.org/agenda/2020/01/one‐trillion‐trees‐world‐economic‐forum‐launches‐plan‐to‐help‐nature‐and‐the‐climate/).However, things are way more complicated than they appear: large‐scale tree planting schemes are rarely a viable solution and can even be harmful. “[A] large body of literature shows that even the best planned restoration projects rarely fully recover the biodiversity of intact forests, owing to a lack of sources of forest‐dependent flora and fauna in deforested landscapes, as well as degraded abiotic conditions resulting from anthropogenic activities”, commented Karen Holl from the University of Caliornia, Santa Cruz, and Pedro Brancalion from the University of São Paulo (Holl & Brancalion, 2020). A common problem of tree plantations, for example, is the low survival rate of seedlings, mostly because the wrong tree species are selected and due to poor maintenance after planting. Moreover, grasslands and savannas, which are often targeted for establishing new forests, are themselves treasure troves of biodiversity. Ending indiscriminate deforestation, improving the protection of existing forests, and promoting their restoration would therefore be a more efficient strategy to preserve biodiversity in the shorter term. If tree planting is indeed necessary, it should be well planned by selecting the right areas for reforestation, using suitable tree species that can maximize biodiversity, and involving local populations to maintain the plantations, Holl and Brancalion argue (Holl & Brancalion, 2020).

…even the best planned restoration projects rarely fully recover the biodiversity of intact forests, owing to a lack of sources of forest‐dependent flora and fauna in deforested landscapes…

The health of soil, where a high proportion of biodiversity is hosted, is another problem the new strategy should address in a more focused manner. “In my opinion, the EU Biodiversity Strategy is already a leap forward in terms of policy interest in soils in general and in soil biodiversity in particular. Compared with other nations/regions of the world, Europe is by far in the forefront regarding this issue”, commented Carlos António Guerra at the German Centre for Integrative Biodiversity Research (iDiv) in Leipzig, Germany, and Co‐leader of the Global Soil Biodiversity Observation Network (https://geobon.org/bons/thematic‐bon/soil‐bon/). “Nevertheless, the connection between soil biodiversity and ecological functions needs further commitments. Soils allow for horizontal integration of several policy agendas, from climate to agriculture and, very importantly, nature conservation. This is not explicit in the EU Biodiversity Strategy in regard to soils”. It remains to be seen if EU restoration plan will emphasize soil biodiversity, or consider it as a mere side effect of other initiatives, Guerra added. “A soil nature conservation plan should be proposed”, he said. “Only such a plan, that implies that current and future protected areas have to consider, describe and protect their soil biodiversity would make a significant push to help protect such a valuable resource”.More generally, research shows that the current paradigm of protection must be shifted to prevent further losses to biodiversity. In fact, an analysis of LIFE projects—a cornerstone of EU nature protection—found that conservation efforts are extremely polarized and strongly taxonomically biased (Mammola et al, 2020). From 1992 to 2018, investment in vertebrates was sixfold higher than that for invertebrates, with birds and mammals alone accounting for 72% of the targeted species and 75% of the total budget. In relative terms, investment per species for vertebrates has been 468 times higher than for invertebrates (Fig 4). There is no sound scientific reasoning behind this uneven conservation attention, but just popularity. “[T]he species covered by a greater number of LIFE projects were also those which attracted the most interest online, suggesting that conservation in the EU is largely driven by species charisma, rather than objective features”, the researchers wrote (Mammola et al, 2020).Open in a separate windowFigure 4Taxonomic bias in EU fauna protection effortsBreakdown of the number of projects (A) and budget allocation (B) across main animal groups covered by the LIFE projects (n = 835). (C) The most covered 30 species of vertebrates (out of 410) and invertebrates (out of 78) in the LIFE projects analyzed (n = 835). The vertical bar represents monetary investment and the blue scatter line the number of LIFE projects devoted to each species. Reproduced from (Mammola et al, 2020), with permission.     

Involving society in science: Reflections on meaningful and impactful stakeholder engagement in fundamental research

Open Science calls for transparent science and involvement of various stakeholders. Here are examples of and advice for meaningful stakeholder engagement. Subject Categories: Economics, Law & Politics, History & Philosophy of Science

The concepts of Open Science and Responsible Research and Innovation call for a more transparent and collaborative science, and more participation of citizens. The way to achieve this is through cooperation with different actors or “stakeholders”: individuals or organizations who can contribute to, or benefit from research, regardless of whether they are researchers themselves or not. Examples include funding agencies, citizens associations, patients, and policy makers (https://aquas.gencat.cat/web/.content/minisite/aquas/publicacions/2018/how_measure_engagement_research_saris1_aquas2018.pdf). Such cooperation is even more relevant in the current, challenging times—even apart from a global pandemic—when pseudo‐science, fake news, nihilist attitudes, and ideologies too often threaten social and technological progress enabled by science. Stakeholder engagement in research can inform and empower citizens, help render research more socially acceptable, and enable policies grounded on evidence‐based knowledge. Beyond, stakeholder engagement is also beneficial to researchers and to research itself. In a recent survey, the majority of scientists reported benefits from public engagement (Burns et al, 2021). This can include increased mutual trust and mutual learning, improved social relevance of research, and improved adoption of results and knowledge (Cottrell et al, 2014). Finally, stakeholder engagement is often regarded as an important factor to sustain public investment in the life sciences (Burns et al, 2021).

Stakeholder engagement in research can inform and empower citizens, help render research more socially acceptable and enable policies grounded on evidence‐based knowledge

Here, we discuss different levels of stakeholder engagement by way of example, presenting various activities organized by European research institutions. Based on these experiences, we propose ten reflection points that we believe should be considered by the institutions, the scientists, and the funding agencies to achieve meaningful and impactful stakeholder engagement.