Category Archives: Human Genetic Engineering

Click on any icon to hear that co-authors perspective on what the proposed guidelines mean for the region in which they work. Map compiled by Stephanie Dutchen

HMNews: What is the main goal of having a set of international guidelines?

Kendra Sirak: While some countries have developed rigorous standards that guide the scientific analysis of human remains, many others have few or no guidelines that ensure that this work is carried out responsibly and is both scientifically robust and sensitive to community perspectives. Everyone wants practical guidance that will be positive about the research enterprise while embracing high ethical standards.

Its our hope that these guidelines will raise the integrity of ancient DNA research around the world by minimizing damage to collections of human remains; ensuring sensitivity to the perspectives of stakeholder groups, especially when these groups are marginalized; and reducing opportunities for the misuse of results. We expect these guidelines will undergo further development as the field continues to evolve.

HMNews: Why now?

Jakob Sedig: Ancient DNA as a field has been growing rapidly, evolving from a promising technology to a mature field. The discussion about how to handle human remains and how to meaningfully involve diverse stakeholders has not yet caught up. More and more people are calling for clear, strong guidance that all researchers engaged in ancient DNA work can embrace.

Ancient DNA analysis has contributed vital new insights about the human past and has helped us understand the genetic roots of human diversity. It has disrupted nationalist and xenophobic narratives. It has challenged what many of us thought we knew about who we are and where we came from. But like any field that matters, its complex.

Because of the number of ancient individuals being analyzed, the socialand political nature of the work, and the challenges that ancient DNA findings have raised about theories proposed before we had such data, people are paying attention to ancient DNA. That makes it even more vital to articulate and adopt strong guidelines that work well everywhere.

HMNews: How did the team come up with these five guidelines?

Sedig: We took cues from archaeology and modern human genetics, which have established protocols for carrying out analyses on human remains and establishing stakeholder consent. We built on aspects of existing guidelines, such as those crafted by a group of North American scholars, including Indigenous scholars, published last year in the American Journal of Human Genetics.

Our diverse co-author groupparticularly those in Central and South America, Africa, Europe, South Asia, the Pacific, and East Asiafelt that these and other suggestions, while valuable, were not applicable in all world regions. Our virtual workshop led to monthslong discussions that took many different value systems and histories into account and sought balance between local contexts and general principles. We then wrote the manuscript.

Given that there was near-unanimous support and excitement about the final document among the workshop participants, we hope the broader community will embrace and build on these proposals. It would be wonderful if the proposals form a basis for official guidelines in the future.

HMNews: Why not just follow national or local government regulations wherever a project is being conducted?

Sirak: There are some places where laws are robust enough for that to be appropriate, but in other locales, we feel that researchers need to hold themselves to a higher standard than required by the laws currently in place.

HMNews: What are some of the needs and unique circumstances in different regions that shaped the guidelines?

Sirak: We have found that guidelines that work well for one region can come across as condescending or even colonialist in another. Many co-authors on this manuscript raised the point that indigeneity has different meanings in different places and is even used in some regions as a framework for oppression and discrimination against minority groups argued to be non-Indigenous. Thus, basing research ethics on a single definition can inadvertently reinforce rather than mitigate power imbalances in conducting and interpreting genetic analyses.

The videos our co-authors have shared speak to the many nuances of ethical ancient DNA research in the places where they live and work.

HMNews: Some critics say that ancient DNA research, which to a large extent has focused on and been conducted by white people from wealthy nations, has been a colonialist endeavor that siphons agency from marginalized groups. How do the proposed guidelines address these discussions about power and ownership?

Sedig: These are important conversations. We cant reiterate enough that our goal is to learn about the past in a sensitive, thoughtful, and ethical way. We do not want to contribute to exploitation; we want to do the opposite. We need to listen to and respect the people who are stakeholders in ancient DNA studiesincluding groups from the place of origin of the human remains being studiedand make sure their perspectives are represented in discussions about study design, research questions, and whether a project should proceed at all. Theres been a huge amount of progress in recent years in seeking local perspectives from the start to the conclusion of a study and incorporating that feedback into the project and publication. We have increasingly diverse groups of people who conduct the research as well.

We want to minimize harm and reduce inequity, and I believe the ancient DNA community has an extraordinary track record of providing arguments that do so. We know that in regions with histories of settler colonialism, we have to center Indigenous perspectives. We have to confront the colonial legacies of human remains collected in unethical ways and often sent abroad, and we should seek ways to mend the harms done, such as by considering how our research findings or the methods we are using might be helpful tools for facilitating repatriation of remains. We must ensure that local scientists and communities are as engaged as can be in ancient DNA research, particularly in places with histories of scientists conducting exploitative research. Researchers working in countries outside their own must prioritize establishing equitable collaborations that benefit local scholars and avoid carrying out parachute research at all costs.

When possible, those of us in positions of privilege should contribute to reducing structural inequities. Some ideas we propose in the guidelines are to help educate and train local community members and other stakeholders, assist with raising the curatorial standards of collections or developing museum exhibits, provide funds for training or attending professional meetings, and advocate for funding agencies to build more capacity for equitable ancient DNA research. We also need to ensure that we communicate results in ways that are accessible to nonscientists and the broader scholarly community. Lastly, we have to oppose those who use genetic data to support narratives of group superiority or to justify exclusionary policies.

At the same time, as scientists we need to make sure we can proceed in a way consistent with the scientific method. We cant ethically conduct a study without the guarantee that we can follow the data where they lead. This means that once stakeholder communities agree that publishing results would not cause them harm, the relevant portion of a manuscript wont be restricted. It also means the data must be made accessible at least so others can replicate or reevaluate results.

We have a loyalty to the facts we uncover as we learn about our shared humanity. In cases where the data we generate dont align with other forms of knowledge, such as traditional expertise or cultural beliefs, it is not our job to discredit or diminish that knowledge. Rather, those discrepancies highlight how complex an undertaking it is to understand the past and should be flagged in papers that result from the work.

Regarding ownership, we believe that whenever researchers are granted permission to study the remains of ancient individuals, they become stewards of that material with a responsibility to care for and respect it. They do not assume ownership of the remainsor of the data that arise from sequencing it.

HMNews: Some groups assert that stakeholder communities should decide whether and how certain kinds of ancient DNA data can be used in future analyses. How does this fit with the teams push for open data?

Sirak: We advocate for stakeholders having input into how data should be distributed and we advocate for open data. We believe that both goals can coexist.

Many of our co-authors felt strongly that ancient DNA data should always be made fully and publicly available. Other co-authors argued that when it comes to data from remains that might be meaningfully connected to present-day Indigenous communities, it could be appropriate to have usage restrictions. This was one of many debates we had, and in listening to one another, some of us changed our positions.

We all agreed that open data for ancient DNA is something to strive for. The data must be made available after publicationeither through full open access, which is ideal, or distributed by a professional organization without a stake in the research resultsso scholars can reproduce or challenge analyses. This also lowers the chances study results will be misused. We are proud that the raw data for nearly all ancient genomes published so far was made publicly available at or before the time of publication.

Finally, we agreed that Indigenous-led data repositories such as those now being developed could help mediate permissions when scholars wish to use data for purposes beyond those articulated in an original study plan.

HMNews: Given that equity is a priority, how accessible will this paper be to those who, for example, dont have paid access to the journal in which its being published or who arent fluent in English?

Sirak: Weve made our paper open access and applied the most flexible Creative Commons license to it, known as CC BY 4.0. That means its available for free to anyone in the public to read, distribute, adapt, and build upon. Our team members also have translated the text into more than 20 languages that they speak.

HMNews: Do you expect pushback from scientists who feel that the guidelines are too onerous and will make it harder to carry out research?

Sedig: We did receive feedback during the review process that the guidelines were too strongthat they would create a heavy burden for researchers from smaller labs or who are in the early stages of their careers. We respect this perspective and understand that were requesting a lot in terms of engaging with stakeholders and what could be called overhead beyond the research itself. However, we firmly believe that all ancient DNA studies, from an early-career stage onwards, should meet these ethical standards.

In a way, the proposals are merely concretizing the standards that are already emerging in the field. We believe that authors and journal editors feel their way toward this ethical framework during the review process. We believe that the proposals are practical and that early-career researchersincluding many who co-authored our articlewill benefit from having the principles clearly articulated and the guesswork reduced as they aim to carry out their research in an ethically principled way.

HMNews: What enforcement would there be if someone involved in ancient DNA research didnt follow these guidelines?

Sirak: Our co-authors do not represent any official organization, so we cannot make or enforce rules for anyone except ourselves. What our paper does represent is a grassroots, community-led pledge from representatives of a nontrivial faction of worldwide researchers engaged in this type of work. We have committed to adhering to a set of strong principles, and we invite others to hold us accountable to them.

It would be a great outcome if scientific journals, professional societies, or granting agencies found these proposals useful enough to turn into official guidelines, which would mean there could be professional repercussions for not adhering to them. The fact that scholars from such a diverse array of nations and disciplines have signed on to the guidelines at this stage makes us optimistic that they will be embraced in practice by laboratories and research groups as well as other groups engaged in ancient DNA research all over the world. But either way, its important to continue the global conversation.

This work was supported by the Australian Research Council Discovery Project (DP160100811), National Research Foundation South Africa, Brazilian National Council for Scientific and Technological Development (302163/2017-4), So Paulo Research Foundation/FAPESP (2018/23282-5), Francis Crick Institute (FC001595), Cancer Research UK, UK Medical Research Council, Wellcome Trust, Dutch Research Council (VI.C.191.070), Hungarian Academy of Sciences, Science and Engineering Research Board of India, Council of Scientific and Industrial Research in India (Ministry of Science and Technology, Government of India), European Research Council (ERC-2017-StG 804844-DAIRYCULTURES), Werner Siemens-Stiftung, John Templeton Foundation (6122), Howard Hughes Medical Institute, Max Planck Society, and the Max Planck Harvard Research Center for the Archaeoscience of the Ancient Mediterranean, and the National Geographic Society.

Interviews were edited for length and clarity.

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Proceeding with Caution | Harvard Medical School - Harvard Medical School

September 24, 2019

The Pew Research Center has reported that more and more people identify themselves as spiritual but not religious. How can this be explained in our highly technoscientific age? Since technoscience is taken to be secular, how can we make sense of the relationship between our radical technoscientific advances and our search for spirituality?

A group of Arizona State University researchers will explore these and other questions through a project titled Beyond Secularization: A New Approach to Religion, Science and Technology, which has received a $1.7M grant from the Templeton Religion Trust.

The Center for the Study of Religion and Conflict will serve as the lead unit for this major interdisciplinary initiative that seeks to explore the underlying assumptions about science and technology research, exploring whether religious ideas shape scientific research directions and revealing new models for understanding ideas of progress.

Conflicts at the borders of religion, science and technology have been a major research area of the centers since its inception in 2003. Partnering withHava Tirosh-Samuelson, now a Regents Professor and director of Jewish studies, the center launched a faculty seminar in 2004 that met for almost 15 years. Several externally funded projects that grew out of the seminar supported a major lecture series, international research conferences and numerous publications.

All of this work positioned the center for this latest project, which has the potential to have a major impact in how we understand not only the interplay between religion, science and technology in public life, but also how we understand ideas and meanings of progress.

Beyond Secularization builds on a small pilot project that produced over 20 articles, including a cover story in the January issue of Sojourners magazine. It will establish a collaboratory that will include graduate students, postdocs and faculty who will develop and advance new research methods and understandings over the next three to four years.

To learn more about the subject, ASU Now sat down with Tirosh-Samuelson,Ben Hurlbut,School of Life Sciences associate professor,andGaymon Bennett, School of Historical, Philosophical and Religious Studies associate director of research and associate professor,who will serve as co-principal investigators.

Question: What does the title of this project refer to?

Hurlbut: The project looks at the relationships between religion, science and technology in several important domains of public life: in environmental movements, in shifting ideas of the spiritual self that draw upon science, in arenas of high-technology innovation that are reshaping how we live and in the ways societies debate and govern the ethical implications of biotechnological transformation of life, including human life. We want to understand how science, technology and religion are related in those domains, including how lines are drawn between them. There is a pretty widespread assumption that as scientific knowledge and technological capacity increase, religion retreats into the background. And yet, if you look at how people think and talk, things are a lot messier. Go to Silicon Valley and you will encounter a lot of people who are imagining a technological future in terms of its potential to bring a kind of redemption and transcendence, a kind of eschatology. In other domains, like in public debate about biotechnologies, like human genome editing, there is a lot of drawing of lines between scientifically-grounded ethical views versus religious ones. But in all these areas, the boundaries are less clear than we tend to assume. They are a lot more mixed, a lot more hybrid, a lot fuzzier. And understanding that is important for how we think about the relationships between science, technology and religion in contemporary public life.

Q: How is this project unique?

Tirosh-Samuelson: The core work of this project will be done by a collaborative lab (co-lab, for short), which will include the three principal investigators, invited faculty, postdoctoral fellows and graduate students. This group will be studying together and will host visiting scholars from other universities around the world who will help enrich the discussion about big picture questions. The work of the co-lab will be distinctly interdisciplinary, crossing boundaries between history, science and technology studies, religious studies, sociology and anthropology. Our basic conviction is that to understand the interplay between religion, science and technology, we need to pose new questions and engage new methods. The artificial dichotomy between science and religion is no longer valid and even talking about a dialogue between religion and science is insufficient. We need to develop deeper ways to understand how these domains operate in our public life, and to do so, we must engage new disciplines that previously have not been applied to this field of inquiry. Since the project engages religion, science and technology in public life, it will have a public component, including public lectures that will involve the entire ASU community as well as an outreach program to people outside the ASU community, such as high-tech innovators in various innovations enclaves (e.g. Silicon Valley). The public aspect of the project exemplifies ASUs commitment to social embeddedness and to breaking the boundaries between the academy and the community.

"Theres been this sort of assumption that as technology progresses, as knowledge progresses, we get less religious, we become more secular."

Ben Hurlbut,School of Life Sciences associate professor

Q: Why do we see such pronounced boundaries between the religious and the secular in academia?

Hurlbut: Theres been this sort of assumption that as technology progresses, as knowledge progresses, we get less religious, we become more secular. That assumption has also been built into the way some fields study modern life, whether or not that actually corresponds with people's lived experience. So one of the things that we want to do is ask, "What are the things that we're overlooking?" Because we have operated in the social sciences, to a very significant degree, under the assumption that secularization is an inevitable result of modernization and progress, religion is either left behind or pushed to the side. It drops out of public life and becomes privatized. So, the disciplines have sort of carved themselves up in ways that are mapped onto assumptions about the world and knowledge that may not actually be correct.

Q: How have the boundaries between the religious and the secular changed over time?

Bennett: Theres this widespread belief today that if you want to transform the world, you don't really need religion. Your just need science and technology. And yet if you go someplace like Silicon Valley and you walk down Sand Hill Road and walk into a coffee shop and you sit and listen to innovators talk about what they're doing, theyre all talking about transforming the most fundamental aspects of what it means to be human. And if you tune in closely, all sorts of kinds of topics that we used to associate with religion or spirituality are being talked about in relation to technology. Questions like what does it mean to be a being with a finite body? Can we overcome our own frailty and even cure aging? What does it mean to be connected to other people and to our environments? What does it mean for us to be able to build infrastructures in the world that promised to united us together but have become the engine for so much division?

"When we study religious environmentalism, we have to think anew about terms such as 'secular,' 'religious,' 'worldliness' and 'otherworldliness.'"

Hava Tirosh-Samuelson, Regents Professor and director of Jewish studies

Q: What are some other areas where we see this happening?

Tirosh-Samuelson: The area that I work on is religious environmentalism. This movement emerged in the U.S. in the 1960s when people began to be aware of the ecological crisis. Interestingly, some of the scientists who were first to note the crisis were religious practitioners who considered the environmental crisis an assault on Gods created world. The interreligious movement of religious environmentalism and the academic discourse on religion and ecology illustrate the porous boundaries between science and religion or between the religious and secular aspects of life. For religious environmentalists, the natural world, or the environment, is not simply inert matter that can be known only through science, but rather the expression of divine creativity. When we study religious environmentalism, we have to think anew about terms such as secular, religious, worldliness and otherworldliness. Our analysis of religious environmentalism is not only historically grounded, it is also attentive to religious diversity and religious differences. The way we think about the relationship between religion and science reflects the legacy of Christianity. But other world religions, for example Judaism, Islam, Hinduism or Buddhism approach these issues quite differently. In addition to religious diversity, we are going to interrogate the category of spirituality as a hybrid category that fuses the secular and the religious. We can see it in regard to environmentalism but also in other domains such as medicine and the wellness industry. But what does it mean to be spiritual but not religious and how does spirituality express itself? We will seek to address these questions.

"What does it mean to alter a world our children will inherit?"

Gaymon Bennett,School of Historical, Philosophical and Religious Studies associate director of research

Q: How are these questions relevant to peoples everyday lives?

Bennett: It's not incidental that the three research areas for this project are three areas that are some of the major areas of collective crisis in the world today. On one level, these areas seem so timely, so current the question of bioengineering will transform our bodies, or how digital innovation will change our sense of ourselves. But on another level, these are really old, really fundamental questions: What does it mean to alter a world our children will inherit? How do our religious and spiritual views of reality shape what gets to count as important, or desirable or dangerous? Our lives are saturated with science and technology. Its fundamentally changing how we relate to ourselves our bodies, our planet, our food, our lovers, our sense of a higher reality. And then of course theres the environmental crisis and the question of what we modern people have done to our relationship with nature, whether it has intrinsic meaning and what that might be. All of these areas cut across time, place, culture and tradition, and are some of the most pressing issues that humanity is facing today.

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ASU event to address human dignity and technoscience - ASU Now

Its the rumour that wont go away that SARS-CoV-2 was accidentally leaked from a high biosecurity lab in Wuhan, China. The allegation is that the laboratory was conducting gain of function (GOF) research, and that this produced a potent version of coronavirus that led to the pandemic.

This has led to some scepticism and distrust of the field of research and whether it is necessary to conduct experiments using GOF techniques.

Essentially, GOF research is used to learn how viruses gain new functions through mutation and evolution.

A function is simply a property of an organism, such as plants that are more tolerant to drought or disease, or enzymes that evolved to make our bodies work.

The language about GOF has become loaded with negative connotations that associate this work with dangerous or risky research. But like rhetoric about genetic modification, these connections dont represent the diversity of the field or the security precautions that regulate the research. At its core, though, the research does exactly what the name suggests.

GOF research observes these mutations and sees how certain stimuli might affect evolutionary changes and properties of a virus or organism.

However, in our current climate its often spoken about in a much narrower context, as though its specifically about how a virus changes to move more easily between humans, or how viruses become more lethal. This just doesnt represent the full picture of GOF research.

Viruses evolve rapidly thats why there are so many new SARS-CoV-2 variants. GOF seeks to understand why and how these changes occur, and what environmental factors might influence the process.

In a sense, this is a know-your-enemy approach.

Beyond the benefit to fundamental biology research about the nature of viruses and evolution, GOF contributes to three clear areas: pandemic preparedness, vaccine development, and identification of new or potential pathogens.

GOF research can help us understand the rate at which mutations occur, and how many generations may be needed for a virus to change in a way that will require extra precautions in the community, which is information that is fed into epidemiological modelling.

This GOF information helps predict things such as how likely a virus is to become a nasty variant in a certain population size or density, during a certain season, or within a particular period or time. This informs how we react to a pandemic. Beyond this, it also informs how quickly a virus might mutate to overcome vaccines, and provides genetic information that may be useful in vaccine development. Specifically, GOF research can accumulate potential vaccine candidates in a database that can be accessed if an outbreak occurs because of natural evolution.

In turn, this means vaccine development can be sped up exponentially because candidates are already available.

For instance, a report from a 2015 GOF risk-assessment workshop for expert organisations revealed the genomics information from GOF research. This showed that bat-borne, SARS-like coronaviruses had many strains and mutations that had pandemic potential against which countermeasures need to be developed.

This information led to current pandemic responses and vaccine development the pandemic was already predicted because of a thorough understanding of the evolution of coronaviruses.

In another example, GOF experiments about influenza showed that the virus had the potential to be transmitted between different mammals with only a few changes to the genetic code, and has contributed to seasonal flu vaccines.

GOF research is based on observed evolution and changes to DNA or RNA.

The genome is the sum of all the genetic information in an organism. Some of this DNA or RNA is made up of genes, which often hold information on how to make a protein. These proteins perform functions in our body to make everything work.

These genes can naturally change a bit every generation. This happens because, to reproduce, the DNA of the parent must be replicated. The mechanisms that do this arent perfect, so little mistakes can be made when the DNA is copied.

Most of the time, the changes are tiny just a single unit of DNA (called a nucleotide) could be changed, and it may have no effect on the proteins made. At other times, the tiny change of a single nucleotide can make a gene gain a whole new function, which could be beneficial to an organism.

Natural mutations that occur during reproduction are one example of evolution in action.

These changes happen every generation, so organisms that can breed quickly, such as flies, can also evolve quickly as a species.

This process happens in essentially the same way with viruses, except that viruses have RNA instead of DNA and reproduce asexually. They still make proteins, and they still accumulate mutations, but the major difference is that they can reproduce very, very fast they can start reproducing within hours of being born and evolve at an exceptionally rapid rate.

This is why we have identified so many new variants of SARS-CoV-2 since the beginning of 2020. Every time the virus enters a new host, it reproduces rapidly, and mutations occur. Over time these mutations change the properties of the virus itself.

For example, new mutations may end up making the virus more virulent or cause worse symptoms because the proteins have changed their properties.

In these cases, we would say that the mutant strain has gained a function, and this is what GOF research aims to understand.

The viruses in a lab dont have a human host in which to grow, so researchers grow them in Petri dishes or animals instead.

There are two ways of using GOF in a lab: you can observe the virus mutate on its own (without intervention), or you can control small changes through genetic modification.

The first type of use involves putting the virus in different situations to see how it will evolve without intervention or aid.

This video is an example of GOF research with bacteria (not a virus, but the method is similar). The researchers put bacteria onto a giant petri dish with different concentrations of antibiotics. They leave the bacteria and watch how it naturally evolves to overcome the antibiotic.

The new strains of bacteria were able to be genetically sequenced to see what genetic changes had caused them to become antibiotic-resistant. This experiment can show how quickly the bacteria evolve, which can inform when or how often antibiotics are given, and whether there is a high-enough concentration of antibiotic that can halt the speed at which the antibiotic is overcome by resistance.

Similar experiments can be conducted with viruses to see how they might change to overcome human antibodies and other immune system protections.

Read more: What happens in a virology lab?

The second type of use is through small changes using genetic modification. This type of experiment occurs after a lot of other genetic information has already been gathered to identify which nucleotides in virus RNA might particularly contribute to a new function.

After these have been identified, a single or small nucleotide change will be made to the virus to confirm the predictions gained from genomic research. The modified virus will then be placed on a petri dish or inserted into an animal, such as a rabbit or a mouse, to see how the change affects the properties of the virus.

This type of research is done in specialised laboratories that are tightly controlled and heavily regulated under biosecurity laws that involve containment and decontamination processes.

Read more: How are dangerous viruses contained in Australia?

While the benefits of virus GOF research centre around pandemic preparedness, concerns have been raised about whether the research is ethical or safe.

In 2005, researchers used this technique for viruses when they reconstructed influenza (H1N1) from samples taken in 1918. The aim was to learn more about the properties of influenza and future pandemics, as influenza still circulates, but the controversial study sparked heavy debate about whether it should be acceptable.

The two major concerns are about whether this poses any threat to public health if a virus escapes the lab, or whether the techniques could be used for nefarious purposes.

In the past year, 16 years after the H1N1 study, there has been debate about whether SARS-CoV-2 had spontaneous zoonotic origins, or whether it was created in a lab in GOF experiments, and then escaped.

So now, 16 years after the first controversial H1N1 study, this speculation has pushed GOF research back into the public eye and led to many criticisms of the research field, and regulation of laboratories that use this technique.

In 2017, the US government lifted bans on GOF pathogen research after the National Institute of Health concluded that the risks of research into influenza and MERS were outweighed by the benefits, and that few posed significant threats to public health.

Following concerns about the origins of SARS-CoV-2, however, the rules surrounding GOF research, risk assessments and disclosure of experiments are now under review again, in order to clarify policy.

Read more: The COVID lab-leak hypothesis: what scientists do and dont know

Beyond this, the speculation has sparked further inquiries into the origin of SARS-CoV-2, although the World Health Organization concluded that viral escape from a laboratory was very unlikely.

Regardless, its never a bad thing to review biosafety, biosecurity and transparency policy as new evidence becomes available, and they have been frequently reviewed throughout history.

As for the concern that a government or private entity might abuse scientific techniques for malevolent purposes, scientists can, and do, support bans on research they deem ethically irresponsible, such as the controversial CRISPR babies.

Ultimately, the parameters around how scientific techniques like GOF are used and by whom is not a scientific question, but one that must be answered by ethicists.

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What is gain of function research in genetics? - Cosmos Magazine

Amid the devastating Covid-19 pandemic, two researchers are proposing a drastic way to stop future pandemics: using a technology called a gene drive to rewrite the DNA of bats to prevent them from becoming infected with coronaviruses.

The scientists aim to block spillover events, in which viruses jump from infected bats to humans one suspected source of the coronavirus that causes Covid. Spillover events are thought to have sparked other coronavirus outbreaks as well, including SARS-1 in the early 2000s and Middle East respiratory syndrome (MERS).

This appears to be the first time that scientists have proposed using the still-nascent gene drive technology to stop outbreaks by rendering bats immune to coronaviruses, though other teams are investigating its use to stop mosquitoes and mice from spreading malaria and Lyme disease.

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The scientists behind the proposal realize they face enormous technical, societal, and political obstacles, but want to spark a fresh conversation about additional ways to control diseases that are emerging with growing frequency.

With a very high probability, we are going to see this over and over again, argues entrepreneur and computational geneticist Yaniv Erlich of the Interdisciplinary Center Herzliya in Israel, who is one of two authors of the proposal, titled Preventing COVID-59.

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Maybe our kids will not benefit, maybe our grandchildren will benefit, but if this approach works, we could deploy the same strategy against many types of viruses, Erlich told STAT.

As the Covid-19 pandemic has killed more than 3.9 million people and triggered $16 trillion in economic losses, scientists, public health officials, ecologists, and many others have called for deeper investments in longstanding pandemic prevention measures.

Such measures include boosting global health funding, reducing poverty and health inequity, strengthening disease surveillance networks and community education, preventing deforestation, controlling the wildlife trade, and beefing up investments in infectious disease diagnostics, treatments, and vaccines.

Erlich and his co-author, immunologist Daniel Douek at the U.S. National Institute of Allergy and Infectious Diseases, now propose an additional measure: creating a gene drive to render wild horseshoe bats immune to the types of coronavirus infections that are thought to have triggered the SARS, MERS, and Covid-19 pandemics. They shared the proposal Wednesday on the Github publishing and code-sharing platform.

Though there is heated debate about whether the Covid-19 virus originated in a lab, most scientists say the virus is most likely to have originated in wild animals. There is strong evidence, for instance, that horseshoe bats carry the coronavirus that caused the SARS outbreak.

A gene drive is a technique for turbocharging evolution and spreading new traits throughout a species faster than they would spread through natural selection. It involves using a gene editing technology such as CRISPR to modify an organisms genome so that it passes a new trait to its offspring and throughout the species.

The idea of making a gene drive in bats faces such enormous scientific, technical, social, and economic obstacles that scientists interviewed by STAT called it folly, far-fetched, and concerning. Among other objections, they worried about unintended consequences with so radically tampering with nature.

We have other ways of preventing future Covid-19 outbreaks, argued Natalie Kofler, a trained molecular biologist and bioethicist and founder of Editing Nature, a group focused on inclusive decision-making about genetic technologies.

We need to be thinking about changing the unhealthy relationship of humans and nature, not to gene drive a wild animal so that we can continue our irresponsible and unsustainable behavior that is going to come back to bite us in the ass in the future.

Coming from anyone else, the idea might be laughed off.

But Erlich has a reputation as a visionary. In 2014, for instance, he and another scientist predicted that genetic genealogy databases might one day be used to reveal peoples identities. Four years later, that happened, when law enforcement officials used the method to identify a former California police officer as the notorious Golden State Killer. Erlich has since become chief scientific officer of the genetic genealogy company MyHeritage and he is also founder of a biotech startup, Eleven Therapeutics.

Now, Erlich says, its worth thinking about how a gene drive could work in bats.

Erlich proposes to modify bat genomes so that they would block coronavirus infections. He would create a genetic element, called a shRNA, that targets and destroys coronaviruses. He would then use CRISPR to insert this element into the bat genome. The insertion would also contain a component that pushes bats to preferentially pass the shRNA to their offspring, so that entire bat populations would soon resist coronavirus infection.

Its almost like creating a self-propagating vaccine in these bats, Erlich said.

The idea is intriguing, said geneticist and molecular engineer George Church of the Wyss Institute for Biologically Inspired Engineering at Harvard University.

Most of the proposals Ive heard involving gene drives have seemed quite attractive, and this is probably the most attractive, he said.

Creating a gene drive in bats would be enormously difficult, and perhaps impossible, other scientists say. Researchers have created gene drives in mosquitoes and mice in the lab, but none has been released in the wild. The most advanced gene drive projects intended for field use involve modifying mosquitoes to prevent the spread of malaria and attempting to engineer mice to stop them from causing ecological damage.

But its been difficult to engineer effective gene drives in mammals. Developmental geneticist Kim Cooper and her team at the University of California, San Diego, engineered a gene drive that spread a genetic variant through 72% of mouse offspring in her lab. That isnt efficient enough to quickly spread the desired trait in the wild.

Whats more, creating a gene drive in bats would be much harder than it is in mice, because bat researchers lack the genetic tools available in mice, said Paul Thomas, a developmental geneticist at the University of Adelaide in Australia, who is trying to engineer mouse gene drives.

And unlike mice, which can breed at 6 to 8 weeks of age, bats take two years to reach sexual maturity, so it would take much longer for a trait to spread throughout wild bat populations than in lab mouse populations.

They say the proposal is not an easy feat from a technical standpoint, and I think that underplays how hard it might be, Cooper said.

Biologists also say that Erlichs proposal is unlikely to work in the wild even if researchers get bat gene drives to work in a lab because bats are incredibly diverse.

There are 1,432 bat species, including multiple horseshoe bat species that carry coronaviruses and pass them among each other.

Wild viruses similar to the human Covid-19 virus have been found in bats across Asia, and in pangolins. And in June, Weifeng Shi of the Shandong First Medical University & Shandong Academy of Medical Sciences in Taian, China, found 24 coronavirus genomes in bat samples taken from in and around a botanical garden in Yunnan province, in southern China.

Engineering one gene drive in just one bat species would not solve the problem, biologists say.

Youd have to develop systems for entire bat communities, said evolutionary biologist Liliana Dvalos of Stony Brook University. Its the job of visionaries to come up with creative ideas, but this is a giant blind spot in their thinking.

Biologists are also concerned about focusing on bats themselves, because they may not be the most important source of human epidemics. No one has found the exact bat analog to the human Covid-19 virus, or definitively proven that spillover from bats did start the pandemic. Coronaviruses have also been found in other species, including palm civets, pangolins, and camels.

Further, nobody knows how eliminating coronaviruses might affect bats.

We dont know the implications of wiping out coronaviruses in bat populations, because we dont know how bats have evolved to coexist with these viruses, said virologist Arinjay Banerjee of the Vaccine and Infectious Disease Organization at the University of Saskatchewan in Saskatoon, Canada.

Some scientists, though, welcomed Erlichs proposal, hoping that it will focus attention on what it would take to create successful mammalian gene drive systems.

Royden Saah, for instance, coordinates the Genetic Biocontrol of Invasive Rodents (GBIRd) program, which is trying to engineer gene drives in mice to prevent island bird extinctions. He wants to see more funding to help scientists solve the technical obstacles to such projects, and involve more communities in discussions about these ideas.

I would be concerned if this proposal detracted from the need to fund public health infrastructure, said Saah. But with that caveat, he added, I think this proposal could make people think, OK, if we were to use this technology in this animal in this system, what would we need to do? There would need to be a foundation of ethical development, of clear understanding, of social systems and trust, and technology built in a stepwise manner.

Virologist Jason Kindrachuk of the University of Manitoba said that there are numerous technical and political challenges to a bat gene drive project, and that preventing future outbreaks should mainly involve tackling the challenges that drive spillover events, such as underfunded public health systems, poverty, food insecurity and climate-change-driven ecological disruption. But, he said, given the enormous economic and human toll of Covid-19 and other recent outbreaks, scientists and public health officials might also need to consider new approaches.

In the past, maybe we were blinded a little bit by our belief that we would just be able to increase surveillance and identify these pathogens prior to them spilling over, Kindrachuk said. We now realize that this is going to take a lot of different efforts, so theres an aspect from a research standpoint where we continue to look at things like this, and say, what are the top 5 to 10 things we should invest in.

Erlich acknowledges the obstacles to his proposal, but thinks they arent insurmountable. He thinks the project would require an international investment involving a multidisciplinary consortium.

While we totally agree about the technical complexities, technology advances at exponential rates, Erlich said. Things that are nearly impossible now can be totally reachable within a decade or so.

He also thinks a gene drive could be a better alternative than culling bats, which has been tried (unsuccessfully) in communities around the world, and that scientists could monitor for negative impacts on bat populations.

Lets discuss the idea and think about what we can do to identify a very rigorous and cautious way to test this approach, Erlich said. We dont like to mess with nature, but the current situation is not sustainable.

Excerpt from:
Could editing the genomes of bats prevent future pandemics? - STAT - STAT

For Baric, that research started in the late 1990s. Coronaviruses were then considered low risk, but Barics studies on the genetics that allowed viruses to enter human cells convinced him that some might be just a few mutations away from jumping the species barrier.

That hunch was confirmed in 200203, when SARS broke out in southern China, infecting 8,000 people. As bad as that was, Baric says, we dodged a bullet with SARS. The disease didnt spread from one person to another until about a day after severe symptoms began to appear, making it easier to corral through quarantines and contact tracing. Only 774 people died in that outbreak, but if it had been transmitted as easily as SARS-CoV-2, we would have had a pandemic with a 10% mortality rate, Baric says. Thats how close humanity came.

As tempting as it was to write off SARS as a one-time event, in 2012 MERS emerged and began infecting people in the Middle East. For me personally, that was a wake-up call that the animal reservoirs must have many, many more strains that are poised for cross-species movement, says Baric.

By then, examples of such dangers were already being discovered by Shis team, which had spent years sampling bats in southern China to locate the origin of SARS. The project was part of a global viral surveillance effort spearheaded by the US nonprofit EcoHealth Alliance. The nonprofitwhich has an annual income of over $16 million, more than 90% from government grantshas its office in New York but partners with local research groups in other countries to do field and lab work. The WIV was its crown jewel, and Peter Daszak, president of EcoHealth Alliance, has been a coauthor with Shi on most of her key papers.

By taking thousands of samples from guano, fecal swabs, and bat tissue, and searching those samples for genetic sequences similar to SARS, Shis team began to discover many closely related viruses. In a cave in Yunnan Province in 2011 or 2012, they discovered the two closest, which they named WIV1 and SHC014.

Shi managed to culture WIV1 in her lab from a fecal sample and show that it could directly infect human cells, proving that SARS-like viruses ready to leap straight from bats to humans already lurked in the natural world. This showed, Daszak and Shi argued, that bat coronaviruses were a substantial global threat. Scientists, they said, needed to find them, and study them, before they found us.

Many of the other viruses couldnt be grown, but Barics system provided a way to rapidly test their spikes by engineering them into similar viruses. When the chimera he made using SHC014 proved able to infect human cells in a dish, Daszak told the press that these revelations should move this virus from a candidate emerging pathogen to a clear and present danger.

To others, it was the perfect example of the unnecessary dangers of gain-of-function science. The only impact of this work is the creation, in a lab, of a new, non-natural risk, the Rutgers microbiologist Richard Ebright, a longtime critic of such research, told Nature.

To Baric, the situation was more nuanced. Although his creation might be more dangerous than the original mouse-adapted virus hed used as a backbone, it was still wimpy compared with SARScertainly not the supervirus Senator Paul would later suggest.

In the end, the NIH clampdown never had teeth. It included a clause granting exceptions if head of funding agency determines research is urgently necessary to protect public health or national security. Not only were Barics studies allowed to move forward, but so were all studies that applied for exemptions. The funding restrictions were lifted in 2017 and replaced with a more lenient system.

If the NIH was looking for a scientist to make regulators comfortable with gain-of-function research, Baric was the obvious choice. For years hed insisted on extra safety steps, and he took pains to point these out in his 2015 paper, as if modeling the way forward.

The CDC recognizes four levels of biosafety and recommends which pathogens should be studied at which level. Biosafety level 1 is for nonhazardous organisms and requires virtually no precautions: wear a lab coat and gloves as needed. BSL-2 is for moderately hazardous pathogens that are already endemic in the area, and relatively mild interventions are indicated: close the door, wear eye protection, dispose of waste materials in an autoclave. BSL-3 is where things get serious. Its for pathogens that can cause serious disease through respiratory transmission, such as influenza and SARS, and the associated protocols include multiple barriers to escape. Labs are walled off by two sets of self-closing, locking doors; air is filtered; personnel use full PPE and N95 masks and are under medical surveillance. BSL-4 is for the baddest of the baddies, such as Ebola and Marburg: full moon suits and dedicated air systems are added to the arsenal.

There are no enforceable standards of what you should and shouldnt do. Its up to the individual countries, institutions, and scientists.

In Barics lab, the chimeras were studied at BSL-3, enhanced with additional steps like Tyvek suits, double gloves, and powered-air respirators for all workers. Local first-responder teams participated in regular drills to increase their familiarity with the lab. All workers were monitored for infections, and local hospitals had procedures in place to handle incoming scientists. It was probably one of the safest BSL-3 facilities in the world. That still wasnt enough to prevent a handful of errors over the years: some scientists were even bitten by virus-carrying mice. But no infections resulted.

In 2014, the NIH awarded a five-year, $3.75 million grant to EcoHealth Alliance to study the risk that more bat-borne coronaviruses would emerge in China, using the same kind of techniques Baric had pioneered. Some of that work was to be subcontracted to the Wuhan Institute of Virology.

Read the original:
Inside the risky bat-virus engineering that links America to Wuhan - MIT Technology Review

ROME, July 2 A United Nations-backed scientific research centre hasteamedupwith an Italian tech firm to explore whetherlaserlight can be used to kill coronavirusparticles suspended in the air and help keep indoor spaces safe.

The joint effort between the International Centre for Genetic Engineering and Biotechnology (ICGEB) of Trieste, a city in the north ofItaly, and the nearby Eltech K-Lasercompany, was launched last year as COVID-19 was battering the country.

They created a device that forces air through a sterilization chamber which contains alaserbeam filter that pulverizesviruses and bacteria.

I thoughtlasers were more for a shaman rather than a doctor but I have had to change my mind. The device proved able to kill theviruses in less than 50 milliseconds, said Serena Zacchigna, groupleader for Cardiovascular Biology at the ICGEB.

Healthy indoor environments with a substantially reduced pathogen count are deemed essential for public health in the post COVID-19 crisis, a respiratory infection which has caused more than four million deaths worldwide in barely 18 months.

Zacchigna hookedupwith Italian engineer Francesco Zanata, the founder of Eltech K-Laser, a firm specialised in medicallasers whose products are used by sports stars to treat muscle inflammation and fractures.

Some experts have warned against the possible pitfalls of using light-based technologies to attack thevirusthat causes COVID-19.

A study published by the Journal of Photochemistry & Photobiology in November 2020 highlighted concerns ranging from potential cancer risks to the cost of expensive light sources.

But Zacchigna and Zanata dismissed any health issues, saying thelasernever comes into contact with human skin.

Our device uses nature against nature. It is 100% safe for people and almost fully recyclable, Zanata told Reuters.

The technology, however, does not eliminateviruses and bacteria when they drop from the air onto surfaces or the floor. Nor can it prevent direct contagion when someone who is infected sneezes or talks loudly in the proximity of someone else.

Eltech K-Laserhas received a patent from Italian authorities and is seeking to extend this globally.

The portable version of the invention is some 1.8 metres (5.9 ft) high and weighs about 55 lb. The company said the technology can also be placed within air-conditioning units.

In the meantime, the first potential customers are liningup, including Germanys EcoCare, a service provider of testing and vaccination solutions.

The company aims to license the technology for German and UAE markets, an EcoCare spokesperson said in an email to Reuters.

See the rest here:
Science, industry team up in Italy to zap COVID with laser - New York Post