1. National and Global Impacts of Genetically Modified Crops

    Casper Worm Hansen

    Asger Mose Wingender

    Summary 

    We estimate the impact of genetically modified (GM) crops on countrywide yields, harvested area, and trade using a triple-differences rollout design that exploits variation in the availability of GM seeds across crops, countries, and time. We find positive impacts on yields, especially in poor countries. Our estimates imply that without GM crops, the world would have needed 3.4 percent additional cropland to keep global agricultural output at its 2019 level. We also find that bans on GM cultivation have limited the global gain from GM adoption to one-third of its potential. Poor countries would benefit most from lifting such bans.

    Citation

    Hansen, Casper Worm, and Asger Mose Wingender. 2023. "National and Global Impacts of Genetically Modified Crops." American Economic Review: Insights, 5 (2): 224-40.

    DOI: 10.1257/aeri.20220144


    0

    Add a comment


  2. Enhanced International Standards Bolster Biotechnology Risk Management

    David Tribe 


    The preceding post explored gene technology risk management and outlined the strategies embraced by Australia's Office of the Gene Technology Regulator (OGTR), particularly the utilisation of the international risk management standard ISO 31000:2009, which served as a cornerstone in the development of their 2013 management manual. Inherent in the field of risk management is the necessity for continual adaptation and refinement, a requirement made all the more pressing by the rapidly evolving landscape of biotechnology. Accordingly, in 2018, the ISO organisation issued a substantial revision, ISO 31000:2018. Far from a mere update, this document signifies a thoughtful evolution, aiming to enhance the framework initially employed in the 2013 OGTR manual. It is worth emphasising that ISO standards are crafted by specialists in risk management to furnish broad non-specific guidance, thus preserving the relevance of OGTR's 2013 manual's specific instructions on risk assessment for environmental releases of genetically modified organisms. At first glance, ISO 31000:2018 might seem to maintain a close alignment with its 2009 predecessor, both in scope and structure. A more critical examination, however, reveals significant refinements, such as more explicit definitions, honed principles, and more efficiently organised frameworks. Comprehensive analyses of ISO 31000:2018 can be accessed publicly online, complete with descriptive diagrams that illuminate its pertinent role and application in the continually evolving sphere of gene technology risk management. This briefing endeavors to shed light on these valuable developments, affording insight on their contribution to fortifying and adapting risk management practices within the biotechnology sector


    In this resource, we delve into six pivotal features of ISO 31000:2018:


    Introduction – It underscores the role of risk management in creating and protecting organisational value, decision-making, objective-setting, performance enhancement.

    Terms and definitions – The updated standard includes the logical application of "risk analysis" and replaces "hazard" with "risk source" for clarity.

    Principles – These provide robust assistance for all dimensions of risk management.

    Framework – It provides a structure designed to better integrate risk management into all aspects of an organisation.

    Process – This involves a systematic application of diverse tools to the myriad activities necessary for risk assessment, monitoring, review, recording, and reporting.


    The aim is to equip graduate-level specialists in biotechnology regulation with a thorough understanding of these updated standards and their practical applications in the field.


    ISO 31000:2018 introduction.

    The introduction of ISO 31000:2018 delineates how this standard forms a systematic process that identifies, evaluates, and mitigates potential risks while advocating for judicious decision-making across all organisational strata. Its relevance is particularly salient in enhancing the safety assurance quality and effectiveness within gene technology, an area fraught with intricate technical, legal, organisational, and regulatory hurdles. The introduction earmarks three main levers to achieve this - principles, framework, and process. It provides a roadmap for approaching risk management, which is invaluable for graduate level specialists navigating the complex terrain of biotechnology regulation.


    Terms and definitions

    The concept of "risk source," as defined by the AS ISO 31000:2018 standard, is a crucial notion for understanding risk management within biotechnology. It describes an element or combination of elements with the potential to give rise to risk.


    To put it in perspective for those familiar with food safety assurance under Codex Alimentarius standards, the term "risk source" closely aligns with the Codex concept of a "hazard." However, it's critical to distinguish the conceptual difference between hazard and risk, as conflating them has historically led to misunderstandings about technology risks, particularly in biotechnology and fields involving chemical and biological entities.


    Here's why the distinction matters: a hazard is a potential source of harm, whereas risk is the likelihood that the harm will occur, factoring in the severity of the potential harm and its possible consequences. In other words, a "risk source" or "hazard" might possess the potential to cause harm, but the "risk" also involves the chance or probability that this harm will indeed occur.


    Therefore, the term "risk source" serves as a more precise tool in understanding the nuanced relationship between hazards and risks. It points directly to the potential origin of risk without conflating it with the probability and consequences of the harm, providing a clearer and more effective approach to risk management in biotechnology. Understanding this distinction is vital for public discussion of risks of biotechnology.


    The significance of precise definitions and nuanced distinctions, as illustrated in ISO 31000:2018, becomes even more pronounced when we look at real-world regulatory applications, such as those by Health Canada (2022) in their recent regulations on food crop breeding. They emphasise a risk-proportionate regulatory approach that encompasses both conventional and precision breeding.


    Lack of exposure to a risk source means there is no risk.

    A key point in their discourse is the fundamental difference between risk source and risk. While a risk source is an element that may potentially engender risk, it only translates into a tangible risk when there's actual exposure at a sensitive target. This underlines the idea that the inherent safety risk of genetically engineered (GE) foods is not tied to the process or technology of genetic engineering itself, but rather to the final product's characteristics and mode of consumption.


    Health Canada uses the example of stone fruits to illustrate this point. The fruit stones in apricots and peaches contain compounds that can produce toxic cyanide, hence qualifying as risk sources. However, because of the way we consume these fruits—avoiding the stone—the risk source doesn't translate into a genuine risk.

    Difference between a source of risk (hazard) and a harmful event from exposure to risk.



    This example underscores the essence of food risk sources or hazards as components that could potentially cause harm if uncontrolled. However, risk assessment must also consider the likelihood of harm under normal food consumption patterns and preparation methods, which inherently limit the chances of harmful outcomes. In other words, ISO 31000:2018's terminology helps to clarify the crucial distinction between potential hazards (risk sources) and actual risks, a concept that is central to risk management in biotechnology regulation.


    Principles of Risk Management.

    The articulation of well formulated general principles of risk management are an important way to improve regulatory outcomes recognised for example in the United States Coordinated Framework for Biotechnology, and management principles have long been a part of ISO approaches to management, as shown for example ISO 9000 discussions provided by David Hoyle.  The development of principles in ISO 31,000:2018 takes presentation of these principles to a new level even though it is very concise in the form of a diagram and short considered statements of principles.


    The principles of ISO 31000:2018 advocate for a risk management approach to gene technology that is integrated, structured, and customised to the organisation's specific context. It encourages inclusivity by valuing stakeholder inputs, and flexibility to adapt to emerging, changing or disappearing risks. The approach is informed by the best available information, cognisant of its inherent limitations and uncertainties. It recognizes the significant influence of human behaviour and culture, and is dedicated to ongoing improvement through learning and experience. These principles underpin effective management of uncertainties in gene technology, thus driving sound decision-making and fostering the responsible development and application of biotechnologies.


    Framework for Management

    The purpose of the risk management framework outlined in ISO 31000:2018 is to enable organisations to embed risk management into their crucial activities and functions. Its effectiveness hinges on how well it's integrated into an organisation's governance and decision-making processes. This task demands support and commitment from all stakeholders, with an essential role for top management. It's more than a theoretical guide; it's a practical toolkit designed to weave risk management into the very fabric of an organisation's operations. 


    The framework builds upon the original scientific management concept of "Plan, Do, Check, Act," but extends this with a new five-step approach: "Design, Implementation, Evaluation, Improvement, and Integration." This progressive approach reflects the complexities of modern organisations and the environments they operate in.


    Design: This involves shaping the risk management framework to align with the organisation's objectives, strategies, and culture.


    Implementation: The risk management framework is brought to life in this phase, integrated into the organisation's overall processes.


    Evaluation: The effectiveness of the risk management framework is measured and assessed in relation to the organisation's evolving context.


    Improvement: Based on evaluations, the risk management processes are refined and improved continuously to ensure they remain effective and relevant.


    Integration: Risk management is interwoven into all aspects of the organisation, reinforcing its importance across all operations.


    Each term is carefully defined within ISO 31000:2018, reflecting the rigour and precision required in a universally applicable standard. The framework underscores the pivotal role of leadership and commitment, emphasising that successful risk management is as much about culture and engagement as it is about processes. For students at all levels interested in organisational management and risk mitigation, understanding this advanced, integrated approach is crucial.


    Risk Management Process.

    ISO 31000:2018 elucidates the process of risk management in a more refined and comprehensible manner than its predecessors, such that used in  2013 OGTR risk management manual. A primary illustration of this enhanced clarity is the comprehensive diagram provided in the ISO 31000:2018 standard, which excellently visualises the risk management process.



    ISO 31000:2018 schematic for the Risk Management Process. From web-preview



    This diagram, readily available on the internet, starts with "scope, context, and criteria" which define the boundaries and priorities of the risk management process. Subsequently, the process moves through stages of "risk identification, risk analysis, and risk evaluation." These phases are articulated with semantic consistency and clarity, providing an upgrade from previous models like the Codex Alimentarius' use of "Risk Analysis" as an umbrella term for risk management.


    Furthermore, the diagram incorporates "recording and reporting" activities, ensuring that the documentation and communication aspects of the process are not overlooked. An essential feature is the surrounding arrows, visually emphasising that risk management is not a one-off task, but a cyclical, iterative process of continuous improvement over time. Both communication and consultation, shown in the figure, are vital elements in the development of well crafted regulations that are achieved when regulatory agencies and governments take full advantage of stakeholder engagement.


    For anyone engaged in or impacted by the regulation of biotechnology - be they students, practitioners, regulators, consumers, or policy makers - ISO 31000:2018 offers indispensable insights. Its diagrams and concepts serve as a guiding compass, helping all stakeholders navigate the intricate landscape of risk management. By facilitating clear, logical, and effective communication, this standard paves the way for more informed decision-making and productive dialogue in the ever-evolving field of biotechnology regulation. It underscores our collective responsibility to ensure the safe, responsible and beneficial advancement of this transformative technology. ISO 31000:2018 concepts complement, not replace, earlier simple frameworks (eg. FSANZ 2013, OGTR 2013) which have continuing value for effective communication with other audiences (see previous post.)




    Bibliography.


    (Australian Standard/New Zealand Standard) ISO 31,000:2009 Risk Management – Principles and Guidelines 


    (Australian Standard)  ISO 31,000:2018 Risk Management Guidelines.


    Executive Office of the President. 2017. Modernizing the Regulatory System for Biotechnology Products: An Update to the Coordinated Framework for the Regulation of Biotechnology. Available at https://obamawhitehouse.archives.gov/sites/default/files/microsites/ostp/2017_coordinated_framework_update.pdf


    FSANZ 2013 Risk Analysis in Food Regulation


    Health Canada (2022) Scientific opinion on the regulation of gene-edited plant products within the context of Division 28 of the Food and Drug Regulations (Novel Foods), especially the Executive summary 



    Health Canada (2022a) June, 2006 Updated: July 2022 Guidelines for the Safety Assessment of Novel Foods especially Appendix I 


    Hoyle, David 2009. Chapter 1 Getting Started in ISO 9000 Quality Systems Handbook, Routledge.


    ISO 2018. ISO 31000:2018 web preview

    Office of the Gene Technology Regulator 2013. Risk Analysis Framework.


    Tribe, D 2023. Gene technology regulations Part 1. Current treatment of new breeding technologies by the existing Gene Technology Regulations in Australia (Blogpost at GMO Pundit)


    Tribe, D 2023. Gene technology regulations Part 2. How to start doing risk management: OGTR 2013 Risk Analysis Framework Overview: Attention to Context. (Blogpost at GMO Pundit)




    (Version 2 revised to improve clarity 10 Aug 2023)

     

    0

    Add a comment

  3.  


    OGTR 2013 Risk Analysis Framework Overview: Attention to Context

    David Tribe 2023

    Next post in this series: Gene technology regulations Part 3: Enhanced International Standards Bolster Biotechnology Risk Management

    The Office of the Gene Technology Regulator (OGTR) 2013 Risk Analysis Framework (RAF) is a robust and comprehensive approach that outlines how the Australian government deals with risks related to the use of genetically modified organisms (GMOs). Based on the Gene Technology Act 2000 and the Gene Technology Regulations 2001, this framework delineates a clear, consistent methodology for conducting risk assessments, managing identified risks, and effectively communicating these risks to a wide array of stakeholders.

    The overall RAF encompasses three main components: Risk Context, Risk Assessment, and Risk Management, each of which operates within the bounds of the legislation. The Risk Communication component is embedded within all stages of the RAF, ensuring transparency, openness, and inclusivity (see figure).



    Figure. Risk analysis method for GMO licence application.

     

    Risk context is the initial step in this process, providing a framework for understanding and categorizing potential risks. This step involves defining the scope and boundaries of the risk evaluation process, outlining key parameters such as the subject and trigger for regulation, the method for achieving protection goals, and the definitions of key terms.

    The risk criteria considered range from the properties of the parent organism, the effects of genetic modification on this organism, measures for limiting GMO dissemination, to the scale of proposed dealings. The risk consequences focus on both the level and nature of potential harm to human health and safety, as well as to the environment.

    One facet of the OGTR's Risk Context is the acknowledgement of not only the physical harm posed by GMOs, but also the perception of that harm. This reflects an understanding that public attitudes and understanding are a critical component of risk management in gene technology.

    The Risk Assessment Context of the RAF emphasises a case-by-case approach, recognising the unique nature of each GMO and its specific application. It takes into account not only the specifics of the GMO, proposed dealings, and the parent organism, but also the environment into which the GMO will be released. It acknowledges that these environments are dynamic and can change over time, necessitating a flexible and adaptable risk assessment.

    In the Risk Management Context, the RAF outlines protocols for managing identified risks, focusing on key protection goals, legislative matters, decision-making processes, licence conditions, and provisions for audits and monitoring. It also includes risk management considerations for parent species and sanctions for non-compliance.

    Finally, the Risk Communication Context details the communication and consultation procedures, underscoring the importance of open dialogue and consultation with a variety of stakeholders to ensure transparency and build trust.

    For proponents of GMO technologies aiming for a successful licence application, understanding and effectively addressing the RAF's comprehensive risk management considerations is crucial. A thorough understanding of the risk context, as described by the OGTR 2013 RAF, is fundamental to achieving this.

    Applicants need to carry out rigorous and scientifically sound risk assessments, considering both the physical and perceived risks associated with the GMOs. They must take into account not only the nature of the modification and its application but also the environment in which the GMO will be released. Applicants must also propose effective risk management strategies and demonstrate how they will achieve the protection goals, comply with legislative matters, and adhere to the conditions of the licence.

    Moreover, they must be prepared to engage in open dialogue and consultation, taking on board the views of a wide range of stakeholders. In particular, transparency and engagement with the public are crucial elements of the RAF and can be a critical factor in a successful license application.

    In conclusion, a well-prepared application within the context of the OGTR's Risk Analysis Framework requires a combination of solid scientific analysis, effective risk management strategies, and excellent stakeholder communication skills.

    Source document

    Office of the Gene Technology Regulator 2013, Department Of Health and Ageing 2013. Risk Analysis Framework 2013

    Next post in this series: Gene technology regulations Part 3: Enhanced International Standards Bolster Biotechnology Risk Management



    0

    Add a comment

  4. David Tribe.

    (Based on Australian Gene Technology Regulations 2001 F2019L00573 20 October 2020).

    The current treatment of new breeding technologies, such as gene editing, under the existing Gene Technology Act 2000 and Gene Technology Regulations 2001 in Australia provides a nuanced approach towards distinguishing between organisms modified through gene technology (genetically modified organisms, or GMOs) and those that aren't.

    Under the current legislation, the use of gene editing technology can fall under either the definition of gene technology or not, depending on the specifics of the technique employed.

    Key Definitions from the Act:

    The Act defines gene technology as any technique for the modification of genes or other genetic material, excluding sexual reproduction, homologous recombination, or any other technique specified in the regulations.

    A genetically modified organism, as per the Act, is an organism that has been modified by gene technology, or has inherited particular traits from an organism because of gene technology, or anything declared by the regulations to be a GMO. This does not include a human being that has undergone somatic cell gene therapy or an organism declared by the regulations not to be a GMO.

    Relevance to Gene Editing and New Breeding Technologies:

    The way that gene editing is treated under the current regulations largely hinges on Schedules 1A, 1B, and 1 of the regulations. These schedules clarify which techniques and resulting organisms are or aren't considered as involving gene technology.

    • Schedule 1B, Item 2: An organism modified by repair of single-strand or double-strand breaks of genomic DNA induced by a site-directed nuclease, if a nucleic acid template was added to guide homology-directed repair, is still considered a product of gene technology.
    • Schedule 1, Item 4: An organism that has been modified by repair of single-strand or double-strand breaks of genomic DNA induced by a site-directed nuclease, if a nucleic acid template was NOT added to guide homology-directed repair, is not considered a GMO.

    This suggests that gene editing can be classified as either (i) gene technology or (ii) not gene technology based on whether a nucleic acid template was used to guide the repair process. If a guide template is used, the organism is considered a GMO. If no guide template is used, the organism isn't considered a GMO, as the change might have occurred naturally or through traditional mutagenesis methods that have a long history of safe use.

    Considerations for Innovators

    Gene Editing Flexibility under Australian Gene Technology Regulations

    1. Technique Matters: The type of gene-editing technique used is crucial in determining if the organism will be considered a GMO.
    2. Use of Guide Templates: Using a nucleic acid template to guide DNA repair during gene editing means the organism is a GMO. Not using templates can keep the organism outside of the GMO classification.
    3. Analogy to Traditional Mutagenesis: Techniques that mimic the damage caused by traditional mutagenesis methods aren't considered gene technology.
    4. Regulatory Scope: Clear comprehension of the regulatory guidelines can prevent legal complications.
    5. Dynamic Landscape: The rapidly evolving field of biotechnology and the legislation surrounding it demand regular updates on the latest regulatory changes.

     

    Information resources:

    National Gene Technology Scheme (webpage).

    The National Gene Technology Scheme is a collaboration between all Australian governments, supporting a nationally consistent regulatory system for gene technology in Australia.

    National Gene Technology Scheme 2017 – Third review (webpage)

    The third review of the National Gene Technology Scheme considered technical, regulatory, governance and social and ethical issues. It also looked at modernising and future proofing the scheme.

    Gene Technology Regulations 2001 F2020C00957  20 October 2020

    Gene Technology Act 2000 C2016C00792 13 July 2016


    Later posts in this series

    Gene technology regulations Part 2.How to start doing risk management: OGTR 2013 Risk Analysis Framework Overview: Attention to Context

    Gene technology regulations Part 3: Enhanced International Standards Bolster Biotechnology Risk Management


    0

    Add a comment

  5.  

    Pexels/Marcus Aurelius
    Paul Griffin, The University of Queensland

    After having low rates of influenza (flu) transmission in recent years thanks to our COVID control strategies, case numbers are now rising.

    So far this year, Australia has had more than 32,000 lab-confirmed cases of the flu and 32 deaths.

    Getting a flu vaccine is the best way to protect against getting the flu. These are reformulated each year to protect against the most widely circulating strains – if our predictions are right.

    Below you’ll find everything you need to know about the 2023 flu vaccine. But first, some flu basics.

    What are the different types of flu?

    There are two main types of influenza: influenza A and influenza B. On the surface of the influenza virus there are two main proteins, the hemagglutinin (HA or H) and neuraminidase (NA or N).

    Different strains are named after their versions of the H and N proteins, as in H1N1 or “swine flu”.

    HA is the yellow spike, while the NA is the green oval. Shutterstock

    Minor changes in the proteins (HA and NA) on the surface are common because the enzyme the virus uses to make copies of itself is prone to errors.

    Sometimes the influenza virus can change more abruptly when it mixes up components from different influenza viruses – including influenza viruses that typically infect birds, pigs or bats – to create a virus that’s basically new.

    The regular change in the virus is the reason the vaccine is updated every year. The Australian Influenza Vaccine Committee meets late in the year to plan what should be included in the vaccine for the following season, after considering what happened in our last flu season and in the Northern hemisphere winter.

    What strains does this year’s flu shot protect against?

    Modern flu vaccines typically protect against four strains. For this year’s vaccine, the committee has recommended it includes:

    • an A/Sydney/5/2021 (H1N1)pdm09-like virus

    • an A/Darwin/9/2021 (H3N2)-like virus

    • a B/Austria/1359417/2021 (B/Victoria lineage)-like virus

    • a B/Phuket/3073/2013 (B/Yamagata lineage)-like virus.

    The naming of the viral components can sometimes be confusing. The name is derived from the virus type (A or B)/the place it was first isolated/strain number/year isolated (virus subtype).

    This year’s vaccine therefore includes an influenza A virus similar to the 2009 pandemic-causing H1N1 isolated from Sydney in 2021 and a second influenza A virus (H3N2) isolated in Darwin in 2021.

    Influenza B viruses are classified into 2 lineages: Victoria and Yamagata. This year’s vaccine includes an influenza B isolated from Austria in 2021 (Victoria lineage) and an influenza B isolated in Phuket in 2013 (Yamagata lineage).

    People on a beach in Darwin
    This year’s flu vaccine protects against a strain isolated in Darwin. Shutterstock

    Who should get a flu shot?

    Health authorities recommend everyone aged six months of age or over should get the flu vaccine every year.

    Some groups are at greater risk of significant disease from the flu and can access the flu vaccine for free. This includes:

    • Aboriginal and Torres Strait Islander people aged six months and over

    • children aged six months to five years

    • pregnant women at any stage of pregnancy

    • people aged 65 years or over

    • people aged five years to 65 years who have certain underlying health conditions affecting the heart, lungs, kidneys or immune system, and those with diabetes.

    How can I get it?

    You can get a flu shot from your local general practice or pharmacy. Or you may have an opportunity to get vaccinated at your workplace if your employer supplies it.

    While the vaccine is free for those in the above groups, there can be a consultation or administration fee, depending on where you get your vaccine.

    If you aren’t eligible for a free vaccine, it usually costs around A$20-$30.

    Nurse vaccinates woman
    Some people can get the shot for free, while others pay $20 to $30. Shutterstock

    Are there different options?

    For over 65s, whose immune systems may not work as well as when they were younger, a specific vaccine is available that includes an adjuvant which boosts the immune response. This is free for over-65s under the national immunisation program.

    A high-dose vaccine is also available for people aged 60 and over. However this isn’t currently funded and costs around $70 on a private prescription.

    People with egg allergies can safely get the egg-based flu vaccine. However there is also a cell-based immunisation for people who don’t want a vaccine made in eggs. When vaccines are grown in eggs, sometimes the virus can change and this might affect the level of protection. Cell-based vaccines aim to address this issue.

    The cell-based vaccine isn’t funded so patients will pay around $40 for a private prescription.

    How well do they work?

    The vaccine’s effectiveness depends on how well the strains in the vaccine match those circulating. It generally reduces the chance of being admitted to hospital with influenza by 30-60%.

    What are the side effects?

    You can’t get the flu from the vaccine as there’s no live virus in it.

    When people get a flu-like illness after the vaccine, it can be due to mild effects we sometimes see after vaccination, such as headaches, tiredness or some aches and pains. These usually go away within a day or two.

    Alternatively, symptoms after getting a flu shot may be due to another respiratory virus such as respiratory syncytial virus (RSV) that circulates in winter.

    When’s the best time to get your flu shot?

    The vaccine provides peak protection around three to four months after you get it.

    The peak of the flu season is usually between June and September, however this changes every year and can vary in different parts of the country.

    Given this, the best time to get the vaccine is usually around late April or early May. So if you haven’t already, now would be a good time to get it.The Conversation

    Paul Griffin, Associate Professor, Infectious Diseases and Microbiology, The University of Queensland

    This article is republished from The Conversation under a Creative Commons license. Read the original article.

    0

    Add a comment

  6.  


    From the tropics to the poles, from the sea surface to hundreds of feet below, the world’s oceans are teeming with one of the tiniest of organisms: a type of bacteria called Prochlorococcus, which despite their minute size are collectively responsible for a sizable portion of the oceans’ oxygen production. But the remarkable ability of these diminutive organisms to diversify and adapt to such profoundly different environments has remained something of a mystery.

    Now, new research reveals that these tiny bacteria exchange genetic information with one another, even when widely separated, by a previously undocumented mechanism. This enables them to transmit whole blocks of genes, such as those conferring the ability to metabolize a particular kind of nutrient or to defend themselves from viruses, even in regions where their population in the water is relatively sparse.

    The findings describe a new class of genetic agents involved in horizontal gene transfer, in which genetic information is passed directly between organisms — whether of the same or different species — through means other than lineal descent. The researchers have dubbed the agents that carry out this transfer “tycheposons,” which are sequences of DNA that can include several entire genes as well as surrounding sequences, and can spontaneously separate out from the surrounding DNA. Then, they can be transported to other organisms by one or another possible carrier system including tiny bubbles known as vesicles that cells can produce from their own membranes.

    The research, which included studying hundreds of Prochlorococcus genomes from different ecosystems around the world, as well as lab-grown samples of different variants, and even evolutionary processes carried out and observed in the lab, is reported today in the journal Cell, in a paper by former MIT postdocs Thomas Hackl and Raphaël Laurenceau, visiting postdoc Markus Ankenbrand, Institute Professor Sallie “Penny” Chisholm, and 16 others at MIT and other institutions.

    Chisholm, who played a role in the discovery of these ubiquitous organisms in 1988, says of the new findings, “We’re very excited about it because it’s a new horizontal gene-transfer agent for bacteria, and it explains a lot of the patterns that we see in Prochlorococcus in the wild, the incredible diversity.” Now thought to be the world’s most abundant photosynthetic organism, the tiny variants of what are known as cyanobacteria are also the smallest of all photosynthesizers.

    Hackl, who is now at the University of Groningen in the Netherlands, says the work began by studying the 623 reported genome sequences of different species of Prochlorococcus from different regions, trying to figure out how they were able to so readily lose or gain particular functions despite their apparent lack of any of the known systems that promote/boost horizontal gene transfer, such as plasmids or viruses known as prophages.    

    What Hackl, Laurenceau, and Ankenbrand investigated were “islands” of genetic material that seemed to be hotspots of variability and often contained genes that were associated with known key survival processes such as the ability to    assimilate essential, and often limiting, nutrients such as iron, or nitrogen, or phosphates. These islands contained genes that varied enormously between different species, but they always occurred in the same parts of the genome and sometimes were nearly identical even in widely different species — a strong indicator of horizontal transfer.

    But the genomes showed none of the usual features associated with what are known as mobile genetic elements, so initially this remained a puzzle. It gradually became apparent that this system of gene transfer and diversification was different from any of the several other mechanisms that have been observed in other organisms, including in humans.

    Hackl describes what they found as being something like a genetic LEGO set, with chunks of DNA bundled together in ways that could almost instantly confer the ability to adapt to a particular environment. For example, a species limited by the availability of particular nutrients could acquire genes necessary to enhance the uptake of that nutrient.       

    The microbes appear to use a variety of mechanisms to transport these tycheposons (a name derived from the name of the Greek goddess Tyche, daughter of Oceanus). One is the use of membrane vesicles, little bubbles pouched off from the surface of a bacterial cell and released with tycheposons inside it. Another is by “hijacking” virus or phage infections and allowing them to carry the tycheposons along with their own infectious particles, called capsids. These are efficient solutions, Hackl says, “because in the open ocean, these cells rarely have cell-to-cell contacts, so it’s difficult for them to exchange genetic information without a vehicle.”

    And sure enough, when capsids or vesicles collected from the open ocean were studied, “they’re actually quite enriched” in these genetic elements, Hackl says. The packets of useful genetic coding are “actually swimming around in these extracellular particles and potentially being able to be taken up by other cells.”

    Chisholm says that “in the world of genomics, there’s a lot of different types of these elements” — sequences of DNA that are capable of being transferred from one genome to another. However, “this is a new type,” she says. Hackl adds that “it’s a distinct family of mobile genetic elements. It has similarities to others, but no really tight connections to any of them.”

    While this study was specific to Prochlorococcus, Hackl says the team believes the phenomenon may be more generalized. They have already found similar genetic elements in other, unrelated marine bacteria, but have not yet analyzed these samples in detail. “Analogous elements have been described in other bacteria, and we now think that they may function similarly,” he says.

    “It’s kind of a plug-and-play mechanism, where you can have pieces that you can play around with and make all these different combinations,” he says. “And with the enormous population size of Prochlorococcus, it can play around a lot, and try a lot of different combinations.”

    Nathan Ahlgren, an assistant professor of biology at Clark University who was not associated with this research, says “The discovery of tycheposons is important and exciting because it provides a new mechanistic understanding of how Prochlorococcus are able to swap in and out new genes, and thus ecologically important traits. Tycheposons provide a new mechanistic explanation for how it’s done.” He says “they took a creative way to fish out and characterize these new genetic elements ‘hiding’ in the genomes of Prochlorococcus.

    He adds that genomic islands, the portions of the genome where these tycheposons were found, “are found in many bacteria, not just marine bacteria, so future work on tycheposons has wider implications for our understanding of the evolution of bacterial genomes.”

    The team included researchers at MIT’s Department of Civil and Environmental Engineering, the University of Wuerzburg in Germany, the University of Hawaii at Manoa, Ohio State University, Oxford Nanopore Technologies in California, Bigelow Laboratory for Ocean Sciences in Maine, and Wellesley College. The work was supported by the Simons Foundation, the Gordon and Betty Moore Foundation, the U.S. Department of Energy, and the U.S. National Science Foundation.

    0

    Add a comment

  7.  The silverleaf whitefly is a major crop pest in the tropics and subtropics. After studying its genome, INRAE and the CNRS identified 49 plant genes transferred to the insect’s own genome. Such a large number of genes transferred between plants and an insect had never before been detected. These findings open the door to new research on relationships between plants and insects that could lead to innovative pest control methods and reduce pesticide use.


    QQ截图20221011134825.jpg

    illustration An insect pest acquires multiple plant genes © US Department of Agriculture - Stephen Ausmus


    The war between plants and plant-eating insects goes back millions of years and has led both protagonists into an arms race. As plants deploy signalling and erect physical and chemical barriers, insects develop clever strategies to bypass those roadblocks. But the genes involved in insect adaptation sometimes have a surprising origin. For the very first time, recent studies from 2020 and 2021 (Lapadula et al., 2020 and Xia et al., 2021) showed the transfer of two plant genes to the genome of the silverleaf whitefly (Bemisia tabaci), with one gene that gives the whitefly the ability to neutralise toxins produced by plants as a defence mechanism. Intrigued by this finding, two scientists – one from INRAE and one from CNRS – sought to learn how many plant-derived genes were found in the whitefly genome, which was fully sequenced in 2016.

    49 plant-derived genes in the insect genome

    By undertaking a bioinformatics analysis, the researchers identified 49 plant genes in the whitefly genome deriving from 24 independent horizontal gene transfer events. Most of these genes show features of functionality, meaning they are expressed in insects and have sequences with signs of evolutionary pressure, and so play a potential role in insects. The researchers’ results also show that most of the identified genes, such as those that are involved in producing enzymes that break down plant cell walls, play a known role in relationships between plants and their parasites. This likely reflects the result of a process of natural selection of plant genes in insects, which may have  allowed the whitefly to adapt to a large range of plant species. The origin and mechanism behind these transfers is still unknown, but they all go back several million years.

    This is the first time that so many gene transfers between plants and insects have been identified. This study opens the door to new research on plant-pest relationships as well as crop pest control methods. Understanding the role of transferred genes for plants and insects could lead to innovative pest control methods based on plant breeding (varietal selection) that could reduce pesticide use.

    References

    Clément Gilbert and Florian Maumus, Multiple horizontal acquisitions of plant genes in the whitefly Bemisia tabaci, Genome Biology and Evolution, evac141, https://doi.org/10.1093/gbe/evac141

    Studies from 2020 and 2021

    Lapadula, W.J., Mascotti, M.L. & Juri Ayub, M. Whitefly genomes contain ribotoxin coding genes acquired from plants. Sci Rep 10, 15503 (2020). https://doi.org/10.1038/s41598-020-72267-1

    Xia, J., Guo, Z., Yang, Z., Han, H., Wang, S., Xu, H., Yang, X., Yang, F., Wu, Q., Xie, W., et al. (2021). Whitefly hijacks a plant detoxification gene that neutralizes plant toxins. Cell, Volume 184, Issue 13, 24 June 2021, Pages 3588 https://doi.org/10.1016/j.cell.2021.02.014

    0

    Add a comment

  8. Shutterstock
    C Raina MacIntyre, UNSW Sydney; Brendan Crabb, Burnet Institute, and Nancy Baxter, The University of Melbourne

    COVID is an exceptional disease and was at its deadliest this year, causing more deaths in Australia between June and August 2022 than at any other time. There have been 288 deaths from influenza so far this year compared to more than 12,000 deaths from COVID.

    The number of deaths from COVID in Australia in the first nine months of 2022 is more than ten times the annual national road toll of just over 1,000 – but we are not rushing to remove seat belts or drink-driving laws so people can have more freedom.

    Isolation flattens the COVID curve by stopping infectious people from infecting others, and is a key pillar of COVID control.

    Removing isolation will not help the workforce

    Workforce shortages have been felt in every sector during the pandemic. Shortages of health workers have resulted in the need to import workers from overseas, and deadly outcomes for patients in some cases.

    During epidemic peaks this year, the workforce was so badly affected that supermarket shelves could not be stocked. Removing the isolation period is hoped to ease workforce shortages – but any relief will be short-lived.

    Woman looking at empty supermarket shelf
    During epidemic peaks this year, the workforce was so badly affected, supermarket shelves could not be stocked. Mari Nelson/Shutterstock

    At times when COVID numbers are increasing, allowing infectious people to mingle freely at work and socially will create epidemic growth and make the crisis even worse. At the current time, when cases are relatively low, removing isolation mandates will not materially benefit the workforce, but will make the workplace and schools less safe.

    Eliminating isolation rules provides the opportunity for governments to save costs. Without mandatory isolation support, payments for workers needing to isolate will end.

    While politicians spin this as trusting Australians to take “personal responsibility”, sadly many Australians will simply not have the means to take time off work. With elimination of mandatory isolation periods, essential workers in low paying jobs will find themselves at even more risk of contracting COVID in the workplace.

    The pandemic is not over

    Newer variants of SARS-CoV-2, the virus that causes COVID, are more immune-evasive than ever. Immunity from vaccines wanes within two to three months, and so too does immunity from infection. Hybrid immunity is cited as a reason for abandoning isolation, but is unlikely to eventuate.

    Indeed, we saw this with the recent BA5 wave leading to more hospitalisations and deaths than the January/February BA1 wave, despite the presence of much higher vaccine and infection-based immunity in the community. While no doubt this immunity prevented an even worse outcome, it clearly did not keep pace with virus evolution.

    While it was hoped hybrid immunity from vaccines and prior infection would reduce subsequent infections, this has not been the reality. Reinfection is becoming more common with variants that are increasingly distant from the original virus. And evidence is accruing that reinfection can cause severe disease.

    The most vulnerable may be forced to withdraw from society and from unsafe workplaces to protect themselves. But it is a misconception that COVID is trivial for everyone else. People who are happy and healthy today could become disabled or chronically ill from COVID.

    The long-term complications of COVID are substantial, and can include effects on the lungs, heart, brain and immune system. At 12 months after infection, the risk of heart attacks, strokes, blood clots and other complications including sudden death are about double compared to people who were never infected. Chronic complications can occur even after mild infection – including heart failure, strokes and dementia.

    Dropping isolation will increase COVID transmission and result in an increase in serious chronic illness. It could be a mass disabling event and so drive major economic and societal losses.

    The availability of treatments has been cited as a reason to cease isolation – but these are restricted to limited subgroups, and not available to everyone.

    COVID is an epidemic disease and has behaved in a predictable way since 2020, causing recurrent epidemic waves.

    Ceasing isolation will hasten the onset of the next wave. Allowing mass infection also creates favourable conditions for emergence of new variants which have been more contagious or more vaccine or treatment resistant.

    What we need to do instead

    To maximise productivity, health and social success, instead of ignoring COVID, we should tackle it with a layered approach to mitigation of transmission. This includes raising rates of boosters, widening access to antivirals and other treatments, masks, safe indoor air, and widely accessible testing.

    Making isolation a rule, and supporting people financially to do so, has been a key pillar of our defences. This is still needed as viral evolution continues to outpace immunity.

    We just had our worst wave and there is nothing to suggest the next won’t be similarly bad. Workplace absenteeism is a function of transmission, so better control of SARS-CoV-2 will result in greater productivity, less disruption to families and businesses, and a more successful way forward to living with COVID. The Conversation

    C Raina MacIntyre, Professor of Global Biosecurity, NHMRC Principal Research Fellow, Head, Biosecurity Program, Kirby Institute, UNSW Sydney; Brendan Crabb, Director and CEO, Burnet Institute, and Nancy Baxter, Professor and Head of Melbourne School of Population & Global Health, The University of Melbourne

    This article is republished from The Conversation under a Creative Commons license. Read the original article.

     

    0

    Add a comment

  9.  

    Note the Proline (P) residue adjacent to insert in SARS 2 


    Thread on Twitter today plus key cited reports


    SARS-CoV-2 furin cleavage site was not engineered

    Robert F. Garry

    Carolina (UNC) and the Wuhan Institute of Virology (WIV) based on an eight-amino-acid sequence similarity between the furin cleavage site (FCS) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike and one of the FCSs of human amiloride-sensitive epithelial sodium channel α subunit (ENaC) (2). Both proteins have the sequence RRARSVAS (Fig. 1A). Harrison and Sachs cite work on rat ENaC from UNC (3, 4) and suggest that the UNC and WIV coronavirologists may have mimicked human ENaC FCS to make SARS-CoV-2 more infectious for lung epithelia.

    Numerous features of SARS-CoV-2 FCS demonstrate that it was not engineered to mimic human ENaC:

    • Alignment of the nucleotide sequence of the SARS-CoV-2 Spike gene with the closest known coronavirus Spike gene from Laotian bat coronavirus BANAL-20-52 (5) clearly shows that four extra amino acids (PRRA), not eight, were added to the SARS-CoV-2 Spike protein (Fig. 1B).
    • There was an insertion of 12 nucleotides into the Spike gene (Fig. 1B, box) (6). This nucleotide insertion is out of frame (6, 7).
    • The insertion adds a proline not present in ENaC.
    • Except for one codon (cgu that encodes arginine 685), each of the codons for RRARSVAS is different in human ENaC and SARS-CoV-2 (Fig. 1B).
    • Five of eight amino acids (RSVAS; underlined in Fig. 1A, red box in Fig. 1C) in or near the ENaC FCS sequence shared with SARS-Cov-2 Spike are present in Spikes of sarbecoviruses, such as BANAL-20-52. It would be illogical to use the FCS from ENac rather than from a FCS of another coronavirus.

    Harrison and Sachs’s (1) claim that alignment of sarbecovirus Spike amino acid sequences illustrates “the unusual nature of the [SARS-CoV-2] FCS” is misleading. FCSs are common in coronaviruses, and present in representatives of four out of five betacoronavirus subgenuses (8). The highly variable nature of the S1/S2 junction is easily ascertained by inspecting a precise alignment of sarbecovirus Spikes (Fig. 1C).

    After commenting about the “unusual nature” of the SARS-CoV-2 FCS, Harrison and Sachs (1) then argue the opposite. With regard to our earlier publication (7), they write, “In fact, the assertion that the FCS in SARS-CoV-2 has an unusual, nonstandard amino acid sequence is false.” We made no such assertion. Rather, we noted that the SARS-CoV-2 FCS is “suboptimal.” We also noted, correctly, that placing the insertion out of frame would be “an unusual and needlessly complex feat of genetic engineering.”

    The immediate proximal ancestor of SARS-CoV-2 did not come directly from a bat to a human, but first evolved in an intermediate host. Two related lineages of SARS-CoV-2—lineage A and lineage B—first infected humans via the wildlife trade at the Huanan Market in Wuhan (9, 10). For the ENaC hypothesis to be true, UNC or WIV researchers would have had to possess the direct SARS-CoV-2 progenitor isolated from another animal—not a bat.

    Harrison and Sachs (1) allege that scientists at NIH and elsewhere, including myself and colleagues, conspired to suppress theories of a laboratory origin of SARS-CoV-2. This is false. A possible laboratory origin of SARS-CoV-2 was discussed in our earlier publications (6, 7). 

    References

    1. N. L. Harrison, J. D. Sachs, A call for an independent inquiry into the origin of the SARS-CoV-2 virus. Proc. Natl. Acad. Sci. U.S.A. 119, e2202769119 (2022).
    2. P. Anand, A. Puranik, M. Aravamudan, A. J. Venkatakrishnan, V. Soundararajan, SARS-CoV-2 strategically mimics proteolytic activation of human ENaC. eLife 9, e58603 (2020).
    3. A. García-Caballero, Y. Dang, H. He, M. J. Stutts, ENaC proteolytic regulation by channel-activating protease 2. J. Gen. Physiol. 132, 521–535 (2008).
    4. P. Kota, M. Gentzsch, Y. L. Dang, R. C. Boucher, M. J. Stutts, The N terminus of α-ENaC mediates ENaC cleavage and activation by furin. J. Gen. Physiol. 150, 1179–1187 (2018).
    5. S. Temmam et al., Bat coronaviruses related to SARS-CoV-2 and infectious for human cells. Nature 604, 330–336 (2022).
    6. K. G. Andersen, A. Rambaut, W. I. Lipkin, E. C. Holmes, R. F. Garry, The proximal origin of SARS-CoV-2. Nat. Med. 26, 450–452 (2020).
    7. E. C. Holmes et al., The origins of SARS-CoV-2: A critical review. Cell 184, 4848–4856 (2021).
    8. Y. Wu, S. Zhao, Furin cleavage sites naturally occur in coronaviruses. Stem Cell Res.50, 102115 (2020).
    9. J. E. Pekar et al., The molecular epidemiology of multiple zoonotic origins of SARS-CoV-2. Science 377, 960–966 (2022).
    10. M. Worobey et al., The Huanan Seafood Wholesale Market in Wuhan was the early epicenter of the COVID-19 pandemic. Science 377, 951–959 (2022).

     

    https://orcid.org/0000-0002-5683-3250

    rfgarry@tulane.edu

    September 29, 2022 PNAS USA 119 (40) e2211107119

    https://doi.org/10.1073/pnas.2211107119


    Continuation of thread:





    Sander, AL., Moreira-Soto, A., Yordanov, S. et al. Genomic determinants of Furin cleavage in diverse European SARS-related bat coronaviruses. Commun Biol 5, 491 (2022). https://doi.org/10.1038/s42003-022-03421-w


    Summary

    The furin cleavage site (FCS) in SARS-CoV-2 is unique within the Severe acute respiratory syndrome–related coronavirus (SrC) species. We re-assessed diverse SrC from European horseshoe bats and analyzed the spike-encoding genomic region harboring the FCS in SARS-CoV-2. We reveal molecular features in SrC such as purine richness and RNA secondary structures that resemble those required for FCS acquisition in avian influenza viruses. We discuss the potential acquisition of FCS through molecular mechanisms such as nucleotide substitution, insertion, or recombination, and show that a single nucleotide exchange in two European bat-associated SrC may suffice to enable furin cleavage. Furthermore, we show that FCS occurrence is variable in bat- and rodent-borne counterparts of human coronaviruses. Our results suggest that furin cleavage sites can be acquired in SrC via conserved molecular mechanisms known in other reservoir-bound RNA viruses and thus support a natural origin of SARS-CoV-2.



    0

    Add a comment


  10. Results of clinical research published19 Sep 2022: 

    Clinical Perspective

    What Is New?

    • In a cohort study of 48 million adults in England and Wales, COVID-19 was associated with substantial excess incidence of both arterial thromboses and venous thromboembolism, which declined with time from COVID-19 diagnosis.

    • Excess incidence was higher, for a longer time, after hospitalized than non-hospitalized COVID-19.

    • There were an estimated 10 500 excess arterial thromboses and venous thromboembolic events after 1.4 million COVID-19 diagnoses.

    What Are the Clinical Implications?

    • Strategies to prevent vascular events after COVID-19 are particularly important after severe COVID-19 leading to hospitalization and should include an early review in primary care and risk factor management.

    • After severe COVID-19, individuals at high risk of vascular events should be prescribed preventive therapies and counseled about the importance of adherence to them.

    • New simple treatment strategies to reduce infection-associated venous thromboembolism and arterial thromboses are needed.

    From 
    Association of COVID-19 With Major Arterial and Venous Thrombotic Diseases: A Population-Wide Cohort Study of 48 Million Adults in England and Wales
    Rochelle KnightVenexia WalkerSamantha Ip, and others

    Originally published
    19 Sep 2022
    Circulation. 2022;146:892–906



    0

    Add a comment

Subscribe
Subscribe
Loading