Israeli Company Plans to Produce Cultivated Fat, Whole Steaks at Its Forthcoming Pilot Facility

Jennifer Marston wrote . . . . . . . . .

Bioprinting startup MeaTech 3D this week became the latest cultivated meat company to announce a pilot production facility, which the company intends to have operational in 2022. The plant’s location is yet to be announced. MeaTech said they will use the facility to increase the production of cultured chicken fat from Peace of Meat, a Belgian company MeaTech acquired in December of 2020.

MeaTech says cultured fat can “significantly enhance” the texture, flavor, and mouthfeel of plant-based meat alternatives, giving them an altogether “meatier” taste than is available with current plant-based meat analogues. MeaTech said in this week’s announcement that it plans to license its cultivated fat tech — including cell lines and bioprocesses — to other companies wishing to improve their plant-based products.

However, cultivated fat is only one part of MeaTech’s overall plan. In tandem, the company will continue to develop a process for whole cuts of cultivated meat — namely steak and chicken breast — using 3D bioprinting tech.

Developing full cuts of cultivated meat is far more difficult than making minced products for burgers or chicken bites. With full cuts of meat, the various cells, including those for muscle, fat, blood vessels, and connective tissue, have to grow together, on scaffolding, to achieve the desired cut of meat. This is a significantly more intricate process than simply growing the different cells then manually combining them at the end, as can be done for a patty or nugget.

Aleph Farms, also based in Israel, is the other notable company attempting to produce whole cuts of cultivated meat. Earlier this year, the company said they had developed a 3D bioprinted Ribeye steak from cultivated protein.

So far, MeaTech has printed a carpaccio-like layer of meat. A full steak or chicken breast is in all likelihood years away. While the forthcoming pilot production facility will first be used to scale up production of Peace of Meat’s cultured fat, it will eventually incorporate MeaTech’s bioprinting tech to produce the aforementioned whole cuts of meat.

Source: The Spoon

How mRNA Technology Could Change the World

Derek Thompson wrote . . . . . . . . .

Synthetic mRNA, the ingenious technology behind the Pfizer-BioNTech and Moderna vaccines, might seem like a sudden breakthrough, or a new discovery. One year ago, almost nobody in the world knew what an mRNA vaccine was, for the good reason that no country in the world had ever approved one. Months later, the same technology powered the two fastest vaccine trials in the history of science.

Like so many breakthroughs, this apparent overnight success was many decades in the making. More than 40 years had passed between the 1970s, when a Hungarian scientist pioneered early mRNA research, and the day the first authorized mRNA vaccine was administered in the United States, on December 14, 2020. In the interim, the idea’s long road to viability nearly destroyed several careers and almost bankrupted several companies.

The dream of mRNA persevered in part because its core principle was tantalizingly simple, even beautiful: The world’s most powerful drug factory might be inside all of us.

People rely on proteins for just about every bodily function; mRNA—which stands for messenger ribonucleic acid—tells our cells which proteins to make. With human-edited mRNA, we could theoretically commandeer our cellular machinery to make just about any protein under the sun. You could mass-produce molecules that occur naturally in the body to repair organs or improve blood flow. Or you could request our cells to cook up an off-menu protein, which our immune system would learn to identify as an invader and destroy.

In the case of the coronavirus that causes COVID-19, mRNA vaccines send detailed instructions to our cells to make its distinctive “spike protein.” Our immune system, seeing the foreign intruder, targets these proteins for destruction without disabling the mRNA. Later, if we confront the full virus, our bodies recognize the spike protein again and attack it with the precision of a well-trained military, reducing the risk of infection and blocking severe illness.

But mRNA’s story likely will not end with COVID-19: Its potential stretches far beyond this pandemic. This year, a team at Yale patented a similar RNA-based technology to vaccinate against malaria, perhaps the world’s most devastating disease. Because mRNA is so easy to edit, Pfizer says that it is planning to use it against seasonal flu, which mutates constantly and kills hundreds of thousands of people around the world every year. The company that partnered with Pfizer last year, BioNTech, is developing individualized therapies that would create on-demand proteins associated with specific tumors to teach the body to fight off advanced cancer. In mouse trials, synthetic-mRNA therapies have been shown to slow and reverse the effects of multiple sclerosis. “I’m fully convinced now even more than before that mRNA can be broadly transformational,” Özlem Türeci, BioNTech’s chief medical officer, told me. “In principle, everything you can do with protein can be substituted by mRNA.”

In principle is the billion-dollar asterisk. mRNA’s promise ranges from the expensive-yet-experimental to the glorious-yet-speculative. But the past year was a reminder that scientific progress may happen suddenly, after long periods of gestation. “This has been a coming-out party for mRNA, for sure,” says John Mascola, the director of the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases. “In the world of science, RNA technology could be the biggest story of the year. We didn’t know if it worked. And now we do.”

1. The Long Road to Breakthrough

For more than 40 years, synthetic RNA couldn’t do anything useful. In 1978, Katalin Karikó was a young scientist at the Biological Research Centre in Szeged, Hungary, when she started working on the idea that it could. She left Hungary for the U.S. in the 1980s. At the University of Pennsylvania, she still struggled to design mRNA that the body did not immediately reject. When her research failed to attract the support of government grants and university colleagues, she was demoted.

After a decade of fits and starts, Karikó and her research partner Drew Weissman finally broke through in the early 2000s. To sneak synthetic mRNA past the cell’s defenses, they realized that they had to tweak one of its molecular building blocks, the nucleosides that comprise a strand of RNA. “The solution, Karikó and Weissman discovered, was the biological equivalent of swapping out a tire,” the journalists Damian Garde and Jonathan Saltzman wrote for the science website Stat.

In the U.S., the paper caught the attention of a brash group of postdoctoral researchers, professors, and venture capitalists. They started a company whose name smushed the words modified and RNA: Moderna. In Germany, Ugur Sahin and Özlem Türeci, a married couple with a background in immunotherapy research, also saw huge potential. They founded several companies, including one to research mRNA-based treatments for cancer: BioNTech.

“There was a lot of skepticism in the industry when we started, because this was a new technology with no approved products,” Türeci told me. “Drug development is highly regulated, so people don’t like to deviate from paths with which they have experience.” BioNTech and Moderna pressed on for years without approved products, thanks to the support of philanthropists, investors, and other companies. Moderna partnered with the NIH and received tens of millions of dollars from DARPA, the Defense Advanced Research Projects Agency, to develop vaccines against viruses, including Zika. In 2018, Pfizer signed a deal with BioNTech to develop mRNA vaccines for the flu.

“The technology initially appealed to us for the flu because of its great speed and flexibility,” Philip Dormitzer, who leads Pfizer’s viral-vaccines research and development programs, told me. “You can edit mRNA very quickly. That is quite useful for a virus like the flu, which requires two updated vaccines each year, for the Northern and Southern Hemisphere.”

By the time the coronavirus outbreak shut down the city of Wuhan, China, Moderna and BioNTech had spent years fine-tuning their technology. When the outbreak spread throughout the world, Pfizer and BioNTech were prepared to shift immediately and redirect their flu research toward SARS-CoV-2. “It was really a case of our researchers swapping the flu protein for the coronavirus spike protein,” Dormitzer said. “It turned out that it wasn’t that big a leap.”

Armed with years of mRNA clinical work that built on decades of basic research, scientists solved the mystery of SARS-CoV-2 with astonishing speed. On January 11, 2020, Chinese researchers published the genetic sequence of the virus. Moderna’s mRNA vaccine recipe was finalized in about 48 hours. By late February, batches of the vaccine had been shipped to Bethesda, Maryland, for clinical trials. Its development was accelerated by the Trump administration’s Operation Warp Speed, which invested billions of dollars in several vaccine candidates, including Moderna’s. With the perfect timing of a Hollywood epic, mRNA entered the promised land after about 40 wandering years of research. Scientific progress had proceeded at its typical two-speed pace—slowly, slowly, then all at once.

2. Faster, Faster!

Speed and nimbleness were the qualities that first interested both DARPA and Pfizer in mRNA. And if the technology unlocks more breakthroughs after this pandemic, speed and nimbleness will play starring roles.

Malaria kills more than 400,000 people every year, mostly young children. It is not caused by a virus or bacteria, but rather by an organism belonging to a separate phylum, called plasmodium. Plasmodia have a host of shape-shifting strategies to evade our immune systems. With most diseases, you catch it once and develop some protection going forward. But malaria shakes off our cellular defenses, making it possible to catch the disease over and over again. That also makes malaria hard to inoculate against: The only existing vaccine doesn’t work very well, even after a four-shot regimen.

Last month, a patent was approved for an RNA-based vaccine against malaria that showed promise in mice. “We’ve been working on this vaccine for years, but the entire landscape has changed in the last six months because of the success of COVID vaccines,” Richard Bucala, the vaccine’s co-inventor and a scientist at the Yale School of Medicine, told me.

The malaria vaccine uses self-amplifying RNA, or saRNA, which is subtly distinct from the mRNA technology used by Moderna and Pfizer. The vaccines against COVID-19 work by injecting up front all of the messenger RNA that you’re going to get. But self-amplifying RNA is designed to replicate itself inside our cells. This copy-paste function means, in theory, that each person needs only a tiny dose of vaccine to have a large immune response.

“The replication function of saRNA is critical, because it’s not vaccines that prevent infection but vaccinations that prevent infection,” Bucala said. A miracle drug that’s not administered is no better than a worthless medicine that’s never approved. “The Pfizer and Moderna vaccines need a lot of mRNA, and it’s expensive to make, which is why it’s been slower to get to many countries outside the U.S.,” he went on. “With saRNA, we could inject one-hundredth of the material to have the same effect. That would make it easier to scale against a widespread disease.”

Then there’s cancer. Scientists may never devise a single vaccine for cancer, because cancer is not a single disease but a constellation of more than 100 maladies, which we usually name for the place on the body where they originate. But what if we could respond to these hundreds of cancers with our own constellation of therapies that could train the body to attack a specific tumor?

This is the idea behind BioNTech’s cancer-immunotherapy research. It works something like this: For each cancer patient, BioNTech takes a tissue sample from a tumor to perform a genetic analysis. Based on that test, the company designs an individually tailored mRNA vaccine, which tells the patient’s cells to produce proteins associated with that specific tumor’s specific mutation. The immune system learns to search-and-destroy similar tumor cells throughout the body.

This cycle of analysis and design is not so different from the way BioNTech and Moderna swiftly analyzed Chinese scientists’ sequencing of SARS-CoV-2, identified the spike protein for attack, and made an effective therapy. “We hope that everything we’ve learned from COVID about producing and manufacturing mRNA can cross-fertilize the work on our off-the-shelf cancer treatments,” BioNTech’s Özlem Türeci told me. The company is currently in clinical trials for personalized vaccines in “basically every solid cancer,” she said, including melanoma, breast cancer, and ovarian cancer. A 2021 analysis by University of North Carolina researchers in the journal Molecular Cancer pointed out that these cancer treatments have been slow to develop in recent years but that the COVID-19 breakthrough coincided with “promising” clinical trials in cancer vaccines. “We envision the rapid advancing of mRNA vaccines for cancer immunotherapy in the near future,” they concluded.

3. We Make Our Own Luck

In March 2020, Peter Hotez, a vaccine scientist at Baylor College of Medicine, didn’t think that mRNA technology would win the race against COVID-19. His bet was on the pharmaceutical company Merck, which had recently developed an astonishingly successful vaccine against Ebola using a modified livestock virus called vesicular stomatitis virus, or VSV. But Merck discontinued its COVID-19 vaccines when its promising new technology failed in clinical trials.

Hotez sees Merck’s failures as a critical lesson about science—and a cautionary tale about mRNA.“The technology that works for one epidemic might not work for the next one, and you won’t know what works until you try it,” he told me. “That’s why I say it’s too soon to call mRNA vaccines a miracle. They might not work against the next target.”

Even mRNA’s biggest proponents concede the point. “This is not a magic bullet, and it’s not perfect for everything,” Pfizer’s Dormitzer told me. His partners at BioNTech concurred. “I do not claim that mRNA is the holy grail for everything,” Türeci said. “We are going to find that there are diseases where mRNA is surprisingly successful and diseases where it’s not. We have to prove it for each and every infectious disease, one by one.”

mRNA may not produce a great second act in the next decade, or ever. Perhaps the scientific establishment will conclude that the technology benefited in the pandemic from a uniquely simple nemesis. “The coronavirus might be one of the easiest vaccine targets we’ve seen in modern times,” Hotez agreed. “Just about everything we’ve thrown at it has worked.”

Maybe we got lucky. But luck is downstream from preparation. The coronavirus was an easy target only because science made it easy. Four years ago, following the outbreak of Middle East Respiratory Syndrome in the Arabian Peninsula and South Korea, 18 scientists from the NIH, Vanderbilt University, Dartmouth College, and other institutions published a detailed examination of the shape and behavior of the coronavirus’s most notable feature: the spike protein. This paper decoded the mysteries and vulnerabilities of the virus long before anybody knew that this tiny pathogen would soon shut down the world. “Our studies,” they presciently concluded in their 2017 paper, “provide a foundation for the structure-based design of coronavirus vaccines.” Without this detective work, the mRNA breakthrough might not have happened.

Today’s vaccines were forged from science’s successes, but also from its failures. For decades, researchers have struggled to design a workable vaccine for HIV, and many observers considered this field a dead end. But a new paper argues that these repeated failures forced HIV-vaccine researchers to spend a lot of time and money on strange and unproven vaccine techniques—such as synthetic mRNA and the viral-vector technology that powers the Johnson & Johnson vaccine. Nearly 90 percent of COVID-19 vaccines that made it to clinical trials used technology that “could be traced back to prototypes tested in HIV vaccine trials,” Jeffrey E. Harris, the economist at MIT who authored the paper, wrote. He points out that if one HIV vaccine had succeeded, the company behind it would have won big. Instead, all of the competitors in the vaccine field learned from collective failure and contributed to collective wisdom. The many false starts of HIV vaccination sired an explosion of new technologies and helped usher in a possible new golden age of vaccines.

4. The Tree of Progress

We can call our record-breaking vaccine-development process good luck. Or we can call it what it really is: a ringing endorsement for the essential role of science in the world.

“Five years ago, we were in a state of ignorance about mRNA,” Mascola, of the NIH, told me. “And five years from now, we will learn that we are, at this very moment, in another state of ignorance. That’s why mRNA is such a beautiful scientific story. So many researchers, philanthropists, government organizations, and companies took a huge risk on a technology whose initial responses were marginal. And together, they figured out how to make it work.”

As a parable of scientific progress, I sometimes imagine the life cycle of a tree. Basic scientific research plants a variety of seeds. Some of these seeds fail entirely; the research goes nowhere. Some seeds become tiny shrubs; the research doesn’t fail entirely, but it produces little of value. And some seeds blossom into towering trees with abundant fruit that scientists, companies, and technologists pluck and turn into the products that change our lives. For years, mRNA technology looked like a shrub. In 2020, it blossomed in full view.

You cannot know in the early stages whether you’re planting a dud or a revolution. Even if it is a revolution, you cannot know what kind. Pfizer jumped into mRNA research for its potential to work against influenza, only to make history fighting a completely different virus. But this uncertainty risk is exactly why countries like the U.S. ought to encourage more basic science and highly novel research.

The triumph of mRNA, from backwater research to breakthrough technology, is not a hero’s journey, but a heroes’ journey. Without Katalin Karikó’s grueling efforts to make mRNA technology work, the world would have no Moderna or BioNTech. Without government funding and philanthropy, both companies might have gone bankrupt before their 2020 vaccines. Without the failures in HIV-vaccine research forcing scientists to trailblaze in strange new fields, we might still be in the dark about how to make the technology work. Without an international team of scientists unlocking the secrets of the coronavirus’s spike protein several years ago, we might not have known enough about this pathogen to design a vaccine to defeat it last year. mRNA technology was born of many seeds.

Source: The Atlantic

New System Uses Smartphone or Computer Cameras to Measure Pulse and Respiration Rate

Sara McQuate wrote . . . . . . . . .

Telehealth has become a critical way for doctors to still provide health care while minimizing in-person contact during COVID-19. But with phone or Zoom appointments, it’s harder for doctors to get important vital signs from a patient, such as their pulse or respiration rate, in real time.

A University of Washington-led team has developed a method that uses the camera on a person’s smartphone or computer to take their pulse and respiration signal from a real-time video of their face. The researchers presented this state-of-the-art system in December at the Neural Information Processing Systems conference.

Now the team is proposing a better system to measure these physiological signals. This system is less likely to be tripped up by different cameras, lighting conditions or facial features, such as skin color. The researchers will present these findings at the ACM Conference on Health, Interference, and Learning.

“Machine learning is pretty good at classifying images. If you give it a series of photos of cats and then tell it to find cats in other images, it can do it. But for machine learning to be helpful in remote health sensing, we need a system that can identify the region of interest in a video that holds the strongest source of physiological information — pulse, for example — and then measure that over time,” said lead author Xin Liu, a UW doctoral student in the Paul G. Allen School of Computer Science & Engineering.

“Every person is different,” Liu said. “So this system needs to be able to quickly adapt to each person’s unique physiological signature, and separate this from other variations, such as what they look like and what environment they are in.”

The team’s system is privacy preserving — it runs on the device instead of in the cloud — and uses machine learning to capture subtle changes in how light reflects off a person’s face, which is correlated with changing blood flow. Then it converts these changes into both pulse and respiration rate.

The first version of this system was trained with a dataset that contained both videos of people’s faces and “ground truth” information: each person’s pulse and respiration rate measured by standard instruments in the field. The system then used spatial and temporal information from the videos to calculate both vital signs. It outperformed similar machine learning systems on videos where subjects were moving and talking.

But while the system worked well on some datasets, it still struggled with others that contained different people, backgrounds and lighting. This is a common problem known as “overfitting,” the team said.

The researchers improved the system by having it produce a personalized machine learning model for each individual. Specifically, it helps look for important areas in a video frame that likely contain physiological features correlated with changing blood flow in a face under different contexts, such as different skin tones, lighting conditions and environments. From there, it can focus on that area and measure the pulse and respiration rate.

While this new system outperforms its predecessor when given more challenging datasets, especially for people with darker skin tones, there’s still more work to do, the team said.

“We acknowledge that there is still a trend toward inferior performance when the subject’s skin type is darker,” Liu said. “This is in part because light reflects differently off of darker skin, resulting in a weaker signal for the camera to pick up. Our team is actively developing new methods to solve this limitation.”

The researchers are also working on a variety of collaborations with doctors to see how this system performs in the clinic.

“Any ability to sense pulse or respiration rate remotely provides new opportunities for remote patient care and telemedicine. This could include self-care, follow-up care or triage, especially when someone doesn’t have convenient access to a clinic,” said senior author Shwetak Patel, a professor in both the Allen School and the electrical and computer engineering department. “It’s exciting to see academic communities working on new algorithmic approaches to address this with devices that people have in their homes.”

Source: University of Washington

New Technology Enables Ultrafast Identification of COVID-19 Biomarkers

Researchers from Charité – Universitätsmedizin Berlin and the Francis Crick Institute have developed a mass spectrometry-based technique capable of measuring samples containing thousands of proteins within just a few minutes. It is faster and cheaper than a conventional blood count.

To demonstrate the technique’s potential, the researchers used blood plasma collected from COVID-19 patients. Using the new technology, they identified eleven previously unknown proteins which are markers of disease severity. The work has been published in Nature Biotechnology.

Thousands of proteins are active inside the human body at any given time, providing its structure and enabling reactions which are essential to life. The body raises and lowers the activity levels of specific proteins as required, including when responding to external factors such as pathogens and drugs. The detailed patterns of the proteins found inside cells, tissues and blood samples can therefore help researchers to better understand diseases or make diagnoses and prognoses.

In order to obtain this ‘protein fingerprint’, researchers use mass spectrometry, a technology known to be both time-consuming and cost-intensive. ‘Scanning SWATH’, a new mass-spectrometry-based technology, promises to change this. Developed under the leadership of Prof. Dr. Markus Ralser, Director of Charité’s Institute of Biochemistry, this technology, which is much faster and cost-effective than previous methods, enables researchers to measure several hundred samples per day.

“In order to speed up this technology, we changed the mass spectrometer’s electric fields. The data produced are of such extreme complexity that humans can no longer analyze them,” explains Einstein Professor Prof. Ralser, who is also a Group Leader at the Francis Crick Institute in London. He adds: “We therefore developed computer algorithms that are based on neural networks and which use these data to extract the relevant biological information. This enables us to identify thousands of proteins in parallel and greatly reduces measuring timescales. Fortunately, this method is also more precise.”

This high-throughput technology has a broad range of potential applications, ranging from basic research and large-scale drug development to the identification of biological markers (biomarkers), which can be used to estimate an individual patient’s risk. The technology’s suitability for the latter was demonstrated by the researchers’ study on COVID-19.

As part of this research, the team analyzed blood plasma samples from 30 Charité inpatients with COVID-19 of varying degrees of disease severity, comparing the protein patterns obtained with those of 15 healthy individuals. The actual measurements conducted on individual samples only took a few minutes.

The researchers were able to identify a total of 54 proteins whose serum levels varied according to the severity of COVID-19. While 43 of these proteins had already been linked to disease severity during earlier studies, no such relationship had been established for 11 of the proteins identified. Several of the previously unknown proteins associated with COVID-19 are involved in the body’s immune response to pathogens which increases clotting tendency.

“In the shortest of timeframes, we discovered protein fingerprints in blood samples which we are now able to use to categorize COVID-19 patients according to severity of disease,” says one of the study’s lead authors, Dr. Christoph Messner, who is a researcher at Charité’s Institute of Biochemistry and the Francis Crick Institute. He continues: “This type of objective assessment can be extremely valuable, as patients will occasionally underestimate the severity of their disease. However, in order to be able to use mass spectrometry analysis for the routine categorization of COVID-19 patients, this technology will need to be refined further and turned into a diagnostic test. It may also become possible to use rapid protein pattern analysis to predict the likely course of a case of COVID-19. While the initial findings we have collected are promising, further studies will be needed before this can be used in routine practice.”

Prof. Ralser is convinced that mass spectrometry-based investigations of the blood could one day complement conventional blood count profiles. “Proteome analysis is now cheaper than a complete blood count. By identifying many thousands of proteins at the same time, proteomic analysis also produces far more information. I therefore see enormous potential for widespread use, for instance in the early detection of diseases. We will therefore continue to use our studies to develop proteome technology for this type of application.”

Source: Charité – Universitätsmedizin Berlin

Pizza Hut Launches The Hut Lane — A Digital-First Carryout Option

After becoming the first national pizza brand to offer Contactless Curbside Pickup, Pizza Hut is doubling down on safety and convenience and launching The Hut Lane™, a dedicated digital order pick-up window available at over 1,500 locations across the U.S. with more to come.

As customer preferences shifted during the early months of the pandemic, Pizza Hut adapted to offer a way for customers to place digital orders without ever having to leave their vehicles. The Hut Lane represents the next evolution of this breakthrough experience, offering safety, convenience and speed without customers ever having to park their cars.

“We are giving our customers a variety of options to optimize their pizza-eating experience as we build on our business momentum,” said Nicolas Burquier, Chief Customer & Operations Officer, Pizza Hut. “Not only do we offer industry-leading, innovative menu items that are only available at Pizza Hut, we also offer several digital-first pick-up options for our customers, and The Hut Lane is a great example of that.”

The Hut Lane service can be accessed through the Pizza Hut app and and is also available for those placing orders over the phone. Upon arrival, customers can simply pull up to the dedicated window, grab their order and go. If The Hut Lane is not available at your local Pizza Hut, the app will automatically offer Pizza Hut’s Contactless Curbside Pickup so you can still stay in your car to pick up your order.

Source: PR Newswire