thescientist--2020-08-14--Opinion: Science in a Time of Crisis

Opinion: Science in a Time of Crisis

The speed of the COVID-19 outbreak has forced humanity to conduct research , craft policies , and make decisions at an unprecedented rate , outside of wartime .
The pandemic has highlighted and amplified some of the cracks in these processes .
I present evidence of these failings in my book , The State of Science .
COVID-19 is truly a wicked problem .
Because of its contradictory , incomplete , intertwined , and rapidly changing components , the pandemic seems resistant to resolution .
Epidemiologists have been predicting and preparing for a viral outbreak such as COVID-19 for many @ @ @ @ @ @ @ can act as viral mixing bowls ; increased world travel ; and population density have made a pandemic pretty much inevitable .
Despite this , we weren ’ t ready .
The combined budgets of federal agencies that might have funded and conducted research to better prepare the US for this situation—specifically the National Institutes of Health and the National Science Foundation—are only 7 percent of what the United States spends on defense .
The country was prepared for terrorist attacks and war , but not SARS-CoV-2 , the virus that causes COVID-19 @ @ @ @ @ @ @ pandemic has highlighted not only the lack of scientific knowledge among elected officials , but the devaluation of scientific expertise , as well as the consequences of budget cuts in government science agencies , including the Centers for Disease Control and Prevention .
A whole section of my latest book , The State of Science , is devoted to “ bad science , ” which is research mispresented for personal or political gain .
During the pandemic , it has been more important than ever to get peer-reviewed information out quickly .
But @ @ @ @ @ @ @ quick turnaround times .
The researchers most qualified to review virology , epidemiology , and modeling papers are working on COVID-19 projects and don ’ t have time to review papers .
Preprint servers should have filled the void , but they were swamped by COVID-19 submissions .
As the crisis grew initially , everyone was an expert , everyone wanted a slice of the pie , and there weren ’ t enough experts doing thorough quality control .
These conditions resulted in a breeding ground for bad science and misinformation .
The @ @ @ @ @ @ @ 1991 to more than 1.6 billion in 2018 .
We have instant access to more news and information than ever before .
Neighborhood gossip has been magnified by websites and social media .
Manlio De Domenico is the head of the Complex Multilayer Networks Research Unit at the Bruno Kessler Foundation in Trento , Italy .
He and his colleagues used machine learning to analyze more than 112 million COVID-related tweets in 64 languages About 30 percent of those posts were from “ unreliable ” sources , as defined by nine publicly available @ @ @ @ @ @ @ unreliable and low-quality information preceded the arrival of the epidemic , exposing countries to irrational social behavior and serious threats to public health .
De Domenico ’ s team also tracked the level of misinformation rising exponentially and then , in some countries , falling as the pandemic progressed .
In places where misinformation eventually decreased , local leaders tended to play their part and stop spreading misinformation themselves .
For example , German Chancellor Angela Merkel , who holds a doctorate in quantum chemistry , has gained her nation ’ s trust @ @ @ @ @ @ @ publicly on the expertise of a handful of qualified experts .
US President Donald Trump , French President Emmanuel Macron , and UK Prime Minister Boris Johnson have not done the same .
The COVID-19 pandemic has resulted in an increased focus on science , which ironically has an associated risk of further eroding the public ’ s trust in science , especially amongst those who do not understand the nonlinear , consensus-establishing nature of scientific research .
Today ’ s high-profile expert assertions can be disproven by tomorrow ’ s events , @ @ @ @ @ @ @ science .
This is how science works .
Epidemiological models , like climate models , are mathematical tools designed to predicted the probability ( with large error bars ) of certain outcomes under a prescribed set of conditions and assumptions .
They are not crystal balls .
When asked what keeps him awake at night , virologist Christian Drosten recently told The Guardian about something he calls the “ prevention paradox.
” If social distancing works and the curve is flattened people will ask : “ Why did we close businesses ?
Why @ @ @ @ @ @ @ use this argument when they claim that the low rates of diseases that are vaccinated against are evidence that the vaccine wasn ’ t needed in the first place .
If all of our mitigation efforts and preventive actions work , the outcome is that we don ’ t get sick .
But not being sick was the state we were in before we took those actions , so it could appear as if science did nothing .
If science works to stem the spread and toll of COVID-19 , will it reflect @ @ @ @ @ @ @ the public ’ s eyes ?
To mitigate COVID-19 resurgence and to prevent future pandemics , trust in science and global cooperation is essential .
The US ’ s decision to withdraw from the World Health Organization , along with similarly isolating policy decisions , are not going to help .
It will just antagonize our allies , which may further weaken our medical supply chains and endanger our epidemiological early warning systems .
The reckless COVID-19 blame-game and associated political machinations are endangering US-China cooperation and America ’ s influence overseas at @ @ @ @ @ @ @ inquiry is desperately required to deal with the virus .
Marc Zimmer is the Jean C. Tempel ’ 65 Professor of Chemistry at Connecticut College .
Read an excerpt of The State of Science .

Epidemiologists have been predicting and preparing for a viral outbreak such as COVID-19 for many years. Live animal markets, which can act as viral mixing bowls; increased world travel; and population density have made a pandemic pretty much inevitable. Despite this, we weren’t ready. The combined budgets of federal agencies that might have funded and conducted research to better prepare the US for this situation—specifically the National Institutes of Health and the National...
The speed of the COVID-19 outbreak has forced humanity to conduct research, craft policies, and make decisions at an unprecedented rate, outside of wartime. The pandemic has highlighted and amplified some of the cracks in these processes. I present evidence of these failings in my book, The State of Science. COVID-19 is truly a wicked problem. Because of its contradictory, incomplete, intertwined, and rapidly changing components, the pandemic seems resistant to resolution.
A whole section of my latest book, The State of Science, is devoted to “bad science,” which is research mispresented for personal or political gain. During the pandemic, it has been more important than ever to get peer-reviewed information out quickly. But the peer-review process is not designed for quick turnaround times. The researchers most qualified to review virology, epidemiology, and modeling papers are working on COVID-19 projects and don’t have time to review papers. Preprint servers should have filled the void, but they were swamped by COVID-19 submissions. As the crisis grew initially, everyone was an expert, everyone wanted a slice of the pie, and there weren’t enough experts doing thorough quality control. These conditions resulted in a breeding ground for bad science and misinformation.
The internet has grown from one website in 1991 to more than 1.6 billion in 2018. We have instant access to more news and information than ever before. Neighborhood gossip has been magnified by websites and social media. Manlio De Domenico is the head of the Complex Multilayer Networks Research Unit at the Bruno Kessler Foundation in Trento, Italy. He and his colleagues used machine learning to analyze more than 112 million COVID-related tweets in 64 languages About 30 percent of those posts were from “unreliable” sources, as defined by nine publicly available databases such as MediaBias/FactCheck. Waves of unreliable and low-quality information preceded the arrival of the epidemic, exposing countries to irrational social behavior and serious threats to public health. De Domenico’s team also tracked the level of misinformation rising exponentially and then, in some countries, falling as the pandemic progressed. In places where misinformation eventually decreased, local leaders tended to play their part and stop spreading misinformation themselves. For example, German Chancellor Angela Merkel, who holds a doctorate in quantum chemistry, has gained her nation’s trust. She has relied heavily and very publicly on the expertise of a handful of qualified experts. US President Donald Trump, French President Emmanuel Macron, and UK Prime Minister Boris Johnson have not done the same.
The COVID-19 pandemic has resulted in an increased focus on science, which ironically has an associated risk of further eroding the public’s trust in science, especially amongst those who do not understand the nonlinear, consensus-establishing nature of scientific research. Today’s high-profile expert assertions can be disproven by tomorrow’s events, but this is not a shortcoming of science. This is how science works. Epidemiological models, like climate models, are mathematical tools designed to predicted the probability (with large error bars) of certain outcomes under a prescribed set of conditions and assumptions. They are not crystal balls.
When asked what keeps him awake at night, virologist Christian Drosten recently told The Guardian about something he calls the “prevention paradox.” If social distancing works and the curve is flattened people will ask: “Why did we close businesses? Why did we overreact?” Anti-vaxxers commonly use this argument when they claim that the low rates of diseases that are vaccinated against are evidence that the vaccine wasn’t needed in the first place. If all of our mitigation efforts and preventive actions work, the outcome is that we don’t get sick. But not being sick was the state we were in before we took those actions, so it could appear as if science did nothing. If science works to stem the spread and toll of COVID-19, will it reflect badly on science, at least in the public’s eyes?
To mitigate COVID-19 resurgence and to prevent future pandemics, trust in science and global cooperation is essential. The US’s decision to withdraw from the World Health Organization, along with similarly isolating policy decisions, are not going to help. It will just antagonize our allies, which may further weaken our medical supply chains and endanger our epidemiological early warning systems. The reckless COVID-19 blame-game and associated political machinations are endangering US-China cooperation and America’s influence overseas at a time when global cooperation in scientific inquiry is desperately required to deal with the virus.
Marc Zimmer is the Jean C. Tempel ’65 Professor of Chemistry at Connecticut College. Read an excerpt of The State of Science.


thescientist--2020-08-17--Characteristics that Give Viruses Pandemic Potential

Even before COVID-19 swept across the globe this year , coronaviruses were on scientists ’ radar as pathogens that could one day ignite a pandemic .
They ’ d threatened to before—in 2002–03 , the SARS virus infected 8,000 people in more than two dozen countries and killed almost 800—and they checked off several specific boxes that emerging infectious disease specialists worry about in a virus .
But they ’ re not the only group of viruses that researchers are concerned about .
Influenza and a handful of other viruses have long been viewed as pandemic threats .
One aspect @ @ @ @ @ @ @ is having an RNA , rather than DNA , genome .
That ’ s because the process of copying RNA typically doesn ’ t include a proofreader like DNA replication does , and so RNA viruses have higher mutation rates than the DNA variety .
“ This means they can change and become more adaptable to human infection and human transmission , ” says Steve Luby , an epidemiologist at Stanford University .
Researchers on the lookout for dangerous pathogens also pay close attention to viruses with track records of leaping from animals @ @ @ @ @ @ @ Ebola , and HIV all originated in animals , as Luby estimates that 80 percent of our most devastating infections did .
Once a virus makes the zoonotic leap from animals to humans , it must then transmit from one person to the next if it is to cause an epidemic .
In this respect , SARS-CoV-2 seems to outperform the original and deadlier SARS coronavirus , MERS coronavirus , and some bird flu strains .
But these less-transmissible viruses could always acquire some new mutation that revs up their R0 , the @ @ @ @ @ @ @ person , increasing their potential to spread rapidly through human populations , says Raina Plowright , an infectious disease researcher at Montana State University .
How a virus is transmitted is yet another consideration when evaluating its pandemic potential .
The most concerning situation is when a virus can spread through respiratory droplets , allowing it to jump from person to person through close interactions , as is the case for the seasonal flu and also SARS-CoV-2 .
“ An RNA virus that causes respiratory tract infections can evolve into something we haven @ @ @ @ @ @ @ , ” says Ralph Baric , a virologist at the University of North Carolina , Chapel Hill .
Measles , an RNA paramyxovirus spread through respiratory secretions , is perhaps the most contagious disease known in humans .
As the world continues to grapple with SARS-CoV-2 , The Scientist asked virologists to rank viruses with the greatest potential to cause a future pandemic .
Three answers routinely popped up : influenza , coronaviruses , and paramyxoviruses , a large family of viruses that includes mumps and respiratory syncytial virus ( RSV ) , @ @ @ @ @ @ @ researchers say poses the biggest pandemic threat among them .
“ There are lots of concerns to keep communicable disease epidemiologists up at night , ” says Luby .
Prior to the SARS-CoV-2 outbreak , most virologists rated influenza as the most likely agent to trigger a deadly pandemic .
The 1918 flu pandemic caused an estimated 50 million to 100 million deaths over two years , and there have been three flu pandemics since—in 1957–58 , in 1968 , and most recently in 2009 .
Influenza is an RNA virus and thus @ @ @ @ @ @ @ new seasonal flu vaccine each year .
Virologists classify influenza strains according to two surface proteins : the hemagglutinin ( H ) protein that binds to a receptor on target cells and the neuraminidase ( N ) protein that virus particles use to escape host cells .
There are 18 hemagglutinin subtypes and 11 neuraminidase subtypes .
It ’ s likely that all permutations occur influenza viruses that affect in influenza viruses that affect birds but only a handful have cropped up in those that infect people .
“ Over the last one @ @ @ @ @ @ @ had pandemics and seasonal epidemics caused by only three of the eighteen H subtypes and two of the eleven N subtypes , ” says virologist Kanta Subbarao , director of the World Health Organization ( WHO ) Collaborating Centre for Reference and Research on Influenza in Melbourne .
From time to time , influenza viruses in ducks and shorebirds spill over to infect domestic poultry and sometimes pigs .
The H protein is critical .
Concern mounts whenever the H protein of a bird flu virus gains the ability to infect human cells @ @ @ @ @ @ @ to humans , introducing people to a new strain with avian proteins to which they have little or no immunity .
So far , says Luby , “ the H7N9 and H5N1 viruses still primarily connect to the cellular receptors in birds , but sometimes they infect people and cause serious disease.
” The concern is that some of the viruses with killer characteristics might change in a way that allows them to more easily spread from person to person .
Indeed , influenza has a radical way to shapeshift .
Its RNA @ @ @ @ @ @ @ When two different subtypes of virus , be they bird or mammalian strains , are in one cell , viral segments can be shuffled to create entirely new strains .
Pigs are suspected to be ideal viral melting pots .
“ Pigs carry similar receptors to humans , and they can be infected by avian and mammalian viruses , ” says Subbarao .
“ The 1957 and 1968 flu pandemics were caused by reassortant viruses , with some gene segments from avian influenza viruses and other segments from circulating human flu viruses .
@ @ @ @ @ @ @ mixing ] happened in an intermediate host , possibly pigs.
” The WHO has a constellation of national labs to watch for emerging strains of flu , and now collaborates closely with the World Organisation for Animal Health .
“ We want to pick up any novel influenza viruses in animals , ” Subbarao explains .
Scientists recently became concerned , for example , when a swine influenza variant of H1N1 , called G4 , circulating in pigs was shown to be able to infect and replicate in human epithelial cells .
The @ @ @ @ @ @ @ that caused the 2009 flu pandemic .
Pandemic pathogens are rare , however , and are by their nature difficult to predict .
“ We do know there are some things we should worry about , ” Luby says , yet “ we tend to get caught off guard.
” Both the SARS and MERS coronaviruses are deadlier than SARS-CoV-2 .
Fortunately , human-to-human transmission of SARS and MERS is relatively low .
But there is a tremendous diversity of coronaviruses in bat species .
They mostly infect the gut , but can @ @ @ @ @ @ @ After the SARS outbreak in 2002–03 , scientists searched for coronaviruses in bats in Chinese caves and found a trove of them in common insectivorous species .
Moreover , antibodies identified in the blood of people in southern China suggest that some human populations are routinely exposed to bat coronaviruses .
This gives the viruses ample opportunity to adapt to people .
Harbingers of coronaviruses ’ propensity to jump to new species are the lethal outbreaks that often occur on farms .
Three devastating swine coronavirus strains have emerged in pigs in the @ @ @ @ @ @ @ viruses are on the move , ” says Baric .
He worries that we have “ toggled on a switch ” to promote coronavirus emergence from animal reservoirs into other mammalian species , including ourselves .
This is mostly linked to human behavior , such as consumption and farming of wild animals in certain countries .
“ Markets where lots of animals are in cages together can mean more animal transmission and more humans getting infected , ” says Luby , who says he believes China should close all its wet markets .
@ @ @ @ @ @ @ first SARS outbreak are not the first we have experienced .
MERS coronavirus seems to have been in camels for decades , occasionally infecting people .
It has now caused 2,400 cases , mostly in the Arabian Peninsula .
Some virologists say that the coronaviruses that are now endemic in people , causing common cold symptoms , may have sparked deadly pandemics when they first made the jump from animals to humans .
The OC43 coronavirus , for example , seems to have come from bats via cattle and there is evidence that @ @ @ @ @ @ @ , says Baric .
Now , with the ongoing COVID-19 pandemic , some researchers rank coronaviruses as the biggest threat .
“ I ’ d put coronavirus ahead of flu , ” says Luby .
“ It demonstrated higher case fatality—not with SARS-CoV-2 , but we have seen it with SARS and MERS , ” and it looks like the live markets in China are allowing coronaviruses associated with bats to spread to other mammals .
“ Our immediate highest risk is coronaviruses.
” In 1994 , a mysterious disease broke out in @ @ @ @ @ @ @ Australia , called Hendra .
Twenty-one horses fell severely ill from a pathogen that was soon named Hendra virus .
Then , a vet attending to the sick horses died from the virus , whose origin was traced to fruit bats in the genus Pteropus ( aka , flying foxes ) .
Four years later , a related virus called Nipah virus was identified as the cause of an outbreak among pig farmers in Malaysia .
Two million infected pigs were slaughtered , halting the outbreak .
In 2001 , researchers realized that @ @ @ @ @ @ @ each year in Bangladesh , primarily from people drinking the sap of date trees that was contaminated with bat urine .
But there didn ’ t appear to be human-to-human transmission .
In 2018 , however , an outbreak in southern India suggested that human-to-human transmission of Nipah virus was possible through close contact .
A 27-year-old villager , who may have contracted the virus from fruit contaminated by bat saliva or urine , was admitted to the hospital in Kerala state and infected nine other people , including fellow patients , visiting @ @ @ @ @ @ @ was referred to another hospital , where more patients and medical workers were infected .
Twenty-one of the 23 infected people died from severe respiratory sickness and/or brain inflammation .
“ One reason it doesn ’ t take off is because it makes people so sick so quickly that they tend to be hospitalized and isolated , ” says Plowright , who studies bats and Nipah virus outbreaks .
But Nipah virus ’ s fatality rate of between 50 percent and 100 percent is exactly what makes it such a concern .
Nipah @ @ @ @ @ @ @ paramyxoviruses now called henipavirus , and there are many more strains harbored in flying foxes in Asia , Oceania , and Africa , says Plowright .
Although henipaviruses have not yet caused widespread outbreaks in people , other paramyxoviruses , such as measles and mumps , have .
“ Some of these viruses spread really well , ” says Rebecca Dutch , a molecular biologist at the University of Kentucky .
If Nipah moved efficiently from one person to another , perhaps mutating so it transmits before making someone really sick , “ @ @ @ @ @ @ @ Luby , “ more like the Black Plague.
” Viruses that did not top the list but still demand attention are filoviruses such as Ebola and Marburg virus , which cause hemorrhagic fever and can infect apes , monkeys , and bats , in addition to humans .
“ The fact that Ebola requires blood or body fluids to be transmitted means that it is harder to transmit and so less likely to be a global threat , ” explains Luby .
And as with Nipah virus infections , people get sick quickly @ @ @ @ @ @ @ a filovirus to cause a pandemic , it would need to be transmissible in respiratory form or spread readily in diarrhea , experts say , and it ’ s not yet clear how easily that might happen .
“ The big question is , what is the diversity of the Ebola viruses in nature ?
” says Baric .
Other viruses that scientists are keeping tabs on include those in the Bunyavirus and Arenavirus families , which primarily infect rodents , and mosquito-transmitted dengue , Zika virus , and West Nile virus .
@ @ @ @ @ @ @ infect two billion people , ” says Baric , “ but if you are in the northern latitudes it may be low risk for you.
” As the geographical range of mosquitoes spreads to higher latitudes with climate change , however , so too will the diversity of the pathogens they carry .
There is also “ disease X.
” The WHO uses this term to acknowledge that a serious epidemic could be caused by a pathogen currently unknown to cause human disease .
But studying an undescribed pathogen is a tall order @ @ @ @ @ @ @ , those who study coronaviruses had trouble getting anyone to fund their research , ” says Dutch .
“ There certainly could be things out there we don ’ t know about.
” Experts warn that humans are creating conditions for more viral spillover events by disrupting natural habitats and by packing different wild animals together in wildlife markets .
“ We are creating the perfect storm for new viruses to emerge , ” says Plowright , who recently coauthored a review on bat-borne virus diversity , spillover , and emergence .
Despite @ @ @ @ @ @ @ unable to accurately forecast future outbreaks , she adds .
“ No one predicted that a flu pandemic [ 2009 ] would come from pigs in Mexico , ” says Plowright .
“ We have to keep an open mind as to what the next pathogen outbreak is going to be.
” But researchers are hopeful that our experience with COVID-19 will turn the tide of pandemic preparedness .
As Luby says , “ I anticipate there will be more attention to these threats.
” Viruses that Threaten to Spark Another Pandemic

ABOVE: © ISTOCK.COM, DKOSIG
Even before COVID-19 swept across the globe this year, coronaviruses were on scientists’ radar as pathogens that could one day ignite a pandemic. They’d threatened to before—in 2002–03, the SARS virus infected 8,000 people in more than two dozen countries and killed almost 800—and they checked off several specific boxes that emerging infectious disease specialists worry about in a virus. But they’re not the only group of viruses that researchers are concerned about. Influenza and a handful of other viruses have long been viewed as pandemic threats.
One aspect that signals pandemic potential in a virus is having an RNA, rather than DNA, genome. That’s because the process of copying RNA typically doesn’t include a proofreader like DNA replication does, and so RNA viruses have higher mutation rates than the DNA variety. “This means they can change and become more adaptable to human infection and human transmission,” says Steve Luby, an epidemiologist at Stanford University.
Researchers on the lookout for dangerous pathogens also pay close attention to viruses with track records of leaping from animals to people. Smallpox, measles, Ebola, and HIV all originated in animals, as Luby estimates that 80 percent of our most devastating infections did.
An RNA virus that causes respiratory tract infections can evolve into something we haven’t seen before and spread rapidly. —Ralph Baric, University of North Carolina, Chapel Hill
Once a virus makes the zoonotic leap from animals to humans, it must then transmit from one person to the next if it is to cause an epidemic. In this respect, SARS-CoV-2 seems to outperform the original and deadlier SARS coronavirus, MERS coronavirus, and some bird flu strains. But these less-transmissible viruses could always acquire some new mutation that revs up their R0, the expected number of infections caused by one person, increasing their potential to spread rapidly through human populations, says Raina Plowright, an infectious disease researcher at Montana State University.
How a virus is transmitted is yet another consideration when evaluating its pandemic potential. The most concerning situation is when a virus can spread through respiratory droplets, allowing it to jump from person to person through close interactions, as is the case for the seasonal flu and also SARS-CoV-2. “An RNA virus that causes respiratory tract infections can evolve into something we haven’t seen before and spread rapidly,” says Ralph Baric, a virologist at the University of North Carolina, Chapel Hill. Measles, an RNA paramyxovirus spread through respiratory secretions, is perhaps the most contagious disease known in humans.
As the world continues to grapple with SARS-CoV-2, The Scientist asked virologists to rank viruses with the greatest potential to cause a future pandemic. Three answers routinely popped up: influenza, coronaviruses, and paramyxoviruses, a large family of viruses that includes mumps and respiratory syncytial virus (RSV), as well as Nipah virus, which researchers say poses the biggest pandemic threat among them. “There are lots of concerns to keep communicable disease epidemiologists up at night,” says Luby.
Influenza
Prior to the SARS-CoV-2 outbreak, most virologists rated influenza as the most likely agent to trigger a deadly pandemic. The 1918 flu pandemic caused an estimated 50 million to 100 million deaths over two years, and there have been three flu pandemics since—in 1957–58, in 1968, and most recently in 2009.
Influenza is an RNA virus and thus prone to mutation, which necessitates a new seasonal flu vaccine each year. Virologists classify influenza strains according to two surface proteins: the hemagglutinin (H) protein that binds to a receptor on target cells and the neuraminidase (N) protein that virus particles use to escape host cells. There are 18 hemagglutinin subtypes and 11 neuraminidase subtypes. It’s likely that all permutations occur influenza viruses that affect in influenza viruses that affect birds but only a handful have cropped up in those that infect people. “Over the last one hundred or so years, we have had pandemics and seasonal epidemics caused by only three of the eighteen H subtypes and two of the eleven N subtypes,” says virologist Kanta Subbarao, director of the World Health Organization (WHO) Collaborating Centre for Reference and Research on Influenza in Melbourne.
From time to time, influenza viruses in ducks and shorebirds spill over to infect domestic poultry and sometimes pigs. The H protein is critical. Concern mounts whenever the H protein of a bird flu virus gains the ability to infect human cells. This allows the virus to jump to humans, introducing people to a new strain with avian proteins to which they have little or no immunity. So far, says Luby, “the H7N9 and H5N1 viruses still primarily connect to the cellular receptors in birds, but sometimes they infect people and cause serious disease.”
The concern is that some of the viruses with killer characteristics might change in a way that allows them to more easily spread from person to person. Indeed, influenza has a radical way to shapeshift. Its RNA genome is split into eight segments. When two different subtypes of virus, be they bird or mammalian strains, are in one cell, viral segments can be shuffled to create entirely new strains. Pigs are suspected to be ideal viral melting pots. “Pigs carry similar receptors to humans, and they can be infected by avian and mammalian viruses,” says Subbarao. “The 1957 and 1968 flu pandemics were caused by reassortant viruses, with some gene segments from avian influenza viruses and other segments from circulating human flu viruses. It is long proposed that this [mixing] happened in an intermediate host, possibly pigs.”
The WHO has a constellation of national labs to watch for emerging strains of flu, and now collaborates closely with the World Organisation for Animal Health. “We want to pick up any novel influenza viruses in animals,” Subbarao explains. Scientists recently became concerned, for example, when a swine influenza variant of H1N1, called G4, circulating in pigs was shown to be able to infect and replicate in human epithelial cells. The virus carries genes from the H1N1 subtype that caused the 2009 flu pandemic.
Pandemic pathogens are rare, however, and are by their nature difficult to predict. “We do know there are some things we should worry about,” Luby says, yet “we tend to get caught off guard.”
Coronavirus
Both the SARS and MERS coronaviruses are deadlier than SARS-CoV-2. Fortunately, human-to-human transmission of SARS and MERS is relatively low. But there is a tremendous diversity of coronaviruses in bat species. They mostly infect the gut, but can replicate in lung tissue as well. After the SARS outbreak in 2002–03, scientists searched for coronaviruses in bats in Chinese caves and found a trove of them in common insectivorous species. Moreover, antibodies identified in the blood of people in southern China suggest that some human populations are routinely exposed to bat coronaviruses. This gives the viruses ample opportunity to adapt to people.
Harbingers of coronaviruses’ propensity to jump to new species are the lethal outbreaks that often occur on farms. Three devastating swine coronavirus strains have emerged in pigs in the last couple of decades. “These viruses are on the move,” says Baric. He worries that we have “toggled on a switch” to promote coronavirus emergence from animal reservoirs into other mammalian species, including ourselves. This is mostly linked to human behavior, such as consumption and farming of wild animals in certain countries. “Markets where lots of animals are in cages together can mean more animal transmission and more humans getting infected,” says Luby, who says he believes China should close all its wet markets.
Our immediate highest risk is coronaviruses. —Steve Luby, Stanford University
The current coronavirus pandemic along with the first SARS outbreak are not the first we have experienced. MERS coronavirus seems to have been in camels for decades, occasionally infecting people. It has now caused 2,400 cases, mostly in the Arabian Peninsula. Some virologists say that the coronaviruses that are now endemic in people, causing common cold symptoms, may have sparked deadly pandemics when they first made the jump from animals to humans. The OC43 coronavirus, for example, seems to have come from bats via cattle and there is evidence that it caused a pandemic in the 1890s, says Baric.
Now, with the ongoing COVID-19 pandemic, some researchers rank coronaviruses as the biggest threat. “I’d put coronavirus ahead of flu,” says Luby. “It demonstrated higher case fatality—not with SARS-CoV-2, but we have seen it with SARS and MERS,” and it looks like the live markets in China are allowing coronaviruses associated with bats to spread to other mammals. “Our immediate highest risk is coronaviruses.”
Nipah virus
In 1994, a mysterious disease broke out in horses in a suburb of Brisbane, Australia, called Hendra. Twenty-one horses fell severely ill from a pathogen that was soon named Hendra virus. Then, a vet attending to the sick horses died from the virus, whose origin was traced to fruit bats in the genus Pteropus (aka, flying foxes). Four years later, a related virus called Nipah virus was identified as the cause of an outbreak among pig farmers in Malaysia. Two million infected pigs were slaughtered, halting the outbreak. In 2001, researchers realized that outbreaks of Nipah virus in people happened each year in Bangladesh, primarily from people drinking the sap of date trees that was contaminated with bat urine. But there didn’t appear to be human-to-human transmission.
In 2018, however, an outbreak in southern India suggested that human-to-human transmission of Nipah virus was possible through close contact. A 27-year-old villager, who may have contracted the virus from fruit contaminated by bat saliva or urine, was admitted to the hospital in Kerala state and infected nine other people, including fellow patients, visiting relatives, and medical staff. He was referred to another hospital, where more patients and medical workers were infected. Twenty-one of the 23 infected people died from severe respiratory sickness and/or brain inflammation. “One reason it doesn’t take off is because it makes people so sick so quickly that they tend to be hospitalized and isolated,” says Plowright, who studies bats and Nipah virus outbreaks. But Nipah virus’s fatality rate of between 50 percent and 100 percent is exactly what makes it such a concern.
Nipah and Hendra belong to a group of paramyxoviruses now called henipavirus, and there are many more strains harbored in flying foxes in Asia, Oceania, and Africa, says Plowright. Although henipaviruses have not yet caused widespread outbreaks in people, other paramyxoviruses, such as measles and mumps, have. “Some of these viruses spread really well,” says Rebecca Dutch, a molecular biologist at the University of Kentucky. If Nipah moved efficiently from one person to another, perhaps mutating so it transmits before making someone really sick, “this would be devasting,” says Luby, “more like the Black Plague.”
Other potential threats
Viruses that did not top the list but still demand attention are filoviruses such as Ebola and Marburg virus, which cause hemorrhagic fever and can infect apes, monkeys, and bats, in addition to humans. “The fact that Ebola requires blood or body fluids to be transmitted means that it is harder to transmit and so less likely to be a global threat,” explains Luby. And as with Nipah virus infections, people get sick quickly and thus are isolated early. For a filovirus to cause a pandemic, it would need to be transmissible in respiratory form or spread readily in diarrhea, experts say, and it’s not yet clear how easily that might happen. “The big question is, what is the diversity of the Ebola viruses in nature?” says Baric.
Other viruses that scientists are keeping tabs on include those in the Bunyavirus and Arenavirus families, which primarily infect rodents, and mosquito-transmitted dengue, Zika virus, and West Nile virus. “Vector-borne pathogens have the potential to infect two billion people,” says Baric, “but if you are in the northern latitudes it may be low risk for you.” As the geographical range of mosquitoes spreads to higher latitudes with climate change, however, so too will the diversity of the pathogens they carry.
There is also “disease X.” The WHO uses this term to acknowledge that a serious epidemic could be caused by a pathogen currently unknown to cause human disease. But studying an undescribed pathogen is a tall order. “Until SARS emerged in 2002, those who study coronaviruses had trouble getting anyone to fund their research,” says Dutch. “There certainly could be things out there we don’t know about.”
Experts warn that humans are creating conditions for more viral spillover events by disrupting natural habitats and by packing different wild animals together in wildlife markets. “We are creating the perfect storm for new viruses to emerge,” says Plowright, who recently coauthored a review on bat-borne virus diversity, spillover, and emergence. Despite this, the scientific community is largely unable to accurately forecast future outbreaks, she adds. “No one predicted that a flu pandemic [2009] would come from pigs in Mexico,” says Plowright. “We have to keep an open mind as to what the next pathogen outbreak is going to be.”
But researchers are hopeful that our experience with COVID-19 will turn the tide of pandemic preparedness. As Luby says, “I anticipate there will be more attention to these threats.”


thescientist--2020-08-17--Table: Viruses that Threaten to Spark Another Pandemic

Water birds , poultry , and domestic pigs .
Some outbreaks in dogs and horses .
Huge diversity in insectivorous @ @ @ @ @ Horseshoe bats ( genus Rhinolophus ) in Southeast Asia harbor SARS-like coronaviruses .
Four “ @ @ @ @ @ have origins in bats , possibly in last few centuries .
SARS caused an outbreak @ @ @ @ @ to infect people , presumably jumping from camels .
Numerous pandemics throughout human history were @ @ @ @ @ Confirmed flu pandemics include the devastating 1918 pandemic , as well as pandemics in 1957–58 @ @ @ @ @ .
Hendra virus infected horses and people first in 1994 .
Nipah virus first recorded @ @ @ @ @ 1998 .

Water birds, poultry, and domestic pigs. Some outbreaks in dogs and horses.
Huge diversity in insectivorous bats and fruit-eating bats. Horseshoe bats (genus Rhinolophus) in Southeast Asia harbor SARS-like coronaviruses.
Spillover history
Four “common cold” coronaviruses may have origins in bats, possibly in last few centuries. SARS caused an outbreak during 2003–04. MERS continues to infect people, presumably jumping from camels.
Numerous pandemics throughout human history were likely due to flu. Confirmed flu pandemics include the devastating 1918 pandemic, as well as pandemics in 1957–58, 1969, and 2009.


thescientist--2020-08-17--The Push to Deploy At-Home Antigen Tests for COVID-19

Testing backlogs , reagent shortages , and limited access have contributed to inadequate testing for COVID-19 in the US and elsewhere .
But in recent months , new types of assay that promise to offer quicker , cheaper , and more user-friendly features have begun to roll out .
Saliva tests , for one , are gaining traction as screening tools for universities and professional basketball teams .
Antigen testing is another approach that , if given regulators ’ blessings , might give consumers the ability to take their own tests at home and get results on the spot .
@ @ @ @ @ @ @ gain regulatory approval and bring products like this to market in huge numbers .
“ This is like a wartime effort , there are many fronts that we ’ re trying to fight this disease , ” says Stephen Tang , president and CEO of OraSure , which is working on a test that members of the public could take themselves .
The firm plans to manufacture millions of antigen tests annually .
Results from such tests can be available in less than an hour and the fact that people could take them @ @ @ @ @ @ @ could be a game-changer in fighting the pandemic .
“ These simple tools can bring a sense of normalcy and security back to society , ” rapid test advocate and Harvard epidemiologist Michael Mina tweeted August 12 .
There is also potential for high-throughput antigen tests to be used in lab settings as well , to speed up mass testing across whole countries or regions .
In essence , antigen tests are the reverse of antibody tests .
In the latter , viral proteins , the antigens , are distributed across a plate @ @ @ @ @ @ @ individual ’ s blood sample contains antibodies against SARS-CoV-2 , those antibodies will bind to the antigens , triggering an emission of light or color change , indicating a positive result .
Antigen tests , in contrast , contain antibodies on the plate instead .
These are just like those generated naturally by people and animals to fight off a COVID-19 infection .
When a sample , usually a nasal swab , containing virus particles is applied to the assay , the antibodies bind to the viral antigens and similarly trigger a visible @ @ @ @ @ @ @ infected .
Compared to PCR and antibody tests , antigen tests take a bit longer to develop because manufacturers have to be sure that they have identified the ideal antibodies that bind to SARS-CoV-2 and not to proteins from other viruses or microbes .
Then the production of those antibodies using animal models is scaled up .
At least two firms , Quidel and BD , have already obtained Emergency Use Authorization ( EUA ) from the US Food and Drug Administration ( FDA ) for antigen tests designed to be administered by @ @ @ @ @ @ @ sensitivity of its test—the extent to which true positives are detected—is 96.7 percent .
In BD ’ s case , the reported sensitivity is 84 percent .
Both firms claim their tests have a specificity of 100 percent , meaning the tests should produce no false positives .
But earlier this month , Ohio Governor Mike DeWine tested positive on a Quidel antigen test only for three subsequent PCR tests to show he was in fact negative for SARS-CoV-2 infection .
“ We take the issue regarding Governor DeWine very seriously and we @ @ @ @ @ @ @ Management System , trying to learn the specifics of the issue in order to get to the root cause .
At this time , there is nothing to suggest that there is a problem with the Sofia® 2 instrument or the Sofia SARS Antigen FIA rapid test , ” a spokeswoman for Quidel wrote in an email to The Scientist .
The World Health Organization ( WHO ) does not currently recommend antigen tests for clinical diagnosis because there is not enough data to support their accuracy .
In fact , based on @ @ @ @ @ @ @ other respiratory infections such as influenza , the WHO says the sensitivity of antigen tests for COVID-19 could lie between 34 percent and 80 percent , far below the performance of traditional PCR-based diagnostics for SARS-CoV-2 infection .
This has not stopped India , to name one country , using antigen tests en masse .
Health providers there have used antigen tests for months now to screen many thousands of people .
And in July , authorities approved a new rapid antigen test developed by Indian firm MyLab Discovery Solutions .
It is @ @ @ @ @ @ @ 6 per test .
Only a few North American companies developing at-home rapid antigen tests have released validation results so far but Sona Nanotech is one of them .
CEO Darren Rowles says that in evaluations using about 30 different viruses , bacteria , and fungi , the antibodies selected by Sona Nanotech only formed a successful bond with SARS-CoV-2 and SARS-CoV , the original SARS virus that emerged in 2002 .
Antigen test developers can decide to target a particular type of protein on the virus .
“ In our instance , @ @ @ @ @ @ @ proteins on the surface , ” says Rowles .
Quidel ’ s and BD ’ s antigen tests , in contrast , target the nucleocapsid ( N ) protein .
In lab experiments using 30 swab samples from healthy individuals , the Sona Nanotech test correctly identified 29 of the samples as negative .
The SARS-CoV-2 virus was then artificially added to these 29 samples and the test subsequently identified 28 as positive .
The company has not yet reported the results of studies in the field using a mix of positive and @ @ @ @ @ @ @ are published , Rowles says , the firm hopes to apply for EUA from Health Canada and the FDA .
“ The idea is for healthcare workers to be taking it first and then some modifications to the test platform to allow at-home use , ” he explains .
Various other firms are vying with Sona Nanotech to become the next to achieve EUA for their tests , including E25Bio , Iceni Diagnostics and OraSure .
OraSure ’ s at-home test will require the user to perform a quick nasal swab and then @ @ @ @ @ @ @ which itself will function very much like a pregnancy test , says Tang .
“ You can read the test in under an hour , ” he explains .
“ It reads as a control line and a test line so if there are two lines present , you are coronavirus positive and should seek to self-isolate yourself.
” OraSure has not published any validation data for its tests yet but the firm has committed to manufacturing them in large volumes if EUA is granted .
The company recently announced that it would @ @ @ @ @ @ @ help increase capacity .
“ We ’ re going to devote a considerable amount of that capacity to COVID-19 , ” says Tang .
There are real benefits to increasing the availability of tests for COVID-19 , says biomedical scientist David Grenache , the chief scientific officer at TriCore Reference Laboratories .
“ By deploying more antigen tests that can be done rapidly , we will increase the likelihood that we ’ ll detect infected individuals , ” says Grenache , who is not involved in the development of antigen tests himself .
@ @ @ @ @ @ @ consider .
“ There ’ s always concern about patients doing their own tests because they ’ re not trained in laboratory techniques , ” says Grenache .
Inadequate swabbing could mean an inaccurate result .
And then there are politics .
Because mask-wearing has become a politicized issue in the United States , he notes , the uptake of at-home antigen tests might not be spread evenly across all parts of society .
Antigen tests may also struggle to correctly identify people as positive if they have lower levels of the virus @ @ @ @ @ @ @ the latter stages of an infection when the worst of the illness is over .
That ’ s not necessarily a deal-breaker , says Eleanor Riley , an immunologist at the University of Edinburgh in the UK .
“ Very low levels of virus aren ’ t a problem because you ’ re probably not infectious , ” she says .
Riley points out that rapid antigen tests for malaria are widely used .
These are often self-administered by travelers , for example .
“ The precedent is there and those cost a @ @ @ @ @ @ @ she adds .
We ’ re still months away at the very least from having millions of at-home rapid antigen tests available for people to use .
In order for that to happen , governments would likely have to plough billions of dollars into the manufacturing of such tests .
But the other place that antigen tests could make a difference is in professional labs , which are currently processing huge numbers of PCR tests every day around the world .
Lab-based analysis of antigen tests is more sensitive than the rapid tests @ @ @ @ @ @ @ of care , Grenache says , because the light-detecting machines in a lab used to identify the reaction associated with antibody-antigen binding are much more accurate than the systems built in to self-testing kits .
And , in principle , lab-based antigen tests could be quicker to do than the PCR assays we ’ ve relied on so far .
“ Those tests will be much easier to scale up , ” says Grenache .
“ Once those are available , assuming the performance is good , that ’ s the type of @ @ @ @ @ @ @ .
”

ABOVE: © ISTOCK.COM, SHIVENDU JUAHARI
Testing backlogs, reagent shortages, and limited access have contributed to inadequate testing for COVID-19 in the US and elsewhere. But in recent months, new types of assay that promise to offer quicker, cheaper, and more user-friendly features have begun to roll out. Saliva tests, for one, are gaining traction as screening tools for universities and professional basketball teams. Antigen testing is another approach that, if given regulators’ blessings, might give consumers the ability to take their own tests at home and get results on the spot.
Several diagnostics firms are currently working to gain regulatory approval and bring products like this to market in huge numbers.
“This is like a wartime effort, there are many fronts that we’re trying to fight this disease,” says Stephen Tang, president and CEO of OraSure, which is working on a test that members of the public could take themselves. The firm plans to manufacture millions of antigen tests annually.
Results from such tests can be available in less than an hour and the fact that people could take them themselves has convinced some that antigen tests could be a game-changer in fighting the pandemic.
“These simple tools can bring a sense of normalcy and security back to society,” rapid test advocate and Harvard epidemiologist Michael Mina tweeted August 12.
There is also potential for high-throughput antigen tests to be used in lab settings as well, to speed up mass testing across whole countries or regions.
In essence, antigen tests are the reverse of antibody tests. In the latter, viral proteins, the antigens, are distributed across a plate within the test device. If an individual’s blood sample contains antibodies against SARS-CoV-2, those antibodies will bind to the antigens, triggering an emission of light or color change, indicating a positive result.
Antigen tests, in contrast, contain antibodies on the plate instead. These are just like those generated naturally by people and animals to fight off a COVID-19 infection. When a sample, usually a nasal swab, containing virus particles is applied to the assay, the antibodies bind to the viral antigens and similarly trigger a visible result to show that someone is presently infected.
Compared to PCR and antibody tests, antigen tests take a bit longer to develop because manufacturers have to be sure that they have identified the ideal antibodies that bind to SARS-CoV-2 and not to proteins from other viruses or microbes. Then the production of those antibodies using animal models is scaled up.
At least two firms, Quidel and BD, have already obtained Emergency Use Authorization (EUA) from the US Food and Drug Administration (FDA) for antigen tests designed to be administered by healthcare workers.
Quidel reports that the sensitivity of its test—the extent to which true positives are detected—is 96.7 percent. In BD’s case, the reported sensitivity is 84 percent. Both firms claim their tests have a specificity of 100 percent, meaning the tests should produce no false positives. But earlier this month, Ohio Governor Mike DeWine tested positive on a Quidel antigen test only for three subsequent PCR tests to show he was in fact negative for SARS-CoV-2 infection.
“We take the issue regarding Governor DeWine very seriously and we are investigating the matter through our Quality Management System, trying to learn the specifics of the issue in order to get to the root cause. At this time, there is nothing to suggest that there is a problem with the Sofia® 2 instrument or the Sofia SARS Antigen FIA rapid test,” a spokeswoman for Quidel wrote in an email to The Scientist.
The World Health Organization (WHO) does not currently recommend antigen tests for clinical diagnosis because there is not enough data to support their accuracy. In fact, based on the accuracy of rapid diagnostic tests for other respiratory infections such as influenza, the WHO says the sensitivity of antigen tests for COVID-19 could lie between 34 percent and 80 percent, far below the performance of traditional PCR-based diagnostics for SARS-CoV-2 infection.
This has not stopped India, to name one country, using antigen tests en masse. Health providers there have used antigen tests for months now to screen many thousands of people. And in July, authorities approved a new rapid antigen test developed by Indian firm MyLab Discovery Solutions. It is already on sale and costs roughly $6 per test.
Only a few North American companies developing at-home rapid antigen tests have released validation results so far but Sona Nanotech is one of them. CEO Darren Rowles says that in evaluations using about 30 different viruses, bacteria, and fungi, the antibodies selected by Sona Nanotech only formed a successful bond with SARS-CoV-2 and SARS-CoV, the original SARS virus that emerged in 2002.
Antigen test developers can decide to target a particular type of protein on the virus. “In our instance, it’s specific to the spike proteins on the surface,” says Rowles. Quidel’s and BD’s antigen tests, in contrast, target the nucleocapsid (N) protein.
In lab experiments using 30 swab samples from healthy individuals, the Sona Nanotech test correctly identified 29 of the samples as negative. The SARS-CoV-2 virus was then artificially added to these 29 samples and the test subsequently identified 28 as positive. The company has not yet reported the results of studies in the field using a mix of positive and negative samples from participants. Once they are published, Rowles says, the firm hopes to apply for EUA from Health Canada and the FDA.
“The idea is for healthcare workers to be taking it first and then some modifications to the test platform to allow at-home use,” he explains.
Various other firms are vying with Sona Nanotech to become the next to achieve EUA for their tests, including E25Bio, Iceni Diagnostics and OraSure.
OraSure’s at-home test will require the user to perform a quick nasal swab and then apply a solution to the swab, which itself will function very much like a pregnancy test, says Tang.
“You can read the test in under an hour,” he explains. “It reads as a control line and a test line so if there are two lines present, you are coronavirus positive and should seek to self-isolate yourself.”
OraSure has not published any validation data for its tests yet but the firm has committed to manufacturing them in large volumes if EUA is granted. The company recently announced that it would be hiring an additional 177 staff to help increase capacity.
“We’re going to devote a considerable amount of that capacity to COVID-19,” says Tang.
There are real benefits to increasing the availability of tests for COVID-19, says biomedical scientist David Grenache, the chief scientific officer at TriCore Reference Laboratories.
“By deploying more antigen tests that can be done rapidly, we will increase the likelihood that we’ll detect infected individuals,” says Grenache, who is not involved in the development of antigen tests himself.
However, there are stumbling blocks to consider. “There’s always concern about patients doing their own tests because they’re not trained in laboratory techniques,” says Grenache. Inadequate swabbing could mean an inaccurate result.
And then there are politics. Because mask-wearing has become a politicized issue in the United States, he notes, the uptake of at-home antigen tests might not be spread evenly across all parts of society.
Antigen tests may also struggle to correctly identify people as positive if they have lower levels of the virus in their system, such as during the latter stages of an infection when the worst of the illness is over.
That’s not necessarily a deal-breaker, says Eleanor Riley, an immunologist at the University of Edinburgh in the UK. “Very low levels of virus aren’t a problem because you’re probably not infectious,” she says.
Riley points out that rapid antigen tests for malaria are widely used. These are often self-administered by travelers, for example. “The precedent is there and those cost a dollar a pop or less,” she adds.
We’re still months away at the very least from having millions of at-home rapid antigen tests available for people to use. In order for that to happen, governments would likely have to plough billions of dollars into the manufacturing of such tests. But the other place that antigen tests could make a difference is in professional labs, which are currently processing huge numbers of PCR tests every day around the world.
Lab-based analysis of antigen tests is more sensitive than the rapid tests used at home or at the point of care, Grenache says, because the light-detecting machines in a lab used to identify the reaction associated with antibody-antigen binding are much more accurate than the systems built in to self-testing kits. And, in principle, lab-based antigen tests could be quicker to do than the PCR assays we’ve relied on so far.
“Those tests will be much easier to scale up,” says Grenache. “Once those are available, assuming the performance is good, that’s the type of test we would offer in my lab.”


thescientist--2020-08-17--FDA Approves New Saliva-Based COVID-19 Test

The US Food and Drug Administration has given Emergency Use Authorization to a fifth saliva-based test for COVID-19 .
The low-cost and noninvasive procedure developed by the Yale School of Public Health requires minimal processing and retains much of the accuracy of traditional nasopharyngeal swabs .
The United States has struggled to implement consistent and widespread testing throughout the pandemic , making it difficult for public health officials to track the spread of the virus .
In addition , the equipment and reagents needed to carry out PCR tests have frequently run low , from the swabs needed to collect @ @ @ @ @ @ @ viral RNA .
In a recent paper , published August 4 on the preprint server medRxiv , a team led by Yale postdoc Chantal Vogels detailed the new tool called SalivaDirect .
A team composed of many of the same researchers had previously shown that saliva could be collected in any sterile container and that the saliva remained largely stable even when warm , negating the need for special tubes or preservatives .
“ This is a huge step forward to make testing more accessible , ” Vogels said in a recent press @ @ @ @ @ @ @ an idea in our lab soon after we found saliva to be a promising sample type of the detection of SARS-CoV-2 , and now it has the potential to be used on a large scale to help protect public health.
” See “ Saliva Tests : How They Work and What They Bring to COVID-19 ” Traditional COVID-19 testing is a two-part process : once the sample is collected , the virus ’ s RNA must be extracted before it can be detected by sensitive , PCR-based methods .
SalivaDirect removes the extraction @ @ @ @ @ @ @ that ’ s really simple .
You add an enzyme , you heat it up , so you lose the most expensive step and the most time consuming and the most skilled [ steps ] , ” Nathan Grubaugh , an epidemiologist at Yale and a coauthor on the study , tells NPR .
The new test , which still relies on PCR to convert viral RNA to DNA and then amplify sequences , can run approximately 90 samples in fewer than three hours , STAT reports , with the potential to scale @ @ @ @ @ @ @ .
While most tests , spit or otherwise , are analyzed using PCR-based methods , there are other promising alternatives , such as loop-mediated isothermal amplification ( LAMP ) , that have also received Emergency Use Authorization for testing using nasopharyngeal swabs .
Yale is offering SalivaDirect ’ s protocol open source , meaning researchers worldwide can take and adapt the method for use in their own labs depending on what resources they have available .
The authors say they engineered their protocol to be as adaptive as possible to different PCR kits @ @ @ @ @ @ @ this type of flexibility for processing saliva samples to test for COVID-19 infection is groundbreaking in terms of efficiency and avoiding shortages of crucial test components like reagents , ” Food and Drug Administration ( FDA ) Commissioner Stephen Hahn says in a press release announcing the emergency use authorization .
This same flexibility and relatively streamlined protocol also make SalivaDirect a cheaper alternative to traditional PCR tests , the authors say .
The total cost of the reagents needed for one test is roughly $ 5 , meaning it could be offered @ @ @ @ @ @ @ perhaps as little as $ 10 .
“ This could be one the first major game changers in fighting the pandemic , ” Andy Slavitt , a former acting administrator of the Centers for Medicare and Medicaid Services , tweeted in response to the news .
“ Rarely am I this enthusiastic .
.
.
[ With ] a $ 10 test , you can test every day or every couple days.
” When compared to nasopharyngeal swabs , the authors found a “ high agreement ” of greater than 94 percent in @ @ @ @ @ @ @ .
In his Twitter thread , Slavitt gave a more conservative estimate of 88 percent to 94 percent accuracy when comparing SalivaDirect against both swabs and other saliva tests .
Martin Burke , a chemist at the University of Illinois at Urbana-Champaign who developed a similar saliva test , tells NPR that even a test with only 88 percent sensitivity can be extremely useful if it is plentiful enough for the kind of mass , repeated testing being carried out at his university .
“ If you do that twice a week , @ @ @ @ @ @ @ % of the people—98 % of the people , ” Burke says .
SalivaDirect has already been used voluntarily by several teams of professional basketball players .
Coaches , staff , and players from both the NBA and the National Basketball Players Association began voluntarily using the test in June , and their participation was central in gaining FDA Emergency Use Authorization .
Yale is now partnering with the sports agencies to study asymptomatic spread .
“ We ’ re hopeful that our contributions to this work will help to advance the research @ @ @ @ @ @ @ minimally invasive testing , ” John DiFiori , the NBA ’ s director of sports medicine , tells USA Today .

ABOVE: © ISTOCK.COM, ONCEAWITKIN
The US Food and Drug Administration has given Emergency Use Authorization to a fifth saliva-based test for COVID-19. The low-cost and noninvasive procedure developed by the Yale School of Public Health requires minimal processing and retains much of the accuracy of traditional nasopharyngeal swabs.
The United States has struggled to implement consistent and widespread testing throughout the pandemic, making it difficult for public health officials to track the spread of the virus. In addition, the equipment and reagents needed to carry out PCR tests have frequently run low, from the swabs needed to collect the sample to the reagents that extract viral RNA.
In a recent paper, published August 4 on the preprint server medRxiv, a team led by Yale postdoc Chantal Vogels detailed the new tool called SalivaDirect. A team composed of many of the same researchers had previously shown that saliva could be collected in any sterile container and that the saliva remained largely stable even when warm, negating the need for special tubes or preservatives.
“This is a huge step forward to make testing more accessible,” Vogels said in a recent press release. “This started off as an idea in our lab soon after we found saliva to be a promising sample type of the detection of SARS-CoV-2, and now it has the potential to be used on a large scale to help protect public health.”
Traditional COVID-19 testing is a two-part process: once the sample is collected, the virus’s RNA must be extracted before it can be detected by sensitive, PCR-based methods. SalivaDirect removes the extraction step, replacing it “with something that’s really simple. You add an enzyme, you heat it up, so you lose the most expensive step and the most time consuming and the most skilled [steps],” Nathan Grubaugh, an epidemiologist at Yale and a coauthor on the study, tells NPR.
The new test, which still relies on PCR to convert viral RNA to DNA and then amplify sequences, can run approximately 90 samples in fewer than three hours, STAT reports, with the potential to scale much higher in larger labs with automation. While most tests, spit or otherwise, are analyzed using PCR-based methods, there are other promising alternatives, such as loop-mediated isothermal amplification (LAMP), that have also received Emergency Use Authorization for testing using nasopharyngeal swabs.
Yale is offering SalivaDirect’s protocol open source, meaning researchers worldwide can take and adapt the method for use in their own labs depending on what resources they have available. The authors say they engineered their protocol to be as adaptive as possible to different PCR kits already on the market.
“Providing this type of flexibility for processing saliva samples to test for COVID-19 infection is groundbreaking in terms of efficiency and avoiding shortages of crucial test components like reagents,” Food and Drug Administration (FDA) Commissioner Stephen Hahn says in a press release announcing the emergency use authorization.
This same flexibility and relatively streamlined protocol also make SalivaDirect a cheaper alternative to traditional PCR tests, the authors say. The total cost of the reagents needed for one test is roughly $5, meaning it could be offered to the public for much less, perhaps as little as $10.
“This could be one the first major game changers in fighting the pandemic,” Andy Slavitt, a former acting administrator of the Centers for Medicare and Medicaid Services, tweeted in response to the news. “Rarely am I this enthusiastic . . . [With] a $10 test, you can test every day or every couple days.”
When compared to nasopharyngeal swabs, the authors found a “high agreement” of greater than 94 percent in detecting true positives between the two methods. In his Twitter thread, Slavitt gave a more conservative estimate of 88 percent to 94 percent accuracy when comparing SalivaDirect against both swabs and other saliva tests.
Martin Burke, a chemist at the University of Illinois at Urbana-Champaign who developed a similar saliva test, tells NPR that even a test with only 88 percent sensitivity can be extremely useful if it is plentiful enough for the kind of mass, repeated testing being carried out at his university. “If you do that twice a week, you’re going to catch 99% of the people—98% of the people,” Burke says.
SalivaDirect has already been used voluntarily by several teams of professional basketball players. Coaches, staff, and players from both the NBA and the National Basketball Players Association began voluntarily using the test in June, and their participation was central in gaining FDA Emergency Use Authorization. Yale is now partnering with the sports agencies to study asymptomatic spread. “We’re hopeful that our contributions to this work will help to advance the research in the interest of broadly accessible and minimally invasive testing,” John DiFiori, the NBA’s director of sports medicine, tells USA Today.


thescientist--2020-08-04--Biobanking and the Future of Precision Medicine

Researchers require innovative solutions to ensure that their biobanking projects are a success .
From initial sample collection to storage @ @ @ @ @ , precious biospecimens should be handled with care .
Precision medicine research in particular relies @ @ @ @ @ maintain sample integrity and streamline workflows .
In this webinar , brought to you by @ @ @ @ @ Scientific , Erik Steinfelder and Bogi Eliasen will examine the importance of biobanking in precision @ @ @ @ @ to diagnostics and treatments .
• Why biobanking is essential for precision medicine research Bogi @ @ @ @ @ Copenhagen Institute for Future Studies Chair of Danish Unesco Bioethical Committee HIMSS Global Achievement Award @ @

FREE Webinar
Tuesday, September 1, 2020
10:00 - 11:30 AM, Eastern Standard Time
Register Now
Researchers require innovative solutions to ensure that their biobanking projects are a success. From initial sample collection to storage and use in downstream applications, precious biospecimens should be handled with care. Precision medicine research in particular relies on sophisticated biobanking systems to maintain sample integrity and streamline workflows. In this webinar, brought to you by The Scientist and Thermo Fisher Scientific, Erik Steinfelder and Bogi Eliasen will examine the importance of biobanking in precision medicine, from early-stage research to diagnostics and treatments.
Topics to be covered
Why biobanking is essential for precision medicine research
Assessing real-world genomics data
Data management needs for precision medicine success
Register Now
Meet the Speakers:
Erik Steinfelder
Biobanking Market Development Director
Thermo Fisher Scientific
Bogi Eliasen
Director of Health, Copenhagen Institute for Future Studies
Chair of Danish Unesco Bioethical Committee...


thescientist--2020-08-18--Last Chance to Enter Our Annual Top 10 Innovations Contest

The Scientist ’ s annual Top 10 Innovations competition showcases the most clever and useful advances in life science techniques and products .
From disruptive sequencing technology to transformational tweaks on tried-and-true methods , each year ’ s winners represent the future of biomedical research .
We want to hear from you : whether you are an individual tinkering away at the bench or a company with a dedicated R & D team .
What have you brought to market in the past year that could benefit the life sciences ?
Submit your product or technique for consideration in this @ @ @ @ @ @ @ window will close Friday , August 21 , so enter now !
We started the Top 10 Innovations competition more than a decade ago , and over the years we ’ ve feted some pretty neat products .
Last year , our independent panel of expert judges chose a new technology called mass photometry , which researchers use to simultaneously analyze biomolecules within a solution , a novel system that improves multiplexed antibody detection , and eight other impressive products for their list of winners .
As we ’ ve witnessed in years @ @ @ @ @ @ @ make a splash when they come on the scene , they tend to have a long-lasting and profound effect on research .
We ’ re eager to see what products you bring to our attention .
Just make sure that the product you ’ re entering was released after October 1 , 2019 , and complete a brief questionnaire .
To learn more about the history of our Top 10 Innovations competition , read all about previous winners .

The Scientist’s annual Top 10 Innovations competition showcases the most clever and useful advances in life science techniques and products. From disruptive sequencing technology to transformational tweaks on tried-and-true methods, each year’s winners represent the future of biomedical research. We want to hear from you: whether you are an individual tinkering away at the bench or a company with a dedicated R&D team. What have you brought to market in the past year that could benefit the life sciences?
Submit your product or technique for consideration in this year’s competition. The submission window will close Friday, August 21, so enter now!
We started the Top 10 Innovations competition more than a decade ago, and over the years we’ve feted some pretty neat products. Last year, our independent panel of expert judges chose a new technology called mass photometry, which researchers use to simultaneously analyze biomolecules within a solution, a novel system that improves multiplexed antibody detection, and eight other impressive products for their list of winners. As we’ve witnessed in years past, winners don’t just make a splash when they come on the scene, they tend to have a long-lasting and profound effect on research.
We’re eager to see what products you bring to our attention. Just make sure that the product you’re entering was released after October 1, 2019, and complete a brief questionnaire.
To learn more about the history of our Top 10 Innovations competition, read all about previous winners.


thescientist--2020-08-18--Women's Cervical Mucus Prefers Some Sperm Over Others

The causes of infertility are many and yet doctors sometimes can ’ t explain why couples have trouble conceiving .
Scientists have uncovered yet another way our bodies can trip up fertilization .
In a study published today ( August 19 ) in Proceedings of the Royal Society B , researchers found that sperm function better in cervical mucus from women with less similar sequences for the genes that encode the human leukocyte antigen ( HLA ) system , a group of cell-surface proteins that the immune system uses to differentiate self from non-self .
With more-similar genotypes , sperm @ @ @ @ @ @ @ cervical mucus .
“ Quite a lot of these type of effects have been shown in other animals .
.
.
but obviously there ’ s a different importance to understanding this in humans , ” says David Richardson , a biologist at the University of East Anglia in the UK who did not participate in the study .
In birds and fish , for instance , it ’ s clear that having dissimilar genes for the major histocompatibility complex ( MHC ) —the animal equivalent of the HLA system—influences choice of mate @ @ @ @ @ @ @ of fertilization .
This subsequent variety of MHC alleles is thought to prepare offspring to face a wider range of pathogens and therefore increase their chances of survival .
In people , previous work has shown that men and women prefer body odor from individuals with less similar HLA sequences—a kind of pre-mating sexual selection .
Researchers have also determined that HLAs may be present on the surface of sperm and that soluble HLAs are found in cervical mucus , the fluid released by glands in the cervix , raising the possibility that @ @ @ @ @ @ @ a factor in humans , too .
“ In many animal species , not all the male-female combinations are equally compatible at the gamete level , ” says Jukka Kekäläinen , a biologist at the University of Eastern Finland .
Knowledge of gamete compatibility in people is limited , he adds , and could provide insight into human infertility .
There is no routine test for this kind of compatibility in medicine , he adds .
“ Normally , doctors just study whether the sperm quality looks okay and whether there are any @ @ @ @ @ @ @ explain infertility.
” To begin to address this question , Kekäläinen and colleagues collected cervical mucus samples from nine women and sperm samples from eight men .
The researchers also genotyped each subject ’ s HLA sequences .
Then they created all possible one-to-one combinations of diluted cervical mucus and sperm and observed how the sperm fared .
Sperm were more likely to survive in male-female combinations that shared fewer genetic similarities , indicating that immunological compatibility may affect fertility .
It “ is very plausible that it can be advantageous to choose @ @ @ @ @ @ @ optimally set up to recognize pathogens for a highly immunocompetent immune system , ” says Tobias Lenz , a biologist at the Max Planck Institute for Evolutionary Biology who was not involved in the work .
As the authors write in the paper , this question of how HLA genotype can influence post-copulatory sexual selection “ should now be studied in a larger context and with a larger dataset ” to test whether it leads to differential levels of fertilization , he adds .
“ Here , they look at certain fitness traits @ @ @ @ @ @ @ assumed to affect fertilization success , but would then be nice to actually show that in a study.
” Now that Kekäläinen and colleagues have identified this association between sperm viability and HLA genotype , they plan to focus on identifying the mechanism that underlies it .
In another study published August 3 , they uncovered a similar association between the genes for the HLA system and sperm mortality in follicular fluid , which surrounds an unfertilized human oocyte .
They ’ re currently confirming whether or not HLAs are present on the @ @ @ @ @ @ @ gene expression to determine what other genes might be involved in post-copulatory sexual selection .
Unlike in birds or fish , it ’ s hard to determine whether these mechanisms produce more viable or more healthy offspring in people , says Richardson .
“ It wouldn ’ t be that surprising , given what we know about other species , but it would obviously open up lots of opportunity for .
.
.
fertility treatment.
” A. Jokiniemi et al.
, “ Post-copulatory genetic matchmaking : HLA-dependent effects of cervical mucus on human @ @ @ @ @ @ @ Royal Society B , doi:10.1098/rsbp.2020.1682 , 2020 .

ABOVE: © ISTOCK.COM,
DZIKA_MROWKA
The causes of infertility are many and yet doctors sometimes can’t explain why couples have trouble conceiving. Scientists have uncovered yet another way our bodies can trip up fertilization. In a study published today (August 19) in Proceedings of the Royal Society B, researchers found that sperm function better in cervical mucus from women with less similar sequences for the genes that encode the human leukocyte antigen (HLA) system, a group of cell-surface proteins that the immune system uses to differentiate self from non-self. With more-similar genotypes, sperm were less likely to survive exposure to cervical mucus.
“Quite a lot of these type of effects have been shown in other animals . . . but obviously there’s a different importance to understanding this in humans,” says David Richardson, a biologist at the University of East Anglia in the UK who did not participate in the study.
In birds and fish, for instance, it’s clear that having dissimilar genes for the major histocompatibility complex (MHC)—the animal equivalent of the HLA system—influences choice of mate, gamete compatibility, and eventual success of fertilization. This subsequent variety of MHC alleles is thought to prepare offspring to face a wider range of pathogens and therefore increase their chances of survival.
In people, previous work has shown that men and women prefer body odor from individuals with less similar HLA sequences—a kind of pre-mating sexual selection. Researchers have also determined that HLAs may be present on the surface of sperm and that soluble HLAs are found in cervical mucus, the fluid released by glands in the cervix, raising the possibility that a well-matched egg and sperm could be a factor in humans, too.
“In many animal species, not all the male-female combinations are equally compatible at the gamete level,” says Jukka Kekäläinen, a biologist at the University of Eastern Finland. Knowledge of gamete compatibility in people is limited, he adds, and could provide insight into human infertility. There is no routine test for this kind of compatibility in medicine, he adds. “Normally, doctors just study whether the sperm quality looks okay and whether there are any problems in the females that could easily explain infertility.”
To begin to address this question, Kekäläinen and colleagues collected cervical mucus samples from nine women and sperm samples from eight men. The researchers also genotyped each subject’s HLA sequences. Then they created all possible one-to-one combinations of diluted cervical mucus and sperm and observed how the sperm fared. Sperm were more likely to survive in male-female combinations that shared fewer genetic similarities, indicating that immunological compatibility may affect fertility.
It “is very plausible that it can be advantageous to choose your mate so that your offspring is optimally set up to recognize pathogens for a highly immunocompetent immune system,” says Tobias Lenz, a biologist at the Max Planck Institute for Evolutionary Biology who was not involved in the work. As the authors write in the paper, this question of how HLA genotype can influence post-copulatory sexual selection “should now be studied in a larger context and with a larger dataset” to test whether it leads to differential levels of fertilization, he adds. “Here, they look at certain fitness traits of the sperm, which can be assumed to affect fertilization success, but would then be nice to actually show that in a study.”
Now that Kekäläinen and colleagues have identified this association between sperm viability and HLA genotype, they plan to focus on identifying the mechanism that underlies it. In another study published August 3, they uncovered a similar association between the genes for the HLA system and sperm mortality in follicular fluid, which surrounds an unfertilized human oocyte. They’re currently confirming whether or not HLAs are present on the surface of sperm cells and investigating their gene expression to determine what other genes might be involved in post-copulatory sexual selection.
Unlike in birds or fish, it’s hard to determine whether these mechanisms produce more viable or more healthy offspring in people, says Richardson. “It wouldn’t be that surprising, given what we know about other species, but it would obviously open up lots of opportunity for . . . fertility treatment.”
A. Jokiniemi et al., “Post-copulatory genetic matchmaking: HLA-dependent effects of cervical mucus on human sperm function,” Proceedings of the Royal Society B, doi:10.1098/rsbp.2020.1682, 2020.


thescientist--2020-08-18--Marine Biologist John Pearse Dies

Marine Biologist John Pearse Dies

ABOVE : John Pearse ( standing , right ) at work in the field CHRIS BRATT John Pearse , whose long career included some of the earliest marine biology research at Antarctica ’ s McMurdo Station and studies in more temperate ecosystems off the coast of California , died on July 31 at age 84 .
According to a University of California , Santa Cruz ( UCSC ) , obituary , he had been in hospice after undergoing cancer treatment and having a stroke .
“ It ’ s amazing how many people John touched , ” James McClintock , @ @ @ @ @ @ @ Alabama at Birmingham who studied with Pearse , tells The Scientist .
“ John had this infective ability to get you excited about the science and do it in a way that he wasn ’ t talking down to you—he was edging you up and getting you to think about intriguing questions.
” Pearse was born in Boise , Idaho , according to UCSC .
He later told the educational website Shape of Life that his love of nature came from childhood explorations around Washington , DC , and Tucson , Arizona .
@ @ @ @ @ @ @ in cages and loose in our houses—insects , spiders , fishes , reptiles , birds , small mammals ( my parents were very supportive of these interests ) , ” he said .
He explored marine life in the Mediterranean and Red Sea during his first year of college , at American University in Cairo , then finished his undergraduate studies at the University of Chicago .
Pearse then earned a PhD in biology at Stanford University .
For his graduate research , he traveled to McMurdo Station in Antarctica , McClintock tells @ @ @ @ @ @ @ first marine biologists to do research on the continent .
“ He pioneered some of the earliest studies of marine invertebrate reproduction in Antarctica , and sort of laid the groundwork for a lot of exciting reproductive biology and ecology to come over the next many decades , ” McClintock says .
An Antarctic valley was later named after Pearse in recognition of this work there .
After graduating , Pearse returned to American University in Cairo to teach , then worked as a researcher at Caltech before joining the UCSC faculty in @ @ @ @ @ @ @ university ’ s marine science program .
He was known for his work on marine invertebrate reproduction and kelp forest ecology , as well as his continued Antarctic studies , McClintock says .
Pearse ’ s wife , Vicki Buchsbaum Pearse , was a research associate at the university who also studied marine invertebrates .
McClintock credits Pearse with sparking his interest in marine invertebrates when McClintock was an undergraduate ( he originally intended to major in English ) .
McClintock later worked as a postdoc in Pearse ’ s lab .
“ @ @ @ @ @ @ @ see him in his office and then there ’ d be a little chain of students outside the door , ” McClintock says .
“ And when he ’ d come out the door to go down the hall , they ’ d all follow him like little ducklings , trying to get their time with him.
” Pearse continued his research and educational work after he retired in 1994 .
In 2000 , he founded a program that trained high school students to monitor coastal ecosystems .
It eventually grew into a @ @ @ @ @ @ @ Program and Experimental Training for Students ( LiMPETS ) .
He also served as president of the California Academy of Sciences , the International Society of Invertebrate Reproduction and Development , the Society for Integrative and Comparative Biology , and the Western Society of Naturalists , according to UCSC .
Pearse is survived by his wife Vicki , a brother , and his son and granddaughter .

ABOVE: John Pearse (standing, right) at work in the field
CHRIS BRATT
John Pearse, whose long career included some of the earliest marine biology research at Antarctica’s McMurdo Station and studies in more temperate ecosystems off the coast of California, died on July 31 at age 84. According to a University of California, Santa Cruz (UCSC), obituary, he had been in hospice after undergoing cancer treatment and having a stroke.
“It’s amazing how many people John touched,” James McClintock, a marine biologist at the University of Alabama at Birmingham who studied with Pearse, tells The Scientist. “John had this infective ability to get you excited about the science and do it in a way that he wasn’t talking down to you—he was edging you up and getting you to think about intriguing questions.”
Pearse was born in Boise, Idaho, according to UCSC. He later told the educational website Shape of Life that his love of nature came from childhood explorations around Washington, DC, and Tucson, Arizona. “I had a menagerie of animals in cages and loose in our houses—insects, spiders, fishes, reptiles, birds, small mammals (my parents were very supportive of these interests),” he said. He explored marine life in the Mediterranean and Red Sea during his first year of college, at American University in Cairo, then finished his undergraduate studies at the University of Chicago.
John Pearse CHRIS BRATT
Pearse then earned a PhD in biology at Stanford University. For his graduate research, he traveled to McMurdo Station in Antarctica, McClintock tells The Scientist, becoming one of the first marine biologists to do research on the continent. “He pioneered some of the earliest studies of marine invertebrate reproduction in Antarctica, and sort of laid the groundwork for a lot of exciting reproductive biology and ecology to come over the next many decades,” McClintock says. An Antarctic valley was later named after Pearse in recognition of this work there.
After graduating, Pearse returned to American University in Cairo to teach, then worked as a researcher at Caltech before joining the UCSC faculty in 1971. There he helped establish the university’s marine science program. He was known for his work on marine invertebrate reproduction and kelp forest ecology, as well as his continued Antarctic studies, McClintock says. Pearse’s wife, Vicki Buchsbaum Pearse, was a research associate at the university who also studied marine invertebrates.
McClintock credits Pearse with sparking his interest in marine invertebrates when McClintock was an undergraduate (he originally intended to major in English). McClintock later worked as a postdoc in Pearse’s lab. “I used to try to get to see him in his office and then there’d be a little chain of students outside the door,” McClintock says. “And when he’d come out the door to go down the hall, they’d all follow him like little ducklings, trying to get their time with him.”
Pearse continued his research and educational work after he retired in 1994. In 2000, he founded a program that trained high school students to monitor coastal ecosystems. It eventually grew into a statewide citizen science program called Long-Term Monitoring Program and Experimental Training for Students (LiMPETS). He also served as president of the California Academy of Sciences, the International Society of Invertebrate Reproduction and Development, the Society for Integrative and Comparative Biology, and the Western Society of Naturalists, according to UCSC.
Pearse is survived by his wife Vicki, a brother, and his son and granddaughter.