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Category Archives: Human Genetic Engineering

Genomics and genre – Science

If the double helix is an icon of the modern age, then the genome is one of the last grand narratives of modernity, writes Lara Choksey in her new book, Narrative in the Age of the Genome. Hybridizing literary criticism with a genre-spanning consideration of a dozen distinct literary works, and imbued throughout with deep concern for the peripheral, the possible, and the political, the book seeks to challenge the whole imaginative apparatus for constructing the self into a coherent narrative, via the lexicon and syntax of the molecular.

To a reading of Richard Dawkins's The Selfish Gene (1976) as a repudiation of class struggle and E. O. Wilson's Sociobiology (1975) as a defense of warfare, Choksey juxtaposes another kind of ambiguous heterotopia in which genetic engineering is a tool of neoliberal self-fashioning. In Samuel R. Delany's Trouble on Triton (1976), Bron, a transgender ex-gigolo turned informatics expert, is caught between sociobiology and the selfish gene, between the liberal developmentalism of progressive evolution, and the neoliberal extraction and rearrangement of biological information. Even the undulating interruptions and parentheticals of Bron's thoughts [mimic] the description of the activation and silencing of genes, she suggests, tying together gene and genre in a way that encapsulates neoliberal alienation.

Choksey next explores the ways in which collectivist fantasies of biological reinvention under Soviet Lysenkoism fused code and cultivation through a close reading of Arkady and Boris Strugatsky's Roadside Picnic (1972) in which cultivated utopian dreamworlds become contaminated by alien forces, resulting in fundamental ecological transformations beyond the promised reach of human control. The novel brings to light not forgotten Soviet utopias but literal zombies and mutations. In a world where planned cultivation fails entirely in the face of the unfamiliar, even as new biological weapons are being developed, Earth itself viscerally reflects a fractured reality of lost promisesa world in crisis with all meaning gone, and survival itself a chancy proposition.

Framed as a family history, The Immortal Life of Henrietta Lacks is actually a horror story, argues Choksey.

As the promise of precision medicine emerged, so too did new forms of memoir. In Kazuo Ishiguro's Never Let Me Go (2005) and the film Gattaca (1997), for example, the traditional aspirational narrative of a pilgrim's progress is subverted: As the unitary subject disappears into data, algorithms, and commodities, a new grammar of existence emerges, albeit one in which the inherited problems of the pastracism, ableism, and the fiction of heteronormativityremain ever-present.

In Saidiya Hartman's Lose Your Mother (2006) and Yaa Gyasi's Homegoing (2016), Choksey sees a reorientation of genomics away from the reduction of self to code and toward new forms of kinship and belonging that offer a reckoning with the histories of brutalization and displacement upon which liberal humanism is founded. Even as genomics seeks to locate the trauma of enslavement at the level of the molecular, communities seeking reunion and reparation know that technology alone cannot do the cultural work of caring for history that narrative can offer.

Reading Rebecca Skloot's The Immortal Life of Henrietta Lacks (2010) as a biography of Black horror which tries, time and again, to resolve itself as family romance, Choksey identifies the perils of narratives unable to recognize their own genre. She argues that by blurring the lines not between fact and fiction but between horror and family history, the dehumanization of Black lives as experimental biomatter echoes inescapably with larger histories of the extraction of Black flesh for the expansion of colonial-capitalist production.

What emerges as most compelling out of this entire tapestry of readings is the author's interpretation of the limits and failures of the extraordinary cultural power of the genome. Concluding that genomics has privileged a particular conception of the human that is in the process of being reconfigured, Choksey ventures that the uncomplicated subject, the Vitruvian Man of the Human Genome Project, has reached its end. What is left is neither dust, stardust, nor a face erased in the sand (as Foucault would have it) but rather whatever might emerge next from the unwieldy kaleidoscope of possible meanings.

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Genetic Analysis Reveals Evolution of the Enigmatic Y Chromosome in Great Apes – SciTechDaily

Researchers have reconstructed the ancestral sequence of the great ape Y chromosome by comparing three existing (gorilla, human, and chimpanzee) and two newly generated (orangutan and bonobo) Y chromosome assemblies. The new research shows that many gene families and multi-copy sequences were already present in the great ape Y common ancestor and that the chimpanzee and bonobo lineages experienced accelerated gene death and nucleotide substitution rates after their divergence from the human lineage. Credit: Dani Zemba and Monika Cechova, Penn State

Researchers reconstruct the ancestral great ape Y and show its rapid evolution in bonobo and chimpanzee.

New analysis of the DNA sequence of the male-specific Y chromosomes from all living species of the great ape family helps to clarify our understanding of how this enigmatic chromosome evolved. A clearer picture of the evolution of the Y chromosome is important for studying male fertility in humans as well as our understanding of reproduction patterns and the ability to track male lineages in the great apes, which can help with conservation efforts for these endangered species.

A team of biologists and computer scientists at Penn State sequenced and assembled the Y chromosome from orangutan and bonobo and compared those sequences to the existing human, chimpanzee, and gorilla Y sequences. From the comparison, the team was able to clarify patterns of evolution that seem to fit with behavioral differences between the species and reconstruct a model of what the Y chromosome might have looked like in the ancestor of all great apes.

A paper describing the research was published in the journal Proceedings of the National Academy of Sciences.

The Y chromosome is important for male fertility and contains the genes critical for sperm production, but it is often neglected in genomic studies because it is so difficult to sequence and assemble, said Monika Cechova, a graduate student at Penn State at the time of the research and co-first author of the paper. The Y chromosome contains a lot of repetitive sequences, which are challenging for DNA sequencing, assembling sequences, and aligning sequences for comparison. There arent out-of-the-box software packages to deal with the Y chromosome, so we had to overcome these hurdles and optimize our experimental and computational protocols, which allowed us to address interesting biological questions.

The Y chromosome is unusual. It contains relatively few genes, many of which are involved in male sex determination and sperm production; large sections of repetitive DNA, short sequences repeated over and over again; and large DNA palindromes, inverted repeats that can be many thousands of letters long and read the same forwards and backwards.

Previous work by the team comparing human, chimpanzee, and gorilla sequences had revealed some unexpected patterns. Humans are more closely related to chimpanzees, but for some characteristics, the human Y was more similar to the gorilla Y.

If you just compare the sequence identitycomparing the As, Ts, Cs, and Gs of the chromosomeshumans are more similar to chimpanzees, as you would expect, said Kateryna Makova, Pentz Professor of Biology at Penn State and one of the leaders of the research team. But if you look at which genes are present, the types of repetitive sequences, and the shared palindromes, humans look more similar to gorillas. We needed the Y chromosome of more great ape species to tease out the details of what was going on.

The team, therefore, sequenced the Y chromosome of a bonobo, a close relative of the chimpanzee, and an orangutan, a more distantly related great ape. With these new sequences, the researchers could see that the bonobo and chimpanzee shared the unusual pattern of accelerated rates of DNA sequence change and gene loss, suggesting that this pattern emerged prior to the evolutionary split between the two species. The orangutan Y chromosome, on the other hand, which serves as an outgroup to ground the comparisons, looked about like what you expect based on its known relationship to the other great apes.

Our hypothesis is that the accelerated change that we see in chimpanzees and bonobos could be related to their mating habits, said Rahulsimham Vegesna, a graduate student at Penn State and co-first author of the paper. In chimpanzees and bonobos, one female mates with multiple males during a single cycle. This leads to what we call sperm competition, the sperm from several males trying to fertilize a single egg. We think that this situation could provide the evolutionary pressure to accelerate change on the chimpanzee and bonobo Y chromosome, compared to other apes with different mating patterns, but this hypothesis, while consistent with our findings, needs to be evaluated in subsequent studies.

In addition to teasing out some of the details of how the Y chromosome evolved in individual species, the team used the set of great ape sequences to reconstruct what the Y chromosome might have looked like in the ancestor of modern great apes.

Having the ancestral great ape Y chromosome helps us to understand how the chromosome evolved, said Vegesna. For example, we can see that many of the repetitive regions and palindromes on the Y were already present on the ancestral chromosome. This, in turn, argues for the importance of these features for the Y chromosome in all great apes and allows us to explore how they evolved in each of the separate species.

The Y chromosome is also unusual because, unlike most chromosomes it doesnt have a matching partner. We each get two copies of chromosomes 1 through 22, and then some of us (females) get two X chromosomes and some of us (males) get one X and one Y. Partner chromosomes can exchange sections in a process called recombination, which is important to preserve the chromosomes evolutionarily. Because the Y doesnt have a partner, it had been hypothesized that the long palindromic sequences on the Y might be able to recombine with themselves and thus still be able to preserve their genes, but the mechanism was not known.

We used the data from a technique called Hi-C, which captures the three-dimensional organization of the chromosome, to try to see how this self-recombination is facilitated, said Cechova. What we found was that regions of the chromosome that recombine with each other are kept in close proximity to one another spatially by the structure of the chromosome.

Working on the Y chromosome presents a lot of challenges, said Paul Medvedev, associate professor of computer science and engineering and of biochemistry and molecular biology at Penn State and the other leader of the research team. We had to develop specialized methods and computational analyses to account for the highly repetitive nature of the sequence of the Y. This project is truly cross-disciplinary and could not have happened without the combination of computational and biological scientists that we have on our team.

Reference: Dynamic evolution of great ape Y chromosomes by Monika Cechova, Rahulsimham Vegesna, Marta Tomaszkiewicz, Robert S. Harris, Di Chen, Samarth Rangavittal, Paul Medvedev and Kateryna D. Makova, 5 October 2020, Proceedings of the National Academy of Sciences.DOI: 10.1073/pnas.2001749117

In addition to Cechova, Makova, Vegesna, and Medvedev, the research team at Penn State included Marta Tomaszkiewicz, Robert S. Harris, Di Chen, and Samarth Rangavittal. The research was supported by the U.S. National Institutes of Health, the U.S. National Science Foundation, the Clinical and Translational Sciences Institute, the Institute of Computational and Data Sciences, the Huck Institutes of the Life Sciences, and the Eberly College of Science of the Pennsylvania State University, and by the CBIOS Predoctoral Training Program awarded to Penn State by the National Institutes of Health.

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Berkeley Lab Celebrates 90th Anniversary, Imagines the Next 90 Years | Berkeley Lab – Lawrence Berkeley National Laboratory

Ninety years ago, in August of 1931, physics professor Ernest Lawrence created the Radiation Laboratory in a modest building on the UC Berkeley campus to house his cyclotron, a particle accelerator that ushered in a new era in the study of subatomic particles. The invention of the cyclotron would go on to win Lawrence the 1939 Nobel Prize in physics.

From this start, Lawrences unique approach of bringing together multidisciplinary teams, world-class research facilities, and bold discovery science has fueled nine decades of pioneering research at the Department of Energys Lawrence Berkeley National Laboratory (Berkeley Lab). His team science approach also grew into todays national laboratory system.

Over the years, as Berkeley Labs mission expanded to cover a remarkable range of science, this approach has delivered countless solutions to challenges in energy, environment, materials, biology, computing, and physics.

And this same approach will continue to deliver breakthroughs for decades to come.

In 2021, Berkeley Labs 90th year, we invite you to join our anniversary celebration, Berkeley Lab: The Next 90, as we celebrate our past and imagine our future.

The pursuit of discovery science by multidisciplinary teams has brought, and will continue to bring, tremendous benefits to the nation and world, said Berkeley Lab Director Mike Witherell. Our celebration is a chance to honor everyone who has contributed to solving human problems through science, and to imagine what we can accomplish together in the next 90 years.

Berkeley Labs 90th anniversary celebration honors the diverse efforts of the Lab community: from scientists and engineers to administrative and operations staff.

It also celebrates our commitment to discovery science, which explores the fundamental underpinnings of the universe, materials, biology, and more. This research requires patience the dividends can be decades in the future but the results are often surprising and profound, from the cyclotron of yesteryear to todays CRISPR-Cas9 genetic engineering technology.

Its an incredible story were proud to share, and inspired to continue with your support. Over the next several months, well offer many ways to join our celebration. Visit Berkeley Lab: The Next 90 to learn more, and engage with us on Twitter at #BerkeleyLab90.

Here are several ways to join our celebration, all highlighted on the website:

Celebrate the past

90 Breakthroughs: To celebrate Berkeley Labs nine decades of transforming discovery science into solutions that benefit the world, well roll out 90 Berkeley Lab breakthroughs over the next several months.

Interactive Timeline: Explore the Labs many remarkable achievements and events through the decades.

History and photos: Check out our decade-by-decade photo album and historical material.

Imagine the Future

Charitable giving: In 2021, Berkeley Lab will support five non-profit organizations that help prepare young scholars to become leaders and problem solvers.

Basics 2 Breakthroughs: Research at Berkeley Lab often starts with basic science, which leads to breakthroughs that help the world. In this video series, early career scientists discuss their game-changing research and what inspires them.

A Day in the Half Life: This podcast series chronicles the incredible and often unexpected ways that science evolves over time, as told by scientists who helped shape a research field, and those who will bring it into the future.

Speaker series: These monthly lectures offer a look at game-changing scientific breakthroughs of the last 90 years, highlight current research aimed at tackling the nations most pressing challenges, and offer a glimpse into future research that will spur discoveries yet to be made.

Connect

Virtual tours: These live, interactive tours will enable you to learn more about Berkeley Labs research efforts, hear from the scientists who conduct this important work, and peek inside our amazing facilities.

Social media: Join us on social media for fun and engaging content that will help you discover the Labs incredible history, and learn what were imagining for the future. BerkeleyLab#90

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Founded in 1931 on the belief that the biggest scientific challenges are best addressed by teams,Lawrence Berkeley National Laboratoryand its scientists have been recognized with 13 Nobel Prizes. Today, Berkeley Lab researchers develop sustainable energy and environmental solutions, create useful new materials, advance the frontiers of computing, and probe the mysteries of life, matter, and the universe. Scientists from around the world rely on the Labs facilities for their own discovery science. Berkeley Lab is a multiprogram national laboratory, managed by the University of California for the U.S. Department of Energys Office of Science.

DOEs Office of Science is the single largest supporter of basic research in the physical sciences in the United States, and is working to address some of the most pressing challenges of our time. For more information, please visitenergy.gov/science.

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Will We Ever Fully Understand Humans Impact on Nature? – The Nation

Elizabeth Kolbert. (Photo by John Kleiner)

To say that Earth is in crisis is an understatement. Atmospheric warming, ocean warming, ocean acidification, sea-level rise, deglaciation, desertification, eutrophicationthese are just some of the by-products of our speciess success, journalist Elizabeth Kolbert warns us about in her new book, Under a White Sky: The Nature of the Future. Kolbert has been studying the consequences of humanitys impact on Earth for decades as a contributor to The New Yorker and as the author of such books as the 2015 Pulitzer Prizewinning The Sixth Extinction, an exploration of the concept of extinction that posits mankind as a cataclysm as great as the asteroid that annihilated the dinosaurs.

In Under a White Sky, Kolbert ponders the nature of the future by examining a new pattern she attributes to the recursive logic of the Anthropocene: human interventions attempting to answer for past human interventions in the environment. The book chronicles the casualties of short-sighted human meddling with the planet and its resources and the present-day efforts being made to address that meddlingor, as Kolbert puts it, efforts to control the control of nature. Interviews with scientists in a wide array of disciplinesclimate scientists, climate entrepreneurs, biologists, glaciologists, and geneticistsreveal a trend of projects aiming to transform nature in order to save it. From the Mojave to lava fields in Iceland, Kolbert takes readers on a globe-spanning journey to explore these projects while weighing their pros, cons, and ethical implications (the books title refers to the way the sky could be bleached of color as a potential side effect of solar geoengineering, one of the proposed interventions to combat global warming). The issue, at this point, Kolbert writes, is not whether were going to alter nature, but to what end?

I spoke to Kolbert over the phone the day after President Joe Bidens inauguration. We talked about what its like to write a book about a big question you dont yet have the answer to, and what it will take to undo the environmental damage incurred during the Trump years.

Naomi Elias

Naomi Elias: You describe Under A White Sky as a book about people trying to solve problems created by people trying to solve problems. Can you explain that a little?

Elizabeth Kolbert: The pattern that Im looking at in the book is ways in which humans have intervenedor, if you prefer, mucked around withthe natural world and then have decided that the consequences are bad and are now looking for new forms of intervention to try to solve those problems. I start with the example of the Chicago River, which was reversed in an extraordinary engineering project at the beginning of the 20th century. The Chicago River used to flow east into Lake Michigan, which also happened to be Chicagos only source of drinking water. All of Chicagos human and animal waste flowed into Lake Michigan and there were constant outbreaks of typhoid and cholera. So Chicago decided, Well, we really have to do something about it, and what they did was this incredible engineering project, and now it flows basically to the southwest and eventually into the Mississippi, and all of Chicagos waste flows in the same direction. When the canal that reversed the river was put into place, there was a headline in The New York Times that ran something like, Water Flows in the Chicago River Again. It was so thick with muck that people joked a chicken could walk across it without getting its feet wet. That created a big problem that connected two huge drainage systems, the Great Lakes drainage system and the Mississippi drainage system, that has now led to all these species, including many invasive species, crossing from one basin into the other. It was having bad effects on the ecology of both systems, so to try to prevent these species from crossing from one basin to the other, theyve now electrified a significant chunk of this canal. So thats an intervention, as it were, on top of an intervention, and that is really the pattern that the book explores.

NE: The book visits project sites in Iceland, Australia, New Orleans, and the California desert. What drew you to the projects you write about?

EK: The first project that got me started down this whole path was the super coral project, which is currently in Hawaii and partly in Australia. As the oceans warm, corals are having a lot of trouble surviving. We get these coral-bleaching events that Im sure people have heard about. Some scientists were looking at how we can save coral reefs and the idea they came up with was that we need to intervene and try to coax along evolution so that these creatures can survive climate change. That struck me as a really interesting project, and got me thinking about this question of, Can we intervene to redress our own interventions? Once I started seeing that pattern, I started to see it everywhere. I could have gone to many different parts of the world and written stories that made the same point, but the projects that I went to were emblematic in some way. They were taking on different issues like climate change or invasive species, the loss of wetlandsthe list goes on.

NE: Did any of these effortsbe it the Harvard team trying to combat global warming by firing diamonds into the stratosphere or the group looking to reduce rodent populations with genetic manipulationconvince you that our best chance of averting climate apocalypse really is to control the control of nature? Are we digging ourselves out of a hole or just digging a deeper one?

EK: You know, you have identified the question at the center of the book. That is a question that I dont claim to answer. Im not a prophet. Im really trying to tease out that question in the book. Look at it, and have some fun with it, to be honest, and get people to think about the pattern. In many cases, these solutions are working to a certain extent. New Orleans would not exist without massive human intervention to solve the problems of water. In New Orleansa city thats essentially significantly below sea levelit turns out you need flooding to keep the land from subsiding even further because thats actually what built the land, the flooding that dropped a lot of sediment across the Mississippi Delta over many millennia. Are you getting into a trap when you pile these interventions on top of each other? Do you have alternatives? These are the big questions of our time.

If you like this article, please give today to help fund The Nations work.

NE: Id like to talk about your feelings about the popular phrase for the geological epoch were living in, the Anthropocene. In 2017 you gave a lecture at Manhattans New School, in which you said, Thinking scientifically about mans place in the world used to mean acknowledging our insignificance. This new human-centered term, the age of man, completely upends that. Can you talk about your feelings about the term and what it means for how we think about our relationship to the Earth?

EK: I think we are at this interesting turning point thats on some level been the subject of all the books Ive written, and a lot of the articles as well. We first decentered humans, right? It wasnt that the sun revolved around the Earth, it was that the Earth revolved around the sun. Theres a lot of these discoveries that have proved people are not the center of the universe, but then we get to the present moment, where we do have to acknowledge that we are becoming the dominant force in many very essential ways. We have to acknowledge that and, on some level, take responsibility for that. This term, the Anthropocene, is kind of a shorthand for all the ways that humans are affecting the Earth on what is sometimes called a geological scale. We are changing the carbon cycle very dramatically, were changing the nitrogen cycle, were acidifying the ocean. Weve even got to the point where we regularly cause earthquakes. We are definitely driving evolution; we are probably driving speciation. We are at this moment of tremendous human impact and we need to rise to that challenge of thinking about what we want the world to look like now that we are such a dominant force.

NE: In the book, you take note of the way the scientists you speak to encode a sense of moral urgency into their analysis of the climate crisis, which is something I feel present in contemporary climate reporting too. Youve been on the climate beat for decades. Have you felt a shift in the work? Do you feel like you now have an agenda when you write?

EK: Theres definitely been a shift in the sense that, when I started out almost 20 years ago, there was still, among a lot of pretty knowledgeable people, a lot of confusion. What is climate change? Is it real? Do I have to worry about it? The conversation has moved dramatically, at least in a big chunk of the US and a big chunk of the world. But I do not consider myself an advocate. Im a journalist and I try to report stories that I think illuminate the situation that were in. Ive thought about, you know, Should I be writing some sort of prescriptive journalism? But thats not really me.

NE: At the end of that same 2017 lecture you conclude, We are the fate of Earth. You call humans ethical agents and say that were failing as ethical agents if we dont acknowledge our impact.

EK: Yes, I certainly stand by those words. I mean, this book is on the one hand grappling with, on the other hand sort of playing around with, those questions. Our impact on the planet and the untold number of other species with whom we share the planet and whom we frankly dont spend a lot of time thinking aboutand dont even understand to a great extentI think will come to be seen as one of the great tragedies and the great ethical failings of humanity.

NE: So many of the things you discuss in the book were set in motion long before the 2016 election, but its hard to overstate what a setback the last four years of the Trump administration have been for the climate. An analysis from The New York Times cites over 100 environmental protections Trump reversed concerning areas like wetland and wildlife protection, and air and water pollution. In his inauguration speech yesterday, President Biden talked about answering the cry for survival Earth was letting out, and he immediately signed an order to rejoin the Paris climate accord. Im wondering what your thoughts are on what your job is going to look like under the Biden administration, and if you think we dodged some kind of metaphorical asteroid?

EK: I think what Trump did was egregious. It was an attempt to set us off completely on the wrong trajectory. Its a very complicated situation legally because now a lot of regulations will have to be rewritten. Its going to occupy the EPA for years, unfortunately. Thats very sad and just a waste of time and of human effort, when we should be doing a lot of other things. But, you know, there are great forces at work here and fortunately some of those continue to go in the right direction, like the tremendous decrease in prices of wind power and solar power that continued despite Donald Trumps best efforts to try to undermine renewable power. One could spend the next four years doing nothing but looking at the legal ins and outs of trying to undo that, and I think that that would be a noble thing to do. What Im thinking about areI dont want to call them bigger questions, but theyre the questions of our human impact on the planet, which are not going to change because Joe Biden suddenly rejoined the Paris Agreement, unfortunately.

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Will We Ever Fully Understand Humans Impact on Nature? - The Nation

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Could the Immune System Hold the Key To Alzheimer’s Disease? – The Wire Science

Photo: Matt Artz.

For nearly 30 years, the hunt for a cure for Alzheimers disease has focused on a protein called beta-amyloid. Amyloid, the hypothesis goes, builds up inside the brain to bring about this memory-robbing disorder, which afflicts some 47 million people worldwide.

Billions of dollars have poured into developing therapies aimed at reducing amyloid thus far, to no avail. Trials of anti-amyloid treatments have repeatedly failed to help patients, sparking a reckoning among the fields leaders.

All along, some researchers have toiled in the relative shadows, developing potential strategies that target other aspects of cells that go awry in Alzheimers: molecular pathways that regulate energy production, or clean up cellular debris, or regulate the flow of calcium, an ion critical to nerve cell function. And increasingly, some of these scientists have focused on what they suspect may be another, more central factor in Alzheimers and other dementias: dysfunction of the immune system.

With the fields thinking narrowed around the amyloid hypothesis, immunological ideas have struggled to win favour and funding. There was no traction, says Mal Tansey, a University of Florida neuroscientist whose work focuses on immunology of the brain. The committees that review grant applications didnt want to hear about immunological studies, she says.

But over the past decade, the immune system connection to Alzheimers has become clearer. In several massive studies that analysed the genomes of tens of thousands of people, many DNA variants that were linked to heightened Alzheimers risk turned out to be in genes involved in immunity specifically, a branch of the bodys defences known as the innate immune system. This branch attacks viruses, bacteria and other invaders quickly and indiscriminately. It works, in part, by triggering inflammation.

A further connection between inflammation and Alzheimers turned up in March 2020, in an analysis of electronic health records from 56 million patients, including about 1.6 million with rheumatoid arthritis, psoriasis and other inflammatory diseases. When researchers searched those records for Alzheimers diagnoses, they found that patients taking drugs that block a key molecular trigger of inflammation, called tumour necrosis factor (TNF), have about 50 to 70% lower odds of having an Alzheimers diagnosis than patients who were prescribed those drugs but did not take them.

This newer wave of studies opened peoples eyes to the idea that the immune system might be a major driver of Alzheimers pathology, says Sharon Cohen, a behavioural neurologist who serves as medical director at the Toronto Memory Program in Canada. Over time, Cohen says, researchers began thinking that maybe inflammation is not just an aftereffect, but actually a pivotal, early effect.

Tansey is trying to harness this growing realisation to develop new therapies. A drug she helped to develop nearly 20 years ago relieved Alzheimers-like features in mice and recently showed encouraging results in a small study of people with the disease. I think we were onto something way back when, she says.

Early hunch

Tansey got interested in neurodegenerative disease in the late 1990s, while working as a postdoctoral fellow at Washington University in St. Louis. Her research focused on molecules that promote the survival of certain neurons that degenerate in Parkinsons disease in lab dish experiments, anyway. But after six years on a meagre postdoc salary, and with her husband about to start neurology training at UCLA, she took a job at a biotech company in the Los Angeles area, called Xencor. She tackled a project that the company had on the back burner: designing new drugs to inhibit that inflammatory molecule TNF.

At the time, doctors already used two such drugs to treat autoimmune disorders such as psoriasis and rheumatoid arthritis. But these drugs have harmful side effects, largely owing to TNFs complicated biology. TNF comes in two forms: one thats anchored to the membranes of cells, and a soluble form that floats around in the spaces in between. The soluble TNF causes inflammation and can kill cells infected with viruses or bacteria its a necessary job but, in excess, destroys healthy tissues. The membrane-bound form of TNF, on the other hand, confers protection against infection to begin with. The drugs in use at the time inhibited both forms of TNF, leaving people at risk for infections by viruses, bacteria and fungi that typically only cause problems for people with weakened immune systems.

Using genetic engineering, Tansey and her Xencor colleagues designed a drug that prevents this potentially dangerous side effect by targeting only the harmful, soluble form of TNF. It gloms onto the harmful TNF and takes it out of circulation. In tests, injections of the drug reduced joint swelling in rats with a condition akin to arthritis.

By the time the work was published in Science in 2003, Tansey had returned to academia, starting up her own lab at the University of Texas Southwestern Medical Centre in Dallas. And as she scoured the scientific literature on TNF, she began to think again about those experiments shed done as a postdoc, on neurons destroyed during Parkinsons disease. She read studies showing that the brains of Parkinsons patients have high levels of TNF and she wondered if TNF could be killing the neurons. There was a clear way to find out: Put the TNF-blocking drug shed helped to develop at Xencor into the brains of rats that were manipulated to develop Parkinsons-like symptoms and watch to see what happened.

Her hunch proved correct the drug slowed the loss of neurons in Parkinsons rats. And that led Tansey to wonder: Could TNF also be involved in the loss of neurons in other forms of neurodegeneration, including Alzheimers disease? Mulling over the nuanced roles of innate immune cells, which seem to help or hurt depending on the context, she started rethinking the prevailing amyloid hypothesis. Perhaps, she thought, amyloid ends up clumping in the Alzheimers brain because immune cells that would normally gobble it up get sluggish as people age: In other words, the amyloid accumulated as a consequence of the disease, not a cause.

The double-edged nature of immune activity also meant that our immune systems might, if unchecked, exacerbate problems. In that case, blocking aspects of immune function specifically, inflammation might prove helpful.

The idea that blocking inflammation could preserve cognition and other aspects of brain function has now found support in dozens of studies, including several by Tanseys lab. Using an approach that induced Alzheimers-like neurological symptoms in mice, neuroscientist Michael Heneka, a researcher at Germanys University of Bonn, and his colleagues found that mice engineered to lack a key molecule of the innate immune system didnt form the hallmark amyloid clumps found in Alzheimers.

Tansey and colleagues, for their part, showed that relieving inflammation with the drug Tansey helped develop at Xencor, called XPro1595, could reduce amyloid buildup and strengthen nerve cell connections in mice with Alzheimers-like memory problems and pathology. Her team has also found that mice on a high-fat, high-sugar diet which causes insulin resistance and drives up Alzheimers risk have reduced inflammation and improved behavior on tests of sociability and anxiety when treated with XPro1595.

All told, hints from human genetic and epidemiologic data, combined with growing evidence from mouse models, was shifting or pointing toward the role of the immune system, says Heneka, who coauthored a 2018 article in the Annual Review of Medicine about innate immunity and neurodegeneration. And the evidence is growing: In 2019, a study of more than 12,000 older adults found that people with chronic inflammation suffered greater mental losses over a period of 20 years a clue, again, that inflammation could be an early driver of cognitive decline.

The accumulating data convinced Tansey that it was time to test this idea in people that instead of targeting amyloid, we need to start targeting the immune system, she says. And it needs to be early. Once too much damage is done, it may be impossible to reverse.

Targeting innate immunity

Immune-based strategies against Alzheimers are already being pursued, but most are quite different than what Tansey was proposing. Companies mostly work with the adaptive immune system, which attacks pathogens or molecules very specifically, recognising them and marking them for destruction. Experimental therapies include antibodies that recognise amyloid and target it for removal.

INmune Bio, in La Jolla, California, is one of several biotech companies taking a different approach: trying to fight degenerative brain disease by targeting the less specific innate immune system. The immune system is a 50-50 partnership, says RJ Tesi, the CEO. If youre about to have a prize fight, youre not going to jump in with one hand tied behind your back. Likewise, with Alzheimers or cancer, you dont want to go into the ring with half the immune system being ignored. To pursue this strategy, INmune Bio bought commercial rights to XPro1595. (Tansey is a paid consultant for INmune Bio but is not involved in any of the companys trials.)

INmune Bio initially focused on cancer, so when it designed its Alzheimers trial, it used a strategy commonly used in cancer drug trials. In Tesis view, a key reason that experimental cancer drugs succeed far more often than experimental neurology drugs is the use of molecular disease indicators called biomarkers. These are measures such as genetic variants or blood proteins that help to distinguish patients who, from the outside, may all seem to have the exact same disease, but may actually differ from one another.

By using biomarkers to select participants, cancer researchers can enrol the patients most likely to respond to a given drug but many neurology trials enrol patients based solely on their diagnosis. And thats problematic, says Tesi, because scientists are coming to realise that a diagnosis of Alzheimers, for instance, might actually encompass various subtypes of disease each with its own underlying biology and each, perhaps, requiring a different treatment.

In an ongoing trial of XPro1595, INmune Bio aims to enrol 18 people with mild to moderate Alzheimers disease, all of whom have elevated levels of biomarkers for excessive inflammation, including one called C-reactive protein. In July, the company reported early data from six participants who were treated with the TNF inhibitor once a week for 12 weeks and assessed for brain inflammation using a specialised magnetic resonance imaging (MRI) technique.

Over the 12-week period, brain inflammation fell 2.3 percent in three participants who received the high-dose TNF inhibitor compared with a 5.1 percent increase in 25 Alzheimers patients whose data were collected previously as part of a major long-term study of Alzheimers disease. Three participants who got a low dose of XPro1595 had a smaller 1.7% increase in brain inflammation. In this small trial, the researchers did not track changes in cognition. But their MRI analysis showed that inflammation was reduced by about 40 percent in a particular bundle of nerve fibres called the arcuate fasciculus that is important for language processing and short-term memory.

Its early days, Cohen says interim results in just six people. However, in a small sample size like that, you might not expect to see anything. Past studies of anti-inflammatory drugs did not show a benefit in Alzheimers patients, but scientists are now reexamining these trial failures, Cohen says. Maybe the idea of the immune system is important, but our therapies were too blunt, she says.

Its not just INmune Bio that has researchers excited about the prospect of tinkering with innate immunity to tackle brain disease. Alector, a South San Francisco biotech company, is developing potential therapeutics to activate the innate immune system to fight Alzheimers. Some of their experimental drugs are intended to boost the activity of innate immune cells in the brain called microglia. Tiaki Therapeutics in Cambridge, Massachusetts, meanwhile, is using computational methods to identify potential treatments for people with neuroinflammatory diseases who have specific gene signatures. And another company, Shanghai-based Green Valley, is investigating a drug that includes a mix of seaweed sugars that, the company claims, alters gut bacteria to tamp down brain inflammation.

Its encouraging to see so many different approaches to harnessing the innate immune system to fight Alzheimers, Heneka says. He predicts, however, that a variety of treatments will be needed to tackle such a multifaceted, complicated disease.

But Tansey suspects that chronic inflammation is a crucial factor that takes a toll on the brain over the course of many years. Although lowering inflammation will not solve everything, she says, I think it will buy you a lot. Because its the dark passenger of the journey.

This article originally appeared in Knowable Magazine, an independent journalistic endeavour from Annual Reviews.

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Global CRISPR Gene Editing Market: Focus on Products, Applications, End Users, Country Data (16 Countries), and Competitive Landscape – Analysis and…

New York, Feb. 01, 2021 (GLOBE NEWSWIRE) -- Reportlinker.com announces the release of the report "Global CRISPR Gene Editing Market: Focus on Products, Applications, End Users, Country Data (16 Countries), and Competitive Landscape - Analysis and Forecast, 2020-2030" - https://www.reportlinker.com/p06018975/?utm_source=GNW Application Agricultural, Biomedical (Gene Therapy, Drug Discovery, And Diagnostics), Industrial, and Other Applications [Genetically Modified Foods (GM Foods), Biofuel, And Animal (Livestock) Breeding] End-User - Academic Institutes and Research Centers, Biotechnology Companies, Contract Research Organizations (CROs), and Pharmaceutical and Biopharmaceutical Companies

Regional Segmentation

North America U.S., Canada Europe Germany, France, Italy, U.K., Spain, Switzerland, and Rest-of-Europe Asia-Pacific China, Japan, India, South Korea, Singapore, Australia, and Rest-of-Asia-Pacific (RoAPAC) Latin America Brazil, Mexico, and Rest-of-the-Latin America Rest-of-the-World

Growth Drivers

Prevalence of Genetic Disorders and Use of Genome Editing Government and Private Funding Technology Advancement in CRISPR Gene Editing

Market Restraints

CRISPR Gene Editing: Off Target Effects and Delivery Ethical Concerns and Implications with Respect to Human Genome Editing

Market Opportunities

Expanding Gene and Cell Therapy Area CRISPR Gene Editing Scope in Agriculture

Key Companies ProfiledAbcam, Inc., Applied StemCell, Inc., Agilent Technologies, Inc., Cellecta, Inc., CRISPR Therapeutics AG, Thermo Fisher Scientific, Inc., GeneCopoeia, Inc., GeneScript Biotech Corporation, Horizon Discovery Group PLC, Integrated DNA Technologies, Inc., Merck KGaA, New England Biolabs, Inc., Origene Technologies, Inc., Rockland Immunochemicals, Inc., Synthego Corporation, System Biosciences LLC, ToolGen, Inc., Takara Bio

Key Questions Answered in this Report: What is CRISPR gene editing? What is the timeline for the development of CRISPR technology? How did the CRISPR gene editing market evolve, and what is its scope in the future? What are the major market drivers, restraints, and opportunities in the global CRISPR gene editing market? What are the key developmental strategies that are being implemented by the key players to sustain this market? What is the patent landscape of this market? What will be the impact of patent expiry on this market? What is the impact of COVID-19 on this market? What are the guidelines implemented by different government bodies to regulate the approval of CRISPR products/therapies? How is CRISPR gene editing being utilized for the development of therapeutics? How will the investments by public and private companies and government organizations affect the global CRISPR gene editing market? What was the market size of the leading segments and sub-segments of the global CRISPR gene editing market in 2019? How will the industry evolve during the forecast period 2020-2030? What will be the growth rate of the CRISPR gene editing market during the forecast period? How will each of the segments of the global CRISPR gene editing market grow during the forecast period, and what will be the revenue generated by each of the segments by the end of 2030? Which product segment and application segment are expected to register the highest CAGR for the global CRISPR gene editing market? What are the major benefits of the implementation of CRISPR gene editing in different field of applications including biomedical research, agricultural research, industrial research, gene therapy, drug discovery, and diagnostics? What is the market size of the CRISPR gene editing market in different countries of the world? Which geographical region is expected to contribute to the highest sales of CRISPR gene editing market? What are the reimbursement scenario and regulatory structure for the CRISPR gene editing market in different regions? What are the key strategies incorporated by the players of global CRISPR gene editing market to sustain the competition and retain their supremacy?

Market OverviewThe development of genome engineering with potential applications proved to reflect a remarkable impact on the future of the healthcare and life science industry.The high efficiency of the CRISPR-Cas9 system has been demonstrated in various studies for genome editing, which resulted in significant investments within the field of genome engineering.

However, there are several limitations, which need consideration before clinical applications.Further, many researchers are working on the limitations of CRISPR gene editing technology for better results.

The potential of CRISPR gene editing to alter the human genome and modify the disease conditions is incredible but exists with ethical and social concerns. The global CRISPR gene editing market was valued at $846.2 million in 2019 and is expected to reach $10,825.1 million by 2030, registering a CAGR of 26.86% during the forecast.

The growth is attributed to the increasing demand in the food industry for better products with improved quality and nutrient enrichment and the pharmaceutical industry for targeted treatment for various diseases. Further, the continued significant investments by healthcare companies to meet the industry demand and growing prominence for the gene therapy procedures with less turnaround time are the prominent factors propelling the growth of the global CRISPR gene editing market.

Research organizations, pharmaceutical and biotechnology industries, and institutes are looking for more efficient genome editing technologies to increase the specificity and cost-effectiveness, also to reduce turnaround time and human errors.Further, the evolution of genome editing technologies has enabled wide range of applications in various fields, such as industrial biotech and agricultural research.

These advanced methods are simple, super-efficient, cost-effective, provide multiplexing, and high throughput capabilities. The increase in the geriatric population and increasing number of cancer cases, and genetic disorders across the globe are expected to translate into significantly higher demand for CRISPR gene editing market.

Furthermore, the companies are investing huge amounts in the research and development of CRISPR gene editing products, and gene therapies. The clinical trial landscape of various genetic and chronic diseases has been on the rise in recent years, and this will fuel the CRISPR gene editing market in the future.

Within the research report, the market is segmented based on product type, application, end-user, and region. Each of these segments covers the snapshot of the market over the projected years, the inclination of the market revenue, underlying patterns, and trends by using analytics on the primary and secondary data obtained.

Competitive LandscapeThe exponential rise in the application of precision medicine on a global level has created a buzz among companies to invest in the development of novel CRISPR gene editing. Due to the diverse product portfolio and intense market penetration, Merck KGaA, and Thermo Fisher Scientific Inc. have been the pioneers in this field and have been the major competitors in this market. The other major contributors of the market include companies such as Integrated DNA Technologies (IDT), Genscript Biotech Corporation, Takara Bio Inc, Agilent Technologies, Inc., and New England Biolabs, Inc.

Based on region, North America holds the largest share of CRISPR gene editing market due to substantial investments made by biotechnology and pharmaceutical companies, improved healthcare infrastructure, rise in per capita income, early availability of approved therapies, and availability of state-of-the-art research laboratories and institutions in the region. Apart from this, Asia-Pacific region is anticipated to grow at the fastest CAGR during the forecast period.

Countries Covered North America U.S. Canada Europe Germany Italy France Spain U.K. Switzerland Rest-of-Europe Asia-Pacific China India Australia South Korea Singapore Japan Rest-of-Asia-Pacific Latin America Brazil Mexico Rest-of-Latin America Rest-of-the-WordRead the full report: https://www.reportlinker.com/p06018975/?utm_source=GNW

About ReportlinkerReportLinker is an award-winning market research solution. Reportlinker finds and organizes the latest industry data so you get all the market research you need - instantly, in one place.

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Global CRISPR Gene Editing Market: Focus on Products, Applications, End Users, Country Data (16 Countries), and Competitive Landscape - Analysis and...

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