thescientist--2020-09-16--The Immune Hallmarks of Severe COVID-19

The Immune Hallmarks of Severe COVID-19

ABOVE : Scanning electron microscope image of SARS-CoV-2 ( gold ) emerging from the surface of cells cultured in the lab .
The virus shown was isolated from a patient in the US .
Image captured and colorized at NIAID ’ s Rocky Mountain Laboratories ( RML ) in Hamilton , Montana FLICKR , NIAID One of the most striking features of SARS-CoV-2 , the virus that causes COVID-19 , is the exceptional breadth of symptoms it causes in people .
Of the nearly 30 million recorded infections to date , the vast majority of people experienced mild or moderate @ @ @ @ @ @ @ at all to pneumonia or long-term , debilitating neurological symptoms .
A minority ended up with severe respiratory symptoms but eventually recovered .
And some—nearly 940,000 worldwide , of which 196,000 are in the US—took a turn for the worse and died .
Why some people die while others recover is thought to depend in large part on the human immune response , which spirals out of control in severe disease .
Over the past few months , researchers have developed a better understanding of this dysfunctional immune response .
By comparing patients @ @ @ @ @ @ @ they ’ ve catalogued a number of dramatic changes across the human immune arsenal that are often apparent when patients first come into the hospital—from signaling cytokine proteins and first-responder cells of the innate immune system , to the B cells and T cells that confer pathogen-specific adaptive immunity .
The factors that trigger this immune dysregulation have so far remained elusive due to the complexity of the immune system , which consists of seemingly endless biological pathways that twist and turn and feed back on one another like a ball of spaghetti @ @ @ @ @ @ @ conditions such as sepsis , cancer , and autoimmune disease—are gradually building coherent theories of what puts patients en route to severe disease .
Along the way , they ’ re also uncovering signals that clinicians could use to predict disease prognosis and identify potential new treatment avenues .
“ We don ’ t have the clearest picture yet .
Nor do we know why there ’ s variability in this immune response , ” says Nuala Meyer , a critical care physician at the Hospital of the University of Pennsylvania who researches @ @ @ @ @ @ @ that underlying conditions increase the risk for developing severe COVID-19 , “ I definitely see patients with diabetes , obesity , and high lipids that did not become severe [ cases ] , ” she says .
“ I think we have a lot of work to do to understand precisely what accounts for this differential response.
” Earlier this year , researchers learned that some of the body ’ s very first defenses against SARS-CoV-2 seem to be perturbed in patients who develop severe disease .
When SARS-CoV-2 begins to multiply in @ @ @ @ @ @ @ infected and some bystander immune cells release interferons , cytokines that , in general , act to curtail viral replication .
But in May , scientists at the Icahn School of Medicine at Mount Sinai reported strikingly low levels of interferons in infected human cells in culture , and in live ferrets infected with the virus .
Instead of responding with interferons , the cells had boosted their inflammatory pathways .
Then , in a July study of COVID-19 patients ’ blood , researchers in France found that the interferon response seemed to @ @ @ @ @ @ @ critical disease , whereas interferon release was robust in those with mild and moderate symptoms .
Studies on mice infected with the coronaviruses SARS-CoV and MERS-CoV have shown that an early , strong interferon response is critical to resolving the infections , but if the response is delayed , the mice develop inflammatory immune reactions instead .
Some data suggest that SARS-CoV-2 is capable of blocking interferon production in the cells it infects , and it appears to be much more effective in doing so than its cousin SARS-CoV .
But some patients @ @ @ @ @ @ @ mounting an interferon response even in uninfected immune cells , notes Miriam Merad , who directs the Precision Medicine Institute at Mount Sinai .
Either way , without a solid interferon response , the virus will persist , causing damage that activates inflammatory pathways .
“ The higher the damage is , the more the immune system is trying to get rid of the damage , ” says Merad , “ so it gets activated and at some point … it goes completely crazy.
” This over activation is clearly evident in the @ @ @ @ @ @ @ in patients ’ blood—the “ cytokine storm ” that COVID-19 has become known for .
In a recent analysis of nearly 1,500 COVID-19 patients , Merad and her colleagues found that concentrations of IL-6 , IL-8 and TNF-α in their serum upon admission correlated strongly with disease severity and death .
Each cytokine could by itself predict whether a patient would survive .
Interestingly , the nature of COVID-19 ’ s cytokine response is markedly different from the cytokine storm side effect observed in some cancer patients who receive cellular immunotherapies and certain @ @ @ @ @ @ @ , concentrations of certain cytokines tend to be much lower—King ’ s College London immunologist Manu Shankar-Hari describes their increase as a “ cytokine breeze ” rather than a storm .
But the increased cytokine levels are sustained over days and weeks , Merad says .
In a more comprehensive but smaller immunological study of moderate and severe COVID-19 patients , researchers documented a number of immune features that are relatively common in chronic viral infections , such as T cells bearing markers of exhaustion , which could mean they ’ re less @ @ @ @ @ @ @ in severe cases , three cytokines stood out and strongly correlated with the severity of the disease : IL-6 , IL-10 , and particularly IP-10 .
“ Some of the changes are very similar to what people have reported in sepsis previously , ” notes Shankar-Hari , who is a coauthor on the study .
But severely ill patients have the added complication of an impaired interferon response , which he says he sees as the “ core mechanism ” driving these changes in other kinds of cytokines .
Scientists at Yale University @ @ @ @ @ @ @ that the cytokine increase was followed by haphazard-seeming immune responses in severely ill patients .
While people with moderate disease appeared to activate immune machinery designed to fight off viruses , those with severe disease seemed to recruit cells and proteins that are typically associated with combating parasitic worms as well as immune responses designed to go after fungi and bacteria that live outside of cells—an unusual response the team describes as “ immunological misfiring , ” as if the immune system is failing to activate the right program .
And while the @ @ @ @ @ @ @ gradually over time , the heightened activity was maintained in patients with severe disease .
Ultimately , their frenzied cytokine response doesn ’ t do much to stem the virus—based on swabs from the nose and throat , severe and moderate patients began with similar viral loads that only dropped off in the moderate group .
Severe COVID-19 is also marked by dysfunction in the immune cells that are first at the scene of a viral infection , including myeloid cells such as neutrophils and monocytes .
For instance , researchers from Germany @ @ @ @ @ @ @ in the blood of 109 individuals with mild , moderate , and severe COVID-19 .
Although patients with severe disease seemed to be manufacturing larger quantities of such cells , the cells themselves seemed to be only partially activated and dysfunctional .
The neutrophils were largely immature , a feature that is thought to have a suppressive effect on the immune system , while the monocytes tended to have an inflammation-promoting phenotype and often lacked a critical surface protein ( HLA-DR ) needed for presenting viral material to T cells .
The researchers @ @ @ @ @ @ @ in mild or moderate cases .
Perhaps severe COVID-19 isn ’ t a purely inflammatory disease , but rather a dangerous loop of ineffective human immune responses and continuous tissue inflammation , says coauthor Leif Erik Sander , an immunologist and infectious disease specialist at the Charité hospital in Berlin .
Some of these myeloid cells in the blood of severely ill COVID-19 patients are indeed “ functionally sluggish , ” explains Stanford University immunologist Bali Pulendran , who recently found that the cells didn ’ t release cytokines when exposed to viral @ @ @ @ @ @ @ suggested that the vast quantities of blood-borne cytokines weren ’ t coming from these first-responders in the blood , but from the lungs , where researchers have spotted high abundances of inflammatory macrophages and other myeloid-derived cells , he says .
“ The immune response in the lung was excessive inflammation , lots of cytokines .
[ But the ] immune response in the blood was the opposite—it was suppression.
” In contrast , moderately ill patients had significantly fewer suppressive cells in their blood .
Sander notes that the precise sources of @ @ @ @ @ @ @ in driving the severity of the disease , are yet to be elucidated .
But Merad suggests that the lung-dwelling inflammatory macrophages , the first immune cells to detect viral debris , could play an important role in driving the dysregulated cytokine response .
These cells have been implicated strongly in the deleterious effects of aging , obesity , and diabetes—the same comorbidities linked to risk for severe COVID-19 .
Perhaps they ’ re “ giving the wrong tone of inflammation in these patients ” by over-activating T cells and other parts of @ @ @ @ @ @ @ “ It is , I think , really a myeloid-triggered disease.
” As for the sluggish , suppressive cells in the blood , maybe the body is somehow shutting down other parts of the immune response to prevent it from becoming overwhelmed , Pulendran says .
The simultaneous immune suppression and over-activation has also been observed in sepsis , where it ’ s called “ immunoparalysis.
” Other innate immune cells , such as natural killer ( NK ) cells , are also altered in severe cases of COVID-19 compared to non-severe cases @ @ @ @ @ @ @ shown .
NK cells sense stressed cells and kill those infected with pathogens , while also releasing pro-inflammatory cytokines and influencing T cell responses .
NK cells come in different flavors , from less-differentiated ones fresh out of the bone marrow—which are good at proliferating and secreting cytokines—to highly differentiated super killers specialized for taking down virally infected cells .
NK cells were more skewed toward the former group in moderate disease .
But “ a subpopulation of NK cells that are the most terminally differentiated , that are the most skewed towards @ @ @ @ @ @ @ the severely sick patients , ” explains senior author Niklas Björkström , an immunologist at the Karolinska Institute .
Such killer cells have also been spotted in hantavirus and yellow fever virus infections , but it ’ s not clear if they play a deleterious role in driving further immune dysfunction or a protective role .
“ I ’ m a positive person .
So I would still be hoping that the fact that we see them is because we need them for something at that severe stage , and that they are @ @ @ @ @ @ @ ” Björkström adds .
An adaptive immune system out of kilter The components that make up our adaptive immune system also undergo drastic transformations in severe COVID-19 .
Some of these changes are expected .
Like some other infectious disease patients , those with COVID-19 almost always have unusually low numbers of lymphocytes such as B cells and T cells in their blood—perhaps because those cells are dying off for some reason , or because they ’ re rushing into tissues to combat the infection , says Shankar-Hari .
However , despite this @ @ @ @ @ @ @ T cells seemed to be highly activated , says Meyer , speaking of her own recent investigation of 125 hospitalized patients in Pennsylvania .
The combination of depleted yet activated T cells “ was not uniformly seen in all patients , but that was one of the features that did associate with the more severe course and more organ failure , ” Meyer adds .
Other work in critically ill COVID-19 patients finds—somewhat counter-intuitively—that T cells specifically targeted to SARS-CoV-2 proteins are not associated with recovery .
“ Maybe it ’ s not @ @ @ @ @ @ @ but rather has to do with the type of response that the ones present are exhibiting , ” Björkström says .
COVID-19 patients also have vast quantities of antibody-secreting plasmablasts—another unusual feature of the disease .
While other viral infections can provoke such a response , the increase tends to be short-lived , whereas in COVID-19 it seems to persist , Meyer adds .
The blood of COVID-19 patients is also flooded with antibodies .
But interestingly , new data from a study of 22 hospitalized patients suggest that although the quantity of @ @ @ @ @ @ @ and those who died , their function , and which viral proteins they targeted , correlated with severity .
See “ Differences in Antibody Responses Linked to COVID-19 Outcomes ” Another peculiarity of the antibody response in severe COVID-19 patients is the apparent lack of a critical antibody creation process that takes place in the so-called germinal center of the lymph nodes and spleen .
Ordinarily in viral infections , following a wave of initial virus-targeting antibodies that begins in the first few days of an infection , germinal centers form in the @ @ @ @ @ @ @ B cells and T helper cells gather to produce a highly refined batch of antibody-producing cells that are crucial for lasting antibody immunity .
But a study published last month demonstrated that those structures were absent in 11 COVID-19 patients who died from the disease .
The germinal center formation may be stunted due to high levels of certain cytokines , the authors posit , or perhaps due to the defects of antigen-presenting cells that help drive that response , Shankar-Hari notes .
In line with those findings , data reported in a @ @ @ @ @ @ @ researchers show that the abundance of two subtypes of B cells that create short-lived antibodies outside the germinal center correlated strongly with disease severity in 17 hospitalized patients , while those cells were barely present in healthy controls .
The expansion of these B cell types has been primarily associated with flare-ups of autoimmune diseases such as systemic lupus erythematosus , where they ’ re reflective of an overly inflammatory state .
It ’ s possible that this abnormal B cell response is the body ’ s attempt to generate antibodies after being @ @ @ @ @ @ @ centers .
Yet findings from autoimmune diseases also hint that “ it may be that some of these cells are actually worsening the inflammatory cascade , ” says Richard Ramonell , one of the study ’ s coauthors and a fellow in pulmonary and critical care medicine at Emory .
Merad says she thinks these abnormalities of the adaptive immune system are driven by the dysregulated cytokine response , which may be ultimately rooted in myeloid defects .
But the intimate dialog between the innate and adaptive immune systems makes it hard to @ @ @ @ @ @ @ comes up in autoimmune diseases all the time , notes Matthew Woodruff , an immunologist at Emory .
“ You see an autoimmune patient in the clinic , and you ’ ve got this entire system that has already been thrown out of balance in some way .
.
.
.
You ’ ve already established a new homeostatic process , and you can describe it , you can intervene , you can do all of those things .
But the chicken and egg questions continue to be very , very difficult to @ @ @

ABOVE: Scanning electron microscope image of SARS-CoV-2 (gold) emerging from the surface of cells cultured in the lab. The virus shown was isolated from a patient in the US. Image captured and colorized at NIAID’s Rocky Mountain Laboratories (RML) in Hamilton, Montana
FLICKR, NIAID
One of the most striking features of SARS-CoV-2, the virus that causes COVID-19, is the exceptional breadth of symptoms it causes in people. Of the nearly 30 million recorded infections to date, the vast majority of people experienced mild or moderate disease—which itself can range from no symptoms at all to pneumonia or long-term, debilitating neurological symptoms. A minority ended up with severe respiratory symptoms but eventually recovered. And some—nearly 940,000 worldwide, of which 196,000 are in the US—took a turn for the worse and died.
Why some people die while others recover is thought to depend in large part on the human immune response, which spirals out of control in severe disease. Over the past few months, researchers have developed a better understanding of this dysfunctional immune response. By comparing patients with varying degrees of disease severity, they’ve catalogued a number of dramatic changes across the human immune arsenal that are often apparent when patients first come into the hospital—from signaling cytokine proteins and first-responder cells of the innate immune system, to the B cells and T cells that confer pathogen-specific adaptive immunity.
The factors that trigger this immune dysregulation have so far remained elusive due to the complexity of the immune system, which consists of seemingly endless biological pathways that twist and turn and feed back on one another like a ball of spaghetti. But researchers—drawing on knowledge from other conditions such as sepsis, cancer, and autoimmune disease—are gradually building coherent theories of what puts patients en route to severe disease. Along the way, they’re also uncovering signals that clinicians could use to predict disease prognosis and identify potential new treatment avenues.
“We don’t have the clearest picture yet. Nor do we know why there’s variability in this immune response,” says Nuala Meyer, a critical care physician at the Hospital of the University of Pennsylvania who researches sepsis. While it’s well-established that underlying conditions increase the risk for developing severe COVID-19, “I definitely see patients with diabetes, obesity, and high lipids that did not become severe [cases],” she says. “I think we have a lot of work to do to understand precisely what accounts for this differential response.”
Cytokine mayhem in severe COVID-19
Earlier this year, researchers learned that some of the body’s very first defenses against SARS-CoV-2 seem to be perturbed in patients who develop severe disease. When SARS-CoV-2 begins to multiply in cells lining the respiratory tract, both infected and some bystander immune cells release interferons, cytokines that, in general, act to curtail viral replication. But in May, scientists at the Icahn School of Medicine at Mount Sinai reported strikingly low levels of interferons in infected human cells in culture, and in live ferrets infected with the virus. Instead of responding with interferons, the cells had boosted their inflammatory pathways. Then, in a July study of COVID-19 patients’ blood, researchers in France found that the interferon response seemed to be blunted in patients with severe and critical disease, whereas interferon release was robust in those with mild and moderate symptoms.
Studies on mice infected with the coronaviruses SARS-CoV and MERS-CoV have shown that an early, strong interferon response is critical to resolving the infections, but if the response is delayed, the mice develop inflammatory immune reactions instead. Some data suggest that SARS-CoV-2 is capable of blocking interferon production in the cells it infects, and it appears to be much more effective in doing so than its cousin SARS-CoV. But some patients also appear to be less capable of mounting an interferon response even in uninfected immune cells, notes Miriam Merad, who directs the Precision Medicine Institute at Mount Sinai. Either way, without a solid interferon response, the virus will persist, causing damage that activates inflammatory pathways. “The higher the damage is, the more the immune system is trying to get rid of the damage,” says Merad, “so it gets activated and at some point … it goes completely crazy.”
This over activation is clearly evident in the form of high concentrations of pro-inflammatory cytokines in patients’ blood—the “cytokine storm” that COVID-19 has become known for. In a recent analysis of nearly 1,500 COVID-19 patients, Merad and her colleagues found that concentrations of IL-6, IL-8 and TNF-α in their serum upon admission correlated strongly with disease severity and death. Each cytokine could by itself predict whether a patient would survive. Interestingly, the nature of COVID-19’s cytokine response is markedly different from the cytokine storm side effect observed in some cancer patients who receive cellular immunotherapies and certain other hyperinflammatory conditions. In COVID-19 patients, concentrations of certain cytokines tend to be much lower—King’s College London immunologist Manu Shankar-Hari describes their increase as a “cytokine breeze” rather than a storm. But the increased cytokine levels are sustained over days and weeks, Merad says.
In a more comprehensive but smaller immunological study of moderate and severe COVID-19 patients, researchers documented a number of immune features that are relatively common in chronic viral infections, such as T cells bearing markers of exhaustion, which could mean they’re less able to fight off pathogens. But in severe cases, three cytokines stood out and strongly correlated with the severity of the disease: IL-6, IL-10, and particularly IP-10. “Some of the changes are very similar to what people have reported in sepsis previously,” notes Shankar-Hari, who is a coauthor on the study. But severely ill patients have the added complication of an impaired interferon response, which he says he sees as the “core mechanism” driving these changes in other kinds of cytokines.
Scientists at Yale University tracking the progression of COVID-19 patients found that the cytokine increase was followed by haphazard-seeming immune responses in severely ill patients. While people with moderate disease appeared to activate immune machinery designed to fight off viruses, those with severe disease seemed to recruit cells and proteins that are typically associated with combating parasitic worms as well as immune responses designed to go after fungi and bacteria that live outside of cells—an unusual response the team describes as “immunological misfiring,” as if the immune system is failing to activate the right program. And while the immune responses of those who recovered faded gradually over time, the heightened activity was maintained in patients with severe disease. Ultimately, their frenzied cytokine response doesn’t do much to stem the virus—based on swabs from the nose and throat, severe and moderate patients began with similar viral loads that only dropped off in the moderate group.
Trouble in the innate immune system
Severe COVID-19 is also marked by dysfunction in the immune cells that are first at the scene of a viral infection, including myeloid cells such as neutrophils and monocytes. For instance, researchers from Germany recently analyzed the properties of these cells in the blood of 109 individuals with mild, moderate, and severe COVID-19. Although patients with severe disease seemed to be manufacturing larger quantities of such cells, the cells themselves seemed to be only partially activated and dysfunctional. The neutrophils were largely immature, a feature that is thought to have a suppressive effect on the immune system, while the monocytes tended to have an inflammation-promoting phenotype and often lacked a critical surface protein (HLA-DR) needed for presenting viral material to T cells. The researchers didn’t spot these dysfunctional cells in mild or moderate cases.
It is, I think, really a myeloid-triggered disease. —Miriam Merad, Icahn School of Medicine at Mount Sinai
Perhaps severe COVID-19 isn’t a purely inflammatory disease, but rather a dangerous loop of ineffective human immune responses and continuous tissue inflammation, says coauthor Leif Erik Sander, an immunologist and infectious disease specialist at the Charité hospital in Berlin.
Some of these myeloid cells in the blood of severely ill COVID-19 patients are indeed “functionally sluggish,” explains Stanford University immunologist Bali Pulendran, who recently found that the cells didn’t release cytokines when exposed to viral or bacterial debris in vitro. That suggested that the vast quantities of blood-borne cytokines weren’t coming from these first-responders in the blood, but from the lungs, where researchers have spotted high abundances of inflammatory macrophages and other myeloid-derived cells, he says. “The immune response in the lung was excessive inflammation, lots of cytokines. [But the] immune response in the blood was the opposite—it was suppression.” In contrast, moderately ill patients had significantly fewer suppressive cells in their blood. Sander notes that the precise sources of the cytokines, and their exact role in driving the severity of the disease, are yet to be elucidated.
But Merad suggests that the lung-dwelling inflammatory macrophages, the first immune cells to detect viral debris, could play an important role in driving the dysregulated cytokine response.
These cells have been implicated strongly in the deleterious effects of aging, obesity, and diabetes—the same comorbidities linked to risk for severe COVID-19. Perhaps they’re “giving the wrong tone of inflammation in these patients” by over-activating T cells and other parts of the immune system, she says. “It is, I think, really a myeloid-triggered disease.” As for the sluggish, suppressive cells in the blood, maybe the body is somehow shutting down other parts of the immune response to prevent it from becoming overwhelmed, Pulendran says. The simultaneous immune suppression and over-activation has also been observed in sepsis, where it’s called “immunoparalysis.”
Other innate immune cells, such as natural killer (NK) cells, are also altered in severe cases of COVID-19 compared to non-severe cases, research by scientists in Sweden has shown. NK cells sense stressed cells and kill those infected with pathogens, while also releasing pro-inflammatory cytokines and influencing T cell responses. NK cells come in different flavors, from less-differentiated ones fresh out of the bone marrow—which are good at proliferating and secreting cytokines—to highly differentiated super killers specialized for taking down virally infected cells. NK cells were more skewed toward the former group in moderate disease. But “a subpopulation of NK cells that are the most terminally differentiated, that are the most skewed towards killing, they were specifically expanded in the severely sick patients,” explains senior author Niklas Björkström, an immunologist at the Karolinska Institute. Such killer cells have also been spotted in hantavirus and yellow fever virus infections, but it’s not clear if they play a deleterious role in driving further immune dysfunction or a protective role. “I’m a positive person. So I would still be hoping that the fact that we see them is because we need them for something at that severe stage, and that they are rather trying to do something good,” Björkström adds.
An adaptive immune system out of kilter
The components that make up our adaptive immune system also undergo drastic transformations in severe COVID-19. Some of these changes are expected. Like some other infectious disease patients, those with COVID-19 almost always have unusually low numbers of lymphocytes such as B cells and T cells in their blood—perhaps because those cells are dying off for some reason, or because they’re rushing into tissues to combat the infection, says Shankar-Hari. However, despite this shortage of lymphocytes, some patients’ T cells seemed to be highly activated, says Meyer, speaking of her own recent investigation of 125 hospitalized patients in Pennsylvania.
Maybe it’s not a numbers game with the T cells but rather has to do with the type of response that the ones present are exhibiting. —Niklas Björkström, Karolinska Institute
The combination of depleted yet activated T cells “was not uniformly seen in all patients, but that was one of the features that did associate with the more severe course and more organ failure,” Meyer adds. Other work in critically ill COVID-19 patients finds—somewhat counter-intuitively—that T cells specifically targeted to SARS-CoV-2 proteins are not associated with recovery. “Maybe it’s not a numbers game with the T cells but rather has to do with the type of response that the ones present are exhibiting,” Björkström says.
COVID-19 patients also have vast quantities of antibody-secreting plasmablasts—another unusual feature of the disease. While other viral infections can provoke such a response, the increase tends to be short-lived, whereas in COVID-19 it seems to persist, Meyer adds. The blood of COVID-19 patients is also flooded with antibodies. But interestingly, new data from a study of 22 hospitalized patients suggest that although the quantity of antibodies didn’t differ between survivors and those who died, their function, and which viral proteins they targeted, correlated with severity.
Another peculiarity of the antibody response in severe COVID-19 patients is the apparent lack of a critical antibody creation process that takes place in the so-called germinal center of the lymph nodes and spleen. Ordinarily in viral infections, following a wave of initial virus-targeting antibodies that begins in the first few days of an infection, germinal centers form in the lymph nodes and spleen, where specialized B cells and T helper cells gather to produce a highly refined batch of antibody-producing cells that are crucial for lasting antibody immunity. But a study published last month demonstrated that those structures were absent in 11 COVID-19 patients who died from the disease. The germinal center formation may be stunted due to high levels of certain cytokines, the authors posit, or perhaps due to the defects of antigen-presenting cells that help drive that response, Shankar-Hari notes.
In line with those findings, data reported in a preprint by a team of Emory University researchers show that the abundance of two subtypes of B cells that create short-lived antibodies outside the germinal center correlated strongly with disease severity in 17 hospitalized patients, while those cells were barely present in healthy controls. The expansion of these B cell types has been primarily associated with flare-ups of autoimmune diseases such as systemic lupus erythematosus, where they’re reflective of an overly inflammatory state. It’s possible that this abnormal B cell response is the body’s attempt to generate antibodies after being somehow hindered from making them in germinal centers. Yet findings from autoimmune diseases also hint that “it may be that some of these cells are actually worsening the inflammatory cascade,” says Richard Ramonell, one of the study’s coauthors and a fellow in pulmonary and critical care medicine at Emory.
Merad says she thinks these abnormalities of the adaptive immune system are driven by the dysregulated cytokine response, which may be ultimately rooted in myeloid defects. But the intimate dialog between the innate and adaptive immune systems makes it hard to tease out cause and effect—an issue that comes up in autoimmune diseases all the time, notes Matthew Woodruff, an immunologist at Emory. “You see an autoimmune patient in the clinic, and you’ve got this entire system that has already been thrown out of balance in some way. . . . You’ve already established a new homeostatic process, and you can describe it, you can intervene, you can do all of those things. But the chicken and egg questions continue to be very, very difficult to answer.”


thescientist--2020-09-16--University of Michigan Grad Students Strike over COVID-19 Policy

Graduate students and residential advisors at the University of Michigan have gone on strike over the school ’ s COVID-19 response plan , prompting the university ’ s president to seek a court-mandated temporary restraining order and preliminary injunction to force students back to work .
The student workers are striking with the support of their union , the Graduate Employees ’ Organization ( GEO ) , which represents more than 2,000 graduate student instructors and staff assistants .
Since September 8 , they have been joined by more than 100 residential advisers in arguing that the university did not @ @ @ @ @ @ @ personally have not spoken to a single person who thinks our COVID reopening plan was well conceived , ” Silke-Maria Weineck , a professor of comparative literature and German studies at the university , tells Inside Higher Education .
“ What you have right now , I think , is a campus getting close to open revolt.
” At the heart of the strike lies the University of Michigan ’ s fall plans for reopening campus .
Graduate students , who are involved in teaching roughly 3,500 courses , claim the university has @ @ @ @ @ @ @ the well being of students and faculty .
As a result , they have stopped holding classes or carrying out research .
“ We need a fair and just pandemic response , ” Jeff Lockhart , a PhD candidate in sociology and a union member , tells Inside Higher Ed .
“ The university is disregarding all of the best evidence and advice from its own experts in terms of how they should be reopening.
” The university has reopened in a hybrid format , with more than 75 percent of its courses @ @ @ @ @ @ @ to return to campus housing .
Faculty and graduate students have said the administration largely accommodated their requests to teach remotely , but others felt coerced or misled after making their decisions to teach in person in June , when community spread was lower .
The students are also striking against the university ’ s COVID-19 testing protocol , which is less stringent than those at other universities .
Before allowing students back , the school tested only those students living in dorms or involved in fraternity organizations .
Now that classes have @ @ @ @ @ @ @ students with symptoms .
While the school is conducting surveillance testing among undergraduates , participation is voluntary and testing is capped at 3,000 tests per week , Inside Higher Ed reports .
Michigan state officials recently released data showing that college campuses are creating new COVID-19 hotspots .
Within the state , Grand Valley State University has 438 cases among its students , Central Michigan University has 271 cases among students , and Adrian College has 229 cases among both students and staff .
The University of Michigan has so far reported 77 @ @ @ @ @ @ @ The Detroit News .
Students say they don ’ t feel supported by campus officials in trying to make campuses safe .
“ I do feel like they are not taking us seriously , like they can wait us out , ” Alyssa Frizzo , a junior and residential adviser , tells Inside Higher Ed .
“ I don ’ t think throughout this whole process including the town halls they ’ ve really understood how serious we are about this.
” The union is calling for more testing and tracing , the @ @ @ @ @ @ @ documentation , subsidies for student parents , support for international students , funding extensions , and rent freezes for those in campus housing , Inside Higher Ed reports .
Among RAs , their demands include hazard pay , regular testing , personal protective equipment , and greater enforcement of safety measures .
In addition , the union has made cutting ties with local police and federal immigration authorities , as well as a 50 percent reduction in funding to campus police , mandatory for ending the strike .
In an op-ed in The @ @ @ @ @ @ @ of Michigan supported these goals , adding that “ policing is an important public health issue.
” While the strike is being denounced as illegal by university President Mark Schlissel—public employees are not allowed to strike in the state , and the union contract also stipulates a no-strike clause—it has drawn largely positive support from the rest of the university .
More than 680 faculty members and 850 scholars from other institutions have signed open letters in support of the strike , and unionized construction workers and truck drivers have refused to complete @ @ @ @ @ @ @ reports .
Dining hall employees had scheduled a walkout in solidarity , but the event was canceled out of fear of retaliation , according to The Michigan Daily .
Schlissel had previously filed an unfair labor practice charge against the union , but after students voted to continue their strike on Sunday ( September 13 ) , he pursued new charges , including the temporary restraining order and preliminary injunction .
Speaking in a video on Monday , September 14 , Schlissel defended his choice .
“ We want our great classes to @ @ @ @ @ @ @ interference and we don ’ t want anyone to feel threatened simply for wanting to go to class , ” Schlissel said .
“ Going to the court was our only choice after learning the strike would continue .
We ’ d much rather our classes be in session while we work out our differences together.
” The union responded with a written statement stating , “ we always knew legal action was a possibility , and this was a transparent part of our multiple member-wide discussions about the risks of authorizing a @ @ @ @ @ @ @ reports .
“ Moreover , this legal move is a clear sign that withholding our labor is working : The University is feeling our power .
”

ABOVE: © ISTOCK.COM, PAWEL.GAUL
Update (September 18): Students at the University of Michigan have reluctantly ended their strike, noting in a press release reported by Inside Higher Ed, “We won workable pandemic childcare options; substantive support for international graduate students; transparent COVID-19 testing protocols; and incremental but real movement on our policing demands.”
Graduate students and residential advisors at the University of Michigan have gone on strike over the school’s COVID-19 response plan, prompting the university’s president to seek a court-mandated temporary restraining order and preliminary injunction to force students back to work.
The student workers are striking with the support of their union, the Graduate Employees’ Organization (GEO), which represents more than 2,000 graduate student instructors and staff assistants. Since September 8, they have been joined by more than 100 residential advisers in arguing that the university did not provide adequate COVID-19 protections.
“I personally have not spoken to a single person who thinks our COVID reopening plan was well conceived,” Silke-Maria Weineck, a professor of comparative literature and German studies at the university, tells Inside Higher Education. “What you have right now, I think, is a campus getting close to open revolt.”
At the heart of the strike lies the University of Michigan’s fall plans for reopening campus. Graduate students, who are involved in teaching roughly 3,500 courses, claim the university has failed to implement adequate safeguards to protect the well being of students and faculty. As a result, they have stopped holding classes or carrying out research.
“We need a fair and just pandemic response,” Jeff Lockhart, a PhD candidate in sociology and a union member, tells Inside Higher Ed. “The university is disregarding all of the best evidence and advice from its own experts in terms of how they should be reopening.”
The university has reopened in a hybrid format, with more than 75 percent of its courses online, although students have been allowed to return to campus housing. Faculty and graduate students have said the administration largely accommodated their requests to teach remotely, but others felt coerced or misled after making their decisions to teach in person in June, when community spread was lower.
The students are also striking against the university’s COVID-19 testing protocol, which is less stringent than those at other universities. Before allowing students back, the school tested only those students living in dorms or involved in fraternity organizations. Now that classes have started, testing is mostly limited to students with symptoms.
While the school is conducting surveillance testing among undergraduates, participation is voluntary and testing is capped at 3,000 tests per week, Inside Higher Ed reports.
Michigan state officials recently released data showing that college campuses are creating new COVID-19 hotspots. Within the state, Grand Valley State University has 438 cases among its students, Central Michigan University has 271 cases among students, and Adrian College has 229 cases among both students and staff. The University of Michigan has so far reported 77 cases among its students, according to The Detroit News.
Students say they don’t feel supported by campus officials in trying to make campuses safe. “I do feel like they are not taking us seriously, like they can wait us out,” Alyssa Frizzo, a junior and residential adviser, tells Inside Higher Ed. “I don’t think throughout this whole process including the town halls they’ve really understood how serious we are about this.”
The union is calling for more testing and tracing, the option to switch to remote teaching without documentation, subsidies for student parents, support for international students, funding extensions, and rent freezes for those in campus housing, Inside Higher Ed reports. Among RAs, their demands include hazard pay, regular testing, personal protective equipment, and greater enforcement of safety measures.
In addition, the union has made cutting ties with local police and federal immigration authorities, as well as a 50 percent reduction in funding to campus police, mandatory for ending the strike. In an op-ed in The Michigan Daily, faculty from the University of Michigan supported these goals, adding that “policing is an important public health issue.”
While the strike is being denounced as illegal by university President Mark Schlissel—public employees are not allowed to strike in the state, and the union contract also stipulates a no-strike clause—it has drawn largely positive support from the rest of the university. More than 680 faculty members and 850 scholars from other institutions have signed open letters in support of the strike, and unionized construction workers and truck drivers have refused to complete work on campus, Inside Higher Ed reports. Dining hall employees had scheduled a walkout in solidarity, but the event was canceled out of fear of retaliation, according to The Michigan Daily.
Schlissel had previously filed an unfair labor practice charge against the union, but after students voted to continue their strike on Sunday (September 13), he pursued new charges, including the temporary restraining order and preliminary injunction.
Speaking in a video on Monday, September 14, Schlissel defended his choice. “We want our great classes to continue, our students to learn without interference and we don’t want anyone to feel threatened simply for wanting to go to class,” Schlissel said. “Going to the court was our only choice after learning the strike would continue. We’d much rather our classes be in session while we work out our differences together.”
The union responded with a written statement stating, “we always knew legal action was a possibility, and this was a transparent part of our multiple member-wide discussions about the risks of authorizing a work stoppage,” The Michigan Daily reports. “Moreover, this legal move is a clear sign that withholding our labor is working: The University is feeling our power.”


thescientist--2020-09-16--Transplanted Stem Cells Produce Sperm in Sterilized Livestock

Selective breeding and artificial insemination are the cornerstone methods for generating agricultural animals with desired traits .
But a technique called surrogate sire technology—in which males are first sterilized and then transplanted with stem cells to produce sperm from genetically desirable donors—may soon join the list , thanks to proof-of-concept experiments published in PNAS on Monday ( September 14 ) .
“ This is a really great paper that shows for the first time that you can do spermatogonial stem cell transplantation in a variety of large animals , ” says reproductive biologist Thomas Spencer of the University of Missouri @ @ @ @ @ @ @ .
They applied the technique “ to not only one but three agricultural species .
.
.
boars , bucks , and bulls , ” adds Thomas Hansen , a reproduction researcher at Colorado State University , who also did not participate in the study .
“ It ’ s a tremendous amount of work.
” Humans have been controlling the breeding of animals for millennia , selecting for desired traits such as more meaty bodies , increased milk production , and longer fur .
Within the last century , artificial insemination has @ @ @ @ @ @ @ breeding , favored for its efficiency .
“ About eighty percent of dairy cattle are bred by artificial insemination , ” says reproductive biologist Jon Oatley of Washington State University who led the research , but for other animals the technique has limitations .
“ For sheep and goats , in order to do [ artificial insemination ] effectively , it ’ s a surgical procedure , ” Oatley says , adding that such animals also tend to range over large areas of land , rather than being housed in the sort of @ @ @ @ @ @ @ for pigs , which are often artificially inseminated , the practice is not ideal , he says .
The sperm of a boar ( the term for a domesticated , uncastrated pig ) , unlike that of a bull , he explains , does not tolerate freezing well , making its shelf life shorter and limiting its transportation .
The idea behind surrogate sire technology is to transplant sperm-making stem cells from an animal with chosen traits into sterilized male hosts and thus create animals that can continuously provide the desired sperm and @ @ @ @ @ @ @ ’ s “ a way to clone the male , essentially , using surrogates , ” says Hansen .
With the ability to grow spermatogonial stem cells in culture , there may even be the opportunity for direct genetic modifications , which would be the “ ultimate goal , ” suggests Spencer .
For surrogate sires to be truly surrogates , they must have their own sperm-making germ cells eliminated and yet maintain the anatomy necessary for supporting sperm production .
In previous experiments with mice , “ the way that this has @ @ @ @ @ @ @ reagents or irradiation , ” explains reproduction researcher Tessa Lord of the University of Newcastle , Australia , in an email to The Scientist .
But this “ can damage the animals ’ health , and also inadvertently damage the somatic cells in the testis , ” she writes .
Moreover , such treatments “ don ’ t eliminate [ germ cells ] fully , so there ’ s always a mixture of both self- and transplanted- [ spermatogonial cells ] , ” which has stymied the adaption of surrogate sire technology to @ @ @ @ @ @ @ new approach , Oatley and his colleagues have genetically sterilized the animals via the deletion of a gene encoding NANOS2—a protein produced specifically in the testes and essential for generating sperm from germ cells .
“ The production of NANOS2 knockout animals , which are ‘ genetically sterile ’ [ means ] recipient animals no longer need to be exposed to harmful treatments , ” writes Lord , and “ the testes remain undamaged.
” Indeed , the team showed that testicular structure and anatomy appeared normal in NANOS2-lacking male mice , pigs @ @ @ @ @ @ @ , and cattle , yet the germline cells were missing .
When the testes of the mice , pigs , and goats were then provided with spermatogonial stem cells harvested from healthy , unrelated donors , sperm production was reinstated a few months later .
Stem cell transplants were not performed in the cattle .
Interestingly , immune rejection of the donor cells was not a problem , says Oatley .
Although he is not sure why this was the case , it could be due to the immune privileged status of mammalian @ @ @ @ @ @ @ case of the mice , the replenished sperm were shown to be functional .
The transplanted animals could mate with females and produce offspring as early as two-and-a-half months after the transplant procedure .
Non-transplanted male NANOS2-lacking mice never produced offspring .
The team is now working on similar mating experiments in the livestock .
While the approach will need further refinement and regulatory approval before it can be applied to livestock , says Oatley , its further development has potential applications beyond the farmyard .
Surrogate sire technology may be useful for @ @ @ @ @ @ @ Hansen .
And , spermatogonial stem cell harvesting and transplantation may provide an opportunity for men and boys facing chemotherapy to safeguard their future fertility , adds Lord .
Ultimately , she says , the technique “ has implications spanning human medicine , agriculture and conservation of wildlife species.
” M. Ciccarelli et al.
, “ Donor-derived spermatogenesis following stem cell transplantation in sterile NANOS2 knockout males , ” PNAS , doi:10.1073/pnas.2010102117 , 2020 .

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Selective breeding and artificial insemination are the cornerstone methods for generating agricultural animals with desired traits. But a technique called surrogate sire technology—in which males are first sterilized and then transplanted with stem cells to produce sperm from genetically desirable donors—may soon join the list, thanks to proof-of-concept experiments published in PNAS on Monday (September 14).
“This is a really great paper that shows for the first time that you can do spermatogonial stem cell transplantation in a variety of large animals,” says reproductive biologist Thomas Spencer of the University of Missouri who was not involved in the research.
They applied the technique “to not only one but three agricultural species . . . boars, bucks, and bulls,” adds Thomas Hansen, a reproduction researcher at Colorado State University, who also did not participate in the study. “It’s a tremendous amount of work.”
Humans have been controlling the breeding of animals for millennia, selecting for desired traits such as more meaty bodies, increased milk production, and longer fur. Within the last century, artificial insemination has become a widely used version of selective breeding, favored for its efficiency. “About eighty percent of dairy cattle are bred by artificial insemination,” says reproductive biologist Jon Oatley of Washington State University who led the research, but for other animals the technique has limitations.
“For sheep and goats, in order to do [artificial insemination] effectively, it’s a surgical procedure,” Oatley says, adding that such animals also tend to range over large areas of land, rather than being housed in the sort of quarters suitable for animal handling. Even for pigs, which are often artificially inseminated, the practice is not ideal, he says. The sperm of a boar (the term for a domesticated, uncastrated pig), unlike that of a bull, he explains, does not tolerate freezing well, making its shelf life shorter and limiting its transportation.
The idea behind surrogate sire technology is to transplant sperm-making stem cells from an animal with chosen traits into sterilized male hosts and thus create animals that can continuously provide the desired sperm and deliver it to females naturally. It’s “a way to clone the male, essentially, using surrogates,” says Hansen.
With the ability to grow spermatogonial stem cells in culture, there may even be the opportunity for direct genetic modifications, which would be the “ultimate goal,” suggests Spencer.
For surrogate sires to be truly surrogates, they must have their own sperm-making germ cells eliminated and yet maintain the anatomy necessary for supporting sperm production. In previous experiments with mice, “the way that this has been achieved is through treatment with chemotherapy reagents or irradiation,” explains reproduction researcher Tessa Lord of the University of Newcastle, Australia, in an email to The Scientist. But this “can damage the animals’ health, and also inadvertently damage the somatic cells in the testis,” she writes.
Moreover, such treatments “don’t eliminate [germ cells] fully, so there’s always a mixture of both self- and transplanted-[spermatogonial cells],” which has stymied the adaption of surrogate sire technology to livestock, Oatley says. In their new approach, Oatley and his colleagues have genetically sterilized the animals via the deletion of a gene encoding NANOS2—a protein produced specifically in the testes and essential for generating sperm from germ cells.
“The production of NANOS2 knockout animals, which are ‘genetically sterile’ [means] recipient animals no longer need to be exposed to harmful treatments,” writes Lord, and “the testes remain undamaged.”
Genetically sterilized goats lacking the NANOS2 gene Jon OATLEY
Indeed, the team showed that testicular structure and anatomy appeared normal in NANOS2-lacking male mice, pigs, goats (known as bucks), and cattle, yet the germline cells were missing.
See “The Superpowers of Genetically Modified Pigs”
When the testes of the mice, pigs, and goats were then provided with spermatogonial stem cells harvested from healthy, unrelated donors, sperm production was reinstated a few months later. Stem cell transplants were not performed in the cattle. Interestingly, immune rejection of the donor cells was not a problem, says Oatley. Although he is not sure why this was the case, it could be due to the immune privileged status of mammalian testes, he suggests.
In the case of the mice, the replenished sperm were shown to be functional. The transplanted animals could mate with females and produce offspring as early as two-and-a-half months after the transplant procedure. Non-transplanted male NANOS2-lacking mice never produced offspring. The team is now working on similar mating experiments in the livestock.
While the approach will need further refinement and regulatory approval before it can be applied to livestock, says Oatley, its further development has potential applications beyond the farmyard. Surrogate sire technology may be useful for the preservation of endangered species, suggests Hansen. And, spermatogonial stem cell harvesting and transplantation may provide an opportunity for men and boys facing chemotherapy to safeguard their future fertility, adds Lord.
Ultimately, she says, the technique “has implications spanning human medicine, agriculture and conservation of wildlife species.”
M. Ciccarelli et al., “Donor-derived spermatogenesis following stem cell transplantation in sterile NANOS2 knockout males,” PNAS, doi:10.1073/pnas.2010102117, 2020.


thescientist--2020-09-15--Advancing Disease Research with Mass Spectrometry

Mass spectrometry has become an indispensible tool for life scientists , enabling them to monitor a host of biological processes @ @ @ @ @ will explore some of the ways scientists are using mass spectrometry to further our understanding @ @ @ @ @ as well as how they are maximizing accessibility to ever-increasing reams of mass spectrometry-obtained information @ @ @ @ @ The Scientist 's Creative Services team to learn about how mass spectrometry data • Is @ @ @ @ @ for public collaboration

Mass spectrometry has become an indispensible tool for life scientists, enabling them to monitor a host of biological processes and mechanisms. This ebook presents unique mass spectrometry studies that improve comprehension of health and disease and explores how scientists maximize accessibility to mass spectrometry data.
Download this ebook from The Scientist's Creative Services team to learn how mass spectrometry data


thescientist--2020-09-15--Weighing the Benefits of a Clean Balance

An accurate balance is an essential tool in every research laboratory ; however , balances easily become dirty as scientists @ @ @ @ @ compounds .
Properly cleaning these delicate instruments is not a daunting task as long as @ @ @ @ @ precautions .
By following a few easy cleaning steps , researchers can avoid contamination and @ @ @ @ @ instruments .
Download this reference paper from Mettler Toledo to learn about

An accurate balance is an essential tool in every research laboratory; however, balances easily become dirty as scientists weigh and spill numerous chemical compounds. Properly cleaning these delicate instruments is not a daunting task as long as researchers take proper care and precautions. By following a few easy cleaning steps, researchers can avoid contamination and extend the lives of their instruments.
Download this reference paper from Mettler Toledo to learn about


thescientist--2020-09-15--Indian Study Shows No Survival Benefit of Plasma in COVID-19

In the absence of a vaccine or an effective antidote to SARS-CoV-2 , the use of convalescent plasma therapy is in vogue globally .
It involves the infusion of plasma from patients who have recovered from COVID-19 and thus carry protective antibodies into patients who are currently infected with the coronavirus .
The US Food and Drug Administration ( FDA ) recently granted emergency use authorization ( EUA ) for its use , although the absence of randomized controlled trials ( RCTs ) , the gold standard of scientific research , has led to skepticism about its effectiveness among experts @ @ @ @ @ @ @ PLACID ( PLAsma Convalescent InDia ) trial helps fill this gap .
Recently conducted by the Indian Council of Medical Research ( ICMR ) , the apex medical research body in India , it is the first RCT for plasma in COVID-19 patients to be completed in the world .
The study included 464 hospitalized , moderately ill COVID-19 patients—they were on supplemental oxygen but not critically ill with organ damage—across 39 medical centers between April 22 and July 14 .
The trial had two arms : an intervention arm , in which @ @ @ @ @ @ @ of convalescent plasma , 24 hours apart , along with standard of care , and a control arm that received standard of care alone .
The results , posted as a preprint on September 8 with a revision posted two days later , signal that the use of convalescent plasma in COVID-19 patients did not forestall progression to severe disease or mortality .
Study coauthor Pankaj Malhotra , a clinical hematologist at the Postgraduate Institute of Medical Education and Research in Chandigarh , India , says that these results won ’ t have @ @ @ @ @ @ @ where convalescent plasma therapy is hugely popular and where the total number of COVID-19 cases has crossed 4.9 million .
In June , the Indian health ministry recommended off-label use of plasma in COVID-19 patients who showed no improvement despite standard of care .
Malhotra adds that the study could perhaps lead to a decline in the burgeoning illegal trade in plasma in the country .
Arturo Casadevall , an immunologist at Johns Hopkins Bloomberg School of Public Health , tells The Scientist , “ It ’ s the first RCT that was @ @ @ @ @ @ @ that is a significant accomplishment.
” An RCT in China was halted prematurely in late March due to dwindling cases and another in the Netherlands was discontinued as antibody titers in recipients were found to be comparable to that of donors , raising questions about the potential benefit of convalescent plasma .
In the US currently , there are more than 20 RCTs that are actively recruiting patients , but none have been completed .
A large Mayo Clinic study that was part of the US Expanded Access Program for COVID-19 convalescent plasma @ @ @ @ @ @ @ s EUA was nonrandomized .
Despite the lack of survival benefit shown in the ICMR study , some positives gleaned from the trial include improved symptoms and oxygenation and faster viral clearance in patients in the intervention arm compared with the control arm .
Michael Joyner , the lead author of the Mayo Clinic study that prompted the FDA to grant EUA for convalescent plasma therapy to treat COVID-19 in the US , tells The Scientist that the authors , the Indian research council , and the country deserve a lot of credit @ @ @ @ @ @ @ circumstances .
“ I think that ’ s most impressive .
.
.
.
So , high compliments there.
” “ I see the cup being half full in terms of the viral load data and the improved oxygenation and so forth , ” Joyner says .
The half empty part , he adds , is that most of the plasma had low titers of antibodies and was given relatively late during the course of the disease—a median of eight days after onset of symptoms .
“ Those are the two main limitations @ @ @ @ @ @ @ Search for Immune Responses that Stop COVID-19 ” The Mayo Clinic investigators found that early treatment with plasma in hospitalized COVID-19 patients , within three days of diagnosis , with high levels of protective antibodies decreases mortality compared with later treatment using plasma with low titers of antibodies .
Since this study did not include a control arm , however , the researchers can ’ t say if the reduced mortality was due to plasma treatment .
Casadevall , who is involved in two clinical trials at Hopkins to test whether plasma therapy @ @ @ @ @ @ @ results of the Indian study encouraging , and contends that the low titers , likely because many of the donors were younger and fitter and had only mild disease , and the late use of plasma could perhaps account for the lack of survival benefit .
Adrian Newland , a hematologist at Barts Health NHS Trust , tells The Scientist in an email , “ It has also been seen that the antibody titers often fall off quite quickly so the chances of only 200 ml of serum ( given twice ) of @ @ @ @ @ @ @ He adds that the standard of care is continuously improving and contributing to better survival .
“ Therefore , it is likely that if the benefit of convalescent serum is small , the impact is likely to be masked.
” Terry Gernsheimer , a hematologist at the University of Washington School of Medicine , writes in an email to The Scientist , “ The numbers [ in the ICMR study ] are small and we don ’ t know how many patients it would take to treat before we would actually see a @ @ @ @ @ @ @ standard of care is problematic as it is very difficult to keep either the patient or the staff blinded to the treatments that patients are receiving .
In addition , the possible immunomodulatory effects of donor plasma , even plasma that is not convalescent , can not be known .
The best control arm , she says , would be non-convalescent plasma , which was not done .
“ Unfortunately that is true of all studies to date , ” observes Gernsheimer .
Thomas Marron , a cancer immunologist at the Icahn School @ @ @ @ @ @ @ The Scientist in an email , “ I ’ m happy to see that there is finally some randomized data to report .
That said , I still don ’ t think we are testing the appropriate population in many of these trials.
” He says that it is likely that viral control—which the antibodies in plasma are supposed to do—is more important during the early phase , while control of the hyperinflammatory response would be crucial in patients with more advanced disease .
“ I would worry that by the time you @ @ @ @ @ @ @ horse has left the barn , and while we may give antivirals and convalescent plasma to stem any further viral spread , managing the inflammation should be the primary focus.
” There ’ s also the question of antibodies ’ overall utility .
“ There is also the uncertainty of the importance of antibodies in fighting the [ SARS-CoV-2 ] infection , ” writes Newland .
“ There is increasing evidence that T lymphocytes are a more important source of immunity and this is one of the measures used in assessing the effectiveness @ @ @ @ @ @ @ He says , “ I think that , ultimately , convalescent serum has little to offer.
” Gernsheimer , who is involved in studies on convalescent plasma therapy in COVID-19 in the US , is more optimistic .
“ I think the best we can say here , which is what we have noted from the 70,000 patients who received convalescent plasma under a nonrandomized access to the plasma in the US , is that there is no apparent harm and further studies need to be done.
” A. Agarwal et al.
, @ @ @ @ @ @ @ moderate COVID-19 in India : An open-label parallel-arm phase II multicentre randomized controlled trial ( PLACID Trial ) , ” medRxiv , doi:10.1101/2020.09.03.20187252 , 2020 .

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In the absence of a vaccine or an effective antidote to SARS-CoV-2, the use of convalescent plasma therapy is in vogue globally. It involves the infusion of plasma from patients who have recovered from COVID-19 and thus carry protective antibodies into patients who are currently infected with the coronavirus. The US Food and Drug Administration (FDA) recently granted emergency use authorization (EUA) for its use, although the absence of randomized controlled trials (RCTs), the gold standard of scientific research, has led to skepticism about its effectiveness among experts.
In light of this, the PLACID (PLAsma Convalescent InDia) trial helps fill this gap. Recently conducted by the Indian Council of Medical Research (ICMR), the apex medical research body in India, it is the first RCT for plasma in COVID-19 patients to be completed in the world. The study included 464 hospitalized, moderately ill COVID-19 patients—they were on supplemental oxygen but not critically ill with organ damage—across 39 medical centers between April 22 and July 14. The trial had two arms: an intervention arm, in which patients received two doses of 200 ml of convalescent plasma, 24 hours apart, along with standard of care, and a control arm that received standard of care alone.
The results, posted as a preprint on September 8 with a revision posted two days later, signal that the use of convalescent plasma in COVID-19 patients did not forestall progression to severe disease or mortality.
Study coauthor Pankaj Malhotra, a clinical hematologist at the Postgraduate Institute of Medical Education and Research in Chandigarh, India, says that these results won’t have much effect on clinical practice in India where convalescent plasma therapy is hugely popular and where the total number of COVID-19 cases has crossed 4.9 million. In June, the Indian health ministry recommended off-label use of plasma in COVID-19 patients who showed no improvement despite standard of care. Malhotra adds that the study could perhaps lead to a decline in the burgeoning illegal trade in plasma in the country.
Arturo Casadevall, an immunologist at Johns Hopkins Bloomberg School of Public Health, tells The Scientist, “It’s the first RCT that was completed for convalescent plasma and I think that is a significant accomplishment.” An RCT in China was halted prematurely in late March due to dwindling cases and another in the Netherlands was discontinued as antibody titers in recipients were found to be comparable to that of donors, raising questions about the potential benefit of convalescent plasma. In the US currently, there are more than 20 RCTs that are actively recruiting patients, but none have been completed. A large Mayo Clinic study that was part of the US Expanded Access Program for COVID-19 convalescent plasma and that led to the FDA’s EUA was nonrandomized.
Despite the lack of survival benefit shown in the ICMR study, some positives gleaned from the trial include improved symptoms and oxygenation and faster viral clearance in patients in the intervention arm compared with the control arm.
Michael Joyner, the lead author of the Mayo Clinic study that prompted the FDA to grant EUA for convalescent plasma therapy to treat COVID-19 in the US, tells The Scientist that the authors, the Indian research council, and the country deserve a lot of credit for doing this trial under very difficult circumstances. “I think that’s most impressive. . . . So, high compliments there.”
“I see the cup being half full in terms of the viral load data and the improved oxygenation and so forth,” Joyner says. The half empty part, he adds, is that most of the plasma had low titers of antibodies and was given relatively late during the course of the disease—a median of eight days after onset of symptoms. “Those are the two main limitations of the study.”
The Mayo Clinic investigators found that early treatment with plasma in hospitalized COVID-19 patients, within three days of diagnosis, with high levels of protective antibodies decreases mortality compared with later treatment using plasma with low titers of antibodies. Since this study did not include a control arm, however, the researchers can’t say if the reduced mortality was due to plasma treatment.
Casadevall, who is involved in two clinical trials at Hopkins to test whether plasma therapy is effective in COVID-19, finds the results of the Indian study encouraging, and contends that the low titers, likely because many of the donors were younger and fitter and had only mild disease, and the late use of plasma could perhaps account for the lack of survival benefit.
Adrian Newland, a hematologist at Barts Health NHS Trust, tells The Scientist in an email, “It has also been seen that the antibody titers often fall off quite quickly so the chances of only 200 ml of serum (given twice) of providing any significant protection is small.”
He adds that the standard of care is continuously improving and contributing to better survival. “Therefore, it is likely that if the benefit of convalescent serum is small, the impact is likely to be masked.”
Terry Gernsheimer, a hematologist at the University of Washington School of Medicine, writes in an email to The Scientist, “The numbers [in the ICMR study] are small and we don’t know how many patients it would take to treat before we would actually see a difference.”
She adds that randomization against standard of care is problematic as it is very difficult to keep either the patient or the staff blinded to the treatments that patients are receiving. In addition, the possible immunomodulatory effects of donor plasma, even plasma that is not convalescent, cannot be known. The best control arm, she says, would be non-convalescent plasma, which was not done. “Unfortunately that is true of all studies to date,” observes Gernsheimer.
Thomas Marron, a cancer immunologist at the Icahn School of Medicine at Mount Sinai, tells The Scientist in an email, “I’m happy to see that there is finally some randomized data to report. That said, I still don’t think we are testing the appropriate population in many of these trials.”
He says that it is likely that viral control—which the antibodies in plasma are supposed to do—is more important during the early phase, while control of the hyperinflammatory response would be crucial in patients with more advanced disease. “I would worry that by the time you are having moderate respiratory distress, the horse has left the barn, and while we may give antivirals and convalescent plasma to stem any further viral spread, managing the inflammation should be the primary focus.”
There’s also the question of antibodies’ overall utility. “There is also the uncertainty of the importance of antibodies in fighting the [SARS-CoV-2] infection,” writes Newland. “There is increasing evidence that T lymphocytes are a more important source of immunity and this is one of the measures used in assessing the effectiveness of the vaccines now being developed.”
He says, “I think that, ultimately, convalescent serum has little to offer.”
Gernsheimer, who is involved in studies on convalescent plasma therapy in COVID-19 in the US, is more optimistic. “I think the best we can say here, which is what we have noted from the 70,000 patients who received convalescent plasma under a nonrandomized access to the plasma in the US, is that there is no apparent harm and further studies need to be done.”
A. Agarwal et al., “Convalescent plasma in the management of moderate COVID-19 in India: An open-label parallel-arm phase II multicentre randomized controlled trial (PLACID Trial),” medRxiv, doi:10.1101/2020.09.03.20187252, 2020.


thescientist--2020-09-15--Simplifying Protein Expression with myTXTL

myTXTL provides customizable workflows , simple optimization , faster production , and better yields .
Learn more at arborbiosci.com/myTXTL

myTXTL provides customizable workflows, simple optimization, faster production, and better yields. Learn more at arborbiosci.com/myTXTL


thescientist--2020-09-10--October 23, 2020 - Winning Westerns: The Do's and Don'ts of Western Blotting

Western blotting is a foundational technique for any protein scientist .
While Western blotting protocols are straightforward , there are @ @ @ @ @ lead to blot success or failure .
This webinar from The Scientist and sponsored by @ @ @ @ @ of Western blotting , identify common troubleshooting issues , and provide tips for Western blotting @ @

FREE Webinar
Friday, October 23, 2020
10:00 - 11:00 AM, China Standard Time
Register Now
Western blotting is a foundational technique for any protein scientist. While Western blotting protocols are straightforward, there are many critical decision points that lead to blot success or failure. This webinar sponsored by Merck will review the basics of Western blotting, identify common troubleshooting issues, and provide tips for Western blotting success.
Topics to be covered
The basics of Western blotting
Immunobinding and signal detection
Innovations for streamlining Western blotting workflows
Register Now
Meet the speaker:
Kelly Wolfe, PhD
Application Development Scientist
Merck


thescientist--2020-09-10--October 21, 2020 - Winning Westerns: The Do's and Don'ts of Western Blotting

FREE Webinar
Wednesday, October 21, 2020
11:00 AM - 12:00 PM, Eastern Standard Time
Register Now
Western blotting is a foundational technique for any protein scientist. While Western blotting protocols are straightforward, there are many critical decision points that lead to blot success or failure. This webinar sponsored by MilliporeSigma will review the basics of Western blotting, identify common troubleshooting issues, and provide tips for Western blotting success.
Topics to be covered
The basics of Western blotting
Immunobinding and signal detection
Innovations for streamlining Western blotting workflows
Register Now
Meet the speaker:
Kelly Wolfe, PhD
Application Development Scientist
MilliporeSigma


thescientist--2020-09-15--Getting Started with Single Cell Multiomics: Simultaneous Epigenomic and Transcriptomic Profiling fr

Getting Started with Single Cell Multiomics: Simultaneous Epigenomic and Transcriptomic Profiling from the Same Cell

A fundamental challenge in biology is precisely linking gene regulatory networks to the gene expression profiles that define unique cell @ @ @ @ @ an innovative approach to gain multiomic insights into biological complexity using a new method that @ @ @ @ @ RNA-seq ) and chromatin accessibility ( ATAC-seq ) from the same single cells .
By @ @ @ @ @ once , researchers can more deeply characterize complex cell populations , resolve cellular heterogeneity , @ @ @ @ @ driving cell differentiation , development , and disease .
In this webinar brought to you @ @ @ @ @ will discuss tips for running Chromium Single Cell Multiome ATAC + Gene Expression experiments in @ @ @ @ @ to detect mRNA and chromatin accessibility from the same single cells with high sensitivity across @ @ @ @ @ to design a single cell multiomics experiment , from sample prep to data analysis and @

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Wednesday, October 14, 2020
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thescientist--2020-09-18--Frozen Fecal Knives Honored by 2020 Ig Nobel Prizes

ABOVE : A note for 10 trillion Zimbabwean dollars , which was given to all honorees © ISTOCK.COM , SWISSHIPPO Certain scientific advancements—such as the discovery of penicillin or the structure of DNA—are such game-changers that the scientists behind them are honored and immortalized with a Nobel Prize .
And then there is the sort of research that involves giving helium to alligators or identifying narcissists by their eyebrows .
Since 1991 , these scientific misfits have found recognition by the Ig Nobel awards , a product of the Annals of Improbable Research .
On Thursday ( September 17 ) @ @ @ @ @ @ @ esteemed-ish honorees was announced via webcast .
While there is a world of difference in the Ig Nobel ’ s prestige and the prizes founded by Alfred Nobel , the two groups are not mutually exclusive , and there are scientists who are recipients of both .
The 30th First Annual ( not 31st Annual ) Ig Nobel Prize ceremony , held entirely online for the first time due to the ongoing coronavirus pandemic , celebrated truly jaw-dropping studies in 10 categories , six of which were presented by Nobel laureates : Acoustics @ @ @ @ @ @ @ “ for inducing a female Chinese alligator to bellow in an airtight chamber filled with helium-enriched air.
” Economics : Awarded to a team that studied “ the relationship between different countries ’ national income inequality and the average amount of mouth-to-mouth kissing.
” Entomology : Awarded to an American researcher who collected “ evidence that many entomologists ( scientists who study insects ) are afraid of spiders , which are not insects.
” Management : Awarded to five professional hitmen “ who managed a contract for a hit job ( a murder @ @ @ @ @ @ @ way : After accepting payment to perform the murder , Xi Guang-An then instead subcontracted the task to Mo Tian-Xiang , who then instead subcontracted the task to Yang Kang-Sheng , who then instead subcontracted the task to Yang Guang-Sheng , who then instead subcontracted the task to Ling Xian-Si , with each subsequently enlisted hitman receiving a smaller percentage of the fee , and nobody actually performing a murder.
” Materials Science : Awarded to a group of scientists “ for showing that knives manufactured from frozen human feces do not work @ @ @ @ @ @ @ a group of world leaders including President Donald Trump , Prime Minister Boris Johnson , President Vladimir Putin , and President Jair Bolsonaro “ for using the COVID-19 viral pandemic to teach the world that politicians can have a more immediate effect on life and death than scientists and doctors can.
” Medicine : Awarded to doctors “ for diagnosing a long-unrecognized medical condition : Misophonia , the distress at hearing other people make chewing sounds.
” Peace : Awarded to unnamed government officials from India and Pakistan who “ surreptitiously [ rung @ @ @ @ @ @ @ the middle of the night , and then [ ran ] away before anyone had a chance to answer the door.
” Essentially , Ding Dong Ditch with diplomatic immunity .
Physics : Awarded to a team that discovered “ what happens to the shape of a living earthworm when one vibrates the earthworm at high frequency.
” Psychology : Awarded to a pair of scientists “ for devising a method to identify narcissists by examining their eyebrows.
” Winners receive a paper cube ( which the recipients printed and folded themselves ) @ @ @ @ @ @ @ Not US dollars , of course , but a relic from the days of Zimbabwe ’ s hyperinflation .
According to reports , this was the sum required to buy a loaf of bread in 2009 .
Warmest congratulations to all of this year ’ s honorees !

ABOVE: A note for 10 trillion Zimbabwean dollars, which was given to all honorees
© ISTOCK.COM, SWISSHIPPO
Certain scientific advancements—such as the discovery of penicillin or the structure of DNA—are such game-changers that the scientists behind them are honored and immortalized with a Nobel Prize. And then there is the sort of research that involves giving helium to alligators or identifying narcissists by their eyebrows. Since 1991, these scientific misfits have found recognition by the Ig Nobel awards, a product of the Annals of Improbable Research. On Thursday (September 17), this year’s cohort of esteemed-ish honorees was announced via webcast.
While there is a world of difference in the Ig Nobel’s prestige and the prizes founded by Alfred Nobel, the two groups are not mutually exclusive, and there are scientists who are recipients of both.
The 30th First Annual (not 31st Annual) Ig Nobel Prize ceremony, held entirely online for the first time due to the ongoing coronavirus pandemic, celebrated truly jaw-dropping studies in 10 categories, six of which were presented by Nobel laureates:
Acoustics: Awarded to a team of scientists “for inducing a female Chinese alligator to bellow in an airtight chamber filled with helium-enriched air.”
Economics: Awarded to a team that studied “the relationship between different countries’ national income inequality and the average amount of mouth-to-mouth kissing.”
Entomology: Awarded to an American researcher who collected “evidence that many entomologists (scientists who study insects) are afraid of spiders, which are not insects.”
Management: Awarded to five professional hitmen “who managed a contract for a hit job (a murder performed for money) in the following way: After accepting payment to perform the murder, Xi Guang-An then instead subcontracted the task to Mo Tian-Xiang, who then instead subcontracted the task to Yang Kang-Sheng, who then instead subcontracted the task to Yang Guang-Sheng, who then instead subcontracted the task to Ling Xian-Si, with each subsequently enlisted hitman receiving a smaller percentage of the fee, and nobody actually performing a murder.”
Materials Science: Awarded to a group of scientists “for showing that knives manufactured from frozen human feces do not work well.”
Medical Education: Awarded to a group of world leaders including President Donald Trump, Prime Minister Boris Johnson, President Vladimir Putin, and President Jair Bolsonaro “for using the COVID-19 viral pandemic to teach the world that politicians can have a more immediate effect on life and death than scientists and doctors can.”
Medicine: Awarded to doctors “for diagnosing a long-unrecognized medical condition: Misophonia, the distress at hearing other people make chewing sounds.”
Peace: Awarded to unnamed government officials from India and Pakistan who “surreptitiously [rung] each other’s doorbells in the middle of the night, and then [ran] away before anyone had a chance to answer the door.” Essentially, Ding Dong Ditch with diplomatic immunity.
Physics: Awarded to a team that discovered “what happens to the shape of a living earthworm when one vibrates the earthworm at high frequency.”
Psychology: Awarded to a pair of scientists “for devising a method to identify narcissists by examining their eyebrows.”
Winners receive a paper cube (which the recipients printed and folded themselves) and a note for $10,000,000,000,000. Not US dollars, of course, but a relic from the days of Zimbabwe’s hyperinflation. According to reports, this was the sum required to buy a loaf of bread in 2009.
Warmest congratulations to all of this year’s honorees!


thescientist--2020-09-18--Tom Norris, Marine Mammal Acoustician, Dies at 55

ABOVE : Tom Norris sits at a computer listening to the sounds of marine mammals in the Arctic in 2006 .
JEFF JACOBSON Tom Norris , an independent marine scientist and founder of the bioacoustic research company Bio-Waves , died September 9 after a months-long battle against pancreatic cancer .
He was 55 .
Norris ’ s largest contributions to the field of marine bioacoustics and marine mammal research stem from the hydrophone arrays he designed for passive monitoring of the world ’ s whales and dolphins .
Through the company he founded , he worked alongside groups such as @ @ @ @ @ @ @ NOAA ) and the Office of Naval Research ( ONR ) conducting acoustic surveys that ultimately informed federal policies regarding noise pollution and marine mammal conservation .
“ His work as a marine biologist added valuable knowledge to science , and he ran his company with integrity and passion , ” Norris ’ s friends and colleagues shared in a GoFundMe fundraiser to support his wife following his death .
“ He always gave back to the community and could often be found donating equipment to underfunded projects , or mentoring students who @ @ @ @ @ @ @ Originally from San Diego , Norris received a bachelor ’ s degree in zoology from the University of California , Santa Barbara , in 1987 before moving north to attend graduate school at Moss Landing Marine Laboratories .
His research there focused on the acoustics of whales off the coast of Kauai , and he returned to Hawaii at least two dozen times over his 30-year career , according to a 2011 article profiling his work .
Norris ’ s master ’ s thesis focused specifically on how boat noise affects the singing @ @ @ @ @ @ @ calls of whales before and during the time when boats were passing nearby , he was able to show that humpbacks modified the rhythm of their song , decreasing the length of their notes and increasing their tempo .
His results led him to suggest that in addition to the notes themselves , the pauses between might also be important in relaying information .
“ Everyone thinks that the notes and the frequencies are what matters , but Tom was one of the first to propose that it was the space between the @ @ @ @ @ @ @ Zoidis , the founder of the non-profit Cetos Research Organization , tells The Scientist .
“ It just showed Tom ’ s unique way of thinking.
” Even before graduating in 1995 , Norris began working as an independent acoustician , and was one of several involved in the world ’ s first large-scale marine climate study , the Acoustic Thermometry of Ocean Climate ( ATOC ) program .
Between 1996 and 2006 , researchers used acoustic sources located off central California and Hawaii to study temperature throughout the North Pacific , showing @ @ @ @ @ @ @ modeling climate .
Norris worked on the marine mammal research team that studied whether the technology was harmful to animals ; while it remained a contentious issue , scientists on the team largely concluded the technology was safe .
In the early 2000s , Norris began experimenting with designing his own hydrophone arrays , which are towed on long lines behind ships .
He returned to San Diego to launch Bio-Waves in 2006 , and it remains one of the only companies in the world developing customized hydrophone arrays for the study of @ @ @ @ @ @ @ work with NOAA and the Navy focused on minimizing the effects of noise pollution on marine mammals .
Information about the presence and abundance of marine mammals in certain areas is useful to federal agencies looking to comply with the Marine Mammal Protection Act , which protects animals from harassment , including the use of sonar and other sound-based tools .
“ We are providing basic information like how many mammals there are so [ agencies like ] the Navy can make appropriate management and policy decisions based on scientifically based information , @ @ @ @ @ @ @ .
In addition to his ongoing development of new hardware technology , Norris frequently traveled with other Bio-Waves employees to carry out contracted research surveys , including work in Vietnam , Canada , Brazil , and Mexico .
Over three decades , Norris studied killer whales , sperm whales , minke whales , humpbacks , and many species of dolphin , among other marine mammals .
More recently , Bio-Waves harnessed the power of machine learning to create a software called ROCCA that automatically extracts suspected toothed whale calls from raw sound data @ @ @ @ @ @ @ than a dozen different species of whale and dolphin .
Even as the technology advanced , “ Tom was really grounded with respect to his use of the equipment , his interpretation of data , and relating to others where bias might enter the situation , ” Elizabeth Ferguson , the founder of the software company Ocean Science Analytics and a previous Bio-Waves employee , tells The Scientist .
“ I ’ ve never known anybody to put so much thought into how we covered all our bases.
” Norris is survived by @ @ @ @ @ @ @ Peter , and parents Marlies and Patrick .
Moss Landing Marine Laboratories will be establishing a student scholarship in his honor to support emerging marine mammal scientists who embrace creative methods in their research .

ABOVE: Tom Norris sits at a computer listening to the sounds of marine mammals in the Arctic in 2006.
JEFF JACOBSON
Tom Norris, an independent marine scientist and founder of the bioacoustic research company Bio-Waves, died September 9 after a months-long battle against pancreatic cancer. He was 55.
Norris’s largest contributions to the field of marine bioacoustics and marine mammal research stem from the hydrophone arrays he designed for passive monitoring of the world’s whales and dolphins. Through the company he founded, he worked alongside groups such as the National Oceanic and Atmospheric Administration (NOAA) and the Office of Naval Research (ONR) conducting acoustic surveys that ultimately informed federal policies regarding noise pollution and marine mammal conservation.
“His work as a marine biologist added valuable knowledge to science, and he ran his company with integrity and passion,” Norris’s friends and colleagues shared in a GoFundMe fundraiser to support his wife following his death. “He always gave back to the community and could often be found donating equipment to underfunded projects, or mentoring students who had no experience in the field.”
Originally from San Diego, Norris received a bachelor’s degree in zoology from the University of California, Santa Barbara, in 1987 before moving north to attend graduate school at Moss Landing Marine Laboratories. His research there focused on the acoustics of whales off the coast of Kauai, and he returned to Hawaii at least two dozen times over his 30-year career, according to a 2011 article profiling his work.
Norris’s master’s thesis focused specifically on how boat noise affects the singing of humpback whales. By analyzing the calls of whales before and during the time when boats were passing nearby, he was able to show that humpbacks modified the rhythm of their song, decreasing the length of their notes and increasing their tempo. His results led him to suggest that in addition to the notes themselves, the pauses between might also be important in relaying information.
“Everyone thinks that the notes and the frequencies are what matters, but Tom was one of the first to propose that it was the space between the notes that communicated content,” Ann Zoidis, the founder of the non-profit Cetos Research Organization, tells The Scientist. “It just showed Tom’s unique way of thinking.”
Even before graduating in 1995, Norris began working as an independent acoustician, and was one of several involved in the world’s first large-scale marine climate study, the Acoustic Thermometry of Ocean Climate (ATOC) program. Between 1996 and 2006, researchers used acoustic sources located off central California and Hawaii to study temperature throughout the North Pacific, showing that sound was a viable way of modeling climate. Norris worked on the marine mammal research team that studied whether the technology was harmful to animals; while it remained a contentious issue, scientists on the team largely concluded the technology was safe.
Tom Norris and Ann Zoidis studying humpback whales off the coast of Kauai in 1992 DANIEL SHAPIRO
In the early 2000s, Norris began experimenting with designing his own hydrophone arrays, which are towed on long lines behind ships. He returned to San Diego to launch Bio-Waves in 2006, and it remains one of the only companies in the world developing customized hydrophone arrays for the study of marine mammal acoustics. Much of his work with NOAA and the Navy focused on minimizing the effects of noise pollution on marine mammals.
Information about the presence and abundance of marine mammals in certain areas is useful to federal agencies looking to comply with the Marine Mammal Protection Act, which protects animals from harassment, including the use of sonar and other sound-based tools. “We are providing basic information like how many mammals there are so [agencies like] the Navy can make appropriate management and policy decisions based on scientifically based information,” Norris said in a 2016 interview.
In addition to his ongoing development of new hardware technology, Norris frequently traveled with other Bio-Waves employees to carry out contracted research surveys, including work in Vietnam, Canada, Brazil, and Mexico. Over three decades, Norris studied killer whales, sperm whales, minke whales, humpbacks, and many species of dolphin, among other marine mammals.
More recently, Bio-Waves harnessed the power of machine learning to create a software called ROCCA that automatically extracts suspected toothed whale calls from raw sound data. The program can accurately identify more than a dozen different species of whale and dolphin.
Even as the technology advanced, “Tom was really grounded with respect to his use of the equipment, his interpretation of data, and relating to others where bias might enter the situation,” Elizabeth Ferguson, the founder of the software company Ocean Science Analytics and a previous Bio-Waves employee, tells The Scientist. “I’ve never known anybody to put so much thought into how we covered all our bases.”
Norris is survived by his wife Danielle, his older brother Peter, and parents Marlies and Patrick. Moss Landing Marine Laboratories will be establishing a student scholarship in his honor to support emerging marine mammal scientists who embrace creative methods in their research.