The role of fear in modern societies: Our ancient fear response to new situations is not always helpful in a civilised society

The COVID‐19 pandemic highlights how our ancient fear response can be exploited for nefarious purposes with social media lending a helping hand. Subject Categories: S&S: Economics & Business, Ecology, Microbiology, Virology & Host Pathogen Interaction

The COVID‐19 pandemic has underscored more than any previous crisis how fear can be exploited by multiple actors from outright conspiracy theorists with pernicious agendas to governments seeking to maximise public compliance with lockdowns and social distancing. The crisis has also given new urgency to the debate over how to handle fake news and its rapid propagation over social media, as well as the part science should play in leading and supporting governments'' decisions.At a fundamental level, the pandemic has highlighted the balance evolution has struck between fear and its aversion, between risk taking and risk avoidance. Indeed, for many animals, fear is necessary to avoid predation or accidental death, but it must be kept in check to avoid starvation by never setting out to search for food.

At a fundamental level, the pandemic has highlighted the balance evolution has struck between fear and its aversion, between risk taking and risk avoidance.

     

The return of the seasonal flu and cold: Other diseases are set to rebound as Covid‐19 restrictions ease

While the COVID‐19 pandemic has reduced the incidence of respiratory infectious diseases, its economic repercussions have badly hit the fight against HIV and tuberculosis. Subject Categories: Economics, Law & Politics, Microbiology, Virology & Host Pathogen Interaction, Science Policy & Publishing

As restrictions and lockdowns are being relaxed in many countries, the impact of the COVID‐19 pandemic on other diseases is gaining attention. While the overall picture is diverse, it is clear that the incidence of other respiratory diseases, including seasonal influenza and common colds, has declined greatly, especially in temperate climates. On the other hand, the ongoing fight against major tropical diseases has been severely impaired as a result of attention being diverted towards COVID‐19 with grave concerns over a surge in TB cases and a delayed impact on HIV due to reduced testing.     

Strength is in engagement: The rise of an online scientific community during the COVID‐19 pandemic

Many scientists, confined to home office by COVID‐19, have been gathering in online communities, which could become viable alternatives to physical meetings and conferences. Subject Categories: S&S: Careers & Training, Methods & Resources, S&S: Ethics

As COVID‐19 has brought work and travel to a grinding halt, scientists explored new ways to connect with each other. For the gene regulation community, this started with a Tweet that quickly expanded into the “Fragile Nucleosome” online forum, a popular seminar series, and many intimate discussions connecting scientists all over the world. More than 2,500 people from over 45 countries have attended our seminars so far and our forum currently has ~ 1,000 members who have kick‐started discussion groups and mentorship opportunities. Here we discuss our experience with setting up the Fragile Nucleosome seminars and online discussion forum, and present the tools to enable others to do the same.Too often, we forget the importance of social interactions in science. Indeed, many creative ideas originated from impromptu and fortuitous encounters with peers, in passing, over lunch, or during a conference coffee break. Now, the ongoing COVID‐19 crisis means prolonged isolation, odd working hours, and less social interactions for most scientists confined to home. This motivated us to create the “Fragile Nucleosome” virtual community for our colleagues in the chromatin and gene regulation field.

… the ongoing COVID‐19 crisis means prolonged isolation, odd working hours and less social interactions for most scientists confined to home.

While the need to address the void created by the COVID‐19 pandemic triggered our actions, a large part of the international community already has had limited access to research networks in our field. Our initiative offered new opportunities though, in particular for those who have not benefited from extensive networks, showing how virtual communities can address disparities in accessibility. This should not be a stop‐gap measure during the pandemic: Once we come out from our isolation, we still need to address the drawbacks of in‐person scientific conferences/seminars, such as economic disparities, travel inaccessibility, and overlapping family responsibilities (Sarabipour, 2020). Our virtual community offers some solutions to the standing challenges (Levine & Rathmell, 2020), and we hope our commentary can help start conversations about the advantages of virtual communities in a post‐pandemic world.

… once we come out from our isolation we still need to address the drawbacks of in‐person scientific conferences/seminars, such as economic disparities, travel inaccessibility and overlapping family responsibilities…

     

A CRISPR response to pandemics?: Exploring the ethics of genetically engineering the human immune system

Ethical challenges should be addressed before gene editing is made available to improve the immune response against emerging viruses. Subject Categories: S&S: Economics & Business, Genetics, Gene Therapy & Genetic Disease, Immunology

In 1881, Louis Pasteur proved the “germ theory of disease”, namely that microorganisms are responsible for causing a range of diseases. Following Pasteur’s and Robert Koch’s groundbreaking work on pathogens, further research during the 20^th century elucidated how the immune system fends off disease‐causing microorganisms from a molecular perspective.The COVID‐19 pandemic has again focused scientific and public attention on immunology not the least owing to the race of employing vaccines to halt the spread of the virus. Although most countries have now started vaccination programs to immunize a large part of the world''s population, the process will take time, vaccines may not be available to everyone, and a number of unresolved issues remain including the potential contagiousness of vaccinated individuals and the duration of protection (Polack et al, 2020).It would therefore be extremely helpful from a public health perspective—and indeed lifesaving for those with elevated risk of developing severe course of the disease—if we could boost the human immune system by other means to better fight off SARS‐CoV‐2 and possibly other viruses. Recent studies showing that some individuals may be less susceptible to contract severe COVID‐19 depending on their genetic status support such visions (COVID‐19 Host Genetics Initiative, 2020). This could eventually inspire research projects on gene therapy with the aim of generally enhancing immunity against viral infections.

It would therefore be extremely helpful from a public health perspective […] if we could boost the human immune system by other means to better fight off SARS‐CoV‐2 …

The idea of genetically enhancing the human immune response is not new and spread from academic circles to policymakers and the general public even before the pandemic, when He Jiankui announced in November 2018 the birth of genetically edited twins who, he claimed, were resistant to HIV. The public outcry was massive, not only because He violated standards of methodological rigor and research ethics, but also because of fundamental doubts about the wisdom and legitimacy of human germline manipulation (Schleidgen et al, 2020).Somatic gene therapy has been met with a less categorical rejection, but it has also been confronted with skepticism when major setbacks or untoward events occurred, such as the death of Jesse Gelsinger during an early clinical trial for gene therapy in 1999. Nonetheless, given the drastic impact the current pandemic has on so many lives, there may be a motivation to put concerns aside. In fact, even if we managed to get rid of COVID‐19 owing to vaccines—or at least to keep its infectiousness and mortality low—another virus will appear sooner or later; an improved resistance to viral pathogens—including coronaviruses—would be an important asset.Interventions to boost the immune system could in fact make use of either germline gene editing, as has been the case of the Chinese twins, or through somatic gene editing. The first requires time and only the next generation would potentially benefit while the latter could be immediately applied and theoretically used to deal with the ongoing COVID‐19 pandemic.

Interventions to boost the immune system could in fact make use of either germline gene editing, as has been the case of the Chinese twins, or through somatic gene editing.

     

Biology lessons in times of COVID: The pandemic has forced educators to teach and instruct online with varying success and challenges

Since COVID‐19 hit last year, lecturers and professors have been exploring digital and other tools to teach and instruct their students. Subject Categories: S&S: Careers & Training, Methods & Resources

As Director of the Digital Pedagogy Lab at the University of Colorado in Denver, USA, Michael Sean Morris’ work took on new significance as the COVID‐19 pandemic hit campuses around the world. “What happened with the pandemic was a lot of people who weren''t accustomed to teaching online, or dealing with distance learning, or remote learning in any way, shape, or form, really tried to create a live classroom situation on their screen, mostly using Zoom or other similar technologies”, Morris said. “With technology now, we can do things which make us feel closer. So, we can do a Zoom; there can be synchronous chat in technologies like Slack, or discussion forums or what‐have‐you to make you feel like you''re closer, to make you feel like you''re sort of together at the same time. But the majority of online learning actually has been asynchronous, it''s been everyone coming in when they can and doing their work when they can”.Educators have been divided over the use of online learning. But this changed when a deadly pandemic forced everyone from kindergarten to university into digital spaces. Luckily, many digital tools, such as Zoom, Slack, Blackboard Collaborate, or WhatsApp, were available to enable the migration. Nonetheless, teachers, lecturers, and professors struggle to educate their students with knowledge and the hands‐on training that is paramount for teaching biology.

… teachers, lecturers and professors struggle to educate their students with knowledge and the hands‐on training that is paramount for teaching biology.

     

Bioenergetics of early life: Coupling of reaction networks and compartments may have sparked the first life forms

Living cells are powered by intricate networks of chemical reactions of thousands of molecules. Understanding how living systems emerged through the assembly of chemical processes is one of the biggest challenges in science. Subject Categories: Biotechnology & Synthetic Biology, Evolution & Ecology, Metabolism

How can chemistry turn into biology? How can living cells be built from molecules? These are fundamental questions in biology and, despite much research efforts, remain unanswered. Yet, the past two decades have seen considerable advances in our knowledge of how and which (bio)physical and (bio)chemical processes could have driven the emergence of the first living cells. These achievements have led not only to a better understanding of the molecular origins of life, but also spurred significant developments in synthetic biology, biophysics and supramolecular chemistry. Although the exact events that sparked life on Earth will quite likely remain a mystery, at least partially, exploring the chemical origins of life offers clues about our primordial past and could contribute to shaping our future.

Although the exact events that sparked life on Earth will quite likely remain a mystery […] exploring the chemical origins of life offers clues about our primordial past and could contribute to shaping our future.

     

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…

     

Lamarck redux and other false arguments against SARS‐CoV‐2 vaccination: Pseudoscientific arguments against vaccination do not stand up to scrutiny

The COVID‐19 pandemic has triggered a new bout of anti‐vaccination propaganda. These are often grounded in pseudoscience and misinterpretation of evolutionary biology. Subject Categories: Economics, Law & Politics, Microbiology, Virology & Host Pathogen Interaction, Science Policy & Publishing

Towards the end of summer of 2021, there seemed cause for cautious optimism for putting this pandemic behind us. It was clear that the route of viral transmission was airborne and not via surfaces (Goldman, 2021a), which means that masks are very efficient at reducing the spread of SARS‐CoV‐2. The number of cases in the United States and Europe were declining, and the first vaccines became available with many people lining up to get their jabs. But not all. A significant portion of the population have been refusing to get vaccinated, some of whom were fooled or encouraged by pseudoscientific misinformation propagated on the Internet.     

A call for diversity,equity, and inclusion: Highlights from the Consortium of Universities for Global Health 2021 conference

Beryne Odeny reports from the CUGH 2021 virtual conference.

The first virtual Consortium of Universities for Global Health (CUGH) 2021 conference was held in March, 2021 [1]. Two weeks of satellite symposia culminated in this highly prestigious conference, which drew an eclectic group of renowned speakers, global health leaders, program implementers, researchers, and students from across the globe. There were more than 5000 delegates from diverse disciplines including public health, politics, education, medicine, planetary health, and finance. Top of the agenda was addressing critical gaps in global health and development against the backdrop of the COVID-19 pandemic.CUGH is an organization of over 170 academic institutions and organizations throughout the world, engaged in addressing global health challenges [1]. The 2021 conference was meticulously and creatively planned as was evidenced by the dynamic virtual platform, which hosted several global leader interviews, general sessions, 40 concurrent sessions, 7 plenary sessions, over 700 poster programs, and the Pulitzer Center Film festivals–yes, movies were on the menu [2]. Best of all, the platform held up, with minimal technical difficulties. The conference agenda had curated sessions carefully customized to varying attendee interests and expertise. Participants could seamlessly and discreetly shuttle between sessions.The inaugural interviews, with Dr. Anthony Fauci of the United States and Dr. Hugo Lopez-Gatell of Mexico, set the tone with emphasis on a much-needed global response to the ongoing pandemic. “2020 was a watershed moment in Global Health,” said Dr. Fauci. The COVID-19 pandemic indiscriminately unveiled the fragility of health systems in high income countries (HIC) and low- and middle-income countries (LMICs) alike. He unpacked the origins, evolution, and contention around current public health mandates such as mask wearing. He discussed vaccines–exploring vaccine manufacturing in LMICs, open patents, implications of emerging COVID-19 variants, and advice on curbing the prevailing vaccine infodemic (i.e., pandemic of misinformation) [2–4]. Dr. Lopez-Gatell described the pandemic as a “massive social event” fueled by deficits in health systems, politics, and governance, and by the growing tide of non-communicable diseases (NCDs) [5]. In a brief video recording, Dr. Tedros Adhanom Ghebreyesus, WHO’s Director-General, implored global partners to sign the COVID-19 Declaration on vaccine equity which he termed “the defining challenge of 2021” [6].The post-pandemic forecast for global health was dire. COVID-19 has disrupted decades of progress toward attainment of Universal Health Care (UHC) and it will be doubly difficult to restore, by 2035, health indicators to their levels prior to the pandemic [7–9]. A modelling study by Dr. Wenhui Mao of Duke University showed that, even in the most optimistic scenario, it may not be possible to achieve UHC in the next decade without breakthrough technologies and exceptional political commitment. Among four critical indicators of TB mortality rate, HIV mortality rate, under 5 mortality ratio, and maternal mortality ratio, Dr. Mao found that only the HIV indicator had potential for recovery by 2035.The metaphorical elephant in the room, and now its opposite, “the elephant not in the room”, respectively encapsulate two themes: neocolonialism and equity, especially for marginalized groups. Neocolonialism–a progeny of colonialism–resulting from sustained global North-South power imbalances, manifests in low prioritization of the most pressing challenges and diseases in LMICs. Equity was a poignant theme across the CUGH sessions and satellite symposia. Sessions were dedicated to exploring the hegemonic structures and institutional systems that underpin adverse health system performance and outcomes. A sampling of wide-ranging topics on global challenges exacerbated by neocolonialism and inequities comprised: a) elevating the visibility and power of researchers in LMICs, including fragile and conflict affected settings, through equitable access to funding, research autonomy and leadership, access to scholarly publishing, and senior authorship of research articles [10]; b) training next-generation global health professionals and building capacity for resource-challenged settings to address NCDs, including cancer care [5]; c) the Latin American and Caribbean health crises drawn by social gradients and inequities; d) navigating conflicting interests between public health and the corporate food industry; e) the dearth and role of women leaders in global health and in the COVID-19 response; f) the disproportionate incidence of HIV in adolescent girls and young women in sub-Saharan Africa (SSA) [11]; g) the disparate burden of neonatal mortality in LMICs and marginalized communities within HIC; and h) leveraging the power of film to evoke emotion and induce a consolidated response to global challenges. In addition, various facets of the human ecosystem were unpacked including climate change, biodiversity preservation, political climate, and the global kleptocracy, with attention to their implications for the health of the most marginalized populations.Despite the highlighted issues, there is, potentially, a panacea for these inequities and challenges. One speaker, Dr. Lisa Adams of Dartmouth College, proposed a paradigm shift that summarized a wide range of deliberations–“moving global health out of the realm of charity into global citizenship, security, human rights, equal partnership, and interdisciplinary collaboration between LMICs and HICs.” Moving forward, more deliberate effort should be given to some elements. First, rethinking governance and funding at a global level while promoting the autonomy of LMICs and conflict-affected settings to drive their health agenda–independent from HIC interests. Bringing the elephant into the room by making equal space for LMICs to set the agenda at global tables of discussion around funding, research, and development will be pivotal to dismantling neocolonialism. Furthermore, funders and partners should work with in-country systems in LMICs as opposed to bypassing them. This is essential to building resilient health systems unified at national levels to allow for cross-discipline collaborations and swift responses to health threats. Rwanda is a laudable example, having swiftly remodeled its existing health systems including routine electronic information systems for nationwide COVID-19 surveillance, testing, contact tracing, and vaccination. Second, investing time to build trusting relationships between researchers or implementers and policy makers by upholding a participatory approach to research and implementation of evidence-based practices. This is essential globally, to support development of global public goods such as vaccines, free from market dynamics and aimed at universal and equitable access. Third, introduce policies that engage economies to produce with less fragmentation of nature and reduced pollution. These include protected area management, financing of nature-positive projects, and conservationist work for natural capital preservation. Global and public health practitioners need to educate and empower citizens to choose healthy and ecologically sustainable consumption practices. Fourth, promoting development of novel technologies for preventing HIV infection, such as broadly neutralizing antibodies, could overturn the unequal burden of HIV in adolescents and young women in SSA. Finally, HIC have a lot they can learn from LMICs. COVID-19 evidently demonstrated that a country’s Global Health Security Index ranking is not necessarily commensurate to its degree of success in handling pandemics, among other public health threats [8,12,13].Throughout the conference, it was apparent that equity and collectivity in global health are necessary–not optional. Dr. Elvin Geng of Washington University, St. Louis remarked that the path to equity should be measurable with routinely incorporated metrics that track interventions to redress inequity and foster accountability. To achieve this, the tools of implementation science can be employed at both regional and global levels [14]. Overall, the remarkable interlacing of diverse disciplinary sessions at CUGH 2021 not only brought to light pressing world problems but equipped participants with a wellspring of potential remedies and collaborative opportunities. The panelists and speakers effectively portrayed the layered and multidimensional nature of global challenges underscoring the need for similarly multifaceted solutions. CUGH 2021 sparked thought-provoking discourse around global health strategies and re-invigorated the collective passion of global health experts, novices, and everyone in between, to build forward better.     

USP26: a genetic risk factor for sperm X‐Y aneuploidy

Segregation of the largely non‐homologous X and Y sex chromosomes during male meiosis is not a trivial task, because their pairing, synapsis, and crossover formation are restricted to a tiny region of homology, the pseudoautosomal region. In humans, meiotic X‐Y missegregation can lead to 47, XXY offspring, also known as Klinefelter syndrome, but to what extent genetic factors predispose to paternal sex chromosome aneuploidy has remained elusive. In this issue, Liu et al (2021) provide evidence that deleterious mutations in the USP26 gene constitute one such factor.Subject Categories: Cell Cycle, Development & Differentiation, Molecular Biology of Disease

Analyses of Klinefelter syndrome patients and Usp26‐deficient mice have revealed a genetic influence on age‐dependent sex chromosome missegregation during male meiosis.

Multilayered mechanisms have evolved to ensure successful X‐Y recombination, as a prerequisite for subsequent normal chromosome segregation. These include a distinct chromatin structure as well as specialized proteins on the pseudoautosomal region (Kauppi et al, 2011; Acquaviva et al, 2020). Even so, X‐Y recombination fails fairly often, especially in the face of even modest meiotic perturbations. It is perhaps not surprising then that X‐Y aneuploidy—but not autosomal aneuploidy—in sperm increases with age (Lowe et al, 2001; Arnedo et al, 2006), as does the risk of fathering sons with Klinefelter syndrome (De Souza & Morris, 2010).Klinefelter syndrome is one of the most common aneuploidies in liveborn individuals (Thomas & Hassold, 2003). While most human trisomies result from errors in maternal chromosome segregation, this is not the case for Klinefelter syndrome, where the extra X chromosome is equally likely to be of maternal or paternal origin (Thomas & Hassold, 2003; Arnedo et al, 2006). Little is known about genetic factors in humans that predispose to paternal XY aneuploidy, i.e., that increase the risk of fathering Klinefelter syndrome offspring. The general notion has been that paternally derived Klinefelter syndrome arises stochastically. However, fathers of Klinefelter syndrome patients have elevated rates of XY aneuploid sperm (Lowe et al, 2001; Arnedo et al, 2006), implying a persistent defect in spermatogenesis in these individuals rather than a one‐off meiotic error.To identify possible genetic factors contributing to Klinefelter syndrome risk, Liu et al (2021) performed whole‐exome sequencing in a discovery cohort of > 100 Klinefelter syndrome patients, followed by targeted sequencing in a much larger cohort of patients and controls, as well as Klinefelter syndrome family trios. The authors homed in on a mutational cluster (“mutated haplotype”) in ubiquitin‐specific protease 26 (USP26), a testis‐expressed gene located on the X chromosome. Effects of this gene’s loss of function (Usp26‐deficient mice) on spermatogenesis have recently been independently reported by several laboratories and ranged from no detectable fertility phenotype (Felipe‐Medina et al, 2019) to subfertility/sterility associated with both meiotic and spermiogenic defects (Sakai et al, 2019; Tian et al, 2019). With their Klinefelter syndrome cohort findings, Liu et al (2021) also turned to Usp26 null mice, paying particular attention to X‐Y chromosome behavior and—unlike earlier mouse studies—including older mice in their analyses. They found that Usp26‐deficient animals often failed to achieve stable pairing and synapsis of X‐Y chromosomes in spermatocytes, produced XY aneuploid sperm at an abnormally high frequency, and sometimes also sired XXY offspring. Importantly, these phenotypes only occurred at an advanced age: XY aneuploidy was seen in six‐month‐old, but not two‐month‐old Usp26‐deficient males. Moreover, levels of spindle assembly checkpoint (SAC) proteins also reduced in six‐month‐old males. Thus, in older Usp26 null mice, the combination of less efficient X‐Y pairing and less stringent SAC‐mediated surveillance of faithful chromosome segregation allows for sperm aneuploidy, providing another example of SAC leakiness in males (see Lane & Kauppi, 2019 for discussion).Liu et al’s analyses shed some light on what molecular mechanisms may be responsible for the reduced efficiency of X‐Y pairing and synapsis in Usp26‐deficient spermatocytes. USP26 codes for a deubiquitinating enzyme that has several substrates in the testis. Because USP26 prevents degradation of these substrates, their levels should be downregulated in Usp26 null testes. Liu et al (2021) show that USP26 interacts with TEX11, a protein required for stable pairing and normal segregation of the X and Y chromosomes in mouse meiosis (Adelman & Petrini, 2008). USP26 can de‐ubiquitinate TEX11 in vitro, and in Usp26 null testes, TEX11 was almost undetectable. It is worth noting that USP26 has several other known substrates, including the androgen receptor (AR), and therefore, USP26 disruption likely contributes to compromised spermatogenesis via multiple mechanisms. For example, AR signaling‐dependent hormone levels are misregulated in Usp26 null mice (Tian et al, 2019).The sex chromosome phenotypes observed in Usp26 null mice predict that men with USP26 mutations may be fertile, but producing XY aneuploid sperm at an abnormally high frequency, and that spermatogenic defects should increase with age (Fig 1). These predictions were testable, because the mutated USP26 haplotype, present in 13% of Klinefelter syndrome patients, was reasonably common also in fertile men (7–10%). Indeed, sperm XY aneuploidy was substantially higher in fertile men with the mutated USP26 haplotype than in those without USP26 mutations. Some mutation carriers produced > 4% aneuploid sperm. Moreover, age‐dependent oligospermia was also found associated with the mutated USP26 haplotype.Open in a separate windowFigure 1Mutated USP26 as genetic risk factor for age‐dependent X‐Y defects in spermatogenesisMouse genetics demonstrate that deleterious USP26 mutations lead to less‐efficient X‐Y pairing and recombination with advancing age. Concomitant decrease of spindle assembly checkpoint (SAC) protein levels leads to less‐efficient elimination of metaphase I spermatocytes that contain misaligned X and Y chromosomes. This allows for the formation of XY aneuploid sperm in older individuals and subsequently increased age‐dependent risk for fathering Klinefelter syndrome (KS) offspring, two correlates also observed in human USP26 mutation carriers. At the same time, oligospermia/subfertility also increases with advanced age in both Usp26‐deficient mice and USP26 mutation‐carrying men, tempering Klinefelter syndrome offspring risk but also decreasing fecundity.As indicated by its prevalence in the normal control population, the USP26 mutated haplotype is not selected against in the human population. With > 95% of sperm in USP26 mutation carriers having normal haploid chromosomal composition, the risk of producing (infertile) Klinefelter syndrome offspring remains modest, likely explaining why USP26 mutant alleles are not eliminated. Given that full Usp26 disruption barely affects fertility of male mice during their prime reproductive age (Felipe‐Medina et al, 2019; Tian et al, 2019; Liu et al, 2021), there is little reason to assume strong negative selection against USP26 variants in humans. USP26 as the first‐ever genetic risk factor predisposing to sperm X‐Y aneuploidy and paternal origin Klinefelter syndrome offspring in humans, as uncovered by Liu et al, may be just one of many. 90% of Liu et al’s Klinefelter syndrome cases were not associated with USP26 mutations. But even in the age of genomics, discovery of Klinefelter syndrome risk factors is not straightforward, since most sperm of risk mutation carriers will not be XY aneuploid and thus not give rise to Klinefelter syndrome offspring. In addition, as Usp26 null mice demonstrate, both genetic and non‐genetic modifiers impact on penetrance of the XY aneuploidy phenotype: Spermatogenesis in the absence of Usp26 was impaired in the DBA/2 but not the C57BL/6 mouse strain background (Sakai et al, 2019), and in older mice, there was substantial inter‐individual variation in the severity of the X‐Y defect (Liu et al, 2021). In human cohorts, genetic and non‐genetic modifiers are expected to blur the picture even more.Future identification of sex chromosome aneuploidy risk factors has human health implications beyond Klinefelter syndrome. Firstly, XXY incidence is not only relevant for Klinefelter syndrome livebirths—it also contributes to stillbirths and spontaneous abortions, at a 4‐fold higher rate than to livebirths (Thomas & Hassold, 2003). Secondly, persistent meiotic X‐Y defects can, over time, result in oligospermia and even infertility. Since the mean age of first‐time fathers is steadily rising and currently well over 30 years in many Western countries, age‐dependent spermatogenic defects will be of ever‐increasing clinical relevance.     

Postpartum mental illness during the COVID-19 pandemic: a population-based,repeated cross-sectional study

BACKGROUND:It is unclear whether the clinical burden of postpartum mental illness has increased during the COVID-19 pandemic. We sought to compare physician visit rates for postpartum mental illness in Ontario, Canada, during the pandemic with rates expected based on prepandemic patterns.METHODS:In this population-based, repeated cross-sectional study using linked health administrative databases in Ontario, Canada, we used negative binomial regression to model expected visit rates per 1000 postpartum people for March–November 2020 based on prepandemic data (January 2016–February 2020). We compared observed visit rates to expected visit rates for each month of the pandemic period, generating absolute rate differences, incidence rate ratios (IRRs) and their 95% confidence intervals (CIs). The primary outcome was a visit to a primary care physician or a psychiatrist for any mental disorder. We stratified analyses by maternal sociodemographic characteristics.RESULTS:In March 2020, the visit rate was 43.5/1000, with a rate difference of 3.11/1000 (95% CI 1.25–4.89) and an IRR of 1.08 (95% CI 1.03–1.13) compared with the expected rate. In April, the rate difference (10.9/1000, 95% CI 9.14–12.6) and IRR (1.30, 95% CI 1.24–1.36) were higher; this level was generally sustained through November 2020. From April–November, we observed elevated visit rates across provider types and for diagnoses of anxiety, depressive and alcohol or substance use disorders. Observed increases from expected visit rates were greater for people 0–90 days postpartum compared with 91–365 days postpartum; increases were small among people living in low-income neighbourhoods. Public health units in the northern areas of the province did not see sustained elevations in visit rates after July; southern health units had elevated rates through to November.INTERPRETATION:Increased visits for mental health conditions among postpartum people during the first 9 months of the COVID-19 pandemic suggest an increased need for effective and accessible mental health care for this population as the pandemic progresses.

Postpartum mental illness affects as many as 1 in 5 mothers,¹ and can result in maternal suffering and diminished functioning.² Related impaired mother–infant interactions are linked to poor social, cognitive and behavioural outcomes in children across their lifespan.³ When mental illness becomes chronic and recurrent, its effects can extend to the entire family and across generations.⁴ With emergence of the novel coronavirus (SARS-CoV-2), the World Health Organization declared a global COVID-19 pandemic on Mar. 11, 2020. Globally, efforts to contain the virus have led to widespread travel restrictions, physical distancing and work limitations, causing broad social and financial disruption that has been associated with substantial mental health effects.^5,6During the COVID-19 pandemic, people have been reporting concerns about postpartum infection,⁷ and difficulty accessing the extended postpartum social support networks and key community programs that protect against mental illness, such as home visits from public health nurses, breastfeeding clinics and support groups, owing to public health measures.⁸ In Canadian surveys, about 50% of pregnant people reported psychological distress in spring 2020,⁹ and alcohol use increased among women, particularly among those with young children.¹⁰ Whether this represents an increased clinical burden of mental illness or need for care is unknown.Using routinely collected health care data from Ontario, Canada, (population of about 14.6 million), we aimed to examine whether rates of maternal visits to physicians for postpartum mental illness from March to November 2020 differed from expected visit rates based on pre-COVID-19 patterns, and to identify variation by provider type, clinical diagnosis, postpartum timing, parity, income, ethnicity and region of residence.     

Context matters: On the road to responsible biosafety technologies in synthetic biology

Biosafety is a major challenge for developing for synthetic organisms. An early focus on application and their context could assist with the design of appropriate genetic safeguards. Subject Categories: Synthetic Biology & Biotechnology, S&S: Economics & Business

One of the goals of synthetic biology is the development of robust chassis cells for their application in medicine, agriculture, and the food, chemical and environmental industries. These cells can be streamlined by removing undesirable features and can be augmented with desirable functionalities to design an optimized organism. In a direct analogy with a car chassis, they provide the frame for different modules or “plug‐in” regulatory networks, metabolic pathways, or safety elements. In an effort to ensure a safe microbial chassis upfront, safety measures are implemented as genetic safeguards to limit risks such as unwanted cellular proliferation or horizontal gene transfer. Examples of this technology include complex genetic circuits, sophisticated metabolic dependencies (auxotrophies), and altered genomes (Schmidt & de Lorenzo, 2016; Asin‐Garcia et al, 2020). Much like seat belts or airbags in cars, these built‐in measures increase the safety of the chassis and of any organisms derived from it. Indeed, when it comes to safety, synthetic biology can still learn from a century‐old technology such as cars about the significance of context for the development of biosafety technologies.Every car today has seat belts installed by default. Yet, seat belts were not always a standard component; in fact, they were not even designed for cars to begin with. The original 2‐point belts were first used in aviation and only slowly introduced for motorized vehicles. Only after some redesign, the now‐common 3‐point car seat belts would become the life‐saving equipment that they are today. A proper understanding of the context of their application was therefore one of the crucial factors for their success and wide adoption. Context matters: It provides meaning for and defines what a technological application is best suited for. What was true for seat belts may be also true for biosafety technologies such as genetic safeguards.

… when it comes to safety, synthetic biology can still learn from a century‐old technology such as cars about the significance of context for the development of biosafety technologies.

Society has a much higher awareness of technology’s risks compared to the early days of cars. Society today requires that technological risks are anticipated and assessed before an innovation or its applications are widely deployed. In addition, society increasingly demands that research and innovation take into account societal needs and values. This has led to, among others, the Responsible Research and Innovation (RRI; von Schomberg, 2013) concept that has become prominent in European science policy. In a nutshell, RRI requires that innovative products and processes align with societal needs, expectations, and values in consultation with stakeholders. RRI and similar frameworks suggest that synthetic biology must anticipate and respond not only to risks, but also to societal views that frame its evaluation and risk assessment.     

Nadeshiko revisited: The situation of women in Japanese research and the measures taken to increase their representation

The Japanese government has enacted measures to increase the representation of women in research; the situation is improving but there is still much to do. Subject Categories: S&S: Careers & Training, S&S: History & Philosophy of Science, S&S: Ethics

Japanese parents are understandably proud that their 15‐year‐old boys and girls do equally well in the Programme for International Student Assessment (PISA). In 2018, Japanese girls ranked second and third in Science and Mathematics, respectively, among the 40 participating countries, and Japanese boys ranked first in both subjects (https://data.oecd.org/japan.htm). However, Japanese boys and girls face different expectations and take different career paths as they grow up. In this commentary, we discuss how this affects the situation of female scientists in Japan. We start with the proportion of women in academic research and describe the problems they currently face. We underscore the tremendous measures developed and administered by the Japanese government to increase the participation and proportion of women in research. Finally, we mention an emerging grassroots initiative that is currently being implemented. We suggest that female empowerment may be one of the most promising strategies to improve the situation of women in the Japanese scientific community.     

A population-based analysis of the impact of the COVID-19 pandemic on common abdominal and gynecological emergency department visits

BACKGROUND:Reduced use of the emergency department during the COVID-19 pandemic may result in increased disease acuity when patients do seek health care services. We sought to evaluate emergency department visits for common abdominal and gynecologic conditions before and at the beginning of the pandemic to determine whether changes in emergency department attendance had serious consequences for patients.METHODS:We conducted a population-based analysis using administrative data to evaluate the weekly rate of emergency department visits pre-COVID-19 (Jan. 1–Mar. 10, 2020) and during the beginning of the COVID-19 pandemic (Mar. 11–June 30, 2020), compared with a historical control period (Jan. 1–July 1, 2019). All residents of Ontario, Canada, presenting to the emergency department with appendicitis, cholecystitis, ectopic pregnancy or miscarriage were included. We evaluated weekly incidence rate ratios (IRRs) of emergency department visits, management strategies and clinical outcomes.RESULTS:Across all study periods, 39 691 emergency department visits met inclusion criteria (40.2 % appendicitis, 32.1% miscarriage, 21.3% cholecystitis, 6.4% ectopic pregnancy). Baseline characteristics of patients presenting to the emergency department did not vary across study periods. After an initial reduction in emergency department visits, presentations for cholecystitis and ectopic pregnancy quickly returned to expected levels. However, presentations for appendicitis and miscarriage showed sustained reductions (IRR 0.61–0.80), with 1087 and 984 fewer visits, respectively, after the start of the pandemic, relative to 2019. Management strategies, complications and mortality rates were similar across study periods for all conditions.INTERPRETATION:Although our study showed evidence of emergency department avoidance in Ontario during the first wave of the COVID-19 pandemic, no adverse consequences were evident. Emergency care and outcomes for patients were similar before and during the pandemic.

Avoidance of the emergency department for conditions that may require urgent surgery has been a global concern during the COVID-19 pandemic, and could result in higher case severity and morbidity.^1–3 Resource constraints and provider concerns around the safety of surgery^4–6 may influence rates of nonoperative management for abdominal and gynecological emergencies,⁷ even when existing nonoperative options are not optimal. Limited data suggest that patients with appendicitis and cholecystitis, the 2 most common abdominal emergencies that routinely require operative management,^8,9 may be more likely to avoid the hospital,¹⁰ present with more severe illness^9,10 and be managed nonoperatively during the pandemic, with uncertain consequences for patient outcomes.^10–13 Similarly, the management of early pregnancy complications (i.e., miscarriage and ectopic pregnancy) may be medical or surgical, depending on patient preference and pregnancy characteristics (e.g., stability, gestational age).¹⁴ Up to 80% of women experiencing miscarriage routinely access emergency services; however, there are concerns that women requiring emergency care for miscarriages are avoiding the emergency department.¹⁵ Reduced access to emergency care for early pregnancy complications may result in more adverse outcomes; a study in Italy found an increased rate of ruptured ectopic pregnancy in the early months of the pandemic.¹⁶We sought to characterize the impact of COVID-19 on emergency department visits for and management of appendicitis, cholecystitis, miscarriage and ectopic pregnancy. We aimed to determine if there was a difference in the rate of patients presenting to the emergency department before and during the pandemic, whether a reduction in emergency department visits for these conditions resulted in adverse patient outcomes and whether the proportion of patients undergoing operative management differed before and during the pandemic.     

COVID‐19 and the gain of function debates: Improving biosafety measures requires a more precise definition of which experiments would raise safety concerns

The COVID‐19 pandemic has rekindled debates about gain‐of‐function experiments. This is an opportunity to clearly define safety risks and appropriate countermeasures. Subject Categories: Economics, Law & Politics, Microbiology, Virology & Host Pathogen Interaction, Science Policy & Publishing

The so‐called “gain of function” research has been recently debated in the context of viral research on coronaviruses and whether it is too risky to undertake such experiments. However, the meaning of “gain of function” or “GOF” in a science policy context has changed over time. The term was originally coined to describe two controversial research projects on H5N1 avian influenza virus and was later applied to specific experiments on coronavirus. Subsequent policies and discussions have attempted to define GOF in different ways, but no single definition has been widely accepted by the community. The fuzzy and imprecise nature of the term has led to misunderstandings and has hampered discussions on how to properly assess the benefit of such experiments and biosafety measures.

The fuzzy and imprecise nature of the term GOF has led to misunderstandings and has hampered discussions on how to properly assess the benefit of such experiments and biosafety measures

     

Transgenerational epigenetic information through the sperm: Sperm cells not just merely supply half of the genome for new life; they also seem to transmit additional information via epigenetic modifications

The biological cause for the increase in Autism Spectrum Disorder may be fathers’ older age and the epigenetic marks it leaves on sperm cells. Subject Categories: Chromatin, Epigenetics, Genomics & Functional Genomics, Development & Differentiation, Ecology

COVID‐19 is not the only pandemic that is affecting an increasing number of people; autism spectrum disorder (ASD) is another ongoing pandemic that has attracted much less attention despite the fact that its prevalence is rapidly increasing. Between 1975 and 2009, the frequency of ASD in the United States increased from 1/5,000 to 1/110, and the US Centers for Disease Control and Prevention recently reported an incidence as high as 1/54 (see “Further reading”). This is not confined to the United States of course but the same trend can be observed in other countries as well. One possible explanation for this dramatic increase in ASD is the change of diagnostic criteria. These were established in the 1980s and have since been expanded to include milder forms of autism. Along with more public awareness of ASD and more cases being recognized as such, this would explain, at least in part, the increasing number of affected children, but social and diagnostic factors are not sufficient to explain the rise of ASD: there must also be biological factors at play. Indeed, various epidemiological studies suggest that the age of the parents, in particular the father’s age, is an important risk factor.The age at childbirth is related to socioeconomic issues: longer education or higher costs for raising and educating children correlate with older parental age. In addition, assisted reproductive technologies are further increasing the age of birth as this helps women to delay motherhood until into their late 30s or even 40s. However, as both reproductive capacity and the quality of germline cells decline with age, older age at childbirth is associated with lower pregnancy rates, increased risk of miscarriage, and higher risk of various diseases and disorders for the children.     

Konnichiwa: Japanese scientists and their struggle to speak English: More research careers in Japan need less English

Japanese students’ seeming low proficiency of English is not caused by lack of efforts to internationalize, but rather changing career preferences. Subject Categories: S&S: Careers & Training, S&S: Economics & Business, S&S: Ethics

It seems every generation of academics complains about the poor skills of their incoming students: “They are lazy. Unprepared. Spoiled”. In fact, older people lamenting about the perceived faults and shortcomings of the next generation is probably as old as human civilization itself (Protzko & Schooler, 2019). Professors in Japan are no different in claiming that their students lack many skills, including a sufficient proficiency in speaking English.However, when the same observation is made by an outsider, such as the Chief Editor of this journal, it deserves more consideration. At a meeting of the Molecular Biology Society of Japan (MBSJ), Bernd Pulverer was struck by how effortlessly senior Japanese scientists engaged in discussions, whereas their junior colleagues appeared intimidated by the prospect of speaking aloud in English. The experience left the editor worried if there were a generation gap in communication skills that could hamper international collaborations.While English has long been a primary language for science, it has only recently become the primary language. Consider the Solvay Conference in 1927, epitomized by the photo of legendary scientists such as Einstein, Curie, and Bohr, which was a Babylonian debate. Even in the 1990s, the University of Toronto encouraged students in its mathematics program to study French, German, or Russian. Today, however, anyone aspiring to become a scientist is obliged to have a strong grasp of the English language, a point that is not lost on Japanese students.     

Reply to Bronstein and Vinogradov

The response by the author. Subject Categories: S&S: Economics & Business, S&S: Ethics

I thank Michael Bronstein and Sophia Vinogradov for their interest and comments. I would like to respond to a few of their points.First, I agree with the authors that empirical studies should be conducted to validate any approaches to prevent the spread of misinformation before their implementation. Nonetheless, I think that the ideas I have proposed may be worth further discussion and inspire empirical studies to test their effectiveness.Second, the authors warn that informing about the imperfections of scientific research may undermine trust in science and scientists, which could result in higher vulnerability to online health misinformation (Roozenbeek et al, 2020; Bronstein & Vinogradov, 2021). I believe that transparency about limitations and problems in research does not necessarily have to diminish trust in science and scientists. On the contrary, as Veit et al put it, “such honesty… is a prerequisite for maintaining a trusting relationship between medical institutions (and practitioners) and the public” (Veit et al, 2021). Importantly, to give an honest picture of scientific research, information about its limitations should be put in adequate context. In particular, the public also should be aware that “good science” is being done by many researchers; we do have solid evidence of effectiveness of many medical interventions; and efforts are being taken to address the problems related to quality of research.Third, Bronstein and Vinogradov suggest that false and dangerous information should be censored. I agree with the authors that “[c]ensorship can prevent individuals from being exposed to false and potentially dangerous ideas” (Bronstein & Vinogradov, 2021). I also recognize that some information is false beyond any doubt and its spread may be harmful. What I am concerned about are, among others, the challenges related to defining what is dangerous and false information and limiting censorship only to this kind of information. For example, on what sources should decisions to censor be based and who should make such decisions? Anyone, whether an individual or an organization, with a responsibility to censor information will likely not only be prone to mistakes, but also to abuses of power to foster their interests. Do the benefits we want to achieve by censorship outweigh the potential risks?Fourth, we need rigorous empirical studies examining the actual impact of medical misinformation. What exactly are the harms we try to protect against and what is their scale? This information is necessary to choose proportionte and effective measures to reduce the harms. Bronstein and Vinogradov give an example of a harm which may be caused by misinformation—an increase in methanol poisoning in Iran. Yet, as noticed by the authors, misinformation is not the sole factor in this case; there are also cultural and other contexts (Arasteh et al, 2020; Bronstein & Vinogradov, 2021). Importantly, the methods of studies exploring the effects of misinformation should be carefully elaborated, especially when study participants are asked to self‐report. A recent study suggests that some claims about the prevalence of dangerous behaviors, such as drinking bleach, which may have been caused by misinformation are largely exaggerated due to the presence of problematic respondents in surveys (preprint: Litman et al, 2021).Last but not least, I would like to call attention to the importance of how veracity of information is determined in empirical studies on misinformation. For example, in a study of Roozenbeek et al, cited by Bronstein and Vinogradov, the World Health Organization (WHO) was used as reliable source of information, which raises questions. For instance, Roozenbeek et al (2020) used a statement “the coronavirus was bioengineered in a military lab in Wuhan” as an example of false information, relying on the judgment of the WHO found on its “mythbusters” website (Roozenbeek et al, 2020). Yet, is there a solid evidence to claim that this statement is false? At present, at least some scientists declare that we cannot rule out that the virus was genetically manipulated in a laboratory (Relman, 2020; Segreto & Deigin, 2020). Interestingly, the WHO also no longer excludes such a possibility and has launched an investigation on this issue (https://www.who.int/health‐topics/coronavirus/origins‐of‐the‐virus, https://www.who.int/emergencies/diseases/novel‐coronavirus‐2019/media‐resources/science‐in‐5/episode‐21‐‐‐covid‐19‐‐‐origins‐of‐the‐sars‐cov‐2‐virus); the information about the laboratory origin of the virus being false is no longer present on the WHO “mythbusters” website (https://www.who.int/emergencies/diseases/novel‐coronavirus‐2019/advice‐for‐public/myth‐busters). Against this backdrop, some results of the study by Roozenbeek et al (2020) seem misleading. In particular, the perception of the reliability of the statement about bioengineered virus by study participants in Roozenbeek et al (2020) does not reflect the susceptibility to misinformation, as intended by the researchers, but rather how the respondents perceive reliability of uncertain information.I hope that discussion and research on these and related issues will continue.     

Discussions on the quality of antibodies are no reason to ban animal immunization

Debates about the source of antibodies and their use are confusing two different issues. A ban on life immunization would have no repercussions on the quality of antibodies. Subject Categories: S&S: Economics & Business, Methods & Resources, Chemical Biology

There is an ongoing debate on how antibodies are being generated, produced and used (Gray, 2020; Marx, 2020). Or rather, there are two debates, which are not necessarily related to each other. The first one concerns the quality of antibodies used in scientific research and the repercussions for the validity of results (Bradbury & Pluckthun, 2015). The second debate is about the use of animals to generate and produce antibodies. Although these are two different issues, we observe that the debates have become entangled with arguments for one topic incorrectly being used to motivate the other and vice versa. This is not helpful, and we should disentangle the knot.Polyclonal antibodies are being criticized because they suffer from cross‐reactivity, high background and batch‐to‐batch variation (Bradbury & Pluckthun, 2015). Monoclonal antibodies produced from hybridomas are criticized because they often lack specificity owing to genetic heterogeneity introduced during hybridoma generation that impairs the quality of the monoclonals (Bradbury et al, 2018). These are valid criticisms and producing antibodies in a recombinant manner will, indeed, help to improve quality and specificity. But a mediocre antibody will remain a mediocre antibody, no matter how it is produced. Recombinant methods will just produce a mediocre antibody more consistently.Getting a good antibody is not easy and much depends on the nature and complexity of the antigen. And low‐quality antibodies are often the result of poor screening, poor quality control, incomplete characterization and the lack of international standards. Nevertheless, the technologies to ensure good selection and to guarantee consistent quality are much more advanced than a decade ago, and scientists and antibody producers should implement these to deliver high‐quality antibodies. Whether antibodies are generated by animal immunization or from naïve or synthetic antibody libraries is less relevant; they can all be produced recombinantly, and screening and characterization are needed in all cases to determine quality, and if the antibody is fit for purpose.But criticisms on the quality of many antibodies and pleas for switching to recombinant production of antibodies cannot be mixed up with a call to ban animal immunization. The EU Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) recently published a recommendation to stop using animals for generating and producing antibodies for scientific, diagnostic and even therapeutic applications (EURL ECVAM, 2020). This recommendation is mainly supported by scientists who seem to be biased towards synthetic antibody technology for various reasons. Their main argument is that antibodies derived from naïve or synthetic libraries are a valid (and exclusive) alternative. But are they?One can certainly select antibodies from non‐immune libraries, and, depending on the antigen and the type of application, these antibodies can be fit for purpose. In fact, a few of such antibodies have made it to the market as therapeutics, Adalimumab (Humira®) being a well‐known example. But up to now, the vast majority of antibodies continues to come from animal immunization (Lu et al, 2020). And there is a good reason for that. It is generally possible to generate a few positive hits in a naïve/synthetic library; and the more diverse the library, the more hits one is likely to get. But many decades of experience with immunization of animals—especially when they are outbred—shows that they generate larger amounts of antibodies with superior properties. And the more complex your antigen is, the more the balance swings towards animal immunization if you want to have a guarantee for success.There are different factors at work here. First, the immune system of mammals has evolved over millions of years to efficiently produce excellent antibodies against a very diverse range of antigens. Second, presenting the antigen multiple times in its desired (native) conformation to the animal immune system exploits the natural maturation process to fine‐tune the immune response against particular qualities. Another factor is that in vivo maturation seems to select against negative properties such as self‐recognition and aggregation. It also helps to select for important properties that go beyond mere molecular recognition (Jain et al, 2017). In industrial parlance, antibodies from animal immunization are more “developable” and have favourable biophysical properties (Lonberg, 2005). Indeed, the failure rate for antibodies selected from naïve or synthetic libraries is significantly higher.Of course, the properties of synthetic antibodies selected from non‐immune libraries can be further matured in vitro, for example by light chain shuffling or targeted mutagenesis of the complementarity determining region (CDR). While this method has become more sophisticated over the years, it remains a very complex and iterative process without guarantee that it produces a high‐quality antibody.Antibodies are an ever more important tool in scientific research and a growing area in human and veterinary therapeutics. Major therapeutic breakthroughs in immunology and oncology in the past decades are based on antibodies (Lu et al, 2020). The vast majority of these therapeutic antibodies were derived from animals. An identical picture appears when you look at the antibodies in fast‐track development to combat the current COVID‐19 crisis: again, the vast majority are either derived from patients or from animal immunizations. The same holds true for antibodies that are used in diagnostics and epidemiologic studies for COVID‐19.It is for that reason that we need the tools and methods that guarantee antibodies of the highest quality and provide the best chance for success. The COVID‐19 pandemic is only one illustration of this need. If we block access to these tools, both scientific research and society at large will be negatively impacted. We therefore should not limit ourselves to naïve and synthetic libraries. Animal immunization remains an inevitable method that needs to stay. But we all agree that these immunizations must be performed under best practice to further reduce the harm to animals.