Category Archives: Genetic Engineering

The biomedical field is constantly working to make new medical solutions that can help treat patients with various illnesses and conditions. Today, there are numerous medical solutions used today to help ease medical treatment for patients. These solutions include new medical devices, implants, software used to run medical equipment, and information technology systems.

The following are some of the most popular medical technologies that are used today:

Information technologies are another type of technology used today in medicine. For example, imaging systems let doctors examine patients like never before by allowing them to see inside a persons body without performing surgery first. One famous example of this type of medical solution is 3-D imaging software that uses pictures taken with an X-ray machine to give doctors a model to track health changes over time. Another example includes using information technology systems to control medical equipment or devices through smartphone computer programming or apps.

This type of technology allows doctors to use medical equipment with greater accuracy and helps make their work easier. For example, different types of imaging software help provide more transparent images for radiologists when they read X-rays and MRIs. This helps with making a diagnosis quicker. Thats why most hospitals would prefer to work with Wound Care, a web-based EHR tool. Such tools help record patient vitals and wound assessments to track each patients progress and provide better treatment.

These products can be used as medical solutions for people who want to check their health but dont want to visit a doctors office. Wearable health technologies include everything from smartwatches that measure heart rate and blood pressure functions to fitness trackers that help wearers monitor daily activity levels. Even Google has made its smart contact lenses that can track glucose levels for people with diabetes. However, these devices are designed specifically for individuals suffering from chronic diseases such as arthritis or Parkinsons disease in many cases.

Synthetic biology and genetic engineering tools are a technology used to treat illnesses or conditions that affect organs in the body. For example, if a patient has heart disease, they may need a new heart valve. In this case, doctors can use synthetic biology and genetic engineering tools to create a different kind of heart valve from those typically made from cow tissue. These valves have been tested on animals, and now researchers are testing them on humans as well.

Laboratory-grown organs are another medical solution used to help treat patients who need transplants for certain diseases or conditions that may have caused organ failure. A typical example is how stem cells taken from bone marrow can be turned into blood cells and then used to help treat patients with leukemia. Other types of laboratory-grown organs being tested in clinical trials today include partially functional livers and lungs grown from stem cells.

Medical equipment is another technology doctors can use when treating patients. For example, medical imaging devices like CT scanners and MRI machines help provide images of the bodys internal structures for diagnosis so doctors can see problems most other methods cannot detect. Another type of medical equipment includes surgical robots that can be moved by a computer program to perform surgery on a patient. This reduces the need for an incision since some procedures only require small openings or ones that heal very well without stitches or staples closing them up afterward.

Stem cells and stem cell therapies are a type of medical solution used to treat patients who have conditions that can be life-threatening or cause other severe complications. For example, patients with leukemia may need transplanted blood cells from healthy donors. In this case, doctors can use stem cells to develop those types of blood cells that will provide the best chance of curing the patients cancer without harming their body.

Other examples include using cord blood stem cells from newborns to make different kinds of healthy blood and immune system cells for older children and adults with certain diseases or using skin or other non-embryonic stem cells to make insulin-producing pancreatic beta cells for people diagnosed with diabetes Type 1.

Overall, biomedical technologies have been beneficial in making it easier for doctors to diagnose and treat their patients. Thanks to these technologies, many patients can live long, healthy lives with their illnesses or conditions under control. As technology continues advancing over time, even more, advanced solutions will come out, which should further help improve patient care. However, the use of new medical solutions must be approved by a doctor before being used on a patient.

See the article here:
What Are New Medical Solutions That Can Help Treat Patients? - iLounge

We might be discouraged from playing with our food, but people remain remarkably creative when it comes to what they eat.

Technology and tastes have played a leading role in the production, preservation and preparation of peoples' ever-evolving diets.

Traditional modification methods, such as selective breeding and cross-breeding of plants and animals were in the 1970s onwards revolutionized with the advent of genetic engineering.

How our meals are stored was transformed almost one century ago when the modern domestic freezer became a mainstay of many homes in the U.S., after it was introduced en masse by General Electric in 1927.

And cooking times were cut and the concept of ready meals was coined after U.S, engineer Percy Spencer invented the modern microwave oven from World War II radar technology, which was first sold in 1946.

Some would now suggest social media is now driving trends in our eating habits, with attention paid in particular to food's aesthetics to make them more Instagram-friendly.

Read on to learn some of the foods that have amazingly only arrived in the last century.

Despite their name, the French and Belgians have a long-running dispute about where french fries were invented, with both countries claiming ownership.

What is more certain is that fries were introduced in the U.S. by returning World War I soldiers.

This tasty savory treat's ubiquity was later cemented following the invention of the potato water gun knife in 1960, allowing for the mass production of fries by fast-food restaurants.

We've all heard the saying "best invention since sliced bread," and there's little argument it has not been very convenient.

Inventor Otto Frederick Rohwedder cut his first loaf of the food staple in his bread slicing machine at the Chillicothe Baking Company of Chillicothe, Missouri, creating the Kleen Maid Sliced Bread product. It proved an instant success.

The "best invention since..." phrase is believed to have originated in 1962 when Jeanne Boardman wrote a letter to Missouri's St. Joseph Gazette to praise the periodical's Hints from Heloise column "as about the greatest thing since sliced bread."

Bubble gum was invented in 1928 by Walter Diemer, while working at a chewing gum factory as an accountant.

After lengthy experiments, he eventually landed on a formula for a gum both less sticky and extremely stretchy, allowing bubbles to be blown with it.

That pink remains the most popular color for bubble gum can reportedly be traced back to the fact this was the only coloring available when Diemer was coming up with his formula.

Denver lays claim to creating the cheeseburger. In 1935, Louis Ballast melted a slice of cheese on a hamburger at his Humpty Dumpty drive-in restaurant, and patented the resulting dish as the world's first "cheeseburger."

Although the restaurant no longer exists, the U.S. city has erected a memorial to this historic dining event, found at 2776 North Speer Boulevard.

The instant noodle was invented by Momofuku Ando from a tiny shed behind his home in the town in Japan's Osaka Prefecture.

He was dedicated to thinking about food in new and creative ways and worked alone, reportedly sleeping only four hours a night and without ever taking a day off.

Chicken Ramen, the product of many trial and error experiments, was dubbed "magic ramen" and became an instant sensation among consumers.

Then, on a fact-finding trip to America, Momofuku observed supermarket managers breaking up Chicken Ramen noodles, adding them to a cup with hot water, and then eating them with a fork, inspiring Momofuku to create "CupNoodles" in 1971.

The International Rice Research Institute in the Philippines released in 1966 a semi-dwarf, high-yield Indica variety that, in conjunction with high-yield wheat, helped herald an era now known as the Green Revolution.

This rice thrives in tropical regions of Asia and South America, and is considered partially responsible for raising worldwide production by more than 20 percent by 1970.

Scientist Casimir Funk, coined the term "vitamine" in a seminal 1912 scientific paper that for the first time confirmed there were more than only three essential nutrients in food: protein, carbohydrates, and fat.

But it was only by the 1970s that high-dose multivitamins began to be freely available on U.S. store shelves.

McNuggets first debuted at McDonald's locations nationwide in 1983, following a highly successful soft launch in Knoxville, Tennessee.

The popularity of the bite-sized poultry pieces has been attributed to the U.S. government recommendation around this time for people to eat less red meat in favor of chicken.

Chicken Nuggets remain one of the favorite items on the restaurant's menu and McDonald's announced it would remove artificial preservatives from its recipe in 2016.

Quorn was first launched in 1985 by the U.K.'s Marlow Foods, with the versatile meat substitute developed from a fungus found growing in Marlow, Buckinghamshire.

The microorganism is grown in fermentors where it converts carbohydrates into protein, producing a protein-rich, sustainable food source packed with fiber, low in saturated fat and containing no cholesterol.

Quorn revolutionized the vegetarian market and arguably helped pave the way for the Impossible Burger, a patty that looks smells and tastes like meat but contains no beef.

This decade has witnessed the remarkable rise in sustainable animal-friendly options for flexitarians, vegetarians, and vegans alike, in part thanks to vegan options such as the Impossible Burger.

The popular product derives its impressive meat flavor from heme, an iron-rich molecule that helps give meat its taste and smell.

Impossible Foods created this plant-based heme from fermenting genetically engineered yeast infused with DNA from soy plants.

This marriage between Doritos and Taco Bell has become so popular it is now a regular menu item long after its legendary 2012 debut.

The Doritos Locos Taco is a Taco Bell food item first released on March 8, 2012, in Nacho Cheese at a Taco Bell in Toledo, Ohio.

This dish is a crunchy taco with ground beef, lettuce, and real cheddar cheese, in a shell formed from Doritos chips in Nacho Cheese, Cool Ranch, or Fiery flavor.

In the year of its launch alone, Taco Bell sold more than 450 million Doritos Locos Tacos.

The 2013 union of a doughnut and a croissant was the genius brainchild of renowned baker Dominique Ansel.

The pastry expert reported required a doughnut for his menu, but did not know much about them, although he knew plenty about the French breakfast delicacy, the croissant.

After this eureka moment and more than 10 attempts at the perfect balance of texture and flavor, the Cronut was born.

The Cronut went viral in less than a week and with only 350 available daily, you will have to be prepared to queue in the early mornings outside the bakery in New York's SoHo for a chance to eat one of your own.

Although unappetizing to some, insects are packed full of protein, fatty acids, and B vitamins, in addition to being abundantly available.

Charles B. Wilson needed to find alternative protein for his diet, due to food allergies, and landed upon the novel idea of using edible bugs.

He then bought some crickets, ground them up, and was so impressed with the results, he started selling them en masse in 2014.

While Wilson's Cricket Flours company was among the first western companies to utilize crickets as a food source, this appears to be a growing trend, with people increasingly eager to consume more sustainable food.

Ruby chocolate marks the invention of an entirely new type of the traditionally dark brown or white sweet treat.

The oddly-colored bar was unveiled in 2017, following extensive development by Zurich-based cocoa processor Barry Callebaut that reportedly lasted more than a decade.

The creation was the first new naturally colored chocolate since Nestl introduced the world to white chocolate approximately 80 years previously.

With a berry flavor, ruby chocolate is naturally extracted and processed from a specific bean found on the Ivory Coast, Ecuador, and Brazil, while its distinctive reddish hue derives from how the bean is processed.

Single-use water bottles are being increasingly viewed as bad news for the planet, with the plastic containers now known to clog the oceans, city streets and even poison the air we breathe.

However, edible water bottles are a proposed ingenious solution to the plastic problem.

These are constructed by combining brown seaweed and plants that naturally biodegrade in a matter of weeks, creating Notpla

These balls, sachets, and packets are called Ooho, which first came to public attention during 2019's London Marathon, and there is an expectation the restaurant industry may start using this edible innovation for take-away and delivery services.

Read more:
15 Amazing Foods That Were Only Invented in the Last 100 Years - Newsweek

Monsanto, the chemical company with outsized influence and impact on our agricultural practices, is often in the news. Its genetically modified Roundup Ready crop seeds were introduced 25 years ago, and have changed how many of us both eat and think about our food. With immense detail and care, historian Bartow J. Elmore tells the troubling story of the company's past, present, and future in his new book "Seed Money: Monsantos Past and Our Food Future."

The following interview has been edited for length and clarity.

KCRW: Where is Monsanto at right now, in terms of any lawsuits and their fallout?

Bartlow J. Elmore: I never saw any of this coming. It shocked me to the core as I was writing. ... Monsanto is no more, because Monsanto was gobbled up by Bayer, the German life sciences pharmaceutical company, in 2018. And there's a certain irony there, because when Monsanto was founded, the whole point of Monsanto was to be this American chemical company that would be independent of German firms like Bayer. ... After that merger, the first Roundup case [Roundup] is an herbicide that Monsanto created that was very popular went to trial and the plaintiffs won. It was a $280 million-plus verdict, finding that a gardener who had been exposed to Roundup, that his cancer, Non-Hodgkins lymphoma, was linked to that.

Subsequently, two other cases went against Bayer, with juries, again, finding that Roundup exposure was linked to those plaintiffs' cancers. And there has also been a series of other cases that have happened in the interim. Various states across the United States Delaware, Washington, among many others have begun filing suit against Monsanto, now Bayer, for PCB contamination, another chemical that Monsanto produced decades ago that is still affecting folks, even today. And then lastly, there's another herbicide called dicamba that has been causing a lot of problems out in farm country. And there are farmers that are also filing suit against the company for that. And as a result, Bayer stock price has plummeted. And there's a real question as to what the future of this company is going to be, given all those liabilities.

When all those court decisions came down, many of the shareholders, who are German, issued a vote of no confidence against their CEO and the board of management, because they were baffled: How is it that this company could have made the decision to buy a company with [such] extensive liabilities? That had never happened in the history of the DAX, the German exchange. Monsanto had always wanted to be separate from Bayer. It wanted to be this American chemical company. But in some ways, the guy who started Monsanto, John Queeny, may have gotten what he wanted. He may have finally defeated this German firm because they've kind of swallowed a poison pill, in a way.

It's sort of like a bellwether of poor decision making in relation to externalities or unintended consequences.

Yeah, I really went into this knowing full well that a lot of people refer to Monsanto as mon Satan, that it had this reputation. You could see it in polls as being listed as one of the most hated companies in history. And I really wanted to, as a historian, try and tell a human story as much as I could about what happened. Were people in this company just bad? Or are there stories of good people who were in the firm, who are trying to create certain products that then have these consequences that they didn't see coming? And I saw both, really, in the story.

I saw well meaning people like Bob Shapiro, who was the head of the company. I really believe he thought that some of the GMO seeds they would produce would feed the world and have these really outsized influences, in a good way. On the other hand, I also found documents, like one related to PCBs, where an executive sitting in 1969 in a confidential meeting, deciding what to do about this toxic compound, literally wrote in his own handwriting, One of the alternatives is that we could sell the hell out of those PCBs as long as we possibly can, even knowing how toxic it was.

I definitely started to see that there was a kind of toxic culture at times within the firm, in which profits were held out as more important than people. And that was really deeply disturbing to come across. I remember when I saw that particular document, it was jaw dropping, because sell the hell out of them I mean, he went back and actually put in a little indentation to put the hell out of it. It was not like it was an afterthought.

I really went into this knowing full well that a lot of people referred to Monsanto as Monsatan, says Bartow Elmore, who approached researching the company in the hopes of telling its history from a human perspective. Photo by Jonathan Zadra.

I really went into this knowing full well that a lot of people referred to Monsanto as Monsatan, says Bartow Elmore, who approached researching the company in the hopes of telling its history from a human perspective. Photo by Jonathan Zadra.

Tell us more about John Queeny and when he started Monsanto.

Monsanto was started in 1901, going into the Progressive Era. Queeny was not a chemist, and really knew very little about chemistry. He was a drug salesman who had come from Chicago to St. Louis. He was 40 years old when he started this company, naming it after his wife, Olga Monsanto. But he had two kids at the time, and was really somebody just struggling trying to make it on his own. He had actually tried to build a factory in the late 19th century in St. Louis, and it had burned down. And you can see this picture of him in the book, where he's got his family all around him, and I think he's not very happy. And part of that is, I think, the stress of the time.

That says something about the early years of Monsanto. There's a kind of haste to the process, trying to produce these chemicals as fast as you can, and at times at the expense of the workers. The first products they made were ultimately saccharin, artificial sweetener, and caffeine, of all things, which is how I came to the project, because I had been writing a book about Coca Cola. And I had been trying to trace the ingredients that go into Coca Cola. And it brought me to Monsanto, because Coca Cola was the sole buyer of all of Monsantos saccharin and caffeine. Without Coca Cola, there would really be no Monsanto.

When did that happen? And how did the company begin to really dig into an agricultural product portfolio?

They were so far behind the Europeans, especially the Germans and companies like Bayer that they were trying to beat. But both World War One and World War Two are really key, because they cut off supplies of chemicals from overseas from these big powerhouses, and Monsanto, Dow, and these other big chemical companies in the United States had an opportunity to grow in part because of war. So you could say that war really made these companies and that there's a connection between the chemical industries and war. And in a very direct way, when it comes to agriculture.

By the 40s, the US military is trying to find various defoliants, herbicides that can be used to help troops, and particularly the Pacific theater and other places where there are dense jungles. And two of the chemical compounds that comes out of that exploration are 2,4-D and 2,4,5-T. These, incidentally, would become the key ingredients in what we know as Agent Orange that would be sprayed in the Vietnam War. And DDT was one of the other chemicals they were making at that time. ... So that's really the moment these insecticides and pesticides are becoming a much bigger part of their portfolio by the late 1940s.

In Seed Money, historian Bartow Elmore researches the story of Monsanto, uncovering handwritten documents showing concerns for profits over the welfare of people. Photo courtesy of W. W. Norton & Company.

What about the ownership of plant genetics and their foray into seeds?

It comes much later. And how that happened was one of the key questions of the book. Going back to those chemical compounds, by the 50s and 60s, it's very clear that these compounds are toxic. By the end of the Vietnam War, veterans are exposing the public health effects of exposure to these chlorinated compounds. And Monsanto is actually trying to figure out how to make an herbicide that's not as toxic as Agent Orange. And thus is born, in 1970, Roundup active ingredient glyphosate that was a broad spectrum herbicide that could be sprayed on everything. We think of Roundup now as being tied to all these court cases, and according to the World Health Organization, potential links to cancer and things like this. But at the time, the whole point was that Roundup is the environmentally safe herbicide. And actually, Roundup becomes the first billion dollar herbicide in history. It becomes this blockbuster product for Monsanto.

Beginning in the 1980s, Monsanto began heavily investing in genetic engineering to see if they can create crops that can resist or tolerate heavy sprayings of Roundup or glyphosate. Basically, during the growing season, you could grow your crops, and spraying your crops wouldn't hurt them, because they'd be genetically engineered to tolerate Roundup, but it would kill all the weeds. And the thing that was most exciting from the archives was why. The answer has a lot to do with the energy crisis. The archives say internally, Uh oh, 80% of what we make in the 1970s, including a lot of these pesticides, were coming from petrochemical feedstocks from natural gas and oil.

And in 1973 and 74, you have this OPEC oil embargo. And then you have the Iranian Hostage Crisis and disruptions in the Middle East oil trade in 79. And the oil prices are through the roof. And they say internally, We couldn't keep going. We didn't have cheap hydrocarbons to make all these chemicals. Almost no company has done something like that, right? Totally revolutionize themselves and become this biotech company. But I'll emphasize that, even as they did that, because they were so reliant on these billion dollar brands like Roundup, they brought those chemicals into that biotech beyond. These would be genetically engineered seeds that were sold by Monsanto, but they would become packaged with their most profitable herbicide, Roundup. And that's what we started seeing in the 1990s.

What a story.

What was really startling when I was writing about Roundup was that I thought Roundup was going to be the really scary story. But the other chemical that came up in those conversations internally with folks was dicamba, an herbicide that's being sprayed on farmland today. Though many consumers probably don't know it. This is an older chemical that goes back to 1958. And it's been brought in to deal with weeds that have become resistant to Roundup. So we're now spraying a new herbicide, which is actually an older one, to try and deal with those weeds.And what happens when we spray dicamba is that it volatilizes, it vaporizes. So when you spray this chemical on a farm in hot temperatures, it jumps, that's what farmers will say. It actually will vaporize and then spread to farms nearby.

Now Monsanto is selling dicamba-tolerant seeds. ... But if you don't buy Monsanto seeds, this vaporized herbicide can spread onto your farm and damage your farm. I went to the court case in Missouri, where farmers who were hit by this vaporized herbicide filed suit against Monsanto saying, How could you do this? And as I sat in the gallery watching that court case, my jaw dropped as the internal documents were released. ... And sure enough, there's these internal emails that were released, in which they said, We can sell protection from your neighbor as a way to sell these dicamba-tolerant seeds. This was another one of those moments where you said, That's not right. Thats not right to have a system where the product is going to do something like that and force compliance with your seed system. And it really took me aback.

Follow this link:
Sowing the troubling seeds of Monsanto's past, present and future - KCRW

--Focusing on neuroblastoma, the researchers used a multi-omics approach to identify tumor-specific peptides and then used genetic engineering to harness the immune system to destroy tumors--

PHILADELPHIA, Nov. 3, 2021 /PRNewswire/ -- In a breakthrough for the treatment of aggressive solid cancers, researchers at Children's Hospital of Philadelphia (CHOP) have developed a novel cancer therapy that targets proteins inside cancer cells that are essential for tumor growth and survival but have been historically impossible to reach. Using the power of large data sets and advanced computational approaches, the researchers were able to identify peptides that are presented on the surface of tumor cells and can be targeted with "peptide-centric" chimeric antigen receptors (PC-CARs), a new class of engineered T cells, stimulating an immune response that eradicates tumors.

Senior author John M. Maris, MD, pediatric oncologist and Giulio D'Angio Chair in Neuroblastoma Research at CHOP

The discovery, which was described today in Nature, opens the door to treating a broader array of cancers with immunotherapy as well as applying each therapy across a greater proportion of the population.

"This research is extremely exciting because it raises the possibility of targeting very specific tumor molecules, expanding both the cancers that can be treated with immunotherapy and the patient population who can benefit," said Mark Yarmarkovich, PhD, an investigator in the Maris Laboratory at Children's Hospital of Philadelphia and first author of the paper. "By using a multi-omics approach, we were able to identify peptides specific to neuroblastoma tumors, but this method could be used in any cancer, allowing for a more personalized approach to cancer treatment."

The development of CAR T cell-based cancer immunotherapy marked a breakthrough in the treatment of leukemia, but the approach has not yet made significant strides against solid tumors due, at least in part, to a lack of tumor-specific targets. In these cancers, most of the proteins responsible for tumor growth and survival are in the nuclei of tumor cells, not on the cell surface, where they would generally be accessible to CAR T cells. Instead, fragments of these proteins may be presented on the tumor cell surface through the presentation of peptides on the major histocompatibility complex (MHC), which evolved to present viral and bacterial peptides to the immune system. Cancer cells can also present intracellular proteins on MHC, and if these are mutant peptides, they may be recognized as foreign. However, all pediatric cancers and many adult malignancies have few mutations and are rather driven by other factors like dysregulated developmental pathways.

Story continues

Neuroblastoma is an explosively aggressive pediatric cancer that is driven by modifications of gene expression that promote uncontrolled tumor growth. Historically, neuroblastoma has been treated with chemotherapy, surgery, and radiation therapy, but patients often relapse with forms of the disease that are chemotherapy resistant. Additionally, the low mutational burden of the cancer, combined with its low MHC expression, have made it difficult to target with immunotherapies.

Despite these obstacles, the researchers hypothesized that some of the peptides presented on the surface of neuroblastoma tumor cells come from proteins that are essential for tumor growth and survival and could be targeted with synthetic CARs. These PC-CARs would allow for direct targeting and killing of tumor cells. The challenge was differentiating tumor-specific peptides from other, similar looking peptides or peptides that exist in normal tissues to avoid cross-reactivity and lethal toxicity.

To do so, the researchers stripped the MHC molecules off neuroblastoma cells and determined which peptides were present and at what abundance. They used a large genomic dataset that the Maris lab has generated to determine which peptides were unique to neuroblastoma and not expressed by normal tissues. They prioritized peptides that were derived from genes essential to the tumor and had characteristics required to engage the immune system. To weed out any potential antigens that might have cross reactivity with normal tissue, the researchers filtered the remaining tumor peptides against a database of MHC peptides on normal tissues, removing any peptide with a parent gene represented in normal tissue.

Using this multi-omics approach, the researchers pinpointed an unmutated neuroblastoma peptide that is derived from PHOX2B, a neuroblastoma dependency gene and transcriptional regulator that was previously identified and characterized at CHOP. The next major hurdle was developing a PC-CAR that specifically recognized just the peptide, which makes up 2-3% of the peptide-MHC complex. In collaboration with antibody-discovery company Myrio Therapeutics, the researchers developed a PC-CAR targeting this peptide and showed that these PC-CARs recognized the tumor-specific peptide on different HLA types, meaning the treatment could be applied to patients of diverse genetic lineages.

Taking the research a step further, the team tested the PC-CARs in mice and found that the treatment led to complete and targeted elimination of neuroblastoma tumors.

"We are excited about this work because it allows us to now go after essential cancer drivers that have been considered 'undruggable' in the past. We think that PC-CARS have the potential to vastly expand the pool of immunotherapies and significantly widen the population of eligible patients," said senior author John M. Maris, MD, pediatric oncologist and Giulio D'Angio Chair in Neuroblastoma Research at CHOP. "Thanks to the Acceleration grant we received through the Cell and Gene Therapy Collaborative at CHOP, we will bring our PHOX2B PC-CAR to a clinical trial at CHOP in late 2022 or early 2023."

Yarmarkovich et al. "Therapeutic Targeting of Intracellular Oncoproteins with Peptide-Centric CAR T Cells," Nature, November 3, 2021, DOI: 10.1038/s41586-021-04061-6

About Children's Hospital of Philadelphia:Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, Children's Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country. In addition, its unique family-centered care and public service programs have brought the 595-bed hospital recognition as a leading advocate for children and adolescents. For more information, visit http://www.chop.edu

Contact: Jennifer LeeChildren's Hospital of Philadelphia(267) 426-6084LEEJ41@chop.edu

Cision

View original content to download multimedia:https://www.prnewswire.com/news-releases/chop-researchers-develop-a-new-class-of-car-t-cells-that-target-previously-untargetable-cancer-drivers-301414682.html

SOURCE Children's Hospital of Philadelphia

See the original post:
CHOP Researchers Develop a New Class of CAR-T Cells that Target Previously Untargetable Cancer Drivers - Yahoo Finance

Research from the nonprofit U.S. Right to Know has undergirded New York Times reporting on the food system, and outlets ranging from Vanity Fair to the National Review to the Washington Examiner to The Intercept have cited the groups inquiries into the origins of COVID-19.

But the Oakland-based truth and transparency organizations own provenance has gone largely unexamined, even as public interest and political furor over the controversial lab-leak theoryand the even more broadly disputed notion that the novel coronavirus was the result of engineeringhave steadily escalated. However, The Daily Beast found that public documents, including USRTKs own disclosures, show even as the group does not advocate against vaccines, its roots run into a vitriolically anti-vaccine organization that has promoted conspiracy theories about the Sept. 11 attacks and The Great Reset.

That theory posits that pandemic-safety protocols are a prelude to a new global regime of government and corporate control.

Filings with the Internal Revenue Service and the state of California show that USRTK launched in 2014 on a $44,500 grant from the Organic Consumers Association (OCA). For the first two years of USRTKs existence, the Minnesota-based OCA was its lone funder, with contributions swelling as years passed, and totaling more than $1 million in 2021, according to USRTKs own reporting.

While the self-described investigative research group has acquired other contributors, the Organic Consumers Association has far and away remained the largest, with its gifts to USRTK amounting to almost double the sum received from the next biggest donor. The Organic Consumers Association has also been the only organization to grant money to USRTK every year since its inception.

Like USRTK, the 23-year-old Organic Consumers Association began as a group preoccupied with pesticides and genetically modified organisms. But as it gained financial backing from ultra-rich backers in the wellness sectormost notably supplement kingpin Joseph Mercolait adopted their conspiratorial anti-vaccine views, as The Daily Beast previously reported.

Earlier this year, OCA founder Ronnie Cummins, who has also advanced 9/11 truther narratives, co-authored a book with Mercola which purported to expose The Great Reset, Lockdowns, Vaccine Passports, and the New Normal. The books footnotes included multiple citations of USRTK research on COVID-19s origins and, in promoting the book last month, Cummins referred to USRTK as a longtime ally. (Cummins did not respond to a request for comment.)

In late 2020, a USRTK researcher also participated in a Facebook Live event the Organic Consumers Association hosted. A lot of pieces dont fit the animal-origin story thats prevailing, the USRTK staffer asserted, citing what he described as the viruss unusual qualities.

Meanwhile, most scientistsand a recently declassified U.S. intelligence reporthave concluded that the virus was most likely not the product of deliberate genetic engineering.

USRTK co-founder Gary Ruskin, the only staffer at the organization who responded to The Daily Beasts queries, admitted that he had known Cummins for decades and launched the group with his support. But he insisted his group had nothing to do with his patrons more controversial views.

We wanted to start a new organization to stand up for the idea that people have the right to know what's in their food. Ronnie was supportive of this, Ruskin wrote in an email to The Daily Beast. We dont work on the issue of vaccines.

But Cummins is hardly the only anti-vaxxer operation with which the group has fraternized.

Public records show the organization has also received considerable financial contributions from the Westreich Foundation. That group, in turn, has bankrolled multiple anti-inoculation groups, including the National Vaccine Information Center, which experts have long called the most powerful anti-vaccine organization in America. Until last year, the Westreich Foundation maintained a Vaccine Safety page on its website that included false assertions that immunization is total nonsense and that vaccine safety is the greatest lie ever told.

The only phone number for the Westreich Foundation The Daily Beast could find was disconnected.

Further, though it has not echoed his notorious views on vaccines specifically, USRTK has repeatedly used its platforms to amplify Robert F. Kennedy Jr., perhaps Americas most infamous anti-vaxxer. He has in turn amplified themparticularly on the issue of COVID-19s origins. This Spring, USRTK research director Carey Gillam published excerpts of her recent book on agrochemical giant Monsanto on Kennedy Jr.s website, and in June she appeared on his podcast to discuss the issue.

All this time, Gillam has been a regular contributor to The Guardian, where her work has focused on environmental degradation and the food system. Neither Gillam nor Guardian U.S. editor John Mulholland responded to requests for comment, and Ruskin dodged questions about her decision to collaborate with Kennedy Jr., who the Center for Countering Digital Hate identified as one of the biggest purveyors of COVID-19 falsehoods on the Internet.

Robert Kennedy has lots of views about lots of things, Ruskin wrote. I dont really follow them all especially closely.

Dr. David Gorski of Wayne State University, who first identified USRTK as an arm of the Organic Consumers Association on the blog Science-Based Medicine in 2016, argued that the two nonprofits share a similar set of obsessions: namely, perceived tampering with nature. He argued USRTK took reasonable distrust of corporations and righteous calls for accountability to an extreme, tipping into pseudoscience and conspiracy theories.

"They started primarily as anti-GMO and anti-pesticide of any kind, and definitely into various conspiracy theories about Monsanto, [herbicide] glyphosate, etcetera. And that was primarily how I knew them, Gorski said. "Whats fascinating is how fast theyve pivoted to COVID nonsense.

But Gorski also posited the groups intensifying interest in the widely dismissed notion that COVID-19 sprang from so-called gain-of-function experiments at the Wuhan Institute of Virology was a natural evolution from USRTKs original mission.

"Think of it this way: if you come from a belief system where genetically manipulating organisms is dangerous, and its the goal of the corporations to exploit and harm and exploit us, he said, a group like that would be very much attracted to the idea that this horrible, deadly disease came from humans manipulating coronaviruses.

Dr. Kathleen Jamieson, professor of communication at the University of Pennsylvania and author of a recent article on conspiracists exploitation of uncertainty in COVID-19 science, noted USRTKs work flattens out crucial differences between the lab-leak theory with the notion that the virus was artificially modified. She pointed to a USRTK report that contrasted a scientific articles claimThere is currently no credible evidence to support the claim that SARS-CoV-2 originated from a laboratory-engineered CoVwith a private email the group obtained in which one of the same articles authors wrote, We cannot rule out the possibility that it comes from a bat virus leaked out of a lab.

The role of some of the players in that ecosystem is trying to maintain a more professional and trustworthy looking exterior.

Callum Hood

In fact, Jamieson noted, these claims do not contradict each other at all. Some versions of the lab-leak hypothesis have suggested that scientists at the Wuhan lab were studying a naturally occurring coronavirus in bats there, and failed to observe proper safety precautionsnot that they created the pathogen in a petri dish.

The difference between there being lab origin and the virus being genetically engineered in the lab is really important, she asserted. Theres some slippage across the materials you sent me between lab origin and the claim of it being genetically engineered.

Jamieson argued USRTKs work deserved scrutiny because of its funding and affiliations. But she also noted that the organizations published research stopped short of open conspiracy theorizing on the virus origins.

"Their language is not the traditional language of conspiracy theorists, Jamieson told The Daily Beast. My definition of a conspiracy theory is that there are powerful individuals of malign intent who are covering up.

But this may have to do with USRTKs role in what Callum Hood, research director at the Center for Countering Digital Hate, suggests amounts to a larger anti-science/anti-vaccine ecosystem. While Mercola and Cummins group may indulge in wild speculation about nefarious international plots, other organizations like Kennedys Childrens Health Defense and USRTK strive to maintain a respectable sheen.

The role of some of the players in that ecosystem is trying to maintain a more professional and trustworthy looking exterior, Hood said. "Childrens Health Defense is one of those which sort of goes to great lengths to look trustworthy, and U.S. Right to Know also appears to be trying to present itself as a trustworthy investigative organization.

The real target of proponents of the gain-of-function theory, Hood asserted, is Dr. Anthony Fauci. And, going by repeated explosive exchanges between Sen. Rand Paul (R-KY) and Fauci over government funding of groups engaged in gain-of-function research, they are hitting their target.

Some of Rands most recent verbal fusillades came after The Intercept published documents detailing U.S. grants to an organization that collaborated with the Wuhan lab. Although in this case USRTK did not provide the documents, as it had for past Intercept pieces, Ruskin himself donated a quote.

This is a road map to the high-risk research that could have led to the current pandemic, he told the left-leaning outlet.

The Intercepts reporters did not respond to requests for comment. Likewise most of the journalists or news organizations The Daily Beast contacted for this piece did not respond or declined to comment. Those who did requested anonymity in order to speak freely, and attested that they did not know about the depth USRTKs relationship with fringe groups when they accepted its assistance, and maintained they independently verified the authenticity of materials the group sent them.

Ruskin, for his part, denied promoting pseudoscience and conspiracies, and insisted his group had not conflated the lab-leak hypothesis with the bioengineering theory.

We stand by our work, he said, noting the group has published material in peer-reviewed journals. We talk with lots of people about our work, but we dont work on vaccines.

Meanwhile Jamieson, the communications professor and conspiracy theory expert, argued that uncertainty about COVID-19s originsand conspiracy theorieswill fester so long as Chinese authorities continue to resist an open investigation. What is necessary, she argued, is transparency from government actors and investigations that do not begin with presuppositions about how the virus emerged.

There are legitimate, important questions here that need to be answered, she said. "In the absence of certainty of the origins, not finding the host animal for example, or host entity, through which the virus jumped to the human population, you're going to have alternative causes posited, and those alternative causes are going to include some that will suggest malign intent by powerful actors who are covering up what they actually did."

Originally posted here:
This Fave Mainstream Media Source Is Funded by Anti-Vaxxers - The Daily Beast

An international team of researchers has discovered genes linked to plant survival in one of the harshest environments on the planet: Chiles Atacama Desert. Their findings, published in the Proceedings of the National Academy of Sciences (PNAS), may aid scientists in developing resilient crops that can thrive in increasingly arid environments.

In an era of accelerated climate change, it is critical to uncover the genetic basis to improve crop production and resilience under dry and nutrient-poor conditions, said Gloria Coruzzi, Professor in the New York University (NYU) Department of Biology and Center for Genomics and Systems Biology, who co-led the study.

The researchers spent a decade studying Atacama plant life in 22 locations across the barren desert, carefully transporting plant and soil samples back to the lab. Later, they preserved them in liquid nitrogen for genomic analysis.

The study involved botanists, microbiologists, ecologists, evolutionary biologists, and genomic researchers worldwide. The teams unique skills allowed them to identify the plants, microbes, and genes that will enable Atacama plants to adapt to and thrive in harsh desert environments, potentially improving crop growth and reducing food shortages.

Overall, the transcriptomes of 32 of the deserts most dominant plants were sequenced and compared to the transcriptomes of 32 related species from other locations. None of them had genetic adaptations to the Atacama environment.

The goal was to use this evolutionary tree based on genome sequences to identify the changes in amino acid sequences encoded in the genes that support the evolution of the Atacama plant adaptation to desert conditions, Coruzzi says.

The researchers at NYU then used an approach called phylogenomics, which aims to reconstruct evolutionary history using genomic data to identify the genes whose protein sequences were adapted in the Atacama species.

Furthermore, 59 of these genes have been discovered in Arabidopsis, where they have been interconnected with physiological and molecular processes that can improve plant resilience in harsh environments.

In a nutshell, Arabidopsis has already been shown to withstand harsh radiation and temperature stress, regulate floral development and flowering time, aid in pathogen defense and nutrient uptake thanks to the genes positively selected in the Atacama desert plants.

It is a plants evolutionary survival mechanism in harsh and dry environments. Furthermore, some of the same genetics can be found in food crop species, giving us a better understanding of which crops to plant and how to reproduce, fine-tune, and future-proof them.

The study is directly relevant to regions around the world that are becoming increasingly arid, with factors such as drought, extreme temperatures, and salt in water and soil posing a significant threat to global food production, says senior author and plant systems biologist Rodrigo Gutirrez from the Pontifical Catholic University of Chile.

As some Atacama plants are closely related to staple crops, including grains, legumes, and potatoes, the candidate genes we identified represent a genetic goldmine to engineer more resilient crops, a necessity given the increased desertification of our planet.

The findings are reported in PNAS.

Continue reading here:
This Genetic Goldmine In The Atacama Desert Could Be The Key To Feeding The Future - Wonderful Engineering

Some cases of heart failure have root causes surprisingly similar to diseases like Alzheimers, Huntingtons and ALS.

Over time, sometimes quite rapidly, the heart's thick strong muscle tissue becomes thin and weak, causing the left ventricle to swell like a balloon. This makes the heart less able to squeeze efficiently, which can lead to blood clots, irregular heartbeats, and sometimes sudden death when the malfunctioning heart simply stops beating. The origins of cardiomyopathy are diverse, including viral infections, autoimmune diseases, toxic drug exposures, and dozens of gene mutations.

Now, a multi-disciplinary team of clinicians and researchers has deciphered the function of a specific genetic mutation that causes cardiomyopathy. Their findings,published Nov. 3, 2021, in Nature Communications, were made possible by growing gene-edited human heart tissue from induced pluripotent stem cells and measuring the activity, location and binding of this mutant protein.

The team was led by co-corresponding authors Charles Murry, MD, PhD, a regenerative medicine expert at the University of Washington; Bruce Conklin, MD, a genetic engineering expert with the Gladstone Institutes in California, and Nathan Salomonis, PhD, a computational genomics expert at Cincinnati Children's.

"We hope this study will lead to broader insights that could lead to improved heart failure therapies," Conklin says.

Cutting-edge experiments expose more of the heart's inner workings

Over the last several decades, the research community has made many discoveries that have led to improved medications and medical devices that can dramatically extend life by slowing down the progression of heart failure. However, we still lack proven cures.

This study reveals a new mechanism of cardiomyopathy initiation by the RNA binding motif protein 20 (RBM20). This protein helps control RNA splicing in the heart, the process by which RNAs are sliced and diced to give rise to different proteins in different tissues. Normally, RBM20 splices RNAs to make proteins that enable the heart to adapt to stress and contract regularly throughout a person's entire life. But a class of mutations in RBM20 result in severe cardiomyopathy in adulthood.

"We and others had previously studied RBM20's function during heart development, but we had little to no clue of why it stops working in disease. We needed to step up our game if our research was to have a clinical impact," says Alessandro Bertero, PhD, who contributed to the work while at the University of Washington and now leads an Armenise-Harvard Laboratory at the University of Turin in Italy.

Discovering this protein's role was especially complex because knocking out this gene in animal models does not mimic the damaging effects seen in people. Instead, the work required editing the genome of healthy cells and engineering human heart tissue from these cells in a lab dish. Only by producing heart tissue similar to that found in humans could the authors understand the contractile defects and molecular mechanisms underlying this gene's function in a controlled manner.

"That was exactly what we intended when we started this project by genome-editing induced pluripotent stem cells," says co-leading author Yuichiro Miyaoka, PhD, of the Tokyo Metropolitan Institute of Medical Science.

First, the team observed that the engineered muscle tissue carrying the mutant form of RBM20 did not function like tissue engineered with normal RBM20 or lacking the protein all together. The mutated muscle fibers contracted with significantly less force and upstroke velocity, much like a heart affected by cardiomyopathy.

Then, at the single-cell level, the team detected another important clue. Normally, RBM20 is located exclusively within the cell nucleus. However, the mutated form localizes almost entirely out of the nucleus, in the cell's cytoplasm.

This, by itself, did not mean muchuntil the cell was exposed to heavy stress. When that occurred, the mutant protein was detected within tiny "stress granules" made of protein and RNA that cells rapidly produce as a reaction to stress. In contrast, RBM20 in healthy cells remained within the nucleus and distinct from stress granules. This suggests there are additional cellular mechanisms, along with changes in splice-activity, leading to RBM20 cardiomyopathy.

"When the RNA binding landscape of mutant RBM20 was revealed by a technology called enhanced CLIP, it mimicked the binding of other splicing factors that have been implicated in neurodegenerative diseases. These factors, when mutated, also change their activity from RNA splicing to RNA aggregation outside the nucleus," says co-author Gene Yeo, PhD, MBA, a member of the Department of Cellular and Molecular Medicine at the University of California San Diego.

"Over time, such aggregates play havoc with other cell functions, ultimately leading to the tissue-weakening of heart muscle during cardiomyopathy," Salomonis says.

"It is intriguing to note the parallels between our observations with RBM20 and recent findings in neuro-degeneration," the paper states. "Indeed, recent work has hypothesized cytoplasmic RBM20 may be similar to the cytoplasmic RNP granules associated with neurodegeneration (Schneider et al., 2020), such as TAU for Alzheimer s disease, Huntingtin for Huntington s disease, and FUS for amyotrophic lateral sclerosis (ALS)."

Next steps

Co-authors for this study also included scientists from the University of Cincinnati Department of Electrical Engineering and Computer Science, Sana Biotechnology, and the University of California San Francisco.

The co-authors say the 3D heart tissue model they've developed has the potential to be used to test new drugs to block the formation of cytoplasmic granules as a possible treatment for cardiomyopathy, even those without RBM20 mutations.

"RBM20 has been a frustrating protein to study, as animal models don't fully recapitulate human disease pathology," says lead author Aidan Fenix, PhD. "It's exciting to now have an in vitrohuman cell model of RBM20 cardiomyopathy that shows the major clinical feature of dilated cardiomyopathy--reduced contractile force. We hope these models will speed the discovery of therapies to treat RBM20 dilated cardiomyopathy."

About this study

This work was supported by grants from the National Heart, Lung, and Blood Institute (U01 HL099997, P01 HL089707, R01 HL130533, F32 HL156361-01, HL149734, R01 HL128362, R01 HL128368, R01 HL141570, R01 HL146868); the National Institute of Diabetes and Digestive and Kidney (U54DK107979-05S1); the National Science Foundation (NSF CMMI-1661730); a JSPS Grant-in-Aid for Young Scientists, and grants from NOVARTIS, the Mochida Memorial Foundation, SENSHIN Medical Research Foundation, Naito Foundation, Uehara Memorial Foundation, a Gladstone-CIRM Fellowship, and the A*STAR International Fellowship.

SOURCE Cincinnati Children's Hospital Medical Center

http://www.cincinnatichildrens.org

View original post here:
Heart Tissue in a Dish Reveals New Links Between Neurodegeneration and Heart Disease - PRNewswire

CAMBRIDGE, Mass., Nov. 03, 2021 (GLOBE NEWSWIRE) -- Clade Therapeutics, a biopharmaceutical company focused on discovering and delivering scalable, off-the-shelf, next-generation stem cell-based medicines, today announced it has secured an $87 million Series A financing led by Syncona Ltd. with participation from LifeSci Venture Partners, Emerson Collective and Bristol Myers Squibb. Proceeds from this financing will support the development of the Companys proprietary platform, which enables the immune cloaking of induced pluripotent stem cells (iPSCs) and the differentiation of cloaked stem cells into therapeutic cells.

We have reached an era in medicine where insights across genetic engineering, regenerative medicine and immunology have enabled a revolution of cell medicines, said Chad Cowan, Ph.D., Chief Executive Officer of Clade Therapeutics. Clade was founded to overcome the clinical limitations of current cell therapies by addressing durability, patient compatibility, reproducibility and scalability to deliver on the transformative potential of this increasingly important therapeutic modality.

Jim Glasheen, Ph.D., President and Chief Business Officer of Clade Therapeutics, said, We feel very fortunate to partner with a world-class group of investors. The syndicates combination of industry insight, technical expertise, entrepreneurial zeal, and focus on patient impact brings incredible value to the Company.

Martin Murphy, Ph.D., Chief Executive Officer of Syncona Ltd., said, Clades inherent focus on developing therapies derived from a single engineered cell source has the potential to shift the paradigm of cell medicine with unprecedented scalability and standardization. We are thrilled to support Clades aggressive development of broadly accessible, off-the-shelf products with consistent pharmaceutical criteria to expand the reach of cell therapies across patients and indications.

Ryan Cinalli, Ph.D., Chief Scientific Officer of LifeSci Venture Partners, said, Clade has assembled a world-class team of scientific pioneers whose foundational discoveries are integral to the Companys immune cloaking technology platform. We are confident that Clades leadership will innovate the next generation of cell therapies that harness cloaking technology to overcome the immune barriers that have limited durability and redosing in the field.

Neil White, Investment Manager of Emerson Collective, said, The unparalleled expertise and novel approach to generating stem cell-derived adult T, NK and B cells positions Clade as leaders in developing widely accessible cell medicines. With differentiation and cloaking technologies in place, this funding round will accelerate the development of Clades immune cell-focused, cancer therapeutics.

About Clade TherapeuticsClade Therapeutics mission is to discover and deliver next generation cell medicines to improve the lives of patients in need. Our platform technology cloaks human pluripotent stem cells and their adult derivatives enabling the development of immune compatible cell transplantation therapies. Led by a world-class team of company builders and scientific innovators with an unparalleled expertise in generating stem cell-derived adult T, NK and B cells, Clade promises to become a leading innovator in developing widely accessible cell medicines. The company is initially focused on harnessing the potential of cloaked immune cells for cancer treatment. For further information, please visit the company's website athttps://www.cladetx.com/.

About SynconaSyncona's purpose is to invest to extend and enhance human life. We do this by founding and building a portfolio of global leaders in life science to deliver transformational treatments to patients in areas of high unmet need.

Our strategy is to found, build and fund companies around exceptional science to create a diversified portfolio of 15-20 globally leading healthcare businesses for the benefit of all our stakeholders. We focus on developing treatments for patients by working in close partnership with world-class academic founders and management teams. Our balance sheet underpins our strategy enabling us to take a long-term view as we look to improve the lives of patients with no or poor treatment options, build sustainable life science companies and deliver strong risk-adjusted returns to shareholders.

About LifeSci Venture PartnersFormed in 2017, LifeSci Venture Partners is the early stage investing arm of LifeSci Partners, a unique life sciences and healthcare consultancy. We focus on private institutional financing rounds of transformational healthcare companies managed by exceptional founder/entrepreneurs. Our most recent fund, LifeSci Venture Partners II, LP was launched in 2020 and has invested in more than 25 breakthrough biotechnology and healthcare technology companies. For further information, please visit the company's website athttps://www.lifesciventure.com/.

About Emerson CollectiveEmerson Collective deploys a wide range of tools from impact investing to philanthropy to advocacy in pursuit of a more equal and just society. We focus on creating systemic change in education, immigration, climate, and cancer research and treatment.

Forward Looking Statements

This press release contains forward-looking statements including, but not limited to, statements related to Clades iPSC immune cloaking and differentiation platform technology to address compatibility, durability, reproducibility and scalability of cell therapies, Clades ability to develop broadly accessible, off-the-shelf products with consistent pharmaceutical criteria and expand the reach of cell therapies across patients and indications, the funding round resulting in the acceleration of the development of Clades immune cell-focused, cancer therapeutics and the value that the investor syndicate adds to the Company. These forward-looking statements are based on our current expectations and inherently involve significant risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, risks that Clades actual future financial and operating results may differ from its expectations or goals, Clades ability to commercialize and successfully launch its products, risks relating to Clades ability to successfully implement its business strategies, including potential competition, the ability to protect intellectual property and defend patents, regulatory obligations and oversight, including any changes in the legal and regulatory environment in which Clade operates and the effects of the COVID-19 pandemic on the business. We undertake no duty or obligation to update any forward-looking statements contained in this press release as a result of new information.

ContactLigia Vela ReidLifeSci AdvisorsTel: +4407413825310lvela-reid@lifesciadvisors.com

Read the original post:
Clade Therapeutics Raises $87 Million Series A Financing to - GlobeNewswire

Patients with nonsmall cell lung cancer (NSCLC), the most common lung cancer in humans, are frequently treated with an immunotherapy called immune checkpoint blockade (ICB). This therapy induces a population of tumor-infiltrating T cells called CD8 positive T cells to secrete interferon gamma which in turn induces the expression of programmed cell death ligand 1 (PD-L1).

PD-L1 expression in the tumor microenvironment indicates the T cells are poised to kill tumor cells and patients with PD-L1 positive T-cell infiltrated tumors are most likely to respond to ICB. However, only about 35% of NSCLC patients respond to ICB therapy. Not all CD8 positive T cells in lung tumors express PD-L1 and respond to ICB and little is known about the mechanisms that govern ICB resistance in T cells within NSCLC.

In a new study published in Science Immunologytitled, Lack of CD8+ T cell effector differentiation during priming mediates checkpoint blockade resistance in nonsmall cell lung cancer, Stefani Spranger, PhD, professor at the MIT department of biology, and her colleagues uncover what causes some T cells in animal models of NSCLC to fail to respond to ICB, offering a potential way around it.

Jeffrey Bluestone, PhD, professor of metabolism and endocrinology at the University of California, San Francisco, who was not involved with the paper said, The study provides a potential opportunity to rescue immunity in the NSCLC non-responder patients with appropriate combination therapies.

It has been generally held that the continuous fight against tumor cells exhausts T cells which causes them to stop working. The rationale behind ICB therapy, therefore, has been to reinvigorate the exhausted T cells that pass into the tumors microenvironment.

However, experiments conducted by Brendan Horton, PhD, postdoctoral fellow in Sprangers lab, showed some ICB-resistant T cells stop working before they even enter the tumor, indicating exhaustion is not the cause behind their dysfunction.

Instead, the authors found that gene expression in these T cells is altered during their activation in lymph nodes which causes them to stop functioning. Once activated, T cells specialize into different subtypes with distinct functions that can be detected by specific genetic signatures.

According to Spranger, the idea that the dysfunctional state leads to ICB resistance arises before T cells enter the tumor is quite novel.

We show that this state is actually a preset condition, and that the T cells are already nonresponsive to therapy before they enter the tumor, she said. As a result, she explained, ICB therapies that work by reinvigorating exhausted T cells within the tumor are less likely to be effective. This suggests that combining ICB with other forms of immunotherapy that target T cells differently might be a more effective approach to help the immune system combat this subset of lung cancer.

To determine why some tumors are resistant to ICB, the team studied T cells in mouse models of NSCLC. They sequenced mRNA from responsive and non-responsive T cells and used a technique called Seq-Well, developed in the lab of fellow Koch Institute member, J. Christopher Love, PhD, professor of chemical engineering, and a co-author of the study. The technique allows rapid gene expression profiling of single cells. T cells responsive and nonresponsive to ICB show different gene expression patterns at specialized functional states, the single-cell sequencing analysis showed. For instance, nonresponsive T cells express low levels of some cytokinesproteins that control immunity.

Armed with the differential gene expression pattern, the team sought to convert ICB-resistant T cells into ICB-responsive T cells. The researchers treated lung tumors in mouse models with cytokines IL-2 and IL-12. This led the previously nonresponsive T cells to fight cancer cells in the mouse NSCLC.

This is potentially something that could be translated into a therapeutic that could increase the therapy response rate in non-small cell lung cancer, Horton said.

Spranger and Horton suspect cytokine therapy could be used in combination with ICB, although current clinical practices avoid cytokine treatments due to potential adverse side effects, including a condition called cytokine storm that can be fatal.

Spranger feels this work will help researchers develop more innovative cancer therapies, refocusing their efforts from reversing T-cell exhaustion to earlier states of T-cell specialization.

If T cells are rendered dysfunctional early on, ICB is not going to be effective, and we need to think outside the box, she said. Theres more evidence, and other labs are now showing this as well, that the functional state of the T cell actually matters quite substantially in cancer therapies.

To Spranger, this means that cytokine therapy might be a therapeutic avenue for NSCLC patients beyond ICB.

More here:
Lung Cancer Unresponsive to Immunotherapy and a Potential Solution - Genetic Engineering & Biotechnology News

Abstract

Genetic engineering opens new possibilities for biomedical enhancement requiring ethical, societal and practical considerations to evaluate its implications for human biology, human evolution and our natural environment. In this Commentary, we consider human enhancement, and in particular, we explore genetic enhancement in an evolutionary context. In summarizing key open questions, we highlight the importance of acknowledging multiple effects (pleiotropy) and complex epigenetic interactions among genotype, phenotype and ecology, and the need to consider the unit of impact not only to the human body but also to human populations and their natural environment (systems biology). We also propose that a practicable distinction between therapy and enhancement may need to be drawn and effectively implemented in future regulations. Overall, we suggest that it is essential for ethical, philosophical and policy discussions on human enhancement to consider the empirical evidence provided by evolutionary biology, developmental biology and other disciplines.

Lay Summary: This Commentary explores genetic enhancement in an evolutionary context. We highlight the multiple effects associated with germline heritable genetic intervention, the need to consider the unit of impact to human populations and their natural environment, and propose that a practicable distinction between therapy and enhancement is needed.

There are countless examples where technology has contributed to ameliorate the lives of people by improving their inherent or acquired capabilities. For example, over time, there have been biomedical interventions attempting to restore functions that are deficient, such as vision, hearing or mobility. If we consider human vision, substantial advances started from the time spectacles were developed (possibly in the 13th century), continuing in the last few years, with researchers implanting artificial retinas to give blind patients partial sight [13]. Recently, scientists have also successfully linked the brain of a paralysed man to a computer chip, which helped restore partial movement of limbs previously non-responsive [4, 5]. In addition, synthetic blood substitutes have been created, which could be used in human patients in the future [68].

The progress being made by technology in a restorative and therapeutic context could in theory be applied in other contexts to treat non-pathological conditions. Many of the technologies and pharmaceutical products developed in a medical context to treat patients are already being used by humans to enhance some aspect of their bodies, for example drugs to boost brain power, nutritional supplements, brain stimulating technologies to control mood or growth hormones for children of short stature. Assistive technology for disabled people, reproductive medicine and pharmacology, beside their therapeutic and restorative use, have a greater potential for human enhancement than currently thought. There are also dual outcomes as some therapies can have effects that amount to an enhancement as for example, the artificial legs used by the South African sprinter Oscar Pistorius providing him with a competitive advantage.

This commentary will provide general ethical considerations on human enhancement, and within the several forms of so-called human biomedical enhancement, it will focus on genetic engineering, particularly on germline (heritable) genetic interventions and on the insights evolutionary biology can provide in rationalizing its likely impact. These insights are a subject often limited in discussions on genetic engineering and human enhancement in general, and its links to ethical, philosophical and policy discussions, in particular [9]. The rapid advances in genetic technology make this debate very topical. Moreover, genes are thought to play a very substantial role in biological evolution and development of the human species, thus making this a topic requiring due consideration. With this commentary, we explore how concepts based in evolutionary biology could contribute to better assess the implications of human germline modifications, assuming they were widely employed. We conclude our brief analysis by summarizing key issues requiring resolution and potential approaches to progress them. Overall, the aim is to contribute to the debate on human genetic enhancement by looking not only at the future, as it is so often done, but also at our evolutionary past.

The noun enhancement comes from the verb enhance, meaning to increase or improve. The verb enhance can be traced back to the vulgar Latin inaltiare and late Latin inaltare (raise, exalt), from altare (make high) and altus (high), literally grown tall. For centuries human enhancement has populated our imagination outlined by stories ranging from the myths of supernormal strengths and eternal life to the superpowers illustrated by the 20th century comic books superheroes. The desire of overcoming normal human capacities and the transformation to an almost perfect form has been part of the history of civilization, extending from arts and religion to philosophy. The goal of improving the human condition and health has always been a driver for innovation and biomedical developments.

In the broadest sense, the process of human enhancement can be considered as an improvement of the limitations of a natural version of the human species with respect to a specific reference in time, and to different environments, which can vary depending on factors such as, for example, climate change. The limitations of the human condition can be physical and/or mental/cognitive (e.g. vision, strength or memory). This poses relevant questions of what a real or perceived human limitation is in the environment and times in which we are living and how it can be shifted over time considering social norms and cultural values of modern societies. Besides, the impact that overcoming these limitations will have on us humans, and the environment, should also be considered. For example, if we boost the immune system of specific people, this may contribute to the development/evolution of more resistant viruses and bacteria or/and lead to new viruses and bacteria to emerge. In environmental terms, enhancing the longevity of humans could contribute to a massive increase in global population, creating additional pressures on ecosystems already under human pressure.

Two decades ago, the practices of human enhancement have been described as biomedical interventions that are used to improve human form or functioning beyond what is necessary to restore or sustain health [10]. The range of these practices has now increased with technological development, and they are any kind of genetic, biomedical, or pharmaceutical intervention aimed at improving human dispositions, capacities, or well-being, even if there is no pathology to be treated [11]. Practices of human enhancement could be visualized as upgrading a system, where interventions take place for a better performance of the original system. This is far from being a hypothetical situation. The rapid progress within the fields of nanotechnology, biotechnology, information technology and cognitive science has brought back discussions about the evolutionary trajectory of the human species by the promise of new applications which could provide abilities beyond current ones [12, 13]. If such a possibility was consciously embraced and actively pursued, technology could be expected to have a revolutionary interference with human life, not just helping humans in achieving general health and capabilities commensurate with our current ones but helping to overcome human limitations far beyond of what is currently possible for human beings. The emergence of new technologies has provided a broader range of potential human interventions and the possibility of transitioning from external changes to our bodies (e.g. external prosthesis) to internal ones, especially when considering genetic manipulation, whose changes can be permanent and transmissible.

The advocates of a far-reaching human enhancement have been referred to as transhumanists. In their vision, so far, humans have largely worked to control and shape their exterior environments (niche construction) but with new technologies (e.g. biotechnology, information technology and nanotechnology) they will soon be able to control and fundamentally change their own bodies. Supporters of these technologies agree with the possibility of a more radical interference in human life by using technology to overcome human limitations [1416], that could allow us to live longer, healthier and even happier lives [17]. On the other side, and against this position, are the so-called bioconservatives, arguing for the conservation and protection of some kind of human essence, with the argument that it exists something intrinsically valuable in human life that should be preserved [18, 19].

There is an ongoing debate between transhumanists [2022] and bioconservatives [18, 19, 23] on the ethical issues regarding the use of technologies in humans. The focus of this commentary is not centred on this debate, particularly because the discussion of these extreme, divergent positions is already very prominent in the public debate. In fact, it is interesting to notice that the moderate discourses around this topic are much less known. In a more moderate view, perhaps one of the crucial questions to consider, independently of the moral views on human enhancement, is whether human enhancement (especially if considering germline heritable genetic interventions) is a necessary development, and represents an appropriate use of time, funding and resources compared to other pressing societal issues. It is crucial to build space for these more moderate, and perhaps less polarized voices, allowing the consideration of other positions and visions beyond those being more strongly projected so far.

Ethical and societal discussions on what constitutes human enhancement will be fundamental to support the development of policy frameworks and regulations on new technological developments. When considering the ethical implications of human enhancement that technology will be available to offer now and in the future, it could be useful to group the different kinds of human enhancements in the phenotypic and genetic categories: (i) strictly phenotypic intervention (e.g. ranging from infrared vision spectacles to exoskeletons and bionic limbs); (ii) somatic, non-heritable genetic intervention (e.g. editing of muscle cells for stronger muscles) and (iii) germline, heritable genetic intervention (e.g. editing of the CC chemokine receptor type 5 (CCR5) gene in the Chinese baby twins, discussed later on). These categories of enhancement raise different considerations and concerns and currently present different levels of acceptance by our society. The degree of ethical, societal and environmental impacts is likely to be more limited for phenotypic interventions (i) but higher for genetic interventions (ii and iii), especially for the ones which are transmissible to future generations (iii).

The rapid advances in technology seen in the last decades, have raised the possibility of radical enhancement, defined by Nicholas Agar, as the improvement of human attributes and abilities to levels that greatly exceed what is currently possible for human beings [24]. Genetic engineering offers the possibility of such an enhancement by providing humans a profound control over their own biology. Among other technologies, genetic engineering comprises genome editing (also called gene editing), a group of technologies with the ability to directly modify an organisms DNA through a targeted intervention in the genome (e.g. insertion, deletion or replacement of specific genetic material) [25]. Genome editing is considered to achieve much greater precision than pre-existing forms of genetic engineering. It has been argued to be a revolutionary tool due to its efficiency, reducing cost and time. This technology is considered to have many applications for human health, in both preventing and tackling disease. Much of the ethical debate associated with this technology concerns the possible application of genome editing in the human germline, i.e. the genome that can be transmitted to following generations, be it from gametes, a fertilized egg or from first embryo divisions [2628]. There has been concern as well as enthusiasm on the potential of the technology to modify human germline genome to provide us with traits considered positive or useful (e.g. muscle strength, memory and intelligence) in the current and future environments.

To explore some of the possible implications of heritable interventions we will take as an example the editing (more specifically deletion using CRISPR genome editing technology) of several base pairs of the CCR5 gene. Such intervention was practised in 2018 in two non-identical twin girls born in China. Loss of function mutations of the CCR5 had been previously shown to provide resistance to HIV. Therefore, the gene deletion would be expected to protect the twin baby girls from risk of transmission of HIV which could have occurred from their father (HIV-positive). However, the father had the infection kept under control and the titre of HIV virus was undetectable, which means that risk of transmission of HIV infection to the babies was negligible [29].

From an ethical ground, based on current acceptable practices, this case has been widely criticized by the scientific community beside being considered by many a case of human enhancement intervention rather than therapy [29, 30]. One of the questions this example helps illustrate is that the ethical boundary between a therapy that corrects a disorder by restoring performance to a normal scope, and an intervention that enhances human ability outside the accepted normal scope, is not always easy to draw. For the sake of argument, it could be assumed that therapy involves attempts to restore a certain condition of health, normality or sanity of the natural condition of a specific individual. If we take this approach, the question is how health, normality and sanity, as well as natural per se, are defined, as the meaning of these concepts shift over time to accommodate social norms and cultural values of modern societies. It could be said that the difficulty of developing a conceptual distinction between therapy and enhancement has always been present. However, the potential significance of such distinction is only now, with the acceleration and impact of technological developments, becoming more evident.

Beyond ethical questions, a major problem of this intervention is that we do not (yet?) know exactly the totality of the effects that the artificial mutation of the CCR5 may have, at both the genetic and phenotypic levels. This is because we now know that, contrary to the idea of one gene-one trait accepted some decades ago, a geneor its absencecan affect numerous traits, many of them being apparently unrelated (a phenomenon also known as pleiotropy). That is, due to constrained developmental interactions, mechanisms and genetic networks, a change in a single gene can result in a cascade of multiple effects [31]. In the case of CCR5, we currently know that the mutation offers protection against HIV infection, and also seems to increase the risk of severe or fatal reactions to some infectious diseases, such as the influenza virus [32]. It has also been observed that among people with multiple sclerosis, the ones with CCR5 mutation are twice as likely to die early than are people without the mutation [33]. Some studies have also shown that defective CCR5 can have a positive effect in cognition to enhance learning and memory in mice [34]. However, its not clear if this effect would be translated into humans. The example serves to illustrate that, even if human enhancement with gene editing methods was considered ethically sound, assessing the totality of its implications on solid grounds may be difficult to achieve.

Beyond providing the opportunity of enhancing human capabilities in specific individuals, intervening in the germline is likely to have an impact on the evolutionary processes of the human species raising questions on the scale and type of impacts. In fact, the use of large-scale genetic engineering might exponentially increase the force of niche construction in human evolution, and therefore raise ethical and practical questions never faced by our species before. It has been argued that natural selection is a mechanism of lesser importance in the case of current human evolution, as compared to other organisms, because of advances in medicine and healthcare [35]. According to such a view, among many others advances, natural selection has been conditioned by our niche-construction ability to improve healthcare and access to clean water and food, thus changing the landscape of pressures that humans have been facing for survival. An underlying assumption or position of the current debate is that, within our human species, the force of natural selection became minimized and that we are somehow at the end-point of our evolution [36]. If this premise holds true, one could argue that evolution is no longer a force in human history and hence that any human enhancement would not be substituting itself to human evolution as a key driver for future changes.

However, it is useful to remember that, as defined by Darwin in his book On the Origin of the Species, natural selection is a process in which organisms that happen to be better adapted to a certain environment tend to have higher survival and/or reproductive rates than other organisms [37]. When comparing human evolution to human genetic enhancement, an acceptable position could be to consider ethically sound those interventions that could be replicated naturally by evolution, as in the case of the CCR5 gene. Even if this approach was taken, however, it is important to bear in mind that human evolution acts on human traits sometimes increasing and sometimes decreasing our biological fitness, in a constant evolutionary trade-off and in a contingent and/or neutralin the sense of not progressiveprocess. In other worlds, differently from genetic human enhancement, natural selection does not aim at improving human traits [38]. Human evolution and the so-called genetic human enhancement would seem therefore to involve different underlying processes, raising several questions regarding the implications and risks of the latter.

But using genetic engineering to treat humans has been proposed far beyond the therapeutic case or to introduce genetic modifications known to already occur in nature. In particular, when looking into the views expressed on the balance between human evolution and genetic engineering, some argue that it may be appropriate to use genetic interventions to go beyond what natural selection has contributed to our species when it comes to eradicate vulnerabilities [17]. Furthermore, when considering the environmental, ecological and social issues of contemporary times, some suggest that genetic technologies could be crucial tools to contribute to human survival and well-being [2022]. The possible need to engineer human traits to ensure our survival could include the ability to allow our species to adapt rapidly to the rate of environmental change caused by human activity, for which Darwinian evolution may be too slow [39]. Or, for instance, to support long-distance space travel by engineering resistance to radiation and osteoporosis, along with other conditions which would be highly advantageous in space [40].

When considering the ethical and societal merits of these propositions, it is useful to consider how proto-forms of enhancement has been approached by past human societies. In particular, it can be argued that humans have already employedas part of our domestication/selective breeding of other animalstechniques of indirect manipulation of genomes on a relatively large scale over many millennia, albeit not on humans. The large-scale selective breeding of plants and animals over prehistoric and historic periods could be claimed to have already shaped some of our natural environment. Selective breeding has been used to obtain specific characteristics considered useful at a given time in plants and animals. Therefore, their evolutionary processes have been altered with the aim to produce lineages with advantageous traits, which contributed to the evolution of different domesticated species. However, differently from genetic engineering, domestication possesses inherent limitations in its ability to produce major transformations in the created lineages, in contrast with the many open possibilities provided by genetic engineering.

When considering the impact of genetic engineering on human evolution, one of questions to be considered concerns the effects, if any, that genetic technology could have on the genetic pool of the human population and any implication on its resilience to unforeseen circumstances. This underlines a relevant question associated with the difference between health and biological fitness. For example, a certain group of animals can be more healthyas domesticated dogsbut be less biologically fit according to Darwins definition. Specifically, if such group of animals are less genetically diverse than their ancestors, they could be less adaptable to environmental changes. Assuming that, the human germline modification is undertaken at a global scale, this could be expected to have an effect, on the distribution of genetically heritable traits on the human population over time. Considering that gene and trait distributions have been changing under the processes of evolution for billions of years, the impact on evolution will need to be assessed by analysing which genetic alterations have been eventually associated with specific changes within the recent evolutionary history of humans. On this front, a key study has analysed the implications of genetic engineering on the evolutionary biology of human populations, including the possibility of reducing human genetic diversity, for instance creating a biological monoculture [41]. The study argued that genetic engineering will have an insignificant impact on human diversity, while it would likely safeguard the capacity of human populations to deal with disease and new environmental challenges and therefore, ensure the health and longevity of our species [41]. If the findings of this study were considered consistent with other knowledge and encompassing, the impact of human genetic enhancements on the human genetic pool and associated impacts could be considered secondary aspects. However, data available from studies on domestication strongly suggests that domestication of both animals and plans might lead to not only decreased genetic diversity per se, but even affect patterns of variation in gene expression throughout the genome and generally decreased gene expression diversity across species [4244]. Given that, according to recent studies within the field of biological anthropology recent human evolution has been in fact a process of self-domestication [45], one could argue that studies on domestication could contribute to understanding the impacts of genetic engineering.

Beyond such considerations, it is useful to reflect on the fact that human genetic enhancement could occur on different geographical scales, regardless of the specific environment and geological periods in which humans are living and much more rapidly than in the case of evolution, in which changes are very slow. If this was to occur routinely and on a large scale, the implications of the resulting radical and abrupt changes may be difficult to predict and its impacts difficult to manage. This is currently highlighted by results of epigenetics studies, and also of the microbiome and of the effects of pollutants in the environment and their cumulative effect on the development of human and non-human organisms alike. Increasingly new evidence indicates a greater interdependence between humans and their environments (including other microorganisms), indicating that modifying the environment can have direct and unpredictable consequences on humans as well. This highlight the need of a systems level approach. An approach in which the bounded body of the individual human as a basic unit of biological or social action would need to be questioned in favour of a more encompassing and holistic unit. In fact, within biology, there is a new field, Systems Biology, which stresses the need to understand the role that pleiotropy, and thus networks at multiple levelse.g. genetic, cellular, among individuals and among different taxaplay within biological systems and their evolution [46]. Currently, much still needs to be understood about gene function, its role in human biological systems and the interaction between genes and external factors such as environment, diet and so on. In the future if we do choose to genetically enhance human traits to levels unlikely to be achieved by human evolution, it would be crucial to consider if and how our understanding of human evolution enable us to better understand the implications of genetic interventions.

New forms of human enhancement are increasingly coming to play due to technological development. If phenotypic and somatic interventions for human enhancement pose already significant ethical and societal challenges, germline heritable genetic intervention, require much broader and complex considerations at the level of the individual, society and human species as a whole. Germline interventions associated with modern technologies are capable of much more rapid, large-scale impacts and seem capable of radically altering the balance of humans with the environment. We know now that beside the role genes play on biological evolution and development, genetic interventions can induce multiple effects (pleiotropy) and complex epigenetics interactions among genotype, phenotype and ecology of a certain environment. As a result of the rapidity and scale with which such impact could be realized, it is essential for ethical and societal debates, as well as underlying scientific studies, to consider the unit of impact not only to the human body but also to human populations and their natural environment (systems biology). An important practicable distinction between therapy and enhancement may need to be drawn and effectively implemented in future regulations, although a distinct line between the two may be difficult to draw.

In the future if we do choose to genetically enhance human traits to levels unlikely to be achieved by human evolution, it would be crucial to consider if and how our understanding of humans and other organisms, including domesticated ones, enable us to better understand the implications of genetic interventions. In particular, effective regulation of genetic engineering may need to be based on a deep knowledge of the exact links between phenotype and genotype, as well the interaction of the human species with the environment and vice versa.

For a broader and consistent debate, it will be essential for technological, philosophical, ethical and policy discussions on human enhancement to consider the empirical evidence provided by evolutionary biology, developmental biology and other disciplines.

This work was supported by Fundao para a Cincia e a Tecnologia (FCT) of Portugal [CFCUL/FIL/00678/2019 to M.A.].

Conflict of interest: None declared.

Pham

P

Roux

S

Matonti

F

Post-implantation impedance spectroscopy of subretinal micro-electrode arrays, OCT imaging and numerical simulation: towards a more precise neuroprosthesis monitoring tool

J Neural Eng

2013

10

046002

Maghami

MH

Sodagar

AM

Lashay

A

Visual prostheses: the enabling technology to give sight to the blind

J Ophthal Vis Res

2014

9

494

505

Weitz

AC

Nanduri

D

Behrend

MR

Improving the spatial resolution of epiretinal implants by increasing stimulus pulse duration

Sci Transl Med

2015

7

318ra203.

Bouton

CE

Shaikhouni

A

Annetta

NV

Restoring cortical control of functional movement in a human with quadriplegia

Nature

2016

533

247

50

Geddes

L.

First paralysed person to be reanimated offers neuroscience insights. Technique moves mans arm by decoding his thoughts and electrically stimulating his own muscles

Nat News

2016

533

Squires

JE.

Artificial blood

Science

2002

295

1002

5

Lowe

KC.

Blood substitutes: from chemistry to clinic

J Mater Chem

2006

16

Original post:
Human enhancement: Genetic engineering and evolution