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Category Archives: Genetic Engineering

Poseida Therapeutics to Present Update on Approach in Allogeneic CAR-T at Society for Immunotherapy of Cancer 34th Annual Meeting – BioSpace

Posted: November 6, 2019 at 12:44 pm

SAN DIEGO, Nov. 5, 2019 /PRNewswire/ -- Poseida Therapeutics, Inc., a clinical-stage biopharmaceutical company leveraging proprietary non-viral gene engineering technologies to create life-saving therapeutics, today announced it will present preclinical research findings during the Society for Immunotherapy of Cancer (SITC)34th Annual Meeting on its lead allogeneic product candidate, P-BMCA-ALLO1, in multiple myeloma.

At SITC 2019, preclinical results will highlight the potential of Poseida's gene engineering technologies in addressing current challenges with earlier generation autologous CAR-T therapies. Poseida leverages its proprietary piggyBac DNA Modification System in combination with Cas-CLOVER gene editing technology to create P-BCMA-ALLO1, an off-the-shelf allogeneic CAR-T cell product candidate. These technologies enable the development of allogeneic CAR-T therapies with a variety of benefits to patients and the medical community including greater safety and duration of response, as well as manufacturing and patient cost savings.

Poseida will present the following research at SITC 2019:

"Broad adoption of earlier generation CAR-T therapies have been curtailed by serious safety concerns, limited duration of response and difficulty supporting access within the current healthcare system," said Eric Ostertag, M.D., Ph.D., chief executive officer of Poseida. "We are actively problem-solving to address these challenges and our new findings indicate that we are making progress with our allogeneic approach powered by our piggyBac DNA Modification System and Cas-CLOVER gene editing technology."

About P-BCMA-ALLO1P-BCMA-ALLO1 is an allogeneic CAR-T therapy being developed by Poseida for multiple myeloma. It is designed to have the benefits of scale and administration efficiency that come from an allogeneic product. Poseida expects to file an IND for P-BCMA-ALLO1 in 2020. Approximately 32,110 people were diagnosed with multiple myeloma and 12,960 died from the condition in the United States in 2019.

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About Poseida Therapeutics, Inc.Poseida Therapeutics is a clinical-stage biotechnology company translating best-in-class technology into lifesaving cell and gene therapies for patients with high unmet medical need. The company is developing a wholly-owned pipeline of non-viral, allogeneic and autologous CAR-T product candidates and in vivo gene therapies for orphan genetic diseases. Poseida has assembled a suite of industry-leading gene editing technologies, including the piggyBacDNA Modification System and Cas-CLOVER and TAL-CLOVER site-specific nucleases. For more information, visitwww.poseida.com.

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SOURCE Poseida Therapeutics, Inc.

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Poseida Therapeutics to Present Update on Approach in Allogeneic CAR-T at Society for Immunotherapy of Cancer 34th Annual Meeting - BioSpace

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The world’s banana crops are under threat from a deadly fungus. Is gene editing the answer? – National Post

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We expect to have more than one variety of apple to choose from. Even at the most modestly stocked produce stand, youre likely to see mounds of Galas, McIntoshes and Honeycrisps. When it comes to the banana, though no matter where you shop theres only ever one: The Cavendish.

As far removed as we are from tropical growing regions, youd be forgiven for assuming the fruit we recognize as a cheap and reliable staple is the one true banana. In reality, however, there are over a thousand types, each exhibiting a different flavour profile, texture, shape, colour, ripening pattern and durability. And for the second time in recent history, the very existence of the sole breed we rely on which represents the single most exported fresh fruit on the planet is under threat.

Researchers, seeking a solution, are looking towards a new form of genetic modification. Could specific alterations of the genetic makeup of the Cavendish help stave off the disappearance of such a critical commodity?

In August, Colombia declared a state of emergency when scientists confirmed a banana-killing fungus had reached the Americas for the first time. Known by its common name, Panama disease, the strain of fungus Fusarium oxysporum cubense Tropical Race 4 (TR4) has been a known issue since the early 1990s, but until this year, it was largely contained to Asia. Immune to pesticides, the lethal soil-borne organism, for which there is no known cure, obliterates yields by choking banana trees of essential water and nutrients.

The Cavendishs predecessor as worlds presiding banana was the Gros Michel, a variety that dominated fruit stands in temperate regions until it was decimated by fungal strain Tropical Race 1 in the 1950s. That the extreme monoculture approach replicated with the Cavendish would result in a similar fate should have seemed inevitable.

Cavendish bananas are sterile and breeding them requires a cloning process that creates genetically identical plants. Because of their inherent lack of biodiversity, monocultures such as this banana are especially vulnerable to diseases and pests; when theres a weakness, such as little or no resistance against TR4, it can have sweeping and ruinous effects.

Given the bananas immense importance to producers and consumers, researchers have been attempting a variety of methods to create a resistance to the deadly fungus. According to Nature, James Dale, a biotechnologist at Queensland University of Technology in Brisbane, is currently field testing genetically modified bananas in Northern Australia with some success. Dale has added a gene from a wild banana into the Cavendish variety that makes it more resistant to the TR4.

However, even if scientists are able to breed a TR4-immune Cavendish, they wouldnt be permitted to grow or sell them in a significant portion of the world. In Europe, for example, GM crops are restricted. And in Canada, although GMOs have been on the market since the late 1990s, nearly 90 per cent of Canadians believe they should be subject to mandatory labelling.

As a result, researchers like Dale and Leena Tripathi, from the International Institute of Tropical Agriculture in Kenya, have begun experimenting with CRISPR technology. Where GMOs have a foreign gene inserted into the organism, CRISPR allows for the organisms genes to be edited. In the case of Dale, hes discovered a dormant gene in the Cavendish he hopes to activate.

The technique is perhaps best described by Jennifer Kuzma, co-director of the Genetic Engineering and Society Center at North Carolina State University. In an interview with Gastropod, she likened DNA to a book and CRISPR to a pen: You can go in and you can edit the letters in a word, or you can change different phrases, or you can edit whole paragraphs at very specific locations.

CRISPR and GMO are further differentiatedin terms of consumer perception. As a December 2018 study published in Global Food Security found, 47 per cent of Canadian respondents were willing to eat both GM and CRISPR foods, but participants across the board (in Australia, Belgium, Canada, France and the U.S.) were more apt to eat CRISPR than GM food.

Nevertheless, editing the genes of the banana is still in the early stages. Dale told Nature that itll be a couple of years before these get into the field for trials. Can the Cavendish banana wait that long?

In a recent interview with KCRW, Dan Koeppel, author of Banana: The Fate of the Fruit that Changed the World, said I think the time has come to stop looking at bananas as just one kind of fruit when there are thousands. Just as the range of apples at our fingertips is rich and getting richer, perhaps all the different varieties of bananas will prove ripe for discovery.

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CRISPR therapy may reverse autism mutation’s effects well past infancy – Spectrum

Posted: October 22, 2019 at 4:44 am

Running short: Neurons from mice missing SCN2A (right) have signal-receiving branches that are less mature than those in controls (left).

Injecting the gene-editing tool CRISPR into the brains of adolescent mice counteracts the effects of a mutation in a top autism gene. The finding suggests that mutations in this gene, SCN2A, may be treatable at any age.

This gives us hope that this is something thats not just a developmental deficit, and that once all the changes are there that youre stuck with them, says Perry Spratt, a graduate student in Kevin Benders lab at the University of California, San Francisco. Spratt presented the unpublished findings today at the 2019 Society for Neuroscience annual meeting in Chicago, Illinois.

SCN2A encodes a sodium channel that helps neurons propagate electrical signals. The mice have a harmful mutation in one copy of the gene, causing their neurons to fire sluggishly and make immature connections. The treatment reverses the problem by ramping up expression of the intact copy.

The first inkling that the reversal might work even after infancy came in June: The team reported then that introducing an SCN2A mutation into adolescent mice has many of the same effects on neurons as a mutation present from conception.

At the cellular level we see a lot of the same deficits as we see when the genes been gone throughout life, Spratt says.

The team engineered mice in which the mutation in SCN2A can be corrected by injecting an enzyme called Cre recombinase.

Injecting the Cre enzyme into the brains of 4- to 5-week-old mutant mice restored normal expression of SCN2A. It also reversed the problems in the mices neurons.

But this strategy cannot be applied to people because it would require genetic engineering of embryos. So the researchers created a virus that ferries a modified version of CRISPR into cells. This version of the editing tool does not snip DNA but can instead activate any gene.

The researchers injected the virus into the brains of 4-week-old mutant mice, along with synthetic RNA snippets designed to guide CRISPR to SCN2A. The treatment boosted SCN2A expression and reversed the problems in the mices neurons.

The team also tested one important control: They found that the treatment does not cause neurons to become hyperactive and so does not run the risk of triggering seizures.

The remarkable thing about this is that it can go gangbusters without making the cells hyperexcitable, says Bender.

The team is testing ways to deliver the virus to the whole brain. They also plan to test whether CRISPR reverses learning and memory problems in the mutant mice.

For more reports from the 2019 Society for Neuroscience annual meeting, please click here.

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With These 4 Breakthroughs, We’ll Be Able to Write Whole Genomes From Scratch – Singularity Hub

Posted: at 4:44 am

The ability to read genomes has transformed our understanding of biology. Being able to write them would give us unprecedented control over the fabric of life.

Rapid advances in DNA sequencing and gene editing technology mean we are now truly in the age of genomics. For a few hundred dollars, genetic testing companies will give you a detailed rundown of your ancestry and susceptibility to a host of diseases. The first genetically modified humans are about to turn one.

The advent of CRISPR in particular has given us the ability to tweak DNA with incredible precision, but were still largely restricted to switching specific genes on and off or swapping one gene for another. The field of synthetic biology wants to change that by bringing engineering principles to biology.

But theres a long way to go, and a group of leading geneticists have now laid out the technology roadmap required to get there, published last week in a policy paper in Science. Here are the four areas where we need to step up our game.

The ultimate goal of genetic modification is to produce a change in the phenotypethe outward characteristicsin the target organism. But most complex traits are the result of a complicated interplay between multiple genes and an organisms environment, so mapping how DNA tweaks will translate into desired attributes is challenging.

Large-scale genome design will require computer programs that can do this accurately and efficiently. While projects like Synthetic Yeast 2.0 have made the first steps in this direction, the field needs to build complex new models that can predict the results of changes to the genome sequence.

These could still be decades away, but using machine learning to mine the wealth of biology data in public databases could accelerate them. Programs that can automate the design of experiments to cut down the number of rounds of design will also be required, as will the adoption of common data standards to enable collaboration.

Weve been able to synthesize DNA for decades, but the most common approach is restricted to short sections of DNA just a few hundred base pairs long. Building entire genomes requires long sequences of several thousand base pairs, so currently scientists rely on a laborious and error-prone process of stitching many smaller DNA sections together.

Large-scale genome engineering will require much faster, cheaper, and more efficient methods for DNA assembly. One nearer-term possibility is designing new enzymes that can reduce the number of errors and therefore boost the yield of the process. But in the long run, new technologies that can produce long and accurate sequences offer far more potential, and there are some promising enzyme-based approaches that may fit the bill.

While our gene-editing prowess has come a long way, we still struggle to make widespread changes to a genome simultaneously. If we could develop this capability, it could significantly decrease the amount of time it takes to modify organisms and even sidestep the need to build genomes from scratch.

This will mean finding ways to prevent the multitude of guide RNAs (the homing devices that tell CRISPR where in the genome to make changes) required for simultaneous edits to multiple genes from interfering with each other.

It will also be necessary to create libraries of tools for making changes across the genome and accessibility maps that highlight how efficiently different targets can be altered. These will make it easier for scientists to plan where to make changes to achieve their desired results and form the basis of predictive computer models that can streamline the process.

DNA is more than just a string of genes; its packaged into chromosomes, whose number and shape vary across species. Our ability to assemble and manipulate these chromosomes is still rudimentary.

Most efforts so far have relied on yeast to do this for us, and it has been able to deal with viral, bacterial, yeast, and algal chromosomes, as well as fragments of mice and human genomes. But engineering more specialized artificial chromosomes looks to be beyond yeast, so we need to find newer, more flexible organisms that can do this.

Transplanting these chromosomes into the target organism is also a major bottleneck. Techniques like cell fusion and microinjection show promise, but require funding for multidisciplinary work to bridge the gap between microfluidics research and molecular biology. Theres also a need for greater understanding of the fundamental forces that govern the architecture of chromosomes and how they interact.

Achieving all this could take decades, and will require the same kind of massive cross-disciplinary effort seen in the Human Genome Project. It will also require concerted government funding and close involvement of the private sector if its going to become a reality. But the benefits of harnessing the ability to write genetic code from scratch could be enormous for the biomedical, pharmaceutical, agricultural, and chemical industriesand for humanity as a whole.

Image Credit: Zita/Shutterstock.com

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Stream It Or Skip It: ‘Unnatural Selection’ On Netflix, A Docuseries About The Ethics And Ease Of Editing DNA – Decider

Posted: at 4:44 am

With everything youve been hearing about genetic engineering over the years, starting with the idea of genetically-modified fruits and vegetables all the way through gene editing in humans, youve heard a lot about why itshouldnt be done. But what are the positives? And what might happen if gene editing goes mainstream and available to (gulp) everyone? A new Netflix docuseries examines that issue.

Opening Shot: At night, we see a large cage full of barking dogs, likely pit bulls. The location is Mendenhall, Mississippi.

The Gist: The dogs are owned by Paul Ishee, an oil field tech who breeds dogs on the side. He collects sperm from the dogs (in just the way youd expect) because he wants to genetically engineer a better dog. How does he do that? Via CRISPR, a small protein that can be injected via a bacteria into an organism to edit its DNA. One of the big features with CRISPR, which was perfected only a few years ago, is that the protein is easily obtainable. So genetic modifications can be done in expensive labs by trained scientists or by biohackers in their garages.

Unnatural Selection, a docuseries produced and directed by Leeor Kaufman and Joe Egender, examines the new frontier of genetic engineering, and what ethical stumbling blocks there are to adapting gene editing on a wider basis.

The filmmakers interview a mixture of scientists and biohackers, some of whom are both. Dr. Jennifer Doudna, widely regarded as the inventor of the CRISPR method, seems to be in the middle of the debate; she knows how powerful using CRISPR can be when it comes to curing genetic-based diseases and other conditions, but is wary of people who want to use it to engineer superior organisms. Biohackers like Dr. Josiah Zayner, a biophysicist who used to work for NASA, is in favor of the democratization of genetic engineering, sending $140 CRISPR kits to people via Priority Mail. One of those people is Ishee, who wants to make a glowing dog as his first experiment, just to prove that the engineering worked.

Others, such as Dr. Kevin Esvelt, an evolutionary engineer at MIT, want to put genetic engineering into practice by modifying mice to be immune to the bite of Lyme-carrying ticks and then releasing them to breed on a small island in Marthas Vineyard. What will the consequences of that be? Even Esvelt really doesnt know for sure. And thats the problem, and where the ethical issues take hold. Sending genetically modified mice, dogs, or humans into the world may introduce unintended consequences, or might be deadly in the wrong hands. But are people who think its dangerous just being alarmist?

Our Take: Genetic engineering and all of its advantages and ethical quandaries is a complex topic to cover, and in the first part of their four-part docuseries, Kaufman and Egender try to lay out the issue in as balanced a way as possible. But what we got during the feature-length (70-minute) first episode was more of a sense of fear than one of wonder.

Why? Because, while the filmmakers are giving biohackers like Ishee and Dr. Zayner as much time as the more legit scientists, it doesnt help matters when you see Dr. Zayner concocting CRISPR samples in his kitchen or see Ishee looking at YouTube videos of glowing mice and luminescent monkeys for inspiration.

But then we see Jackson Kennedy, a boy from New Jersey who is autistic and was born with poor vision, and we become hopeful again. His parents got genetic testing for him that showed that hes missing a gene that would help him see. And hes going to go for treatment that fixes that gene, which should restore his sight if it works. This is where genetic engineering could make a huge positive impact on the world. But, whether the filmmakers intended it this way or not, there seems to be a whole lot scarier ways the use of CRISPR could go haywire, which makes us as cautious as the anti-engineering activists they interview for the first episode.

Parting Shot: We see Jason right before he goes in for the procedure, excited at the prospect that he might see more than just shapes for the first time.

Sleeper Star: When Jasons mother talked about how he wanted to be an astronaut and how heartbroken he was when he heard that astronauts need 20-20 vision, it almost broke our hearts. While his story will be a through-line through the limited series, were disappointed that there isnt a documentary just about him.

Most Pilot-y Line: There are actually two scenes of Ishee collecting sperm from his dogs. Yuck.

Our Call: STREAM IT. Were wondering how much of what were going to see during the rest ofUnnatural Selection will be more crackpots and less of the positive stuff like Jasons treatment. If its the former, wed likely end up skipping it.

Joel Keller(@joelkeller) writes about food, entertainment, parenting and tech, but he doesnt kid himself: hes a TV junkie. His writing has appeared in the New York Times, Slate, Salon,VanityFair.com,Playboy.com, FastCompany.com,RollingStone.com, Billboard and elsewhere.

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INFOGRAPHIC: The Countries Leading the Way in the Future of Production – BOSS Magazine

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The rise and emergence of technology has truly seen the birth of a completely new and exciting digital age, which has transformed the globe as a result. Innovation and advancements has seen technology grow not only across industries and a variety of businesses but also our personal lives, as we all interact with new devices without even realizing how much we use them on a daily basis.

With technology becoming intertwined and cemented into the 21st century way of living, we have seen the birth of the Fourth Industrial Revolution, which is significantly different from the first revolution back in the 18th century. This new and leading way of production is rapidly changing the manufacturing process across the globe, with the rise of complicated and impressive technologies, such as robotics, 3D printing, genetic engineering, the Internet of Things (IoT), and artificial intelligence. These innovations are being increasingly implemented into all industries, businesses and processes to improve production and boost efficiency.

As a result of the Fourth Industrial Revolution, production levels have improved drastically, with technologies greatly enhancing the speed and accuracy of processes that were often considered tedious and slow, with more room for human error. But in this new production revolution, who is leading the way in embracing these new innovations?

RS Components have produced a graphic analyzing data from the World Economic Forums Readiness for the Future of Production report, to reveal the countries adopting these technologies and leading the way in the future of production as a result. With each country analysed by a series of metrics including global trade and investment, institutional framework, sustainable resources, demand environment and emerging technologies, the countries leading production levels forward have been scored out of 10 to reveal who has come out on top.

The top 10 countries driving the future of production include:

US 8.16

Singapore 7.96

Switzerland 7.92

UK 7.84

Netherlands 7.75

Germany 7.56

Canada 7.56

Hong Kong 7.45

Sweden 7.40

Denmark 7.20

At the top of the leaderboard is the US with an impressive score of 8.16 out of 10. The US dominates the top of each metric excluding Sustainable Resources and Institutional Framework.

With the country holding enormous opportunity and access to digital technologies, it is important for manufacturers to capitalize on this and ensure their employees are prepared for the exciting future of production ahead. The US is known for its innovation and it is its advances, stable and connected technological platform it has built up over the years that allows it to lead the world in the future of production, from research to the manufacturing stage.

Singapore ranks as the second country driving the future of production with a score of 7.96 and Switzerland in third at 7.92. With around 20 percent of its GDP deriving from manufacturing, it is unsurprising that Singapore sits as the worlds fifth largest refinery export hub and among the top 10 global chemical hubs by export volume. Singapore, manufacturers are capitalizing on robots, artificial intelligence and predictive analytics.

Preparing employees for the future of production

With many countries making significant efforts to increase their technological innovations in their production processes, it is important for businesses and industries to address the need to prepare its employees for the change. Educating employees on new technologies and also incorporating information on these advancements into school curriculum will be greatly beneficial in preparing a technologically innovative nation.

With this preparation combined with the technological opportunity for industries and nations to explore, the world of production and manufacturing is set to change astronomically.

What country will be leading the way in the future of production in 10 years time?

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WATCH: What role will microscopic microbial factories play in the future of protein? – FoodNavigator-USA.com

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Its too early to write off farm animals just yet, says Darren Streiler, investment director at ADM Ventures (ADMs corporate venturing arm, which has invested in Geltor, Perfect Day and Sustainable Bioproducts), but this technology is rapidly moving from the laboratory to the real world.

At this stage, a lot of these companies are reaching Series B and they are raising significant amounts of funding and a lot of these companies have pilots that have now been performing for a number of years, said Streiler, who was speaking to FoodNavigator-USA at Rabobanks FoodBytes! pitch competition in Chicago last month (where he served as one of the judges).

So wed characterize this space particularly in the mycoprotein and the fermentation-based and the cell cultured space, all in all, there are probably around 100 companies at this time.

What interesting is that were really able to scale these technologies. For instance, ADM has some of the largest fermentation tanks in the US, and with one of our startups Perfect Day, we have ajoint development agreementto manufacture their fermentation-based dairy proteins. We have 250,000 liter tanks that could really scale this type of technology.

Asked whether proteins produced in cultivators/fermentation tanks/bioreactors (proponents are still arguing over the most consumer-friendly terminology) could ultimately account for a bigger market share than plant-based proteins, he said:Not every type of protein is going to fit every type of customer.

"We see segments in the market and were aiming to provide options to satisfy all of those different segments.

Producing protein from microbes has certain obvious advantages, say startups in the space.

For a start, instead of growing a living breathing animal just to break it down into products, they are designing the most efficient process to produce just the components we need, which can be manufactured from a distributed network of local production facilities (fermentation tanks) using a fraction of the land, water, and inputs required to raise and feed animals.

(Not to mention, it also doesnt involve raising and slaughtering animals on an industrial level.)

The resulting ingredients have the added appeal of consistent quality, a lack of price volatility, and security of supply.

While several food ingredients from enzymes to sweeteners, vitamins, colors, and the heme protein in the Impossible Burger are already produced by tiny microorganisms, a new wave of startups is using microbes to produce things currently produced by mammals, from whey and casein proteins and egg white to sugars and proteins found in human breast milk.

Some companies such asMotif FoodWorks use synthetic biology to write DNA sequences that can be inserted into microorganisms to instruct them to produce animal proteins; others such asSustainable Bioproductshave identified microbes that naturally produce new to the world proteins; while others such asNoblegen are working with microorganisms that can be coaxed into producing multiple high-value ingredients without using genetic engineering.

Others such asAir Protein(which utilizes single-cell organisms called hydrogenotrophs first studied by NASA in the 1960s),Solar Foods,NovoNutrientsandDeep Branch Biotechnologyare converting components found in the air - notably carbon dioxide (which can be recycled from industrial waste) - into proteins.

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Ending a war isn’t the same as winning it – The Japan Times

Posted: at 4:44 am

Japans rugby dream finally ended on Sunday. The Brave Blossoms lost to South Africa in the quarterfinals of the 2019 Rugby World Cup. I take my hat off to the team. Were really proud of what we have achieved, said Japans head coach Jamie Joseph, and so is everybody else in Japan.

Compared to baseball or soccer, rugby has never been a popular sport in Japan. For the past month since the World Cup opened on Sept. 20, however, millions of Japanese sports fans have converted to rugby. Although overpowered by South Africa, Japan performed well with its high-intensity running style of rugby.

Having said that, while watching this past Sundays historic match live on TV, I was contemplating something different. When a commentator said that Japans battle for the world cup was over, I thought no, the battle didnt end. No matter how well the Japan team had fought, it lost the battle. Isnt that the reality?

In a recent Washington Post column, U.S. Republican Sen. Mitch McConnell said, As neo-isolationism rears its head on both the left and the right, we can expect to hear more talk of endless wars. But rhetoric cannot change the fact that wars do not just end; wars are won or lost.

The Senate majority leader from Kentucky eloquently criticized U.S. President Donald Trumps abrupt decision to pull out of Syria to end the endless war. I interpreted this as saying that ending the war in Syria should not be an objective because you are losing, not winning, the war by trying to end it. Isnt that the reality as well?

A similar rhetoric is still dominant in Tokyo. On Aug. 15 every year, Japan the government, people and media alike commemorates the anniversary of the end of the Pacific War. We dont say we lost the war. We behave as if our longest war in Asia and the Pacific had ended spontaneously in 1945.

Since then, the Japanese have forgotten what a war really means. Similarly, a growing number of Americans now indulge themselves in such an illusion. Richard Fontaine of the Center for a New American Security laments this in his latest essay for Foreign Affairs: The Nonintervention Delusion What War Is Good For.

Pacifists in Tokyo always say, Peace loving nations do not go to war. Yes, sometimes they do especially when they must. War is merely a means to physically achieve a nations objective. If an illegal attack on other nations is taking place to change the status quo, a war of self-defense is justified under the United Nations Charter.

Now back to the war in Syria, which the U.S. is losing by ending it. In his column, McConnell presented three principal lessons about combating the complex threat. The lessons are the threat is real and cannot be wished away, there is no substitute for American leadership and we are not in this fight alone.

Unfortunately, the Republican senator wrote, the administrations recent steps in Syria do not reflect these crucial lessons. He may be right, but he needs some connotations for his argument. Here are some additional thoughts to add to his important essay:

First, McConnell said, the threat is real and cannot be wished away. Yes, the threat is real, of course. But we should also keep in mind that threats are often consequences of the past. In the case of the Islamic State or other extremists, they are part of popular reactions to legitimate U.S. support for illegitimate and unpopular presidents or rulers in the region.

Second, McConnell stated, there is no substitute for American leadership. Yes, there is, whether Americans like it or not. There are people, unfortunately, who are willing to submit to dictatorial governance in the Middle East and elsewhere. Those who have no experience in democracy and freedom do not appreciate their true values.

Finally, he argued that we are not in this fight alone. Not at all. But the U.S. would have to be alone if the Trump administration behaved as if America first meant America can do without its friends and allies. You cannot take their commitment and support for granted if you ignore them.

This means that the U.S. must face the troubles in the Middle East that Washington has been partly responsible for. Authoritarian leaders can easily be a substitute for the U.S. leadership. And finally, Americans may have to fight alone if Washington continues to make light of its traditional allies and friends.

Having said that, McConnell is wise and brave in criticizing the incumbent Republican president. He said We will see those troubles anew in Syria and Afghanistan if we abandon our partners and retreat from these conflicts before they are won. Americas wars will be endless only if America refuses to win them.

In order to avoid such endless wars, the U.S. must do two things. First, do something with the Trump administration. In his capacity as Senate majority leader, Americas friends and allies sincerely hope that McConnell will immediately multiply his efforts to make the Republican Party the Grand Old Party once again.

Second, in the medium to long term, as Andrew Krepinevich, a respected member of Americas strategic studies community puts it, the U.S. must be ready for the new forms of warfare. In his testimony last month before the U.S.-China Economic and Security Review Commission, he listed the following three forms:

Algorithmic warfare by artificial intelligence systems, hyper war conducted at unprecedented speeds with advanced cyber or directed energy or hypersonic weaponry and precision biological warfare with advanced genetic engineering techniques.

Is the U.S. ready to do this? Krepinevich says no. If thats the case, how can Tokyo fight and win a defensive war against the status quo challengers? The U.S. and its allies have no time to waste. If we cant restore our alliance, we must work to refine it together maybe with a new administration in Washington.

Kuni Miyake is president of the Foreign Policy Institute and research director at Canon Institute for Global Studies.

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Blade Runner: 5 Things That Are Scientifically Accurate (And 5 That Make No Sense) – Screen Rant

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Ridley Scott'sBlade Runnerwas a game changer in the world of science-fiction. In 1982, the same year that kid-friendly films likeE.T.were released conveying the adventures of a cuddly extra-terrestrial,Scott's vision of the near-future was introducing thought-provoking questions about the advancement of artificial intelligence, humankind's desire to play God, andwhat constituted being "human" with the rise of genetic engineering.

RELATED: 10 Hidden Details Everyone Missed In The Original Blade Runner

Set in 2019 Los Angeles after the degradation of Earth from a nuclear war, resources are scarce and anyone wealthy enough to do so ventures off-world. Off-world planets are colonized by replicants, synthetic beings created for the purpose of slave labor and dangerous activities unfit for humans. After a replicant revolt, they're forbidden from returning to Earth, but a few escape in a shuttle intent on making a better life for themselves. Deckard is the "Blade Runner" sent to "retire" them, along the way discovering more about his own humanity as he hunts those considered "more human than human." Here are five things that are scientifically accurate about the film andfive that make no sense.

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InBlade Runner,Roy Batty pays a visit to the scientist behind the replicant's synthetic eyes. This man deals in eyes, but the rest of replicant's organs are synthetic as well. Today, the technology and science exists to generate organs in a lab that gives hope to those on lists for organ transplants.

Referred to as "bioartificial organ manufacturing technologies," organ substitutes (or artificial organs) will soon be made from cells designed to adapt to the tissue around them and become part and parcel with the individual who needs them. Stem cell research has been instrumental in 3D-printing bio-organs today, such as the thyroid gland.

Blade Runnertakes place in 2019, and the world has been made into an over-crowded, gritty, dystopian environment. In Philip K Dick's book Do Android's Dream of Electric Sheep?, this is due to the "World War Terminus," a nuclear war that left the world almost uninhabitable. Ifyou're wealthy, you move off-world.

RELATED:Blade Runner: 10 Things That Make No Sense

The film never exactly explains why there was a nuclear war, or who started it. As it stands with the state of nuclear weaponry in the world,90% of which is owned by the United States and Russia, both countries are aware that a nuclear holocaust would make the world uninhabitable due to ensuing firestorms, nuclear winters, and radioactive fallout. Ergo, how would all of this advanced technology from the Tyrell Corp even exist?

While we're nowhere near able to make a replicant as advanced as Roy Batty and those seen in the film, the fields of robotics has made significant strides in recent years. Sophia, the social robot programmed with hundreds of different algorithms and 50 facial expressions does a good job of "replicating" a human's appearance enough to interact with her comfortably.

Of course, we as a society have to be ready for such advancements. Even with artificial organ transplants, at what point is a human still a human? What will rights and civil liberties look like as we make advancements in the technology of artificial intelligence to the point that, as the Tyrell Corp says, there are individuals among us that "look more human than human?"

After the nuclear war that devastated the planet, humans had two choices: either scramble for resources on their home planet, or look to outer space for other livable conditions on a new planet. Thanks to the Tyrell Corp and its replicants, other planets can be colonized with minimal danger to humans, allowing them to live off world.

How far away are they from Earth? How far can humans get in this near future? The film takes place in 2019, and we have only just been able to land a chemical-rocket without ditching it out to see on its de-burn into our atmosphere. And is there a lottery to get off-world or is it simply a matter of being able to afford the space travel?

Because of the possibility of replicants going rogue, Tyrell Corp put in a limited lifespan (four years) to act as a sort of "kill switch." Some replicants had displayed erratic behavior around that time, particularly where emotional overload was concerned. Their actions could be dangerous to humans since they were so much stronger and faster, so it also served to make humans more comfortable with the replicant presence.

RELATED:10 Things From Blade Runner That Haven't Aged Well

Today, genetic engineers that have been working with T-cell therapy have already considered this. Since they work with manipulating T-cells outside the body that are then put into a human, there is a chance they'll eventually go rogue or reject their new environment. They could become cancerous and start an attack on the human body.

Roy Batty, a Nexus-6 replicant designed to be a perfect soldier for Earth's military, has a poetic monologue towards the end of the film. He explains to Deckard that he's seen things he can't possibly imagine, like"attack ships off the shoulder of Orion"and something about "glittering C-beams".

This is fantastic for world-building purposes and painting a vivid picture of the sort of interstellar battles Roy Batty has been in during his short four-year life span, but it doesn't explainhow as a society, after anuclear holocaust,we would have the technology at all to build space ships (not chemical-rockets) capable of engaging in skirmishes with...aliens? What exactly were they fighting out there in the off-world colonies?

InBlade Runner,the fictional Voight-Kampff test is used to identify if an individual is a replicant or a human. It's designed to trigger emotions in the subject, which replicants wouldn't be able to have. Through a series of questions and images, it monitors the subject's physiological response, such as reaction time and pupillary movement.

Neuroscientists today use a test that's very similar. A database called the International Affective Picture System contains emotionally disturbing pictures and some neutral ones, and is used to measure a person's emotional response by their reactions. These days it can also be coupled with brain scans, something that wasn't around when Philip K. Dick wrote the novel on whichBlade Runneris based.

Unlike the android Ash of Ridley Scott'sAlien, replicants like Roy Batty are more biological in nature. When you cut them open, you won't see wires, motors, and metal, but soft, genetically-engineered tissue. That being said, there's no mention of what "powers" a replicant.

RELATED: 10 Best Sci-Fi Movies About Artificial Intelligence, Ranked

They appear human, but don't require "sleep" or "food" or "social contact" to exist. They are efficient slave laborers, soldiers, and pleasure bots precisely because they're more effective at their tasks than humans ,who would require time away from their work. Even our most advanced robots today can't handlecertain physical environments, never mind be nimble, store power, and move autonomously for days on end.

One of the biggest ways a replicant differs from a human is their memories. As they were never "born" and had no childhood, but emerge as fully-formed adult humans in appearance when they're constructed, they have to have memories implanted. This is a way for them to have an "anchor" on their emotions, which would override their systems otherwise.

Today, cognition researchers use memory implantation as a technique in relation to cognitive psychology. They make subjects believe a memory happened to them that never actually did. These implanted memories prove how easy it is to distort a human's memory of a past event, casting doubt over the repressed therapy techniques of digging for memories that may not be valid. At that point, would a human and a replicant be so different if they both believed their memories to be true?

The robot-doomsday scenario is a mainstay in the sci-fi genre. In films likeTerminatorandI, Robot,the artificially intelligent beings turn on their human creators and threaten to wipe out humankind. It always boils down to the robot/AI/replicant either becoming "self aware" and wanting to preserve itself over humans who wish to destroy it, or deciding humans should be destroyed because they're inefficient/a danger to themselves (think Ultron inAvengers).

However, the crucial issue with the scenario is that while AI is still programmed by humans, AI doesn't think like humans. Humans can learn from very few examples of failure, but AI must replicate scenarios over and over to learn patterns not to repeat. In this way, they are far from developing consciousness. We should be more afraid of how humans would use AI, than how it would use itself.

NEXT:IO: IO: 5Things That Are Scientifically Accurate (& 5 Things That Make No Sense)

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Buck Bokai: The Last Boy of Summer – Star Trek

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Heres what we know: Its 2026, and Buck Bokai is at the plate. Whether its his first at-bat, his third, or his sixth doesnt matter he has hit safely in 56 games in a row. Its 2026, and with every at-bat, Buck Bokai might break a Major League record that has stood since 1941. The pitcher hurls the ball at the plate, what kind of pitch lost to history Bokai swings, and makes contact. The sound of wood on leather rings out, sharp and sweet, but its a ground ball. Bokai runs. Fielder Eddie Newsom tries to make a play, but the ball just squeaks out under his glove. Bokai is safe. 57 games. A new record. A legend for all time.

Heres what we know: Its 2042, sixteen years later, and Buck Bokai is at the plate. He isnt such a young man anymore. Baseball isnt such a young sport, either. Invented in 1839, the game became the national pastime of America, and loved and played around the world. It survived corruption, scandal, steroids, and two world wars, but the world is turning sour again and it wont survive a third. This is the final World Series. There are 300 people in the stands. The pitcher hurls his ball at the plate. Bokai swings, makes contact. The sound of wood on leather rings out, louder than it should, and its a home run. He rounds the bases, touches home, and thats it for baseball. So long, folks.

Buck Bokai is one of Star Treks odder tragic figures. A once-in-a-lifetime talent who peaked at the decline of his craft, hes remembered solely, so far as we know, by an android playing a holodeck recreation of 20th century San Francisco, the commanding officer of a space station perched tenuously at the mouth of the galaxys only stable wormhole, and that officers son. That hes remembered at all is a miracle given the fate of the sport he played, and the fate of the world some years after he clubbed his last homer. Khan Noonien Singh, after all, was an obscure name in the database of the original starship Enterprises computers, and he was once the undisputed ruler of over a quarter of Earth. Were it not for the long memories of the sports few 24th century devotees, Bokais life, his accomplishments, would have fallen to dust.

Though the episode we see him in, Deep Space Nines If Wishes Were Horses, is more infamous than good, its a gift for anybody with an interest in the fabric of Star Treks vision of humanitys future. The Bokai who breaks DiMaggios hit streak is a nameless figure, a point of data recited by Data on The Next Generation because hes learned the facts of 20th and 21st century life to better fit into his captains Dixon Hill holonovel. The Bokai that appears in Deep Space Nine is a fully realized man, one whose exploits inspire Benjamin Sisko, one of the Federations greatest heroes. He provides context for stories that take place in Earths distant past. He stands as a hero at the intersection of skill and chance. He is, by virtue of his existence, one of the few models were given for what becomes of human sport as we stretch out from earth and take our place among the stars.

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Heres what we know: Captain Jonathan Archer enjoys water polo. Lieutenant Commander Worf brutally learns the differences between human and Klingon physiology when he accidentally kills a classmate during a game of soccer. Captain Jean Luc-Picard loves to fence. Chief Miles OBrien cant help but kayak, even if it means tearing his rotator cuff. Doctor Julian Bashir, as a consequence of his genetic engineering, is too skilled to lose at darts. Doctor Phlox, a Denobulan serving on a human ship, hits shots effortlessly without truly grasping the concept of basketball. As humanity betters itself and encounters new races, its sports become obsolete. Springball, parrises squares, tsunkatse these are the games of the future.

It makes sense. One of the quintessential assertions Star Trek makes about Humanity is that we, as a species, are driven to seek out, introduce ourselves to, and live among other species. We grow attached to the games those species play first as a means of finding a foothold in their culture, then because it presents the unending challenge of mastery. The same is not true of the species we meet. In 2375 the Vulcan Logicians visit Deep Space Nine and destroy Benjamin Siskos Niners 10-1. The Niners one run is framed as a moral victory, but whats a moral victory to a Vulcan? What is baseball to a Vulcan?

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A nostalgist would say that baseball is a living connection to Americas past, though I suspect Abner Doubleday wouldnt recognize the game as its played today as the one he invented in a pre-Civil War America. Its a global game, but not to the extent that Star Trek envisions. The Major Leagues have yet to become the Planetary League, and the Toronto Blue Jays are still the only foreign team eligible to play in the World Series. There are no teams in London, but it seems unlikely that the game is destined for an ignoble end in our time. 2019 is Buck Bokais rookie season for the Crenshaw Monarchs, and if the story of his career is that his genius is as obvious as it is underappreciated, the same cannot be said for generational talents like Mike Trout or Vladimir Guerrero Jr. Even the worst teams in memory, like my beloved 2003 Detroit Tigers, drew more than 300 fans to the ballpark. As long as there is time to pass, theres baseball to be played.

Heres what we know: Its 2063, and humanity has no time left to pass. Zefram Cochrane takes his seat in the cockpit of Earths first warp-capable ship, the Phoenix, and his flight catches the attention of a Vulcan ship nearby. Its been 20 years since Buck Bokai hit his last home run and, at least professionally, there are no home runs in his, or our, future. Buck Bokai is 65 years old. The game of baseball is 224 years old. Most games arent meant to last forever. The legacies of great men are often forgotten. Would Buck Bokai be Benjamin Siskos favorite ballplayer had he struck out, the count 3-2, his legacy that he merely tied with Joltin Joe? Would he be Siskos favorite ballplayer without the tinge of tragedy and finality that came with his last swing of the bat?

Baseball, like many sports, is a medium through which humans tell stories about themselves. In 2063 we learn that there is more to the universe than humanity, a vast number of races with whom we wish to communicate. Try explaining the rules of baseball to someone who doesnt like baseball. Now try explaining the rules of baseball to an alien. Whats more interesting to an interplanetary visitor: the man who broke the warp barrier, or the intricacies of the infield fly rule? Buck Bokai was a great baseball player, but his role in human history is to haunt a corner of it, a story written in a dead language and passed from one hobbyist to the next. Its not that hes the last boy of summer. Its just that summer eventually comes to mean something else.

Colette Arrand (she/her) is a transsexual poet from Athens, Georgia. She is the author of THE FUTURE IS HERE AND EVERYTHING MUST BE DESTROYED (Split Lip Press, 2019) and HOLD ME GORILLA MONSOON (OPO Books & Objects, 2017). She can be found on Twitter @colettearrand

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Buck Bokai: The Last Boy of Summer - Star Trek

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