Biosafety in DIY‐bio laboratories: from hype to policy: Discussions about regulating DIY biology tend to ignore the extent of self‐regulation and oversight of DIY laboratories

Policymakers should treat DIY‐biology laboratories as legitimate parts of the scientific enterprise and pay attention to the role of community norms. Subject Categories: Synthetic Biology & Biotechnology, S&S: Economics & Business, S&S: Ethics

DIY biology – very broadly construed as the practice of biological experiments outside of traditional research environments such as universities, research institutes or companies – has, during the past decade, gained much prominence. This increased attention has raised a number of questions about biosafety and biosecurity, both in the media and by policy makers who are concerned about safety and security lapses in “garage biology”. There are a number of challenges here though when it comes to policies to regulate DIY biology. For a start, the term itself escapes easy definition: synonyms or related terms abound, including garage biotechnology, bio‐hacking, self‐modification/grinding, citizen science, bio‐tinkering, bio‐punk, even transhumanism. Some accounts even use ‘DIY‐bio’ interchangeably with synthetic biology, even though these terms refer to different emerging trends in biology. Some of these terms are more charged than others but each carries its own connotations with regard to practice, norms and legality. As such, conversations about the risk, safety and regulation of DIY‐bio can be fraught.

Synonyms or related terms abound, including garage biotechnology, bio‐hacking, self‐modification/grinding, citizen science, bio‐tinkering, bio‐punk, even transhumanism.

Given the increasing policy discussions about DIY‐bio, it is crucial to consider prevailing practice thoughtfully, and accurately. Key questions that researchers, policy makers and the public need to contemplate include the following: “How do different DIY‐bio spaces exist within regulatory frameworks, and enact cultures of (bio)safety?”, “How are these influenced by norms and governance structures?”, “If something is unregulated, must it follow that it is unsafe?” and “What about the reverse: does regulatory oversight necessarily lead to safer practice?”.The DIY‐bio movement emerged from the convergence of two trends in science and technology. The first one is synthetic biology, which can broadly be defined as a conception of genetic engineering as systematic, modular and programmable. While engineering living organisms is obviously a complex endeavour, synthetic biology has sought to re‐frame it by treating genetic components as inherently modular pieces to be assembled, through rational design processes, into complex but predictable systems. This has prompted many “LEGO” metaphors and a widespread sense of democratisation, making genetic engineering accessible not only to trained geneticists, but also to anyone with an “engineering mindset”.The second, much older, trend stems from hacker‐ and makerspaces, which are – usually not‐for‐profit – community organisations that enable groups of enthusiasts to share expensive or technically complex infrastructure, such as 3D printers or woodworking tools, for their projects. These provide a model of community‐led initiatives based on the sharing of infrastructure, equipment and knowledge. Underpinning these two trends is an economic aspect. Many of the tools of synthetic biology – notably DNA sequencing and synthesis – have seen a dramatic drop in cost, and much of the necessary physical apparatus is available for purchase, often second‐hand, through auction sites.DIY‐bio labs are often set‐up under widely varying management schemes. While some present themselves as community outreach labs focusing on amateur users, others cater specifically to semi‐ or professional members with advanced degrees in the biosciences. Other such spaces act as incubators for biotech startups with an explicitly entrepreneurial culture. Membership agreements, IP arrangements, fees, access and the types of project that are encouraged in each of these spaces can have a profound effect on the science being done.     

The viral era: New biotechnologies give humans an unprecedented control over Nature and require appropriate safeguards

New biotechnologies such as gene drives and engineered viruses herald a viral era that would give humans exceptional power over any organism at the level of the genotype. Subject Categories: Synthetic Biology & Biotechnology, S&S: Economics & Business, Ecology

We are entering a new phase in our relationship with nature: after mechanization, automation and digitalization, a new era of autonomous technical objects is dawning. The most advanced of these technologies are characterized by viral behaviour. The COVID‐19 pandemic has again aptly demonstrated the power of viral systems: not only because of the SARS‐CoV‐2 virus'' ability to jump into and rapidly spread among the human population while wreaking havoc with human societies, but also because some of the vaccines developed against the virus are themselves based on viruses. Both developments give us some ideas of the possible impact of new biotechnologies that aim to create artefacts with viral behaviour in order to shape and control our natural environment. In this essay, the focus is on the use of genetically engineered organisms and the genetic manipulation of wild species. This change has a more direct relationship to our natural environment than autonomous software artefacts such as computer apps or digital viruses that “live” in their artificial “ecosystems” of information‐processing devices. The development of artificial biological systems will therefore require new methods for monitoring and intervention given their potential to autonomously spread within natural ecosystems.     

Are doping tests in sports trustworthy?: Athletes suffer from insufficiently defined criteria for doping tests

The lack of clearly defined criteria for doping tests carries a great risk of punishing innocent athletes and undermines the fight against doping in international sports. Subject Categories: Economics, Law & Politics, Methods & Resources

The World Anti‐Doping Agency (WADA) uses analytic, science‐based methods to detect doping, but it does not always adhere to scientific principles when it evaluates the results from their tests. The criteria for determining whether a sample is positive for an illegal substance often appear to be ambiguous with the risk of rendering evaluations subjective. Statements from WADA laboratories such as “you need to be an expert to clearly identify it” and “we know it when we see it” indicate such subjectivity. Subjective evaluations are troublesome because they erode the trust in WADA’s fight against doping, and have potentially dramatic consequences for athletes.     

Promises and rules: The implications of rethinking the 14‐day rule for research on human embryos

Removing the 14‐day limit for research on human embryos without public deliberation could jeopardize public trust in and support of research on human development. Subject Categories: Development & Differentiation, S&S: Economics & Business, Molecular Biology of Disease

In On Revolution, Hannah Arendt, one of the great political thinkers of the 20^th century, stated that “promises and agreements deal with the future and provide stability in the ocean of future uncertainty where the unpredictable may break in from all sides” (Arendt, 1963). She cited the Mayflower Compact, which was “drawn up on the ship and signed upon landing” on the uncharted territory of the American continent, as such an example of promise in Western history. Human beings are born with the capacity to act freely amid the vast ocean of uncertainty, but this capacity also creates unpredictable and irreversible consequences. Thus, in society and in politics, moral virtues can only persist through “making promises and keeping them” (Arendt, 1959).     

Vaccines beyond antibodies: Spurred by pandemic research,are T‐cell vaccines moving closer to reality?

Lessons learned from the vaccines against SARS‐CoV‐2 has encouraged research and vaccine development aimed at mustering strong T cell responses against the pathogen. Subject Categories: Microbiology, Virology & Host Pathogen Interaction, Pharmacology & Drug Discovery

The new vaccines against SARS‐CoV‐2 elicited strong antibody responses in initial trials, which encouraged optimism amongst immunologists and public health experts who expected good efficacy. “With viral infections, it is almost unheard of to have a prophylactic vaccine that doesn’t work ultimately by generating neutralising antibody responses”, explained immunologist Kingston Mills at Trinity College Dublin in Ireland. However, the antibody response is not the whole story. “Efforts to explain how immunity is working against viruses to the general public has forced everyone to try to make things so simple that now what is left is a ridiculous oversimplified picture of the vertebrate immune system”, commented Antonio Bertoletti, infectious disease scientist at Duke‐National University of Singapore. In fact, there is increasing research focus on the role of T cells in mediating the cellular response to infections and how to stimulate these cells through vaccines.Antibodies work by recognising and attaching to surface structures of a virus or bacterium, which prevents the pathogen from infecting its target cells and mark it for destruction by other immune cells. However, pathogens can escape the antibody response via mutations that decrease the efficiency of antibodies from infection or vaccination. “You will still potentially get infected if you’re vaccinated, because the antibody response is not as strong as it was”, explained immunologist Luke O’Neill at Trinity College Dublin, Ireland. “But then the T cells will kick in and stop the virus when it is inside cells”. Simply put, antibodies tend to prevent infection, while T cells combat infection and illness. Specifically, CD4 helper T cells primarily encourage B cells to generate antibodies whereas CD8 “killer” T cells eliminate cancerous and virally infected cells.     

Cost and availability of novel cell and gene therapies: Can we avoid a catastrophic second valley of death?

Advanced gene and cellular therapies risk a second “valley of death” due to their high costs and low patient population. As these are life‐saving therapies, measures are urgently needed to prevent their withdrawal from the market. Subject Categories: Economics, Law & Politics, Genetics, Gene Therapy & Genetic Disease, Pharmacology & Drug Discovery

During the past years, several advanced gene and cell therapies to target rare genetic diseases have demonstrated long‐lasting efficacy: essentially “curing” severe and previously incurable diseases and returning patients to a normal life. These therapies are classified as advanced therapy medicinal products (ATMPs); a few of these have received marketing authorization in Europe and the USA, and more will conceivably follow in the near future (De Luca et al, ²⁰¹⁹). Their success represents a milestone in medicine that 1 day might be compared with the discovery of antibiotics or the development of vaccines.

… once a therapy is successfully out of this first, biomedical “valley of death” and approved for use, it frequently encounters a second, economic “valley of death” that prevents its use in patients.

As “advanced” implies, the development of these therapies from the research laboratory to clinical trials is a long and very expensive ordeal. Bringing an ATMP to the market takes years, often decades, and still has a high failure rate (Cossu et al, ²⁰¹⁸). However, once a therapy is successfully out of this first, biomedical “valley of death” and approved for use, it frequently encounters a second, economic “valley of death” that prevents its use in patients. This problem needs a solution for medical, ethical and economic reasons; readers are also refereed to recent articles dealing with the same problem for haematopoietic diseases (Aiuti et al, ²⁰²²; Halley et al, ²⁰²²) or genodermatoses (Palamenghi et al, ²⁰²²).     

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…

     

Molecular basis of cross‐species ACE2 interactions with SARS‐CoV‐2‐like viruses of pangolin origin

Correction to: The EMBO Journal (2021) 40: e107786. DOI 10.15252/embj.2021107786 | Published online 8 June 2021The authors would like to add three references to the paper: Starr et al and Zahradník et al also reported that the Q498H or Q498R mutation has enhanced binding affinity to ACE2; and Liu et al reported on the binding of bat coronavirus to ACE2.Starr et al and Zahradník et al have now been cited in the Discussion section, and the following sentence has been corrected from:“According to our data, the SARS‐CoV‐2 RBD with Q498H increases the binding strength to hACE2 by 5‐fold, suggesting the Q498H mutant is more ready to interact with human receptor than the wildtype and highlighting the necessity for more strict control of virus and virus‐infected animals”.to“Here, according to our data and two recently published papers, the SARS‐CoV‐2 RBD with Q498H or Q498R increases the binding strength to hACE2 (Starr et al, 2020; Zahradník et al, 2021), suggesting the mutant with Q498H or Q498R is more ready to interact with human receptor than the wild type and highlighting the necessity for more strict control of virus and virus‐infected animals”.The Liu et al citation has been added to the following sentence:“In another paper published by our group recently, RaTG13 RBD was found to bind to hACE2 with much lower binding affinity than SARS‐CoV‐2 though RaTG13 displays the highest whole‐genome sequence identity (96.2%) with the SARS‐CoV‐2 (Liu et al, 2021)”.Additionally, the authors have added the GISAID accession IDs to the sequence names of the SARS‐CoV‐2 in two human samples (Discussion section). To make identification unambiguous, the sequence names have been updated from “SA‐lsf‐27 and SA‐lsf‐37” to “GISAID accession ID: EPI_ISL_672581 and EPI_ISL_672589”.Lastly, the authors declare in the Materials and Methods section that all experiments employed SARS‐CoV‐2 pseudovirus in cultured cells. These experiments were performed in a BSL‐2‐level laboratory and approved by Science and Technology Conditions Platform Office, Institute of Microbiology, Chinese Academy of Sciences.These changes are herewith incorporated into the paper.     

Relative Influence of Genetics and Shared Environment on Child Mental Health Symptoms Depends on Comorbidity

Background

Comorbidity among childhood mental health symptoms is common in clinical and community samples and should be accounted for when investigating etiology. We therefore aimed to uncover latent classes of mental health symptoms in middle childhood in a community sample, and to determine the latent genetic and environmental influences on those classes.

Methods

The sample comprised representative cohorts of twins. A questionnaire-based assessment of mental health symptoms was used in latent class analyses. Data on 3223 twins (1578 boys and 1645 girls) with a mean age of 7.5 years were analyzed. The sample was predominantly non-Hispanic Caucasian (92.1%).

Results

Latent class models delineated groups of children according to symptom profiles–not necessarily clinical groups but groups representing the general population, most with scores in the normative range. The best-fitting models suggested 9 classes for both girls and boys. Eight of the classes were very similar across sexes; these classes ranged from a “Low Symptom” class to a “Moderately Internalizing & Severely Externalizing” class. In addition, a “Moderately Anxious” class was identified for girls but not boys, and a “Severely Impulsive & Inattentive” class was identified for boys but not girls. Sex-combined analyses implicated moderate genetic influences for all classes. Shared environmental influences were moderate for the “Low Symptom” and “Moderately Internalizing & Severely Externalizing” classes, and small to zero for other classes.

Conclusions

We conclude that symptom classes are largely similar across sexes in middle childhood. Heritability was moderate for all classes, but shared environment played a greater role for classes in which no one type of symptom predominated.     

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.     

Lazy hazy days

Scientists have warned about the looming climate crisis for decades, but the world has been slow to act. Are we in danger of making a similar mistake, by neglecting the dangers of other climactic catastrophes? Subject Categories: Biotechnology & Synthetic Biology, Economics, Law & Politics, Evolution & Ecology

On one of my trips to Antarctica, I was enjoined to refer not to “global warming” or even to “climate change.” The former implies a uniform and rather benign process, while the second suggests just a transition from one state to another and seems to minimize all the attendant risks to survival. Neither of these terms adequately or accurately describes what is happening to our planet''s climate system as a result of greenhouse gas emissions; not to mention the effects of urbanization, intensive agriculture, deforestation, and other consequences of human population growth. Instead, I was encouraged to use the term “climate disruption,” which embraces the multiplicity of events taking place, some of them still hard to model, that are altering the planetary ecosystem in dramatic ways.With climate disruption now an urgent and undeniable reality, policymakers are finally waking up to the threats that scientists have been warning about for decades. They have accepted the need for action (UNFCCC Conference of the Parties, ²⁰²¹), even if the commitment remains patchy or lukewarm. But to implement all the necessary changes is a massive undertaking, and it is debatable whether we have enough time left. The fault lies mostly with those who resisted change for so long, hoping the problem would just go away, or denying that it was happening at all. The crisis situation that we face today is because the changes needed simply cannot be executed overnight. It will take time for the infrastructure to be put in place, whether for renewable electricity, for the switch to carbon‐neutral fuels, for sustainable agriculture and construction, and for net carbon capture. If the problems worsen, requiring even more drastic action, at least we do have a direction of travel, though we would be starting off from an even more precarious situation.However, given the time that it has taken—and will still take—to turn around the juggernaut of our industrial society, are we in danger of making the same mistakes all over again, by ignoring the risks of the very opposite process happening in our lifetime? The causes of historic climate cooling are still debated, and though we have fairly convincing evidence regarding specific, sudden events, there is no firm consensus on what is behind longer‐term and possibly cyclical changes in the climate.The two best‐documented examples are the catastrophe of 536–540 AD and the effects of the Laki Haze of 1783–1784. The cause of the 536–540 event is still debated, but is widely believed to have been one or more massive volcanic eruptions that created a global atmospheric dust‐cloud, resulting in a temperature drop of up to 2°C with concomitant famines and societal crises (Toohey et al, ²⁰¹⁶; Helama et al, ²⁰¹⁸). The Laki Haze was caused by the massive outpouring of sulfurous fumes from the Laki eruption in Iceland. Its effects on the climate, though just as immediate, were less straightforward. The emissions, combined with other meteorological anomalies, produced a disruption of the jetstream, as well as other localized effects. In northwest Europe, the first half of the summer of 1783 was exceptionally hot, but the following winters were dramatically cold, and the mean temperature across much of the northern hemisphere is estimated to have dropped by around 1.3°C for 2–3 years (Thordarson & Self, ²⁰⁰³). In Iceland itself, as well as much of western and northern Europe, the effects were even more devastating, with widespread crop failures and deaths of both livestock and humans exacerbated by the toxicity of the volcanic gases (Schmidt et al, ²⁰¹¹).Other volcanic events in recorded time have produced major climactic disturbances, such as the 1816 Tambora eruption in Indonesia, which resulted in “the year without a summer,” marked by temperature anomalies of up to 4°C (Fasullo et al, ²⁰¹⁷), again precipitating worldwide famine. The 1883 Krakatoa eruption produced similar disruption, albeit of a lesser magnitude, though the effects are proposed to have been much longer lasting (Gleckler et al, ²⁰⁰⁶).Much more scientifically challenging is the so‐called Little Ice Age in the Middle Ages, approximately from 1250 to 1700 AD, when global temperatures were significantly lower than in the preceding and following centuries. It was marked by particularly frigid and prolonged winters in the northern hemisphere. There is no strong consensus as to its cause(s) or even its exact dates; nor even that it can be considered a global‐scale event rather than a summation of several localized phenomena. A volcanic eruption in 1257 with similar effects to the one of 1816 has been suggested as an initiating event. Disruption of the oceanic circulation system resulting from prolonged anomalies in solar activity is another possible explanation (Lapointe & Bradley, ²⁰²¹). Nevertheless, and despite an average global cooling of < 1°C, the effects on global agriculture, settlement, migration and trade, pandemics such as the Black Death and perhaps even wars and revolutions, were profound.Once or twice in the past century, we have faced devastating wars, tsunamis and pandemics that seemed to come out of the blue and exacted massive tolls on humanity. From the most recent of each of these, there is a growing realization that, although these events are rare and poorly predictable, we can greatly limit the damage if we prepare properly. Devoting a small proportion of our resources over time, we can build the infrastructure and the mechanisms to cope, when these disasters do eventually strike.Without abandoning any of the emergency measures to combat anthropogenic warming, I believe that the risk of climate cooling needs to be addressed in the same way. The infrastructure for burning fossil fuels needs to be mothballed, not destroyed. Carbon capture needs to be implemented in a way that is rapidly reversible, if this should ever be needed. Alternative transportation routes need to be planned and built in case existing ones become impassable due to ice or flooding. Properly insulated buildings are not just a way of saving energy. They are essential for survival in extreme cold, as those of us who live in the Arctic countries are well aware—but many other regions also experience severe winters, for which we should all prepare.Biotechnology needs to be set to work to devise ways of mitigating the effects of sudden climactic events such as the Laki Haze or the Tambora and Krakatoa eruptions, as well as longer‐term phenomena like the Little Ice Age. Could bacteria be used, for example, to detoxify and dissipate a sulfuric aerosol such as the one generated by the Laki eruption? Methane is generally regarded as a major contributor to the greenhouse effect, but it is short‐lived in the atmosphere. So, could methanogens somehow be harnessed to bring about a temporary rise in global temperatures to offset short‐term cooling effects of a volcanic dust‐cloud?We already have a global seed bank in Svalbard (Asdal & Guarino, ²⁰¹⁸): It might easily be expanded to include a greater representation of cold‐resistant varieties of the world''s crop plants that might one day be vital to human survival. And, the experience of the Laki Haze indicates a need for varieties capable of withstanding acid rains and other volcanic pollutants, as well as drought and water saturation. An equivalent (embryo) bank for strains of agriculturally important animals potentially threatened by the effects of abrupt cooling of the climate or catastrophic toxification of the atmosphere is also worth considering.It has generally been thought impractical and pointless to prepare for even rarer events, such as cometary impacts, but events that have occurred repeatedly in recorded history and over an even longer time scale (Helama et al, ²⁰²¹) are likely to happen again. We should and can be better prepared. This is not to say that we should pay attention to every conspiracy theorist or crank, or paid advocates for energy corporations that seek short‐term profits at the expense of long‐term survival, but the dangers of climate disruption of all kinds are too great to ignore. Instead of our current rather one‐dimensional thinking, we need an “all‐risks” approach to the subject: learning from the past and the present to prepare for the future.     

The regulation of human blastoid research: A bioethical discussion of the limits of regulation

The creation of human blastoids holds great potential for research on early human development but also raises considerations about the ethics of such research and its regulation. Subject Categories: Development, Economics, Law & Politics

Developmental research has made considerable progress modeling either part of or the entire embryonic development of both humans and non‐human animals. A major step forward was the ability to grow blastocyst‐like structures from pluripotent stem cells: these structures, known as “blastoids,” mimic early embryonic development up to and potentially beyond the blastocyst stage 5–6 days after the first cell division. Blastoids have attracted considerable attention as an effective research tool to understand early human development and to elucidate the causes of infertility, teratogenesis, and other developmental abnormalities.

… many scientists see the use of human blastoids as an exciting scientific opportunity, as it may help to reduce the need for human embryos in research.

Until now, research with blastoids has mainly studied early development in mice, but, as of 2021, research results are also being reported from human blastoids (see “Further Reading”). Indeed, many scientists see the use of human blastoids as an exciting scientific opportunity, as it may help to reduce the need for human embryos in research (Ravindran, ²⁰²¹). However, as with any research that uses human embryos or human stem cells derived from embryos, human blastoid research raises ethical questions and is subject to regulation and approval. The latest ISSCR guidelines state that “[f]orms of research with embryos … and stem cell‐based embryo models … are permissible only after review and approval through a specialized scientific and ethics review process” (ISSCR, ²⁰²¹). Thus, although blastoids are models of embryonic development, they are currently considered to require the same or similar ethical considerations as blastocysts or cells derived from human embryos. In fact, Australia made a decision to regulate blastoid research in the same manner as research on human embryos (Australia NHMRC, ²⁰²¹).     

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.     

#IchbinHannah and the fight for permanent jobs for postdocs: How a fictitious postdoc (almost) triggered a fundamental reform of German academia

Regarding postdocs as disposable labour with limited contracts is damaging for science. Universities need to offer them better career perspectives. Subject Categories: Careers, Science Policy & Publishing

In many academic systems, permanent positions for scientists (“tenure”) are a rare exception. In Germany, 90% of the researchers employed in academia work on temporary contracts, often with less than a year’s duration. Most of the workforce on short‐term contracts are early‐career researchers (ECRs): PhD students, postdocs, or principal investigators aspiring to beome tenured professors. Given the short‐term perspectives and uncertain contract renewals, and because only a small fraction of the ECRs will eventually get a tenured position, planning the future is difficult or even impossible for them. This creates a toxic environment of hypercompetition, perverse incentives, and steep hierarchies underpinning this system, which discourages many highly competent and motivated young scientists who eventually leave in frustration. In the life sciences in particular, decisions about hiring or promotions are often based on indicators such as journal impact factor or the amount of third‐party funding. Such metrics purport to objectively quantify research quality and innovation, but instead, they foster a culture of questionable research practices, selective or non‐reporting, exaggerating the interpretation of results, and an emphasis on quantity over quality. Much has been written about this situation (Alberts et al, 2014), and there is a broad consensus among researchers, research administrators, funders, and learned societies on the need to reform the academic system.

Given the short‐term perspectives and uncertain contract renewals, and because only a small fraction of the ECRs will eventually get a tenured position, planning the future is difficult or even impossible for them.

     

The breakthrough paradox: How focusing on one form of innovation jeopardizes the advancement of science

Research needs a balance of risk‐taking in “breakthrough projects” and gradual progress. For building a sustainable knowledge base, it is indispensable to provide support for both. Subject Categories: Careers, Economics, Law & Politics, Science Policy & Publishing

Science is about venturing into the unknown to find unexpected insights and establish new knowledge. Increasingly, academic institutions and funding agencies such as the European Research Council (ERC) explicitly encourage and support scientists to foster risky and hopefully ground‐breaking research. Such incentives are important and have been greatly appreciated by the scientific community. However, the success of the ERC has had its downsides, as other actors in the funding ecosystem have adopted the ERC’s focus on “breakthrough science” and respective notions of scientific excellence. We argue that these tendencies are concerning since disruptive breakthrough innovation is not the only form of innovation in research. While continuous, gradual innovation is often taken for granted, it could become endangered in a research and funding ecosystem that places ever higher value on breakthrough science. This is problematic since, paradoxically, breakthrough potential in science builds on gradual innovation. If the value of gradual innovation is not better recognized, the potential for breakthrough innovation may well be stifled.

While continuous, gradual innovation is often taken for granted, it could become endangered in a research and funding ecosystem that places ever higher value on breakthrough science.

Concerns that the hypercompetitive dynamics of the current scientific system may impede rather than spur innovative research have been voiced for many years (Alberts et al, 2014). As performance indicators continue to play a central role for promotions and grants, researchers are under pressure to publish extensively, quickly, and preferably in high‐ranking journals (Burrows, 2012). These dynamics increase the risk of mental health issues among scientists (Jaremka et al, 2020), dis‐incentivise relevant and important work (Benedictus et al, 2016), decrease the quality of scientific papers (Sarewitz, 2016) and induce conservative and short‐term thinking rather than risk‐taking and original thinking required for scientific innovation (Alberts et al, 2014; Fochler et al, 2016). Against this background, strong incentives for fostering innovative and daring research are indispensable.     

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.

     

Helpful amnesia: Neuroscience unravels the role of forgetting as a prerequisite for establishing new long‐term memories

As neuroscience has been analysing the mechanisms behind long‐term memory, it demonstrated that forgetting is crucial for being able to remember.

“To be able to forget means sanity,” explained American writer Jack London (The Star Rover) referring to our sometimes infuriating inability to recall past events. In fact, being able to remember everything ever said and done might drive even the strongest mind insane. It is through forgetting and letting go of memories that the brain is able to acquire fresh impressions and new experience to move on, instead of being mired in the past.The importance of forgetting also fits well into and has inspired research to understand the molecular and cognitive basis of long‐term memory and how all the components and processes fit together. This puzzle of what is being remembered and why has been a long‐standing challenge for neuroscience; while progress has been made identifying more of the mechanisms and some of the existential drivers of memory formation, it is only recently that work has begun analyzing how these interact in animal models, often focusing on how the brain “decides” which things to remember and which things to send into oblivion.

This puzzle of what is being remembered and why has been a long‐standing challenge for neuroscience…

As a result, the field now sees collaboration across disciplines, driven by the realization that different parts and processes all play a part in memory formation and long‐term consolidation. This has led to one tangible if still tentative conclusion about long‐term memory, namely that forgetting occurs through loss of retrieval capability rather than erasure. It would appear to confirm the observation attributed to German philosopher Friedrich Nietzsche that “the existence of forgetting has never been proved: we only know that some things do not come to our mind when we want them to.”

The existence of forgetting has never been proved: we only know that some things do not come to our mind when we want them to.

     

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

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

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