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Human Behavior

Frederick Wiseman on the life of American institutions – Minneapolis Star Tribune

NEW YORK Frederick Wiseman has spent more than half a century documenting American institutions.

With a small crew, he has tirelessly made lengthy, sober, engrossing filmic portraits of life in Jackson Heights, Queens; a Texas boxing gym; a Maine fishing village; small-town Indiana; a Massachusetts hospital for the criminally insane; a Philadelphia high school; a Colorado meatpacking plant; the New York public library.

Wiseman, 90, records sound himself, holding the boom microphone. He doesn't research beforehand, instead letting what he sees dictate a film. No one lives more by the dictum of showing, not telling, than Wiseman. After assembling 100-250 hours of rushes, he toils over the footage, assembling sequences that capture life at a certain time and place, stitching together a narrative of expansive, long-take detail. Collectively, the films constitute a sprawling, clear-eyed mosaic of America.

Many consider Wiseman the greatest living documentary filmmaker. In 2016, he received an honorary Academy Award. "It's as important to document kindness, civility and generosity of spirit as it is cruelty, banality and indifference," he said.

In a time of unprecedented strain on federal institutions, Wiseman's latest is a profile of a more local, functioning realm of U.S. civic life. "City Hall," which played to typical acclaim at the Venice, Toronto and New York film festivals over the past few weeks, documents the daily hum and long-range aspirations of the Boston city government under Mayor Marty Walsh. It opens in virtual theaters Oct. 28.

Wiseman, who spoke in a recent interview from the apartment in Paris that's been his most regular home for the past 15 years, finished post-production on "City Hall" just as the pandemic was beginning. Aside from walks to relax, he's stayed mostly inside since March. Asked about his health, he replied, "Well, I'm still breathing." But sitting still is hard for someone who has averaged a movie a year for five decades. "For the first time in 55 years, I don't have a movie to work on," he said.

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AP: The communal worlds of your films where groups of people are so often in rooms talking to one another feels very far away right now, doesn't it?

WISEMAN: At the moment I can't work. It's terrible. To make the kind of movies I make I can encounter a couple hundred people every day. I'm working on a script to a short fiction film that I can shoot in a modest way with a small crew in an isolated place. But not having any work to do is a serious problem. I'm bored out of my mind, actually.

AP: In "City Hall" we see such a wide scope of civic operations, from garbage collection to homeless outreach, from building inspections to mayoral staff meetings.

WISEMAN: City government touches more aspects of our lives than any other form of government. Among other things, it provides the necessary limits as to what we have to do to get along with each other and live together. Speeding limits. Places to park. Minimum health requirements for restaurants. The control of violence. The monopoly on the right to use force. Providing health services. It goes on and on and on. You sort of, or at least I did, take it for granted.

AP: Do you consider "City Hall" a response to Donald Trump?

WISEMAN: If I made "City Hall" when Obama was president, one would be measuring Walsh against Obama. But in the current context, we're measuring him against Trump, so he comes out so much better. Not that he's not good, but the contrast is extreme. The film doesn't in any way suggest the government of Boston is perfect. But it does suggest, I hope, that there's a mayor who cares and is trying to implement programs and raise money for services that will make a difference in people's lives.

AP: What draws you to institutions as subjects?

WISEMAN: The institution is also just an excuse to observe human behavior in somewhat defined conditions. The films are as much about that as they are about institutions. For most of the films, all the encounters take place within a relatively limited geographical framework. Sometimes it's just a building or in the case of "Boxing Gym," a couple of rooms. In the case of "National Gallery," it's a big building. In the case of "Public Housing," it was a housing project. Anything that takes place within the geographic boundaries of the institution is fair game to include in the film. Anything that takes place outside those boundaries is another film.

AP: Are you partly motivated to leave these films behind as time capsules to show the way people talked and dressed and moved?

WISEMAN: You're quite right. I'm very interested in that. I hope 50 years from now they'll be interested in the films because it's a body of films which represent the work of one person exploring contemporary American life. I hope they'll always be interested in them. I made "Law and Order" (about the Kansas City police department) in 1968 and the issues that film tries to deal with are very contemporary.

AP: There's a scene in that where a policeman chokes a black woman.

WISEMAN: That aroused almost no comment when the film was the shown in 1968. It was sort of by the by. It was more tisk-tisk. No protests. There was no political activity in Kansas, Missouri, as a consequence of that sequence, and it's pretty horrible.

AP: Those kinds of incidents of police brutality are more widely recorded now. Do you think them being better documented will change the behavior?

WISEMAN: Ah, that's the million-dollar question. I don't know what changes human behavior. I think human behavior has been set now for 10,000 or 15,000 years.

AP: You've said you watch fiction films more than documentaries. Which filmmakers have had an influence on you?

WISEMAN: I've probably been more influenced by the books I've read than the movies I've seen. I've never consciously drawn on the work of another filmmaker while I'm shooting or editing. When I read a novel or read a poem, I think about the same kind of things that I do when I'm editing. When I went to college a long time ago, it was called close reading. It probably has a fancier name now. But we were taught to pay close attention to the text and not incorporate in our analysis of the text anything outside of it. In other words, we weren't encouraged to read a biography of Ernest Hemingway to read "The Sun Also Rises." So I learned how to pay close attention. So when I'm shooting and in particular when I'm editing, in order to make a film out of 150 hours of rushes, I have to pay close attention to what people are saying and doing and how they're moving and how they're dressed and the language they're using. I have to explain the behavior that I'm seeing and hearing to myself in order to make a judgment. The making of these films involves an effort to be aware, in a sense to be awake.

AP: You have a good line about "verit" filmmaking in which you say you're "somewhat more conscious than a fly."

WISEMAN: The whole notion of a fly on the wall I find disgusting. It's demeaning, really.

AP: And you don't like the word "documentary," right?

WISEMAN: I'm happy with the word "movies." I make movies. Maybe it's because when I was growing up, "documentary" had an aura about it. You were supposed to see it because it was good for you, a bit like ex-lax. I think a movie should be entertaining, instructive, dramatic, funny. You should look for the same qualities in a documentary as in a fiction film. I hate didacticism in writing and I also hate it in movies. I don't like to be told what to think. I like to be asked to work and figure out what's going on, so I discover.

AP: Was "City Hall" enjoyable to make?

WISEMAN: They're all enjoyable to make. One of the reasons I like doing this is because it's fun. Each movie is a new subject. I like to think I learned something. I have an intense absorption in the film, in the shooting and the editing. It's physically and emotionally and intellectually demanding. That's a good combination of things for me.

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Frederick Wiseman on the life of American institutions - Minneapolis Star Tribune

Human Behavior

A Killing Eve-inspired fashion line is on its way – Dazed

Fans of Villanelle can now dress up like their favourite knife-wielding murderess because a Killing Eve-inspired line of clothing is on its way.

According to The Hollywood Reporter, AMC Network and Sid Gentle Films the companies that own the shows licensing rights have signed an agreement with IMG for the BBC America series to develop and manufacture consumer products, experiences, and collaborations. Simply put, it means that we can expect Killing Eve-branded clothes, beauty products, games, and more to appear in the near future.

Killing Eve hits on multiple notes and nuances of human behavior that naturally translate into licensing, said Sherikay Chaffee, VP of licensing at IMG, in a statement. Aside from being one of the most popular and loved shows on TV, its also one of the most clever and stylish. The dual aspect and opposing nature between its two lead characters can be used to tell a story about a product.

While theres no further information as to when we can expect to see these products, Killing Eve is known for serving some major fashion lewks, including frou-frou dresses courtesy of Molly Goddard and tongue-in-cheek Undercover baseball caps, a green, fluffy Charlotte Knowles coat and Gucci tailoring.Needless to say, were excited.

In the meantime, heres some inspo:

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A Killing Eve-inspired fashion line is on its way - Dazed

Human Behavior

‘Boys State’ Reflects Boyish Nature of American Politics – The Emory Wheel

What could go wrong when one thousand Texan high schoolers participate in a government stimulation? Boys State, the latest documentary produced by A24, chronicles the journey of Texan students as they participate in a week-long, mock political government program. In the documentary, filmmakers Jesse Moss and Amanda McBaine follow a diverse group of charismatic, hard-core and entertaining high school participants who lead the gubernatorial campaigns for the 2018 American Legion Boys State annual leadership program. Following these contestants over the course of nearly two hours is not only wildly entertaining but also a politically powerful experience.

The central objective of the Boys State program is to create a new political party with a corresponding political agenda, and then successfully run an election campaign for the coveted position of the governor of Boys State. The attendees are divided into two parties based on historical political parties Nationalists and Federalists and are tasked with voting for a party chair, creating their own agenda and nominating a candidate for the gubernatorial election.

The film finds its rhythm at the onset of the preliminary campaign speeches as the student candidates introduce their platform and themselves to the conference. Instances such as these speeches make it clear that despite their serious and mature proclamations, these are high schoolers. The distinction between serious ideology and comedic performance is sometimes difficult to distinguish.

One of the most thrilling characters to watch in Boys State is Steven Garza, the calm, quiet and collected son of an immigrant. Unlike many of the Boys State attendees, Garza is a self-proclaimed Bernie Sanders supporter and participant in Black Lives Matter protests. Despite these odds, Garza skillfully employs patriotic rhetoric to appeal to core American values shared by most Boys State attendees. Garza lauds hard work and respect for veterans as he queries in his first speech, I want to know what is on your mind. Will we show the world what patriots are made of?

Other key figures in the film include students Ben Feinstein and Rene Otero, who serve as the district chairs for their respective parties. Feinstein is a Ronald Reagan-loving philosophical conservative who exemplifies the realpolitik mindset. Otero, my favorite attendee, joins Garza as a shining beacon of diversity in thought and race: as a leftist and Black man in a sea of white conservative Texans, Otero stands out with his charismatic confidence and razor-sharp rhetoric. As one of the few Black men at Boys State, he tactfully handles racial discrimination and bigotry against him and his campaign.

Although the movie itself does not have a protagonist or antagonist, certain people like Feinstein and gubernatorial candidate Robert MacDougal are depicted as manipulative and even malicious in their political schemings. At one point in the film, Otero moderates a debate session and prevents his opponent from speaking out of turn. Feinstein, a true Machiavellian, pounces and accuses Garza and Otero of biased and unfair moderation; Feinstein continues to bring up this event throughout the rest of the campaign period, much to the chagrin of Garzas campaign.

Robert MacDougal and Steven Garza discuss campaign tactic before delivering a speech in Boys State./Courtesy of Apple

In a Zoom interview with college media outlets, Feinstein admitted he had expected the film to simply portray the fun times he had at Boys State and the success of his campaign. He was surprised by how stressed and controversial his peers appeared in the final cut, and upon reflection, he disapproved of some of his own decisions. Feinsteins reflection here adds an important layer to how this film reflects real political behavior he felt as if he was doing well for both himself and his party, and having fun. However, the documentary paints a more grim picture of self-interest, mudslinging and power dynamics.

Although the program is a mere political simulation, the high schoolers in the film were willing to go against their own morals and beliefs for the sake of attaining political power, and look back at unethical betrayals fondly and wistfully. Unadulterated absurdity and duplicity of American politics are on full display for the masses to witness and gawk at. The expectation that these students should be kinder, more compassionate and more understanding of each others positions because they are young is habitually subverted by their behavior, representing a grand reflection on human behavior as a whole.

MacDougal said he went into this with a cynical mindset, thinking that the whole room would be very red [Garza] showed that you could run on what you believe and have those important conversations with those around you.

MacDougal learned that, regardless of our political differences, coming together and having respectful, productive dialogues is still within reach. But Boys State also reveals the core political assumptions, insidious manipulation and racism that ground the United States more generally. With the election a month away, Boys State is a necessary and critical experience for everyone living in this country.

Most importantly, Boys State underscores the gravity of voting. Make sure to cast a ballot in the 2020 election lest we wish to allow the Machiavellian politics of Boys State to dominate America.

Grade: A

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'Boys State' Reflects Boyish Nature of American Politics - The Emory Wheel

Human Behavior

Historian John Barry compares COVID-19 to the 1918 flu pandemic – University of Rochester

October 6, 2020

John Barry 69 (MA) says that the virulence of the 1918 flu made it a very different disease than COVID-19, but the lessons of that pandemic still resonate.

John Barry studied in the graduate program in history at the University of Rochester. He went on to work as a football coach and then as a journalist in Washington, DC, covering economics and national politics. Hes now adjunct faculty at Tulane Universitys School of Public Health and Tropical Medicine and the author of books including The Great Influenza: The Epic Story of the Deadliest Plague in History, The Rising Tide: The Great Mississippi Flood of 1927 and How It Changed America, and Roger Williams and the Creation of the American Soul: Church, State, and the Birth of Liberty.

When the novel coronavirus went from epidemic to pandemic early this year, John Barry 69 (MA) found himself in rather familiar territory. Barry is the author of The Great Influenza: The Epic Story of the Deadliest Plague in History. When the book was first published, in 2004, the National Academy of Sciences named it the outstanding book of the year on science and medicine. In 2020, Barrys book has returned to bestseller status.

In The Great Influenza, he considers what became known as the Spanish fluso called because the press in Spain, which stayed neutral in World War I, had not clamped down on coverage in the name of moralefrom a broad range of angles: scientists quest to understand a new pathogen, officials efforts (or lack thereof) to contain the spread of infection, and communities and families horrifying experiences of a disease so contagious and lethal that it infected about a quarter of the US population and killed between 50 and 100 million people around the world, the equivalent of 220 to 440 million today.

Anchoring The Great Influenza is Barrys consideration of leadership, science, and society. Trust, he argues, is crucial, because without trust in information people have no reliable knowledge of what is happening. In 1918, when leaders gave wartime morale priority over public health communication, terror overran society, so much so that some flu victims starved to death because others were too frightened to bring them food.

The fundamental lesson of the 1918 pandemic, Barry writes, is this: Those in authority must retain the publics trust. The way to do that is to distort nothing, to put the best face on nothing, to try to manipulate no one.

Barrys expertise drew him into public policy. In the year The Great Influenza was published, he began to collaborate with federal government entities and the National Academies on influenza preparedness and response. He was part of the original group that developed plans for public health measures in a pandemic before a vaccine is developed, and he contributed to pandemic preparedness and response efforts during the administrations of Presidents George W. Bush and Barack Obama.

This conversation has been edited and condensed.

Theyre both animal viruses that jumped to humans. So, theyre novel for the given population. The mode of transmission is identical: primarily droplets, some airborne, maybe some fomite [transmission from contact with objects]nobody knows how much.

Number three, theyre both primarily respiratory viruses.

Number four is less well known, and that is that the 1918 virus infected practically every organ, much like COVID-19. There were notable neurological impacts and cardiovascular eventsthey were very common. Its been noted that even the testes can be affected. That was true in 1918 as well. Thats very unusual and certainly not the case for other influenza viruses.

Its hard to say whats most important, but I guess the most important one is a different target demographic. In 1918, 95 percent, roughly, of the mortality was among people younger than 65. Of course, thats the opposite with COVID.

And number two is duration. This virus moves much more slowly than influenza, whether its the incubation period, how long you shed virus, or how long youre sick.

It has put vastly more stress on the economy because of the duration. We tried to interrupt transmission and save peoples lives, which I think was the right thing to do. But it certainly caused an increase in economic stress.

The most obvious difference is virulencethe rapidity of the viruss spread and its severity. In 1918, it was many times more virulent.

As a general rule, public health is pretty easy compared to the hard science. In the present case, obviously, the reversal on mask usage caused a lot of confusion, though I think right now theres pretty widespread acceptance.

Normally, public health is not a frontier. You may refine your methodsand in this case, the main method has always been there. Social distancing is more important than anything else.

There was a lot more reason to be afraid in 1918. People saw death all around themand in many cases, horrible deaths. There is fear out here now, but its not, in most cases, the same intensity.

I think fear is pretty clearly a much more important and driving motivemuch more effective, lets sayin getting people to act than the idea that you ought to protect some stranger you cross paths with somewhere.

So in terms of getting people to comply with the [public health] advice, I think if people are deeply concerned that they themselves are vulnerable and could be killed, thats much more powerful than worrying, well, you know, maybe this person Im having a drink with might go home and infect their grandmothermaybe.

A lot of countries did the right thing. They were extremely transparent. In those early meetings about nonpharmaceutical interventions [in the advisory groups that Barry joined in 2004], my message was to always tell the truth. And I didnt get a lot of pushback. Every now and then somebody would say, Well, we dont really want to scare people. Yeah, you do, actually. You dont want to use fear as a tool, but you want them to be able to judge the risk themselves, truthfully. And to understand the risk. And be honest. And a lot of countries have done thatnot because they read my book, but because its pretty clearly the best thing to do, whether its South Korea or Singapore or Germany or Austria or New Zealand. A lot of countries were totally transparent and have been pretty effective in containing the virus.

And as you know, the US is pretty close to dead last in the developed world in containing the virus.

Ive never been able to come up with a good explanation as to why theres so little written about the 1918 pandemic. There was quite a bit of pulp fiction written in the 1920s. I didnt know that myself until somebody else who was interviewing me said they collected it. But not serious fiction. There were only a tiny handful [of writers who addressed it], such as William Maxwell and Katherine Anne Porter. John Dos Passos is one of my favorite writers. He got influenza on a troop ship, one of the worst places to get it, and he wrote about two lines in his entire body of work.

When I first started researching this book, which was quite a while ago now, I had an aunt who was then in her 90s. And when I mentioned it to her, she grabbed her chest and said, Oh! It was the only time I saw my father cry. It certainly was burned into her consciousness. And whenever I mentioned it to somebody old enough to have lived through it, I got a similar response. They certainly didnt forget it, but why it didnt register in our literature to a greater degree, I dont know. I mean, it was briefyoure talking about a period of weeks. It also occurred simultaneously with the war. But I have no good explanation.

As far as this pandemic, yes, I think theres a very good chance that this will be a defining event for a generation, depending upon the effectiveness and speed with which we get a vaccine.

In April, I said I didnt expect summer to provide relief. I said I expected something akin to ocean swells rather than waves, depending on how we came out of various phases. I also said that there is a danger of a storm surge. Its relatively easy at this point to predict the behavior of the virus, but you cannot predict human behavior. And you cant predict the weather. If we have a really mild fall and people tend to be outside a lot, deep into the fall, that will have some impact on transmission. If the weather is rotten and people are forced inside earlier, thats something else again.

The key is really behavior. And what worries me most is the real possibility of that storm surge.

And theres still so much we dont know about the virus, such as its long-term impact. We know a significant percentage of those who get sick show some kind of heart damage. Is that permanent? Does it heal? Even people who have no symptoms whatsoever on X-ray show whats referred to as ground glass opacity in the lung. What is that damage? What does that mean long term?

The virus certainly affects blood vessels. What does that mean in terms of stroke and other cardiovascular problems years from now? In 1918, there were complications that didnt surface at all until the 1920s. So, we just dont know.

Tags: Arts and Sciences, COVID-19, Department of History, John Barry

Category: Society & Culture

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Historian John Barry compares COVID-19 to the 1918 flu pandemic - University of Rochester

Immunology

Every COVID-19 case seems different. These scientists want to know why. – Newswise

Newswise LA JOLLAAs scientists around the world develop life-saving COVID-19 vaccines and therapies, many are still wondering exactly why the disease proves deadly in some people and mild in others.

To solve this puzzle, scientists need an in-depth understanding of how the bodys many types of immune cells respond to SARS-CoV-2, the virus that causes COVID-19.

A new international study led by scientists at La Jolla Institute for Immunology (LJI), The University of Liverpool and the University of Southampton is the first to give a detailed snapshot of how the body's CD4+ T cells respond to the SARS-CoV-2 virus. Among the findings, their work suggests that early in the illness, patients hospitalized with severe cases of COVID-19 develop a novel T cell subset that can potentially kill B cells and reduce antibody production.

The study, published on October 6, 2020, in Cell, provides a crucial foundation for further detailed analysisand shows the power of a cutting-edge technique called single-cell RNA sequencing (RNA-seq).

Zooming in on individual cells

This study employs single-cell RNA-seq to analyze RNA molecules expressed by CD4+ T cells that specifically recognize SARS-CoV-2 says LJI Associate Professor Pandurangan Vijayanand, M.D., Ph.D., who led the study with long-time collaborator Christian H Ottensmeier, M.D., Ph.D., FRCP, professor at the University of Liverpool and adjunct professor at LJI. This lets us show, for the first time, the complete nature of the cells that respond to this virus.

This is the beginning, says Ottensmeier, a physician scientist who co-led the study. We needed to have a reference to look back at for further studies, and this work is novel, timely, detailed, innovativeand open.

Vijayanand and his colleagues at LJI have pioneered the use of single-cell RNA-seq in immunology. RNA-seq gives researchers a new window into the gene expression patterns that can make each person's immune response to a virus different. For the new study, the researchers focused on CD4+ T cells, which play many critical roles in fighting infection.

"CD4+ T cells play a central role in orchestrating the immune response," says study co-first author Benjamin Meckiff, Ph.D., postdoctoral fellow at LJI. "They are a heterogeneous population of immune cells carrying out a wide range of functions, and we have been able to specifically analyze their response to SARS-CoV-2."

Vijayanand and Ottensmeier had planned to use single-cell RNA-seq to analyze CD4+ T cells from patients hospitalized for influenza this year. When the pandemic hit, the researchers applied in early March for approval to use samples from COVID-19 patients as well.

We were collecting appropriate samples very early on in the pandemic, says Vijayanand.

The researchers studied samples from 40 COVID-19 patients in two groups. The hospitalized group included 22 patients (with nine treated in the ICU). The non-hospitalized group had 18 patients who had experienced milder COVID-19 symptoms.

The scientists used single-cell RNA-seq to analyze the types of CD4+ T cells that respond to SARS-COV-2 in these patients. Each type of T cell has a role in fighting viruses: some (the "helper" CD4+ T cells) alert the body to infection and recruit other immune cells, while others (TFH cells) signal B cells to make antibodies. Finally, some (Tregs) do the important job of inhibiting other T cells, keeping the immune system from damaging the body's own tissues.

There are multiple flavors of T cells that respond to this virus, says Vijayanand.

The researchers caution that human studies are only correlative and cannot conclude that certain T cell populations are driving disease severity. They do believe some findings warrant a closer look.

For example, the scientists found that hospitalized patients have higher levels of "cytotoxic" TFH cells, which could potentially make an infection worse. Instead of doing their job and helping B cells make antibodies, the cytotoxic TFH cells seen in this study were very similar to cells that have been seen killing B cells in previous studies. The researchers then examined SARS-CoV-2-specific antibody concentrations in patients. Those with dysfunctional TFH cells also had fewer antibodies.

"The TFH cells in hospitalized patients displayed gene signatures that suggest they are dysfunctional and aren't giving the help to B cells that we would expect," says Meckiff.

A baseline for future investigations

Overall, the study gives the scientific community a starting place to explore CD4+ T cell responses to SARS-CoV-2, and the work establishes a baseline for comparing responses in people over time or with different disease severities. To support these efforts, the researchers made their data immediately available online, just two months after the project began.

We had to be quick, says study co-first author Ciro Ramrez-Sustegui, a bioinformatics specialist at LJI. Having the data available for everyone is essential.

Theres definitely more to explore, adds study co-author Vicente Fajardo, an LJI research technician who spearheaded the bioinformatics analysis alongside Ramrez-Sustegui.

In fact, the data and the research method could be important for more than infectious disease research. Ottensmeier explains that a better understanding of how the body responds to viruses can also guide future research into cancer immunotherapies, which would use the bodys own immune system to target and kill cancer cells.

With this study, we levied our long-standing collaboration for a new human health puzzle, says Ottensmeier. Going forward, we can extend this understanding of whats going on in the blood in response to new viruses to understanding what goes on in the tissue when our immune system deals with cancer.

Ottensmeier and Vijayanand are working on further analysis of COVID-19 patients and also plan to expand their collaboration with the wider University of Liverpool community.

The study, titled, "Imbalance of regulatory and cytotoxic SARS-CoV-2-reactive CD4+ T cells in COVID-19," was supported the National Institutes of Health (grants U19AI14274, U19AI142742-0S1, U19AI118626, R01HL114093, R35-GM128938, S10RR027366, S10OD025052), the William K. Bowes Jr Foundation, the Whittaker Foundation, the Wessex Clinical Research Network and the National Institute of Health Research UK.

Additional study authors include co-first author Serena J. Chee, Anthony Kusnadi, Hayley Simon, Simon Eschweiler, Alba Grifoni, Emanuela Pelosi, Daniela Weiskopf, Alessandro Sette, Ferhat Ay and Grgory Seumois.

DOI:https://doi.org/10.1016/j.cell.2020.10.001

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About La Jolla Institute for Immunology

The La Jolla Institute for Immunology is dedicated to understanding the intricacies and power of the immune system so that we may apply that knowledge to promote human health and prevent a wide range of diseases. Since its founding in 1988 as an independent, nonprofit research organization, the Institute has made numerous advances leading toward its goal: life without disease.

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Every COVID-19 case seems different. These scientists want to know why. - Newswise

Immunology

Occupied with immunology and cancer, Merck KGaA hands off osteoarthritis drug to Novartis for 50M cash – Endpoints News

By the time Merck KGaA published promising Phase II data for sprifermin once tapped as a big prospect for the ailing R&D group late last year, the German drugmaker made clear it was looking for a partner to take over its whole osteoarthritis pipeline. While sprifermin is still sitting in the portfolio, its managed to find a buyer for another drug.

Novartis is paying 50 million upfront to license M6495, a Phase II-ready compound that targets an enzyme known as ADAMTS5, with promises of 400 million in milestones.

The deal comes more than three years after Merck KGaA grabbed the Nanobody from Ablynx since acquired by Sanofi with a 15 million payment to reward the preclinical proof-of-concept package. Then known as ALX-1141, the candidate was one of two to emerge from a collaboration dating back to 2011 to tackle osteoarthritis.

Since then Luciano Rossettis team has completed two Phase I studies for M6495, one in healthy volunteers and another in OA patients. With signs that the drug could cut down ARGS (a neoepitope from cleaved aggrecan, found in the synovial fluid and serum of OA patients) levels, the drug had potential in many different types of OA, he said.

The ultimate goal, of course, is to show it can protect against cartilage damage and reduce joint pain. But its now Novartis job to devise the trials needed to prove it.

With this deal we have found the right solution for this asset designed to present an innovative mechanism of action for the potential treatment of osteoarthritis, as we prioritize our pipeline to deliver the greatest impact for patients across our internal areas of expertise, Rossetti, head of global biopharma R&D, said in a statement.

Under Beln Garijo, whos stepping up as Merck KGaAs CEO, the priorities will likely revolve heavily around oncology, immunology and the intersection of the two.

For Novartis, OA falls under its focus on immunology, hepatology and dermatology. Its website lists two early-stage programs dedicated to the disease, one being an ANGPTL3 agonist designed to help regenerate cartilage. The Phase I study was completed in 2018 and a second trial is slate to wrap in 2022.

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Occupied with immunology and cancer, Merck KGaA hands off osteoarthritis drug to Novartis for 50M cash - Endpoints News

Immunology

Risk of Severe COVID May Depend on Your Type of Asthma, Experts Say – HealthDay News

WEDNESDAY, Oct. 7, 2020 (HealthDay News) -- Everyone agrees about the good news -- folks whose asthma is spurred on by allergies don't appear to have an increased risk of life-threatening illness if they contract COVID-19.

"Asthma has not risen as one of the top comorbid diseases for worse COVID-19 outcomes," said Dr. Sandhya Khurana, director of the Mary Parkes Center for Asthma, Allergy and Pulmonary Care at the University of Rochester (N.Y.) Medical Center. "We always worry with asthma and viral infections, because they seem to trigger asthma exacerbation unreasonably. But what we've seen so far is reassuring."

But debate continues to swirl regarding the potential severity of COVID infection in people with non-allergic asthma.

Some studies have suggested that people who have asthma caused by something other than allergies -- exercise, stress, air pollution, weather conditions -- might have an increased risk of severe COVID-19.

For example, Harvard researchers found that having non-allergic asthma increased the risk of severe COVID-19 by as much as 48%. That conclusion was based on data from 65,000 asthma sufferers presented in the June issue of the Journal of Allergy and Clinical Immunology.

"For those people, I think being more cautious would be good for them," said senior researcher Liming Liang, an associate professor of statistical genetics at the Harvard T.H. Chan School of Public Health in Boston. "I think the next wave is coming. We've got to be more cautious."

But other experts note that the data involving COVID and non-allergic asthma sufferers is very limited, and any conclusions that these folks are at higher risk of severe infection could be flawed.

Their asthma could be caused by other lung ailments that are associated with more serious cases of COVID, for instance, said Dr. Mitchell Grayson, chief of allergy and immunology at Nationwide Children's Hospital in Columbus, Ohio.

"There have been several studies that have shown that COPD does increase your risk of more severe disease," he said. "I don't think these studies have done a good job of excluding COPD in these patients."

Grayson agrees with Khurana that in the early days of the COVID-19 pandemic, there was much concern that asthma could be a risk factor -- a reasonable suspicion, given that the coronavirus attacks the lungs.

But everything that came out of the initial epidemic in China suggested that asthma was not a risk factor for life-threatening COVID, Grayson said, and the data continued to confirm that as the coronavirus spread across the globe.

"It's not there in the data. If it is there, it's extremely small risk. It's nothing I can see," he said.

Researchers have speculated that people with allergy-driven asthma might have some protection against COVID, due to the way the coronavirus infects the body.

The SARS-CoV-2 virus that causes COVID-19 enters lung cells by engaging with a type of protein on their surface called an ACE2 receptor, Khurana said.

"In the setting of an allergic type of inflammation, the expression of the ACE2 receptor appears to be downregulated. It appears to be lower. There's not as much receptor," she said.

Because there aren't as many ACE2 receptors available, people with allergic asthma might not be as vulnerable to severe infection, Khurana said. This theory also could help explain why other chronic diseases appear to increase COVID risk, she added.

"Patients in conditions like diabetes or hypertension, this receptor expression is increased," Khurana said. "That's a possible reason why those comorbid diseases are at especially high risk for this infection."

But that only explains why allergic asthma isn't a major risk factor for severe COVID, Grayson said. It doesn't explain why some studies are finding increased risk among people with non-allergic asthma.

Grayson suspects that the purported link between non-allergic asthma and COVID found in these studies is actually a link between a COVID and a host of different lung ailments, especially COPD.

"There are studies showing that COPD increases your risk of more severe COVID, not markedly but a little bit, not to the extent of things like hypertension and diabetes and [being] elderly," he said. "I'm concerned that what they're calling non-allergic asthma actually is COPD, which would skew their data."

In Khurana's view, more study is needed, particularly prospective studies that track people with different types of asthma prior to COVID infection.

"So far, we just don't know enough to make any conclusions. I think we're still scratching the surface here and still have a lot to learn," she said.

In the meantime, it would pay for everyone to protect themselves, Khurana added.

"It's good practice to observe the recommended guidance on hand hygiene and social distancing and masking and avoiding any situation where you could be exposed, even though it's obviously welcome to see that allergic asthma is not as high-risk as some of the other comorbid diseases," Khurana said.

More information

The American Academy of Allergy, Asthma and Immunology has more about COVID-19 myths.

SOURCES: Sandhya Khurana, M.D., director, Mary Parkes Center for Asthma, Allergy and Pulmonary Care, University of Rochester Medical Center, Rochester, N.Y.; Liming Liang, Ph.D., associate professor, statistical genetics, Harvard T.H. Chan School of Public Health, Boston; Mitchell Grayson, M.D., director, allergy and immunology, Nationwide Children's Hospital, Columbus, Ohio

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Risk of Severe COVID May Depend on Your Type of Asthma, Experts Say - HealthDay News

Immunology

IL-21 protein is a major part of immune response to chronic infections in the central nervous system – News-Medical.Net

Reviewed by Emily Henderson, B.Sc.Oct 6 2020

Researchers at Penn State College of Medicine now better understand the role of a protein, interleukin-21 (IL-21), in the immune system response to infections in the nervous system.

The results of their recent study support further investigation into using IL-21 as a therapeutic agent for persistent central nervous system infections.

CD4 T cells in the immune system produce IL-21, which is critical for the development of CD8 tissue-resident-memory (TRM) cells during persistent viral infections of the central nervous system with polyomavirus.

Dr. Aron Lukacher, professor and chair of the Department of Microbiology and Immunology, said the results, published in Science Immunology , demonstrate that IL-21 is an important factor in the development of effective immune responses to chronic infections in the central nervous system including neurodegenerative HIV-AIDS and progressive multifocal leukoencephalopathy (PML), a fatal brain infection caused by JC polyomavirus.

PML starts with symptoms including clumsiness, weakness or difficulty speaking or thinking. As it progresses, patients may develop dementia, have vision problems and become unable to speak.

Lukacher's lab created an animal model of JC polyomavirus in mice, called mouse polyomavirus (MuPyV). Their research focuses on strategies to reduce the harmful effects of MuPyV, with the goal of developing translational approaches to improving outcomes for patients with PML and other immunocompromising conditions.

Prior research demonstrated that IL-21 is a key part of immune responses in the body, but the present study investigated the specific mechanisms and role IL-21 plays in the immune response to infection with MuPyV.

The research team, including medical scientist training program student Heather Ren, studied mice that were unable to produce sufficient CD4 T-cells and had similar defects in gene expression related to the development of CD8 TRM cells. They found that injecting IL-21 into cerebrospinal fluid reduced those deficiencies.

The use of IL-21 as a therapeutic agent for persistent central nervous system infections needs further investigation. Whether it needs to be administered directly into the central nervous system or given peripherally, such as intravenous infusion, will require further testing in our model."

Dr. Aron Lukacher, Researcher and Professor, Chair of the Department of Microbiology and Immunology, Penn State College of Medicine

Lukacher said future studies will examine whether giving IL-21 to mice with persistent MuPyV infection, both under immunocompetent and CD4 T-cell-deficient conditions, may bolster protective antiviral CD8 T cell responses and keep the viral infection in check.

Source:

Journal reference:

Ren, H. M., et al. (2020) IL-21 from high-affinity CD4 T cells drives differentiation of brain-resident CD8 T cells during persistent viral infection. Science Immunology. doi.org/10.1126/sciimmunol.abb5590.

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IL-21 protein is a major part of immune response to chronic infections in the central nervous system - News-Medical.Net

Immunology

Vanderbilt researchers develop publicly available COVID-19 animal susceptibility prediction tool; suggests increased risk to horses – Vanderbilt…

A Vanderbilt team of experts in virology, genetics, structural biology, chemistry, physiology, medicine, immunology and pharmacology have together developed technology to understand and predict animal susceptibility to SARS-CoV-2, the scientific name for the strain of coronavirus causing COVID-19. providing evidence that horses and camels may be at increased risk of the virus. The group has also released a publicly available tool to enable people to understand the likelihood of other animals susceptibility.

The article, Predicting susceptibility to SARS-CoV-2 infection based on structural differences in ACE2 across species, was published in the Federation of American Societies for Experimental Biology (FASEB) Journal on Oct. 5.

The investigators applied a combination of sophisticated genetic sequence alignment and structural analysis of ACE2, the receptor protein for SARS-CoV-2, to a variety of known susceptible and non-susceptible species. Through the analysis they identified five particular amino acid sites within the protein that distinguish virus susceptibility or resistance, and using these sites developed an algorithm to predict susceptibility of unknown species. The algorithm has been made public on a website where people can upload the aligned ACE2 sequence of animals with unknown susceptibility to generate a COVID-19 susceptibility score.

Jacquelyn Brown, a staff scientist at the Vanderbilt Institute for Integrative Biosystems Research and Education, initiated the project. When I first learned that COVID-19 had crossed the species barrier into cats and dogs, I became worried about other animals that might act as reservoirs for the disease or be at risk, explained Brown, an avid equestrian who practices medieval mounted archery. Since MERS infects camels, I was concerned about what would happen if my horse could get it?! Horses have massive lungs and a sensitive respiratory system, and we humans often touch their noses and mouths.

206,000 horses live on horse farms and properties in Tennessee and 3.2 million of the states 10 million farm acres are devoted to the horse industry. Brown proposed a collaborative research project on the topic to Gordon A. Cain University Professor John Wikswo, who holds appointments in physics, biomedical engineering, and molecular physiology and biophysics.

As the director of VIIBRE, an institute established to foster and enhance interdisciplinary research in the biophysical sciences, bioengineering and medicine at Vanderbilt, Wikswo immediately assembled a trans-institutional team spanning Vanderbilt schools and colleges and Vanderbilt University Medical Center. I speak each disciplines language well enough to make the necessary connections, Wikswo said. This proved to be an outstanding group brought together by their interests and skills that produced an important result in very short order.

The project gave meaning to each researcher, at a time when we all were searching for ways to contribute to fighting COVID-19, noted Wenbiao Chen.

The work could not have been achieved without the collaboration of many researchers. The multidisciplinary approach revealed how much information can be wrung from the same basic information, noted Wenbiao Chen, the papers co-corresponding author and associate professor of molecular physiology and biophysics. We found potential targets by sequence comparison but wouldnt have been able to interpret our findings without structural information. The project gave meaning to each researcher, at a time when we all were searching for ways to contribute to fighting COVID-19.

Understanding the animals we should more closely scrutinize based on their susceptibility to COVID-19 can help us protect people, pets, wildlife, livestock and our food sources, said Matthew Alexander, assistant professor of medicine. The algorithm the team developed is particular to SARS-CoV-2 because it focuses on its particular receptor binding protein ACE2, but the approach is broadly applicable to predicting susceptibility to other viruses or during future outbreaks.

There is also the opportunity to investigate if the identified five sites on ACE2 that most distinguish susceptible from non-susceptible species can be used as targets to develop drugs that inhibit these sites specifically. I hope that our results will inspire future research on both rational drug design and closer examination of at-risk species, said Meena Madhur, the papers co-corresponding author, associate professor of medicine and associate director of the Vanderbilt Institute for Infection, Immunology and Inflammation at VUMC.

Of note, the work and collaboration were conducted remotely, with an analysis of publicly available data. This experimental approach of using extensive and rapidly accumulating publicly available data in new ways allowed us to efficiently answer a timely question without having to generate new datasets. The collaboration was fun and rewarding, and we were able to answer an important question that none of us could have solved alone, Alexander, the papers co-first author said. Wikswo pointed out that while the source data was public, the project required massive calculations of how different versions of the virus would bind to each animals ACE2.

Members of the collaborative project also include Distinguished Research Professor of Chemistry Jens Meiler, Clara Schoeder, co-first author and postdoctoral scholar, , Charles Duncan Smart, graduate student in molecular physiology and biophysics, Chris Moth, computational chemist in the biological sciences department, and Tony Capra, research associate professor of biological sciences.

The work was supported by National Institutes of Health grants F32HL144048-01, DK117147, UH3TR002097 and U01TR002383, U19AI117905, U01AI150739, and R01AI141661, R35GM127087, and DP2HL137166 and American Heart Association grants 20PRE35080177 and EIA34480023

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Vanderbilt researchers develop publicly available COVID-19 animal susceptibility prediction tool; suggests increased risk to horses - Vanderbilt...

Immunology

Contract Research Organizations (CROs) Market Worth $64.4 Billion by 2027- Exclusive Report Covering Pre and Post COVID-19 Market Analysis by…

London, Oct. 06, 2020 (GLOBE NEWSWIRE) -- According to a new market research report titled Contract Research Organizations Market by Services (Clinical Research [Phase II, Phase III], Pre-Clinical [Pharmacokinetics, Toxicology], Laboratory Services, and others), Therapeutic Area (Oncology, Immunology), End User (Pharma and Biotech, Medical Device), and Geography - Forecast to 2027 published by Meticulous Research, the contract research organizations market is expected to grow at a CAGR of 6.5% from 2020 to 2027 to reach $64.4 billion by 2027.

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A contract research organization (CRO), also known as a clinical research organization, is a service provider organization, which supports pharmaceutical and biotechnology companies for drug development and medical device companies by providing outsourcing services. Also, CROs assist in conducting clinical trials, with services ranging from site selection and patient enrollment to the final regulatory approvals from the Food and Drug Administration and the European Medicines Agency. Growing demand for biopharmaceuticals, an increasing number of clinical trials, and rising government support for biopharmaceutical manufacturing are the key factors driving the steady growth of the overall contract research organizations market. Also, significant opportunities from emerging markets, increasing demand for biosimilars, and continuous advancements in bioprocessing techniques further support the growth of this market.

According to the U.S. Food and Drug Administration (FDA), in the past five years, the approval of biopharmaceuticals has increased, accounting for more than 25% of total drug approvals. As per the estimations, the number of biologics approved has almost tripled from 6 in 2012 to 17 in 2017. Frequent outbreaks of pandemics such as COVID-19, Ebola, and other infectious diseases burden the healthcare sector, ultimately boosting the demand for biopharmaceuticals and resulting in increased contract-based R&D and clinical trial activities. Similarly, according to Pharmaprojects (a drug development database), the count of drugs entering the pipeline increased to 16,181 in 2019 compared to 10,452 drugs in 2012. The number of companies with active pipelines increased from 2,705 in 2012 to 4,323 in 2019. Due to this increase in numbers, pharmaceutical production has increased globally, boosting the number of clinical trials. As per clinicaltrials.gov (a clinical trial database), in 2012, 137,502 studies were recorded, which increased to 325,846 by 2019. However, the clinical trial data during 2019-2020 showed a drastic fall due to disruptions in the activities as a reflection of the COVID-19 pandemic and are estimated to hinder the market growth to an extent.

Impact of COVID-19 on the Overall CROs Market

The outbreak of COVID-19 has changed various healthcare market functions. With the analysis of the clinical trials database and considering the operations of key players functioning in the CROs market, it has been observed that, during 2019-2020, the CROs market experienced hindrances in its growth. This crisis has imposed a huge burden on the pharmaceutical industry to develop vaccines, diagnostic assays, and breakthrough drugs. The pandemic has affected 208 countries with 2,000-5,000 new cases per day and shifted the healthcare industrys focus only on the diagnosis and treatment of COVID-19.

As a result of which, the previously planned and on-going research & development and clinical trial studies were put on hold or disrupted, and the number of clinical trials declined in the past few months. According to the Clinical Trials Online Magazine, the number of clinical trials was 1,210 in June 2020, which has decreased to 1,180 in August 2020. The majority of the investors are focusing on research and development of treatments and diagnosis for COVID-19, and the planned or on-going contract-based R&D and clinical trial activities are lagging due to the suspension of enrolments, slow enrolment process, delayed initializations, and shortage of funding for non-COVID-19 drugs.

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The global contract research organizations market study presents historical market data in terms of values (2018 and 2019), estimated current data (2020), and forecasts for 2027 - by services (clinical research [phase II and phase III], pre-clinical [pharmacokinetics and toxicology], laboratory services, and others), therapeutic area (oncology and immunology), end user (pharma & biotech and medical device), and geography. The study also evaluates industry competitors and analyzes their market shares at the global and regional levels.

Based on service type, the clinical research services segment is estimated to account for the largest share of the overall contract research organizations market in 2020. The large share of this segment is mainly attributed to an increase in the number of clinical trials globally, growth in outsourcing activities to conduct clinical trials at low costs, and growth in collaborations between key players and clinical service providers to reduce failures.

Based on therapeutic area, the oncology segment is estimated to account for the largest share of the overall contract research organizations market in 2020. The large share of this segment is mainly attributed to an increase in the number of oncology clinical trials globally, growth in government investments for the development of personalized medicines for oncology, and high demand for biosimilars for cancer.

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Based on end user, the pharmaceutical & biotechnology companies segment is estimated to account for the largest share of the overall contract research organizations market in 2020. The major share of this segment is primarily attributed to an increase in R&D investments for drug development, growing collaborations of pharmaceutical companies with CROs to conduct clinical trials, and government initiatives to support the growth of pharmaceutical companies.

The report also includes an extensive assessment of the key strategic developments by leading market participants in the industry over the past four years (2016-2020). The contract research organizations market has witnessed several agreements, collaborations, partnerships, and alliances in recent years. For instance, in March 2020, IQVIAHoldings Inc. (U.S.) and the University of Texas Medical Branch (UTMB)collaborated to develop a novel assay for COVID-19 (SARS-CoV-2) tests. Similarly, in March 2020, Charles River Laboratories International, Inc. (U.S.) and Deciphex (Ireland)partnered to co-develop deep learning-enabled tools to support accelerated pathology analytics in drug discovery and development.

The contract research organizations market is a highly consolidated market with the presence of major players, such as IQVIA Holdings Inc. (U.S.), Laboratory Corporation of America Holdings (U.S.), Charles River Laboratories International, Inc. (U.S.), Wuxi Apptec Co., Ltd. (China), Medpace Holdings, Inc. (U.S.), PRA Health Sciences, Inc. (U.S.), Syneos Health, Inc. (U.S.), PARAXEL International Corporation (U.S.), Envigo RMS LLC (U.S.), ICON plc (Ireland), PPD, Inc. (U.S.), and SGS S.A. (Switzerland) among others.

To gain more insights into the market with a detailed table of content and figures, click here:https://www.meticulousresearch.com/product/CRO-market-5129/

Scope of the Report:

Contract Research Organizations Market, by Service

Contract Research Organizations Market, by Application

(Note: Other therapeutic areas include hepatology, gastroenterology, ophthalmology, gastroenterology, respiratory diseases, dermatology, and muscular disorders)

Contract Research Organizations Market, by End User

Contract Research Organizations Market, by Geography

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Amidst this crisis, Meticulous Researchis continuously assessing the impact of COVID-19 pandemic on various sub-markets and enables global organizations to strategize for the post-COVID-19 world and sustain their growth. Let us know if you would like to assess the impact of COVID-19 on any industry here-https://www.meticulousresearch.com/custom-research.php

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Meticulous Research was founded in 2010 and incorporated as Meticulous Market Research Pvt. Ltd. in 2013 as a private limited company under the Companies Act, 1956. Since its incorporation, the company has become the leading provider of premium market intelligence in North America, Europe, Asia-Pacific, Latin America, and the Middle East & Africa.

The name of our company defines our services, strengths, and values. Since the inception, we have only thrived to research, analyze and present the critical market data with great attention to details. With the meticulous primary and secondary research techniques, we have built strong capabilities in data collection, interpretation, and analysis of data including qualitative and quantitative research with the finest team of analysts. We design our meticulously analyzed intelligent and value-driven syndicate market research reports, custom studies, quick turnaround research, and consulting solutions to address business challenges of sustainable growth.

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Contract Research Organizations (CROs) Market Worth $64.4 Billion by 2027- Exclusive Report Covering Pre and Post COVID-19 Market Analysis by...