thescientist--2020-11-01--How Some Vaccines Protect Against More than Their Targets

As a physician-researcher specializing in infections in newborns , Tobi Kollmann is laser focused on how to stop babies from dying .
While mortality for kids under five years old has dropped substantially in recent decades , he says , there has been little improvement in the rate of deaths in the first week of life .
Indeed , of the 5.2 million children under 5 years old the World Health Organization estimates died last year of preventable or treatable causes , nearly half—2.4 million—died before reaching four weeks of age , and most newborn deaths occurred in the first @ @ @ @ @ @ @ in African countries where neonatal mortality is common and witnessed the frustration of colleagues there with their limited options for preventing it , Kollmann , now at the Telethon Kids Institute in Perth , Australia , says he wanted to find solutions that could be implemented immediately .
So when Kollmann came across a 2011 study that found giving the tuberculosis vaccine ( called bacille Calmette-Guérin , or BCG ) to low-weight infants in Guinea-Bissau at birth cut their mortality rate in their first four weeks of life in half—not because of the @ @ @ @ @ @ @ but by reducing the risk of sepsis and other infections—it caught his attention .
“ That to me was just unimaginable , ” he says .
Around 2012 , Kollmann attended a meeting of researchers studying such off-target effects of vaccines and sat in on a talk by one of the authors of the 2011 study , Dutch anthropologist Peter Aaby , founder of the Bandim Health Project .
Aaby spoke about the history of research on two vaccines linked to declines in all-cause mortality : BCG and the measles vaccine , which @ @ @ @ @ @ @ Kollmann “ was just shocked how such a tool that could potentially be so incredibly effective .
.
.
could have been kept under the wraps for so , so long.
” Kollmann didn ’ t wait long to begin studying what he terms the pathogen-agnostic effects of BCG , coauthoring several reviews on the topic and , more recently , studying the mechanisms of the effects in animals .
Other vaccines , such as the smallpox and live polio vaccines , have also yielded hints in observational studies that they could provide @ @ @ @ @ @ @ from pathogens other than those they target .
In recent years , some randomized controlled trials have provided more-solid evidence for such protections .
Despite decades of reports of vaccines ’ off-target effects , however , the phenomenon has received relatively little attention , and researchers have only a nascent understanding of the mechanisms .
While critics argue that some of the claims made about pathogen-agnostic effects outstrip the available evidence , Kollmann says he thinks many experts have been slow to embrace their potential of pathogen-agnostic effects because of dogmatic thinking about @ @ @ @ @ @ @ People think in boxes , ” he says .
The question of how much protection vaccines such as BCG provide against off-target pathogens , and under what circumstances , has acquired more urgency as COVID-19 sweeps the globe .
Trials are now underway testing the BCG vaccine in groups at high risk of exposure to SARS-CoV-2 to see if it can provide partial , temporary protection against the novel coronavirus—marking the first time a vaccine has been trialed against a specific pathogen other than the one it was designed for .
“ It @ @ @ @ @ @ @ this does not replace a corona-specific vaccine , because , of course , that ’ s what the world needs , ” says Nigel Curtis , a clinician and infectious disease researcher at Murdoch Children ’ s Research Institute and the University of Melbourne who is leading a trial of BCG for COVID-19 .
“ But this might provide a stopgap until one comes along , because it looks like it might be many months or years before that.
” One of the first researchers to note the apparent nonspecific effects of a @ @ @ @ @ @ @ who together with her husband Mikhail Chumakov , the director of the Polio Research Institute in Moscow , observed an unexpected benefit while spearheading large-scale testing of a new polio vaccine beginning in 1959 .
Unlike Jonas Salk ’ s famous vaccine , which used killed virus , the new , oral version , developed by Albert Sabin , used live , attenuated virus .
Voroshilova and Chumakov didn ’ t hesitate to give the inoculation to their own children as well as to millions of other young people .
Voroshilova noticed that @ @ @ @ @ @ @ polio , the vaccine also seemed to be associated with lower-than-expected rates of influenza and other respiratory infections in the months after it was given , an effect backed up by later controlled trials .
It wasn ’ t clear what explained the off-target effect , but Chumakov , Voroshilova , and their colleagues found that the vaccine raised subjects ’ blood levels of interferons , proteins that instruct immune cells to launch an antiviral response .
Other studies looking into the Sabin vaccine ’ s effect on diseases besides polio supported this @ @ @ @ @ @ @ , the oral polio immunization wasn ’ t unique in providing nonspecific protection .
In controlled trials of the BCG vaccine conducted between 1948 and 1961 in the US and the UK , researchers found an average reduction in mortality from causes other than tuberculosis of about 25 percent among those who received the shot compared with those who did not .
BCG even proved itself an early form of immunotherapy after researchers at Queen ’ s University in Ontario published a 1976 report of nine patients with bladder cancer who received an @ @ @ @ @ @ @ the affected organ and had a lower-than-expected recurrence rate .
The vaccine is still used to treat bladder cancer today .
Another vaccine with apparent bonus protective effects was one designed to prevent measles .
In the 1970s , vaccinating children in very poor countries against measles wasn ’ t a priority for international aid groups because , some believed , the children who died from the disease were malnourished and would have died soon of something else .
But when Aaby and his colleagues visited an area of Guinea-Bissau in 1979 to @ @ @ @ @ @ @ the children who died of measles weren ’ t more likely to be malnourished than those who survived the disease .
After public health officials implemented a vaccination program with a live , attenuated measles inoculation in the area , mortality within one year among 6- to 35-month-old children declined sharply , Aaby and his team found—an effect not fully explained by the drop in measles infections .
The study was not a controlled trial , however , so it remains impossible to say if the vaccine was responsible .
To examine this @ @ @ @ @ @ @ non-measles mortality in other settings , Aaby and his colleagues later analyzed the results of 10 cohort and case-control studies on measles vaccination performed in seven developing countries .
The drop in mortality rates after vaccination ranged from 30 percent to 86 percent , outstripping the reductions that could be explained by measles mortality rates alone .
“ These observations suggest that standard titre measles vaccine may confer a beneficial effect which is unrelated to the specific protection against measles disease , ” the authors wrote in their 1995 BMJ paper .
They @ @ @ @ @ @ @ , non-live vaccines , diphtheria-tetanus-pertussis ( DTP ) and a polio immunization .
It was around that time that Christine Stabell Benn , then a medical student at Aarhus University , joined Aaby ’ s team at the Bandim Health Project .
She never left , and the pair has now studied the nonspecific effects of vaccines together for more than two decades , becoming perhaps the most visible advocates of those effects ’ significance .
Through further studies , largely in Guinea-Bissau , Benn and Aaby concluded that vaccines made of live @ @ @ @ @ @ @ polio vaccine , and measles and smallpox immunizations—provoke beneficial nonspecific responses , while vaccines that use bits of killed virus do not .
In fact , Benn suggests that non-live viruses actually make some kids temporarily more susceptible to illnesses other than the one they ’ ve been vaccinated against .
( See “ A Nonspecific Vaccine Risk ?
” below . )
Critics have questioned the existence and strength of nonspecific effects , both beneficial and deleterious .
“ A lot of the evidence is very weak , ” says Paul Fine @ @ @ @ @ @ @ of Hygiene & Tropical Medicine who has written letters in the past to journals challenging the interpretations of study results that indicate such effects .
One problem with observational studies , he says , is that “ vaccines in routine practice are not allocated randomly , and kids who receive vaccines , in any population in the world outside a vaccine trial , are not like the kids who don ’ t receive vaccines .
That ’ s been a main issue ” that can confound results , he says .
To sort @ @ @ @ @ @ @ what implications they might have for vaccine schedules , the World Health Organization ( WHO ) convened a working group in 2013 that included Fine , Benn , and other experts .
( The WHO formulates recommendations for low- and middle-income regions , but each country develops a vaccination schedule based on its own disease threats and other circumstances . )
As part of its research , the group commissioned an independent systematic review of studies on nonspecific effects of BCG , DTP , and the measles vaccine .
The review identified five @ @ @ @ @ @ @ study of low birthweight infants in Guinea-Bissau that had caught Tobi Kollmann ’ s attention a few years earlier , that found a 30 percent average reduction in mortality with the BCG vaccine .
The review ’ s authors noted that “ tuberculosis is now an infrequent cause of death in infants and young children , so if BCG has an effect on all cause mortality it is unlikely to be entirely due to fewer deaths from that disease.
” Similarly , the review identified four controlled trials of the measles vaccine that @ @ @ @ @ @ @ 26 percent , with deaths from measles contributing negligibly to that finding , suggesting that the vaccine also protected from other causes of death .
The reviewers found no clinical trials of nonspecific effects for DTP , and all of the observational studies addressing the question were classified as having a high or very high risk of bias and generated widely varying results .
The working group concluded in 2014 that “ the systematic review neither excludes nor confirms the possibility of beneficial or deleterious non-specific immunological effects of vaccines on all cause-mortality @ @ @ @ @ @ @ of data on what the mechanisms for such effects might be in humans .
The authors suggested that the WHO develop standard protocols for studying nonspecific effects in an ethical and rigorous way , but it ’ s unclear what the current status of that effort is .
A WHO official told The Scientist in July that she would look into the matter but never provided the information despite several follow-up inquiries .
Putting nonspecific effects of vaccines to the test New studies on nonspecific effects have been published since the working group @ @ @ @ @ @ @ the phenomenon has not yet come into focus .
In a 2017 study of low–birth weight infants in Guinea-Bissau , Benn and her colleagues found a 43 percent reduction in the mortality rate from infectious disease in the first 28 days of life among babies who received BCG soon after birth compared with those who got it at around six weeks of age , on the typical local schedule .
Meanwhile , a study comparing the effects of live and non-live polio vaccine on toddlers in Bangladesh found that children who received the @ @ @ @ @ @ @ over the following year than did those who received the killed version .
And this September , infectious diseases specialist Mihai Netea of Radboud University in the Netherlands and colleagues published interim results of a randomized trial of BCG in elderly people in Greece that showed that people who received the vaccine were less likely than controls to develop infections of any kind in the following year ; BCG appeared to be most protective against respiratory viruses .
Other results complicate the case for nonspecific effects .
In a Danish trial of BCG @ @ @ @ @ @ @ no difference between babies who received the vaccine at birth and those who didn ’ t get it at all in terms of hospitalization rates for infection over the first 15 months of life—except among BCG-vaccinated children whose mothers had also been BCG-vaccinated at some point prior to their pregnancies ; these babies had a 35 percent lower hospitalization rate than their non-vaccinated peers .
And two trials of a different strain of the BCG vaccine in low–birth weight infants in India , one of which administered BCG along with live polio vaccine @ @ @ @ @ @ @ the first 28 days after birth .
See “ An Old TB Vaccine Finds New Life in Coronavirus Trials ” Nonspecific effects have garnered some high-profile attention as a potential near-term tool for fighting COVID-19 .
Robert Gallo , best known for his role in identifying HIV as the cause of AIDS in the 1980s , joined with Aaby , Benn , and other authors to pen an opinion article in a June issue of Science calling for studies to determine whether the live polio vaccine could protect against COVID-19 .
( In @ @ @ @ @ @ @ viral strains can mutate and cause disease , but Gallo suggests this could be avoided by only using the other two strains . )
Gallo , a cofounder of both the Institute of Human Virology at the University of Maryland School of Medicine and the Global Virus Network , wasn ’ t successful in persuading the National Institutes of Health to back such trials , he says , but he ’ s working with partners on clinical studies outside the US , chiefly in India .
Netea says he knows of 15 current @ @ @ @ @ @ @ two each of the oral polio and the measles , mumps , and rubella ( MMR ) vaccines .
If ongoing trials demonstrate that BCG reduces the incidence or severity of COVID-19 , that finding could have implications beyond the current pandemic , says Curtis .
It would indicate that the inoculation could also serve as a ready-made stopgap against future outbreaks of new viruses , he notes .
He adds that his current study is examining whether BCG affects rates not just of COVID-19 , but also of more-familiar respiratory infections such @ @ @ @ @ @ @ BCG “ might be something you would just use in population groups like the elderly that are more susceptible ” to infection .
While observations of nonspecific effects are decades old , hints about the mechanisms that might explain the phenomenon have only begun to emerge .
Vaccines are designed to train the adaptive immune system—that is , primarily the T cells that recognize and kill specific pathogens and the B cells that make antibodies—to fight off a particular infection .
To do this , vaccines typically include components of the pathogen they @ @ @ @ @ @ @ viruses or bacteria that are closely related to the target pathogen but don ’ t cause illness .
So it seems counterintuitive that their effects would extend beyond that target pathogen .
Netea , who collaborates with Benn , Aaby , and Curtis , says he thinks the lack of a mechanistic explanation for the non-specific effects seen in early studies led people to “ kind of forget about it.
” He himself only learned about the existing literature on such effects about a decade ago , when a student working in his @ @ @ @ @ @ @ the tuberculosis-causing bacterium after BCG vaccination .
The student had used exposure to a pathogenic fungus as a control , and Netea was surprised to see that BCG helped the cells drawn from human volunteers who received the vaccine mount an immune response not only against Mycobacterium tuberculosis , but the fungus as well .
To find out why this was , Netea led a larger study in which he and his colleagues again tested the blood of healthy volunteers before and after they were inoculated with BCG .
Isolating pathogen-chomping innate immune @ @ @ @ @ @ @ to a variety of pathogens in vitro , the team found that monocytes drawn after inoculation released 50 percent to 100 percent more of the immune cell–stimulating cytokines TNF and IL-1β .
The researchers also identified specific post-inoculation changes to the methyl and acetyl tags on histones packaging the monocytes ’ DNA .
The authors concluded that BCG trains innate immunity via epigenetic alterations .
“ It ’ s like putting marks on the genes that are necessary for host defense , ” Netea says .
“ Then , when you get an @ @ @ @ @ @ @ marked by certain chemical modifications of the histones , and then the transcription factors can bind easier , ” ramping up gene transcription to support a more robust immune response .
His and other groups have since elucidated similar processes in other components of the innate immune system , such as natural killer cells , Netea adds .
And in a study published earlier this year , he and colleagues found that BCG vaccination in adults appears to shift gene transcription patterns in immune precursor cells in the bone marrow to a program @ @ @ @ @ @ @ known as myeloid cells .
Similarly , BCG-vaccinated newborns quickly boost production of neutrophils , a type of myeloid cell , relative to their unvaccinated peers .
( See illustration . )
Why would an infant ’ s immune cells need to be trained , rather than having the epigenetic marks for a robust immune response from the start ?
Netea says he suspects that the answer to that question has to do with the requirements of human pregnancy—namely , that the parent ’ s body not reject the fetus .
Tamping down @ @ @ @ @ @ @ pregnancy could also affect the fetus ’ s , he suggests , leading to babies born vulnerable to infection .
That early vulnerability , counteracted by live-vaccine immune training , may help explain the dramatic lowering of all-cause mortality found with early BCG vaccination in Guinea-Bissau .
But epigenetic effects don ’ t appear to be the full story on how BCG—and potentially other live vaccines—provide nonspecific protections , at least in neonates .
In a study published earlier this year , a team led by Kollmann and Telethon Kids Institute researcher Nelly @ @ @ @ @ @ @ Benn ) treated some newborn mice with BCG and then injected fecal bacteria into their abdomens , and into the abdomens of control animals , to simulate sepsis .
They found that BCG initiated a process known as emergency granulopoiesis , which ramped up the production of neutrophils in the bone marrow .
These cells “ sit in the bone marrow , waiting .
.
.
to gobble up bacteria and many other things , ” Kollmann says .
“ And then , the moment we induce sepsis in these mice that have @ @ @ @ @ @ @ ] released , go to the site of infection .
.
.
and knock off these bacteria within hours of the infectious process starting.
” What most struck Kollmann was the timeline for the emergency granulopoiesis-based protection : the process began within hours of BCG inoculation , and the peak of the neutrophil-based protection came three days later .
It was fast , and it lined up with the findings in the 2011 study that had first drawn his attention to pathogen-agnostic effects .
The speed of the nonspecific protection also meshed with @ @ @ @ @ @ @ the effects of giving BCG at birth versus later—namely , that the vaccine provides dramatic protection that begins almost immediately after inoculation .
Kollmann says he hopes that the finding of a mechanism to back up the clinical trial data will lead to a more uniform practice of giving BCG to babies in high-risk settings immediately after birth .
Longer term , he adds , more research is needed to better understand BCG ’ s beneficial effects .
“ We need to figure out : What is it about BCG that makes this @ @ @ @ @ @ @ can we optimize this , can we make it better , faster ?
”

ABOVE: MODIFIED FROM © ISTOCK.COM, SOPHONK; SORBETTO
As a physician-researcher specializing in infections in newborns, Tobi Kollmann is laser focused on how to stop babies from dying. While mortality for kids under five years old has dropped substantially in recent decades, he says, there has been little improvement in the rate of deaths in the first week of life. Indeed, of the 5.2 million children under 5 years old the World Health Organization estimates died last year of preventable or treatable causes, nearly half—2.4 million—died before reaching four weeks of age, and most newborn deaths occurred in the first week after birth. Having spent time in African countries where neonatal mortality is common and witnessed the frustration of colleagues there with their limited options for preventing it, Kollmann, now at the Telethon Kids Institute in Perth, Australia, says he wanted to find solutions that could be implemented immediately.
So when Kollmann came across a 2011 study that found giving the tuberculosis vaccine (called bacille Calmette-Guérin, or BCG) to low-weight infants in Guinea-Bissau at birth cut their mortality rate in their first four weeks of life in half—not because of the protection it offered against tuberculosis itself, but by reducing the risk of sepsis and other infections—it caught his attention. “That to me was just unimaginable,” he says. Around 2012, Kollmann attended a meeting of researchers studying such off-target effects of vaccines and sat in on a talk by one of the authors of the 2011 study, Dutch anthropologist Peter Aaby, founder of the Bandim Health Project. Aaby spoke about the history of research on two vaccines linked to declines in all-cause mortality: BCG and the measles vaccine, which both incorporate live, attenuated pathogens. Kollmann “was just shocked how such a tool that could potentially be so incredibly effective . . . could have been kept under the wraps for so, so long.”
Trials are now underway testing the BCG vaccine to see if it can provide partial, temporary protection against COVID-19—marking the first time a vaccine has been trialed against a specific pathogen other than the one it was designed for.
Kollmann didn’t wait long to begin studying what he terms the pathogen-agnostic effects of BCG, coauthoring several reviews on the topic and, more recently, studying the mechanisms of the effects in animals. Other vaccines, such as the smallpox and live polio vaccines, have also yielded hints in observational studies that they could provide some protection, at least temporarily, from pathogens other than those they target. In recent years, some randomized controlled trials have provided more-solid evidence for such protections.
Despite decades of reports of vaccines’ off-target effects, however, the phenomenon has received relatively little attention, and researchers have only a nascent understanding of the mechanisms. While critics argue that some of the claims made about pathogen-agnostic effects outstrip the available evidence, Kollmann says he thinks many experts have been slow to embrace their potential of pathogen-agnostic effects because of dogmatic thinking about how the immune system works. “People think in boxes,” he says.
The question of how much protection vaccines such as BCG provide against off-target pathogens, and under what circumstances, has acquired more urgency as COVID-19 sweeps the globe. Trials are now underway testing the BCG vaccine in groups at high risk of exposure to SARS-CoV-2 to see if it can provide partial, temporary protection against the novel coronavirus—marking the first time a vaccine has been trialed against a specific pathogen other than the one it was designed for. “It’s obviously very important to emphasize this does not replace a corona-specific vaccine, because, of course, that’s what the world needs,” says Nigel Curtis, a clinician and infectious disease researcher at Murdoch Children’s Research Institute and the University of Melbourne who is leading a trial of BCG for COVID-19. “But this might provide a stopgap until one comes along, because it looks like it might be many months or years before that.”
Early hints at vaccines’ off-target effects
One of the first researchers to note the apparent nonspecific effects of a vaccine was Soviet virologist Marina Voroshilova, who together with her husband Mikhail Chumakov, the director of the Polio Research Institute in Moscow, observed an unexpected benefit while spearheading large-scale testing of a new polio vaccine beginning in 1959. Unlike Jonas Salk’s famous vaccine, which used killed virus, the new, oral version, developed by Albert Sabin, used live, attenuated virus. Voroshilova and Chumakov didn’t hesitate to give the inoculation to their own children as well as to millions of other young people. Voroshilova noticed that in addition to conferring lasting protection against polio, the vaccine also seemed to be associated with lower-than-expected rates of influenza and other respiratory infections in the months after it was given, an effect backed up by later controlled trials. It wasn’t clear what explained the off-target effect, but Chumakov, Voroshilova, and their colleagues found that the vaccine raised subjects’ blood levels of interferons, proteins that instruct immune cells to launch an antiviral response.
Other studies looking into the Sabin vaccine’s effect on diseases besides polio supported this observation. And as it turned out, the oral polio immunization wasn’t unique in providing nonspecific protection. In controlled trials of the BCG vaccine conducted between 1948 and 1961 in the US and the UK, researchers found an average reduction in mortality from causes other than tuberculosis of about 25 percent among those who received the shot compared with those who did not. BCG even proved itself an early form of immunotherapy after researchers at Queen’s University in Ontario published a 1976 report of nine patients with bladder cancer who received an injection of the BCG vaccine directly into the affected organ and had a lower-than-expected recurrence rate. The vaccine is still used to treat bladder cancer today.
Another vaccine with apparent bonus protective effects was one designed to prevent measles. In the 1970s, vaccinating children in very poor countries against measles wasn’t a priority for international aid groups because, some believed, the children who died from the disease were malnourished and would have died soon of something else. But when Aaby and his colleagues visited an area of Guinea-Bissau in 1979 to investigate this hypothesis, they found that the children who died of measles weren’t more likely to be malnourished than those who survived the disease. After public health officials implemented a vaccination program with a live, attenuated measles inoculation in the area, mortality within one year among 6- to 35-month-old children declined sharply, Aaby and his team found—an effect not fully explained by the drop in measles infections. The study was not a controlled trial, however, so it remains impossible to say if the vaccine was responsible.
A CURIOUS CORRELATION: An oral polio vaccine developed by Albert Sabin (left) with live, attenuated virus appears to confer some short-term protection against influenza and other respiratory infections in addition to long-lasting protection against polio. © SHUTTERSTOCK.COM, UNIVERSAL HISTORY ARCHIVE
To examine this apparent link between the measles vaccine and non-measles mortality in other settings, Aaby and his colleagues later analyzed the results of 10 cohort and case-control studies on measles vaccination performed in seven developing countries. The drop in mortality rates after vaccination ranged from 30 percent to 86 percent, outstripping the reductions that could be explained by measles mortality rates alone. “These observations suggest that standard titre measles vaccine may confer a beneficial effect which is unrelated to the specific protection against measles disease,” the authors wrote in their 1995 BMJ paper. They detected no such effects with two other, non-live vaccines, diphtheria-tetanus-pertussis (DTP) and a polio immunization.
It was around that time that Christine Stabell Benn, then a medical student at Aarhus University, joined Aaby’s team at the Bandim Health Project. She never left, and the pair has now studied the nonspecific effects of vaccines together for more than two decades, becoming perhaps the most visible advocates of those effects’ significance. Through further studies, largely in Guinea-Bissau, Benn and Aaby concluded that vaccines made of live, attenuated pathogens—including BCG, the live polio vaccine, and measles and smallpox immunizations—provoke beneficial nonspecific responses, while vaccines that use bits of killed virus do not. In fact, Benn suggests that non-live viruses actually make some kids temporarily more susceptible to illnesses other than the one they’ve been vaccinated against. (See “A Nonspecific Vaccine Risk?” below.)
Critics have questioned the existence and strength of nonspecific effects, both beneficial and deleterious. “A lot of the evidence is very weak,” says Paul Fine, an epidemiologist at the London School of Hygiene & Tropical Medicine who has written letters in the past to journals challenging the interpretations of study results that indicate such effects. One problem with observational studies, he says, is that “vaccines in routine practice are not allocated randomly, and kids who receive vaccines, in any population in the world outside a vaccine trial, are not like the kids who don’t receive vaccines. That’s been a main issue” that can confound results, he says.
To sort through the evidence on nonspecific effects and what implications they might have for vaccine schedules, the World Health Organization (WHO) convened a working group in 2013 that included Fine, Benn, and other experts. (The WHO formulates recommendations for low- and middle-income regions, but each country develops a vaccination schedule based on its own disease threats and other circumstances.) As part of its research, the group commissioned an independent systematic review of studies on nonspecific effects of BCG, DTP, and the measles vaccine. The review identified five clinical trials of BCG, including the study of low birthweight infants in Guinea-Bissau that had caught Tobi Kollmann’s attention a few years earlier, that found a 30 percent average reduction in mortality with the BCG vaccine. The review’s authors noted that “tuberculosis is now an infrequent cause of death in infants and young children, so if BCG has an effect on all cause mortality it is unlikely to be entirely due to fewer deaths from that disease.” Similarly, the review identified four controlled trials of the measles vaccine that found an average decline in mortality of 26 percent, with deaths from measles contributing negligibly to that finding, suggesting that the vaccine also protected from other causes of death. The reviewers found no clinical trials of nonspecific effects for DTP, and all of the observational studies addressing the question were classified as having a high or very high risk of bias and generated widely varying results.
The working group concluded in 2014 that “the systematic review neither excludes nor confirms the possibility of beneficial or deleterious non-specific immunological effects of vaccines on all cause-mortality,” and also noted a lack of data on what the mechanisms for such effects might be in humans. The authors suggested that the WHO develop standard protocols for studying nonspecific effects in an ethical and rigorous way, but it’s unclear what the current status of that effort is. A WHO official told The Scientist in July that she would look into the matter but never provided the information despite several follow-up inquiries.
How Vaccines Train Innate Immunity While researchers have observed for decades that certain vaccines seem to help recipients ward off more than just the target pathogen, only in recent years have they identified possible mechanisms for these bonus benefits. For example, in a study published this year (depicted here), researchers examined immune cells from the blood and bone marrow of healthy adults before and after they received a live tuberculosis vaccine known as bacille Calmette-Guérin, or BCG. © TERESE WINSLOW In the bone marrow post-vaccination, genes are expressed that trigger hematopoietic stem and progenitor cells to differentiate into monocytes, neutrophils, and other so-called myeloid cells. In a separate analysis of the effects of BCG in newborns, the researchers found that the vaccine ramped up the number of neutrophils in babies’ blood compared with unvaccinated infants. © TERESE WINSLOW Monocytes from the blood displayed epigenetic changes after vaccination that opened chromatin harboring multiple genes involved in driving an inflammatory response, making them more accessible for transcription. Meanwhile, chromatin closed around genes associated with immune tolerance. When exposed to the fungal pathogen Candida albicans in vitro, immune cells sampled from patients’ blood 90 days after vaccination released more of the cytokine interleukin 1β, which mediates inflammation, than did cells from blood drawn from the same individuals before vaccination.
PDF See full infographic: WEB
Putting nonspecific effects of vaccines to the test
New studies on nonspecific effects have been published since the working group concluded, but a full picture of the phenomenon has not yet come into focus. In a 2017 study of low–birth weight infants in Guinea-Bissau, Benn and her colleagues found a 43 percent reduction in the mortality rate from infectious disease in the first 28 days of life among babies who received BCG soon after birth compared with those who got it at around six weeks of age, on the typical local schedule. Meanwhile, a study comparing the effects of live and non-live polio vaccine on toddlers in Bangladesh found that children who received the live vaccine experienced fewer episodes of diarrhea over the following year than did those who received the killed version. And this September, infectious diseases specialist Mihai Netea of Radboud University in the Netherlands and colleagues published interim results of a randomized trial of BCG in elderly people in Greece that showed that people who received the vaccine were less likely than controls to develop infections of any kind in the following year; BCG appeared to be most protective against respiratory viruses.
Other results complicate the case for nonspecific effects. In a Danish trial of BCG also led by Benn, there was no difference between babies who received the vaccine at birth and those who didn’t get it at all in terms of hospitalization rates for infection over the first 15 months of life—except among BCG-vaccinated children whose mothers had also been BCG-vaccinated at some point prior to their pregnancies; these babies had a 35 percent lower hospitalization rate than their non-vaccinated peers. And two trials of a different strain of the BCG vaccine in low–birth weight infants in India, one of which administered BCG along with live polio vaccine, found no effect on mortality in the first 28 days after birth.
See “An Old TB Vaccine Finds New Life in Coronavirus Trials”
Nonspecific effects have garnered some high-profile attention as a potential near-term tool for fighting COVID-19. Robert Gallo, best known for his role in identifying HIV as the cause of AIDS in the 1980s, joined with Aaby, Benn, and other authors to pen an opinion article in a June issue of Science calling for studies to determine whether the live polio vaccine could protect against COVID-19. (In rare cases, one of the three viral strains can mutate and cause disease, but Gallo suggests this could be avoided by only using the other two strains.) Gallo, a cofounder of both the Institute of Human Virology at the University of Maryland School of Medicine and the Global Virus Network, wasn’t successful in persuading the National Institutes of Health to back such trials, he says, but he’s working with partners on clinical studies outside the US, chiefly in India. Netea says he knows of 15 current trials testing BCG against COVID-19, and two each of the oral polio and the measles, mumps, and rubella (MMR) vaccines.
If ongoing trials demonstrate that BCG reduces the incidence or severity of COVID-19, that finding could have implications beyond the current pandemic, says Curtis. It would indicate that the inoculation could also serve as a ready-made stopgap against future outbreaks of new viruses, he notes. He adds that his current study is examining whether BCG affects rates not just of COVID-19, but also of more-familiar respiratory infections such as the flu. If so, BCG “might be something you would just use in population groups like the elderly that are more susceptible” to infection.
Potential mechanisms of vaccines’ broad protection
While observations of nonspecific effects are decades old, hints about the mechanisms that might explain the phenomenon have only begun to emerge. Vaccines are designed to train the adaptive immune system—that is, primarily the T cells that recognize and kill specific pathogens and the B cells that make antibodies—to fight off a particular infection. To do this, vaccines typically include components of the pathogen they aim to protect against, or live viruses or bacteria that are closely related to the target pathogen but don’t cause illness. So it seems counterintuitive that their effects would extend beyond that target pathogen.
Netea, who collaborates with Benn, Aaby, and Curtis, says he thinks the lack of a mechanistic explanation for the non-specific effects seen in early studies led people to “kind of forget about it.” He himself only learned about the existing literature on such effects about a decade ago, when a student working in his lab was testing the immune response to the tuberculosis-causing bacterium after BCG vaccination. The student had used exposure to a pathogenic fungus as a control, and Netea was surprised to see that BCG helped the cells drawn from human volunteers who received the vaccine mount an immune response not only against Mycobacterium tuberculosis, but the fungus as well.
While observations of nonspecific effects are decades old, hints about the mechanisms that might explain the phenomenon have only begun to emerge.
To find out why this was, Netea led a larger study in which he and his colleagues again tested the blood of healthy volunteers before and after they were inoculated with BCG. Isolating pathogen-chomping innate immune cells known as monocytes and exposing them to a variety of pathogens in vitro, the team found that monocytes drawn after inoculation released 50 percent to 100 percent more of the immune cell–stimulating cytokines TNF and IL-1β. The researchers also identified specific post-inoculation changes to the methyl and acetyl tags on histones packaging the monocytes’ DNA. The authors concluded that BCG trains innate immunity via epigenetic alterations. “It’s like putting marks on the genes that are necessary for host defense,” Netea says. “Then, when you get an infection . . . those genes are marked by certain chemical modifications of the histones, and then the transcription factors can bind easier,” ramping up gene transcription to support a more robust immune response.
His and other groups have since elucidated similar processes in other components of the innate immune system, such as natural killer cells, Netea adds. And in a study published earlier this year, he and colleagues found that BCG vaccination in adults appears to shift gene transcription patterns in immune precursor cells in the bone marrow to a program needed to form a class of leukocytes known as myeloid cells. Similarly, BCG-vaccinated newborns quickly boost production of neutrophils, a type of myeloid cell, relative to their unvaccinated peers. (See illustration.)
Why would an infant’s immune cells need to be trained, rather than having the epigenetic marks for a robust immune response from the start? Netea says he suspects that the answer to that question has to do with the requirements of human pregnancy—namely, that the parent’s body not reject the fetus. Tamping down the parent’s immune system during pregnancy could also affect the fetus’s, he suggests, leading to babies born vulnerable to infection.
That early vulnerability, counteracted by live-vaccine immune training, may help explain the dramatic lowering of all-cause mortality found with early BCG vaccination in Guinea-Bissau. But epigenetic effects don’t appear to be the full story on how BCG—and potentially other live vaccines—provide nonspecific protections, at least in neonates.
In a study published earlier this year, a team led by Kollmann and Telethon Kids Institute researcher Nelly Amenyogbe (and also including Aaby and Benn) treated some newborn mice with BCG and then injected fecal bacteria into their abdomens, and into the abdomens of control animals, to simulate sepsis. They found that BCG initiated a process known as emergency granulopoiesis, which ramped up the production of neutrophils in the bone marrow. These cells “sit in the bone marrow, waiting . . . to gobble up bacteria and many other things,” Kollmann says. “And then, the moment we induce sepsis in these mice that have received BCG, [the neutrophils are] released, go to the site of infection . . . and knock off these bacteria within hours of the infectious process starting.”
What most struck Kollmann was the timeline for the emergency granulopoiesis-based protection: the process began within hours of BCG inoculation, and the peak of the neutrophil-based protection came three days later. It was fast, and it lined up with the findings in the 2011 study that had first drawn his attention to pathogen-agnostic effects. The speed of the nonspecific protection also meshed with results from two other trials that compared the effects of giving BCG at birth versus later—namely, that the vaccine provides dramatic protection that begins almost immediately after inoculation.
Kollmann says he hopes that the finding of a mechanism to back up the clinical trial data will lead to a more uniform practice of giving BCG to babies in high-risk settings immediately after birth. Longer term, he adds, more research is needed to better understand BCG’s beneficial effects. “We need to figure out: What is it about BCG that makes this happen? Can we formulate this, can we optimize this, can we make it better, faster?”
A Nonspecific Vaccine Risk? As a growing number of studies—epidemiological, clinical, and mechanistic—suggests that some vaccines arm the immune system for battle against pathogens other than the ones they were designed to target, a smaller and less rigorous body of evidence indicates that in some circumstances, other vaccines may do the opposite. Studies by Christine Stabell Benn and Peter Aaby of the Bandim Health Project and their colleagues point to non-live vaccines such as the diphtheria-tetanus-pertussis (DTP) shot possibly making girls—though not boys—temporarily more susceptible to illnesses other than the ones they’d been vaccinated against, Benn says. In a 2012 cohort study in Guinea-Bissau, for example, the researchers found that the group of girls who received DTP when they were two months old had more than twice the mortality rate between two and six months of age of those who hadn’t been vaccinated . But this study and others that have found a risk of increased all-cause mortality following non-live vaccines have drawn criticism for being observational, and—due to ethics concerns about delaying vaccination for experimental reasons, Benn says—no controlled trials have been published on whether such an effect exists. In a recent study, Benn and her colleagues compared the activity of immune cells from women in the Netherlands whose most recent vaccine was DTP with those whose most recent vaccine was the tuberculosis vaccine (called bacille Calmette-Guérin, or BCG), which consists of live, attenuated bacteria and has been linked to protection against a range of infections. The cells from the former group were less responsive to non-target pathogens than the cells from women who’s had the BCG vaccine, they found, leading Benn to suspect that while live vaccines train the immune system to go after any threat more effectively, non-live vaccines train it to instead tolerate invaders other than the vaccine’s target. She doesn’t advocate for doing away with DTP and other non-live vaccines, but argues that girls, at least, should receive a live vaccine shortly after non-live jabs to retune their immune systems. “What all these studies suggest is that it would be very wise to design different vaccination programs for boys and girls,” she says. Such potentially deleterious nonspecific effects received some attention last year with the rollout of a new malaria vaccine in a pilot program in three African countries, Malawi, Ghana, and Kenya. Benn and Aaby have voiced concerns that the vaccine, which is non-live, could increase all-cause mortality rates in girls, and they point to a post-hoc analysis of data from a Phase 3 trial that showed a higher mortality rate in infant girls who received the vaccine compared with those who didn’t. Kate O’Brien, the director of the World Health Organization’s (WHO) Department of Immunization, Vaccines and Biologicals, says that study wasn’t designed to test all-cause mortality, and notes in an email to The Scientist that “the female mortality in the [malaria] vaccine arm was similar to male mortality in the control and . . . vaccine arms.” The finding of higher all-cause mortality among girls was likely due to chance, she says. Nevertheless, the WHO is monitoring all-cause mortality in the ongoing trial of the vaccine, and so far the data indicate that there is no mortality increase associated with it, O’Brien notes.
Correction (November 13): Incorrect labels of the open and closed chromatin in the graphic have been corrected. The Scientist regrets the error.


thescientist--2020-11-01--Clues Point to Climate Change as a Culprit in Gray Whale Deaths

Bluish-tinged tongue lolling out , the gray whale lay in near silence on the sand of Long Beach , Washington .
The rhythmic whap , whap , whap of small waves lapping its belly punctuated the silence .
An oily , rotten odor surrounded the behemoth , which tipped the scales at 2,200 kilograms , the equivalent of four heavy-duty SUVs .
It was April of 2019 , and this whale was one of 34 that Jessie Huggins , who coordinates responses to marine mammal strandings in Washington State , helped to photograph , dissect , and discard that year @ @ @ @ @ @ @ up on the coast each year is common , she says , but last year 215 of them washed up along the marine mammal ’ s migration route between Alaska and Baja .
And so far this year , there have been more than 160 strandings .
“ Something ’ s clearly going on , ” says Sue Moore , an ecologist at the University of Washington who has studied gray whales for decades .
“ You ’ ve got a big uptick in the number of animals that we ’ re seeing @ @ @ @ @ @ @ the rapid rise in deaths , Moore and a team of scientists from the US , Mexico , and Canada have begun collating data from decades of past research on the species , Eschrichtius robustus .
They ’ re also collecting and analyzing samples from stranded individuals , tracking booms and busts in the gray whale population , and studying changes in the animal ’ s feeding habitats , determined to identify what exactly is killing the marine giants .
In addition to possibly helping to save the whales , says biologist John @ @ @ @ @ @ @ the nonprofit Cascadia Research Collective where Huggins works , understanding their deaths could be an “ incredibly key indicator of .
.
.
changing conditions in our whole global environment.
” A changing climate is one of a handful of leading factors that Moore , Calambokidis , and their collaborators are positing as causes of the gray whale deaths .
Ship strikes , entanglement in fishing gear , killer whale attacks , and the fact that the gray whale population may have hit its carrying capacity—meaning it ’ s outstripped the available food @ @ @ @ @ @ @ a classic murder mystery , the team is working to rule out these suspects one by one .
One of the first steps in the investigation is to examine the body of each gray whale that washes up on a beach .
When researchers arrive at a stranding , they conduct a thorough external exam , measuring the girth of the individual , determining its sex , and looking for markings on the whale ’ s body that could point to possible causes of death .
There may be fishing line or netting @ @ @ @ @ @ @ , body , or fins , for example , or visible bruising that may be a sign that the whale was hit by a boat .
Bruises that surround open gashes or rake marks in the flesh are clues that the animal was attacked by killer whales ( Orcinus orca ) .
Orcas are gray whales ’ number one predator , often targeting their calves .
Youngsters , and sometimes adults , have washed ashore along the grays ’ 12,000-mile spring migration route from Baja to Alaska with signs of such attacks .
@ @ @ @ @ @ @ will ram , harass , and bite the baby to separate it from its mother .
Then , the orcas let their own young make the kill .
In addition to telltale injuries on a gray whale ’ s body , death by killer whale is also evidenced by the absence of a gray whale ’ s tongue and jaw , which the predators typically devour , leaving the rest of it to rot .
Analyzing the autopsy data of 50 mostly young whales that stranded on the Pacific beaches of the United @ @ @ @ @ @ @ and his colleagues found evidence that 19 of the animals were killed by orcas ; an additional eight had rake marks indicating they ’ d been attacked .
Recent acoustic recordings detected more orca vocalizations near the Bering Strait , where many grays go for the summer to feed , than recordings from previous decades did .
These acoustic detections could mean there are more orcas in the gray whales ’ feeding habitat , Moore explains .
Or it could mean there are the same number of orcas but they have become more @ @ @ @ @ @ @ gray whales are in the Arctic .
Recent aerial surveys did not show an uptick in orca numbers , however , and “ there have always been killer whales up in that region , ” explains Moore , who says there ’ s no strong evidence that orca numbers have gone up significantly .
As a result , she and others reason , it ’ s unlikely that orcas are solely to blame for the recent spate of gray whale deaths .
More likely , according to Calambokidis , is that the whale @ @ @ @ @ @ @ there wasn ’ t enough food to go around .
Whale counts and population modeling suggest the species has recently seen a huge surge in numbers , from an estimated 19,000 in 2007 to 27,000 in 2017 .
“ That was pretty eye-popping , ” Moore says .
“ That ’ s a big population of gray whales.
” And now , the whales washing up on the beach seem to be exceptionally skinny , even taking into account that the animals have typically fasted for three to four months in the winter @ @ @ @ @ @ @ the west coast of North America in 2019 , 38 were considered emaciated .
The findings are reminiscent of the last uptick in whale strandings , which started in 1999 .
That year , at least 273 gray whales washed up on the Pacific beaches of North America ; the next year , there were 361 recorded strandings .
Many of those dead whales were also emaciated , seemingly suffering from nutritional stress , or possibly starvation .
As with the recent spike in deaths , researchers suspected the whale population had hit @ @ @ @ @ @ @ from overhunting earlier in the century , when the animals ’ numbers had dropped to as few as 1,000 from perhaps as large , at one point , as 100,000 .
With international protections that went into effect in the 1940s , along with the added security provided by the 1972 Marine Mammal Protection Act , the population rebounded so well that gray whales were removed from the endangered species list in 1994 .
Then came the exceptional number of dead whales washing ashore .
The similar pattern now unfolding , with an @ @ @ @ @ @ @ , fingers carrying capacity as a prime suspect .
But , Calambokidis notes , it ’ s too soon to close the case on the recent gray whale deaths .
That ’ s because the carrying capacity argument doesn ’ t address some key unknowns about the food supply , such as whether the whales ’ diet is changing due to “ the dramatic changes that are occurring in the Arctic environment , ” he says .
Moore agrees that warming temperatures and melting sea ice in the Arctic have to be considered @ @ @ @ @ @ @ little problem with [ the argument that ] all these whales are starving because they ’ ve hit this hard carrying capacity , ” she says , “ is that gray whales are very adept at eating a lot of different things.
” They particularly like to chow down on amphipods during the summer months in the Arctic , and also eat krill and other small crustaceans as well as herring roe while migrating along the North American coast .
For more clues to what ’ s killing gray whales , researchers are @ @ @ @ @ @ @ washed ashore .
If a beached whale has been dead for a day or less , scientists can cut into the animal ’ s skin and blubber to measure the thickness of the fatty layer and take samples to analyze its lipid levels .
“ How thick the blubber is and , more importantly .
.
.
the level of oil and lipids in the blubber and some internal body cavities tell you about the health of the animal , ” Calambokidis says .
While the blubber thickness has been seemingly similar across @ @ @ @ @ @ @ ashore recently have less oily blubber and more watery blubber compared with whales autopsied prior to 2019 , he says .
“ We ’ ve had cases where the blubber layer is still thick , but we ’ ll cut , and we can see it ’ s dry and fibrousy.
” He says it ’ s “ like all the oil and material has been .
.
.
sucked out of it.
” In nine emaciated whales studied last year , the researchers also noticed that the animals ’ blubber was discolored @ @ @ @ @ @ @ than the more rosy color of healthy blubber .
An analysis of the discolored blubber under the microscope revealed a disproportionate increase in collagen fibers relative to fat cells , along with structural changes to some of the fat cells themselves .
The results suggested that the whales weren ’ t getting the nutrition needed to maintain healthy blubber , leading some researchers to suspect that the marine mammals ’ diet could be changing , becoming less nutritious .
“ Polar seas are warming twice as fast as in other places , and @ @ @ @ @ @ @ of the ecosystem , ” says Moore .
Gray whales dine on small , shrimp-like crustaceans called amphipods that they siphon off the bottom of the Bering Sea and the Chukchi Sea in the Arctic .
Warming seas mean less sea ice , which in some ways could be seen as good for the whales because it opens up wider swaths of Arctic seafloor for a longer period to graze .
But the growth of bottom-dwelling amphipods relies on the ice , and particularly on the algae that grow underneath it .
When @ @ @ @ @ @ @ of summer , the algae sink to the seafloor , feeding amphipod populations .
With warming , Moore explains , that sea ice pattern has been very different , with “ the extreme surprise of winter sea ice really being absent in 2018 and 2019.
” That means algae didn ’ t collect on the ice or sink to the seafloor , and that the amphipods didn ’ t get the carbon they needed to thrive .
Without those algae , the crustaceans may fail to bulk up on lipids , the very @ @ @ @ @ @ @ from the dead gray whales ’ blubber .
The link between less-healthy amphipods and lower lipid levels in gray whales is circumstantial at this point , but whales might be emaciated because they are eating amphipods that have less lipids , making them less calorie-dense than the algae-fattened amphipods that the whales are used to feasting on .
The whales may also be eating other critters with lower calorie counts than the algae-fed amphipods .
When Calambokidis , Huggins , and others examined the guts of whales that washed ashore in Washington State @ @ @ @ @ @ @ , bark , eel grass , kelp , and certain crustaceans that gray whales don ’ t normally eat , suggesting the animals were so hungry they may have been foraging for suboptimal food .
“ Another line of research I ’ d like to see .
.
.
is what is the relative caloric value of those .
.
.
amphipods , which we know store a lot of lipid , versus something like a krill or a mysid , which is another type of invertebrate but not as lipid rich , @ @ @ @ @ @ @ are other favorite foods of gray whales that might give them sustenance , but quite possibly not the fat they need to survive yearly fasts during their migrations .
“ When you really start getting into the ecology , and the nutritional value of different types of prey that we know these animals eat , the story gets a little bit more complex than , ‘ There ’ s a lot of whales [ and ] they ’ re all starving , because they ’ ve eaten their way through their food supply @ @ @ @ @ @ @ agrees that identifying a single cause of death for gray whales is unlikely .
Any climate-driven changes in their diet might not kill the grays directly , but could make them more vulnerable to killer whale attacks , toxins , and ship strikes , for example .
Indeed , compared to the 1999–2000 die-offs , there have been more recorded ship strikes and entanglements among stranded whales in the last two years .
The whales are now feeding in different areas , including in shipping lanes near Seattle , San Francisco , and @ @ @ @ @ @ @ where there ’ s more fishing and crabbing gear , explains Frances Gulland , a marine mammal veterinarian at the University of California , Davis .
The pattern of deaths is also different this time around , she notes .
“ It ’ s been very spotty , and there are dead whales , but it ’ s not the continuous elevated mortality that we saw in 2000.
” Because of the lack of continuity in the deaths , Gulland agrees with the others that what ’ s killing gray whales is multifaceted @ @ @ @ @ @ @ accomplice .
“ I think the mistake is to be looking for just one thing , ” she says .
“ We ’ re still really struggling to try to understand what is going on with this population , ” Moore says .
And determining what ’ s killing them is essential , not only for the whales , but also for surveying the health of the ocean .
Gray whales “ are great oceanographers , ” she says .
“ They reflect back to us what ’ s going on in the @ @ @ @ @ @ @ .
”

ABOVE: © ISTOCK.COM, SLOWMOTIONGLI
Bluish-tinged tongue lolling out, the gray whale lay in near silence on the sand of Long Beach, Washington. The rhythmic whap, whap, whap of small waves lapping its belly punctuated the silence. An oily, rotten odor surrounded the behemoth, which tipped the scales at 2,200 kilograms, the equivalent of four heavy-duty SUVs. It was April of 2019, and this whale was one of 34 that Jessie Huggins, who coordinates responses to marine mammal strandings in Washington State, helped to photograph, dissect, and discard that year. Finding a few gray whales washed up on the coast each year is common, she says, but last year 215 of them washed up along the marine mammal’s migration route between Alaska and Baja. And so far this year, there have been more than 160 strandings.
“Something’s clearly going on,” says Sue Moore, an ecologist at the University of Washington who has studied gray whales for decades. “You’ve got a big uptick in the number of animals that we’re seeing dead on the beach.”
Startled by the rapid rise in deaths, Moore and a team of scientists from the US, Mexico, and Canada have begun collating data from decades of past research on the species, Eschrichtius robustus. They’re also collecting and analyzing samples from stranded individuals, tracking booms and busts in the gray whale population, and studying changes in the animal’s feeding habitats, determined to identify what exactly is killing the marine giants.
In addition to possibly helping to save the whales, says biologist John Calambokidis, one of the founders of the nonprofit Cascadia Research Collective where Huggins works, understanding their deaths could be an “incredibly key indicator of . . . changing conditions in our whole global environment.”
Death Map To investigate the deaths of gray whales, researchers have been tracking where they wash ashore along their migration route from Mexico to Alaska. The whales spend summers in the Arctic, where they dine on crustaceans called amphipods that live at the seafloor. Each whale can consume more than 2,000 pounds of food a day, amassing fat to fuel their yearly migration down to warmer waters off the Baja Peninsula, where they spend winters breeding and giving birth. During their 24,000-mile roundtrip journey, the whales eat almost nothing. Only occasionally along the way will they stop at snacking stations, skimming surface sea waters for squid, krill, crab larvae, and herring roe. Those snacks can often be enough for a whale to survive its yearlong fast, but may “not be enough for a pregnant female to bring a calf to term,” Moore says, or produce enough nutritious milk to support the growth of the baby’s blubber before making the trek back north. Sure enough, yearlings and adolescents accounted for most of the 2019 strandings. NOAA FISHERIES/MARINE MAMMAL HEALTH AND STRANDING RESPONSE PROGRAM
PDF See full infographic: WEB
Prime suspects
A changing climate is one of a handful of leading factors that Moore, Calambokidis, and their collaborators are positing as causes of the gray whale deaths. Ship strikes, entanglement in fishing gear, killer whale attacks, and the fact that the gray whale population may have hit its carrying capacity—meaning it’s outstripped the available food supply—are the others. As if solving a classic murder mystery, the team is working to rule out these suspects one by one.
One of the first steps in the investigation is to examine the body of each gray whale that washes up on a beach. When researchers arrive at a stranding, they conduct a thorough external exam, measuring the girth of the individual, determining its sex, and looking for markings on the whale’s body that could point to possible causes of death. There may be fishing line or netting wrapped around the animal’s mouth, body, or fins, for example, or visible bruising that may be a sign that the whale was hit by a boat. Bruises that surround open gashes or rake marks in the flesh are clues that the animal was attacked by killer whales (Orcinus orca).
We’re still really struggling to try to understand what is going on with this population. —Sue Moore, University of Washington
Orcas are gray whales’ number one predator, often targeting their calves. Youngsters, and sometimes adults, have washed ashore along the grays’ 12,000-mile spring migration route from Baja to Alaska with signs of such attacks. Hunting the whales in packs, orcas will ram, harass, and bite the baby to separate it from its mother. Then, the orcas let their own young make the kill. In addition to telltale injuries on a gray whale’s body, death by killer whale is also evidenced by the absence of a gray whale’s tongue and jaw, which the predators typically devour, leaving the rest of it to rot.
Analyzing the autopsy data of 50 mostly young whales that stranded on the Pacific beaches of the United States and Canada in 2019, Calambokidis and his colleagues found evidence that 19 of the animals were killed by orcas; an additional eight had rake marks indicating they’d been attacked. Recent acoustic recordings detected more orca vocalizations near the Bering Strait, where many grays go for the summer to feed, than recordings from previous decades did. These acoustic detections could mean there are more orcas in the gray whales’ feeding habitat, Moore explains. Or it could mean there are the same number of orcas but they have become more vocally active during the periods that the gray whales are in the Arctic.
Recent aerial surveys did not show an uptick in orca numbers, however, and “there have always been killer whales up in that region,” explains Moore, who says there’s no strong evidence that orca numbers have gone up significantly. As a result, she and others reason, it’s unlikely that orcas are solely to blame for the recent spate of gray whale deaths.
More likely, according to Calambokidis, is that the whale population had hit its carrying capacity and there wasn’t enough food to go around. Whale counts and population modeling suggest the species has recently seen a huge surge in numbers, from an estimated 19,000 in 2007 to 27,000 in 2017. “That was pretty eye-popping,” Moore says. “That’s a big population of gray whales.” And now, the whales washing up on the beach seem to be exceptionally skinny, even taking into account that the animals have typically fasted for three to four months in the winter. Of the 53 whales necropsied along the west coast of North America in 2019, 38 were considered emaciated.
SLENDER PROFILE: When examining a stranded whale, researchers consider the depth of the dip behind the whales head. If the whale has a significant dip (top), it is considered skinny and in poor health, but if there is no dip (bottom), the whale is in good condition. THE LAGUNA SAN IGNACIO ECOSYSTEM SCIENCE PROGRAM, A PROJECT OF THE OCEAN FOUNDATION
The findings are reminiscent of the last uptick in whale strandings, which started in 1999. That year, at least 273 gray whales washed up on the Pacific beaches of North America; the next year, there were 361 recorded strandings. Many of those dead whales were also emaciated, seemingly suffering from nutritional stress, or possibly starvation. As with the recent spike in deaths, researchers suspected the whale population had hit its carrying capacity, having recently rebounded from overhunting earlier in the century, when the animals’ numbers had dropped to as few as 1,000 from perhaps as large, at one point, as 100,000. With international protections that went into effect in the 1940s, along with the added security provided by the 1972 Marine Mammal Protection Act, the population rebounded so well that gray whales were removed from the endangered species list in 1994. Then came the exceptional number of dead whales washing ashore.
The similar pattern now unfolding, with an uptick in deaths following a population boom, fingers carrying capacity as a prime suspect. But, Calambokidis notes, it’s too soon to close the case on the recent gray whale deaths. That’s because the carrying capacity argument doesn’t address some key unknowns about the food supply, such as whether the whales’ diet is changing due to “the dramatic changes that are occurring in the Arctic environment,” he says.
Moore agrees that warming temperatures and melting sea ice in the Arctic have to be considered. “The reason I have a little problem with [the argument that] all these whales are starving because they’ve hit this hard carrying capacity,” she says, “is that gray whales are very adept at eating a lot of different things.” They particularly like to chow down on amphipods during the summer months in the Arctic, and also eat krill and other small crustaceans as well as herring roe while migrating along the North American coast.
Arctic warming as a possible killer
For more clues to what’s killing gray whales, researchers are slicing deeper into the animals that have washed ashore. If a beached whale has been dead for a day or less, scientists can cut into the animal’s skin and blubber to measure the thickness of the fatty layer and take samples to analyze its lipid levels. “How thick the blubber is and, more importantly . . . the level of oil and lipids in the blubber and some internal body cavities tell you about the health of the animal,” Calambokidis says.
While the blubber thickness has been seemingly similar across the years, whales that have washed ashore recently have less oily blubber and more watery blubber compared with whales autopsied prior to 2019, he says. “We’ve had cases where the blubber layer is still thick, but we’ll cut, and we can see it’s dry and fibrousy.” He says it’s “like all the oil and material has been . . . sucked out of it.”
Recently stranded whales have less oily blubber and more watery blubber compared with whales autopsied prior to 2019.
In nine emaciated whales studied last year, the researchers also noticed that the animals’ blubber was discolored, appearing as a washed-out pink rather than the more rosy color of healthy blubber. An analysis of the discolored blubber under the microscope revealed a disproportionate increase in collagen fibers relative to fat cells, along with structural changes to some of the fat cells themselves. The results suggested that the whales weren’t getting the nutrition needed to maintain healthy blubber, leading some researchers to suspect that the marine mammals’ diet could be changing, becoming less nutritious. “Polar seas are warming twice as fast as in other places, and we know that that is changing aspects of the ecosystem,” says Moore.
Gray whales dine on small, shrimp-like crustaceans called amphipods that they siphon off the bottom of the Bering Sea and the Chukchi Sea in the Arctic. Warming seas mean less sea ice, which in some ways could be seen as good for the whales because it opens up wider swaths of Arctic seafloor for a longer period to graze. But the growth of bottom-dwelling amphipods relies on the ice, and particularly on the algae that grow underneath it. When the sea ice melts at the beginning of summer, the algae sink to the seafloor, feeding amphipod populations. With warming, Moore explains, that sea ice pattern has been very different, with “the extreme surprise of winter sea ice really being absent in 2018 and 2019.” That means algae didn’t collect on the ice or sink to the seafloor, and that the amphipods didn’t get the carbon they needed to thrive. Without those algae, the crustaceans may fail to bulk up on lipids, the very type of molecule that’s depleted from the dead gray whales’ blubber.
How Climate Change Puts Whales At Risk Over the past two years, hundreds of gray whales have washed ashore along North America’s west coast. Researchers are learning that the answer to the question of why these whales are dying is complex, but likely involves warming ocean waters and melting Arctic sea ice brought on by climate change. So far, the evidence is circumstantial, and scientists are still seeking more-definitive data about what’s killing the marine giants. © LOGAN PARSONS ILLUSTRATION Malnourished whales are probably not as good at fending off orca attacks, toxins, and maladies that make them more vulnerable to death. Without sea ice to collect algae, which would normally fall to the seafloor when the ice melts seasonally, shrimp-like crustaceans called amphipods
that use the algae as a source of carbon become less nutritious food for gray whales, affecting mammals’ ability to pack on blubber for the winter. Having less ice opens more-northern territories for whales to feed. Reduced ice also leads to an increase in commercial shipping along the Northern Sea Route, raising chances for ships to collide with whales. The whales may ingest toxins, such as the neurotoxin domoic acid, from the sediment as they filter feed, which could be damaging to animals that are unhealthy as a result of warming waters.
PDF See full infographic: WEB
The link between less-healthy amphipods and lower lipid levels in gray whales is circumstantial at this point, but whales might be emaciated because they are eating
amphipods that have less lipids, making them less calorie-dense than the algae-fattened amphipods that the whales are used to feasting on. The whales may also be eating other critters with lower calorie counts than the algae-fed amphipods. When Calambokidis, Huggins, and others examined the guts of whales that washed ashore in Washington State, they found remnants of wood chips, bark, eel grass, kelp, and certain crustaceans that gray whales don’t normally eat, suggesting the animals were so hungry they may have been foraging for suboptimal food. “Another line of research I’d like to see . . . is what is the relative caloric value of those . . . amphipods, which we know store a lot of lipid, versus something like a krill or a mysid, which is another type of invertebrate but not as lipid rich,” Moore says. Krill and mysid are other favorite foods of gray whales that might give them sustenance, but quite possibly not the fat they need to survive yearly fasts during their migrations.
“When you really start getting into the ecology, and the nutritional value of different types of prey that we know these animals eat, the story gets a little bit more complex than, ‘There’s a lot of whales [and] they’re all starving, because they’ve eaten their way through their food supply,’” Moore says.
BEACHED: An adult female gray whale measuring more than 12 meters long washed up at California’s Point Reyes National Seashore in April 2019. BARBIE HALASKA, THE MARINE MAMMAL CENTER
Calambokidis agrees that identifying a single cause of death for gray whales is unlikely. Any climate-driven changes in their diet might not kill the grays directly, but could make them more vulnerable to killer whale attacks, toxins, and ship strikes, for example. Indeed, compared to the 1999–2000 die-offs, there have been more recorded ship strikes and entanglements among stranded whales in the last two years. The whales are now feeding in different areas, including in shipping lanes near Seattle, San Francisco, and Los Angeles, and also in areas where there’s more fishing and crabbing gear, explains Frances Gulland, a marine mammal veterinarian at the University of California, Davis.
The pattern of deaths is also different this time around, she notes. “It’s been very spotty, and there are dead whales, but it’s not the continuous elevated mortality that we saw in 2000.” Because of the lack of continuity in the deaths, Gulland agrees with the others that what’s killing gray whales is multifaceted, with climate change acting as an accomplice. “I think the mistake is to be looking for just one thing,” she says.
“We’re still really struggling to try to understand what is going on with this population,” Moore says. And determining what’s killing them is essential, not only for the whales, but also for surveying the health of the ocean. Gray whales “are great oceanographers,” she says. “They reflect back to us what’s going on in the water. They are our ocean sentinels.”


thescientist--2020-11-01--Octopod Sailors, 300 BC-present

Octopod Sailors, 300 BC-present

They were said to float atop the sea surface using their shells as gracile vessels , and to lift two of their eight arms as sails that would catch the wind and propel them through the water while the other arms served as oars .
This legend , which traces back to Aristotle around 300 BC , describes unique octopuses called argonauts , referencing the sailors of the Argo from Greek mythology .
But while argonauts are one of a handful of octopus groups that have left the seafloor to adopt a pelagic lifestyle , they do not , in @ @ @ @ @ @ @ surface .
From Aristotle ’ s time on , “ the story got more and more embellished , ” says Julian Finn , a curator of marine invertebrates at Museums Victoria in Australia and an expert on argonaut taxonomy , biology , and lore .
“ And then people started drawing them based on the story , ” eventually getting to “ this argonaut sailing high above the surface.
” SETTING SAIL : This illustration of Argonauta argo by William Daniell comes from William Wood ’ s 1807 natural history text Zoography .
@ @ @ @ @ @ @ often called a paper nautilus , “ is supplied with eight arms , two of which are furnished at their extremity with an oval membrane that serves for a sail , while the other six , hanging over the sides of the boat , are employed as oars , and occasionally serve to steer by.
” This illustration was likely copied from an earlier one , according to Julian Finn of Museums Victoria ; both illustrations incorrectly show the octopus ’ s “ sails ” —actually membranous webs on its top arms—projecting outward @ @ @ @ @ @ @ reality , the argonaut ’ s webs do not have an open end , but are fully surrounded by the animal ’ s arms , and often stretch out over the sides of their shells .
Biodiversity Heritage Library , Zoography ; or , The beauties of nature displayed .
In select descriptions from the animal , and vegetable , with additions from the mineral kingdom .
SystematicalLY arranged Myths about argonauts ( family Argonautidae ) continued to flourish thanks in part to the fact that the octopuses are elusive , fostering misconceptions @ @ @ @ @ @ @ questions unanswered for millennia .
In the early 19th century , for example , zoologist Georges Cuvier mistook the detached arms of tiny ( 1- to 2-centimeter-long ) , shell-less male argonauts for parasitic worms when he found them inside female octopuses .
In fact , researchers later learned that when a male encounters a potential mate , it releases an arm loaded with sperm that can crawl into the female ’ s mantle cavity .
In the 1830s , French marine biologist Jeanne Villepreux-Power put to bed an age-old rumor that female @ @ @ @ @ @ @ , confirming that they make their own and use it as a brood case for their eggs .
Adding to the aura of mystery around argonauts is the fact that , every so often , thousands or even tens of thousands of them wash up on a beach .
Some people had speculated that air gets trapped in the animals ’ shells and causes them to float and wash ashore , but no one had ever documented the argonauts ’ behavior in their natural environment to find out whether air bubbles in shells @ @ @ @ @ @ @ 2005 and January 2006 , Finn , then a PhD student , went with fishermen off Shimane Peninsula in the Sea of Japan each morning in the hopes that they would see a female greater argonaut ( Argonauta argo ) .
Before long , Finn had scooped up a total of three female argonauts .
He transported them to a nearby harbor , where he would remove all air from the shell of one of the argonauts before he released it just above the seafloor and observed its behavior .
“ Straight away @ @ @ @ @ @ @ see that it just didn ’ t have stability underwater , ” Finn says .
But then the argonaut would jet up to the surface and rock back and forth with its shell sticking out of the water to capture air .
The octopus would use one arm to contain the air in the shell before it dove to a depth where the animal became neutrally buoyant ( Proc Roy Soc B , 277:2967–71 , 2010 ) .
“ And then it just shot off .
.
.
.
It went from being @ @ @ @ @ @ @ being a perfect submarine—it was so graceful.
” So air in an argonaut ’ s shell is probably not what leads to the animal ’ s untimely demise , Finn reasons .
The cause of the mass argonaut strandings , along with much else about these storied creatures , remains a mystery .

ABOVE: JULIAN FINN, MUSEUMS VICTORIA
They were said to float atop the sea surface using their shells as gracile vessels, and to lift two of their eight arms as sails that would catch the wind and propel them through the water while the other arms served as oars. This legend, which traces back to Aristotle around 300 BC, describes unique octopuses called argonauts, referencing the sailors of the Argo from Greek mythology. But while argonauts are one of a handful of octopus groups that have left the seafloor to adopt a pelagic lifestyle, they do not, in fact, sail the water’s surface.
From Aristotle’s time on, “the story got more and more embellished,” says Julian Finn, a curator of marine invertebrates at Museums Victoria in Australia and an expert on argonaut taxonomy, biology, and lore. “And then people started drawing them based on the story,” eventually getting to “this argonaut sailing high above the surface.”
SETTING SAIL: This illustration of Argonauta argo by William Daniell comes from William Wood’s 1807 natural history text Zoography. Wood writes that the bizarre octopus, often called a paper nautilus, “is supplied with eight arms, two of which are furnished at their extremity with an oval membrane that serves for a sail, while the other six, hanging over the sides of the boat, are employed as oars, and occasionally serve to steer by.” This illustration was likely copied from an earlier one, according to Julian Finn of Museums Victoria; both illustrations incorrectly show the octopus’s “sails”—actually membranous webs on its top arms—projecting outward from the arms like flags. In reality, the argonaut’s webs do not have an open end, but are fully surrounded by the animal’s arms, and often stretch out over the sides of their shells. Biodiversity Heritage Library, Zoography; or, The beauties of nature displayed. In select descriptions from the animal, and vegetable, with additions from the mineral kingdom. SystematicalLY arranged
Myths about argonauts (family Argonautidae) continued to flourish thanks in part to the fact that the octopuses are elusive, fostering misconceptions about their biology and leaving many fundamental questions unanswered for millennia. In the early 19th century, for example, zoologist Georges Cuvier mistook the detached arms of tiny (1- to 2-centimeter-long), shell-less male argonauts for parasitic worms when he found them inside female octopuses. In fact, researchers later learned that when a male encounters a potential mate, it releases an arm loaded with sperm that can crawl into the female’s mantle cavity. In the 1830s, French marine biologist Jeanne Villepreux-Power put to bed an age-old rumor that female argonauts steal their shells from other animals, confirming that they make their own and use it as a brood case for their eggs.
Adding to the aura of mystery around argonauts is the fact that, every so often, thousands or even tens of thousands of them wash up on a beach. Some people had speculated that air gets trapped in the animals’ shells and causes them to float and wash ashore, but no one had ever documented the argonauts’ behavior in their natural environment to find out whether air bubbles in shells present an issue.
So in December 2005 and January 2006, Finn, then a PhD student, went with fishermen off Shimane Peninsula in the Sea of Japan each morning in the hopes that they would see a female greater argonaut (Argonauta argo). Before long, Finn had scooped up a total of three female argonauts. He transported them to a nearby harbor, where he would remove all air from the shell of one of the argonauts before he released it just above the seafloor and observed its behavior.
“Straight away, it floundered around and you could see that it just didn’t have stability underwater,” Finn says. But then the argonaut would jet up to the surface and rock back and forth with its shell sticking out of the water to capture air. The octopus would use one arm to contain the air in the shell before it dove to a depth where the animal became neutrally buoyant (Proc Roy Soc B, 277:2967–71, 2010). “And then it just shot off. . . . It went from being this animal that was struggling underwater to being a perfect submarine—it was so graceful.”
So air in an argonaut’s shell is probably not what leads to the animal’s untimely demise, Finn reasons. The cause of the mass argonaut strandings, along with much else about these storied creatures, remains a mystery.


thescientist--2020-11-01--Slingshot Spiders Pull More Gs than Cheetahs

ABOVE : A slingshot spider prepares to launch its cone-shaped web at a flying insect .
To do so , the spider will release a bundle of silk , catapulting both the spider and the web .
LAWRENCE E. REEVES Leg over leg , a furry brownish-black spider tugs on a single silk thread , tightening the frame of its web .
It pulls and pulls , as if removing slack from a slingshot , and then it waits .
Minutes pass , sometimes hours .
Then , when an unsuspecting insect flies by , the spider releases the thread @ @ @ @ @ @ @ web toward its prey .
All of this happens in the blink of an eye , with the spider and its web hurtling through the air at more than 4 meters per second ( 9 miles per hour ) with accelerations exceeding 130 g. That ’ s 130 times the acceleration experienced in freefall , and an order of magnitude greater than that of a sprinting cheetah .
Those eye-watering numbers led Georgia Tech chemical engineer Saad Bhamla to wonder : How the heck are these tiny spiders achieving such fast movements ?
@ @ @ @ @ @ @ with ultra-fast motions in biology , ” he says , so when he spotted one of these spiders flying past his face a few years ago while he was hiking through the Peruvian rainforest , he knew he had to investigate .
He checked the literature and found only a few papers on Theridiosomatidae , the arachnid family comprising spider species that use their webs as slingshots .
The papers were decades old and only described the slingshot motion , not the speeds or g-forces the spiders experienced .
So Bhamla enlisted the @ @ @ @ @ @ @ , and together they “ went out hunting for spiders in the Amazon rainforest , ” Alexander says .
After locating one of the spiders , which measure roughly 2 millimeters in length , the researchers would set up portable high-speed cameras with magnifying lenses to zoom in on and record their motions .
Then , either Alexander or Bhamla would snap their fingers to get the spider to catapult itself through the air .
Only later did the pair learn that a human finger-snap closely matches the frequency of a buzzing mosquito—and @ @ @ @ @ @ @ that set the spiders ’ spring off .
“ It ’ s just amazing that we can snap our fingers and get this magical thing , ” Bhamla says .
Analyzing the footage , Alexander and Bhamla could watch exactly how the spiders oriented themselves on the tension line at the front of their webs .
Facing away from the web , the spider grips its silk net with its four back legs and pulls itself up the tension line with its four front legs , bundling it up in two front appendages @ @ @ @ @ @ @ sensing the sounds of prey nearby-—most likely via its web , which appears to act like a small antenna—the spider releases the tension line .
Although researchers had previously assumed it let go of the silk thread altogether , Alexander and Bhamla ’ s videos show that the spider in fact only releases some of the line while keeping hold of a part of it with its pedipalps , making it easier to reset its slingshot to trap its next victim .
Again and again , the spider captures an insect , wraps @ @ @ @ @ @ @ “ comes right back to that tension line and bundles it up again .
That allows it to reset and reload pretty quickly , ” Alexander says .
The spider can usually slingshot itself several times before the web is destroyed .
The speeds and accelerations of this spider are impressive , but so is the fact that , unlike most web-building spiders , it ’ s actively hunting , Bhamla says .
“ It ’ s changed the function of its web , ” he says .
“ Instead of waiting for @ @ @ @ @ @ @ spider is going after things .
.
.
actually catching flying insects in midair.
” To see the video of this little spider pull on its line , load its web , sense its prey , and then fly through the air to trap it is humbling , says Sheila Patek , a biologist at Duke University who studies tiny spring mechanisms across the natural world but was not involved in this work .
“ We humans always think we ’ re the best at everything , and in the natural world , @ @ @ @ @ @ @ s pretty difficult.
” Other critters , including trap-jaw spiders and mantis shrimp , can move certain appendages such as claws or mouthparts at speeds of 30 to 80 kilometers per hour ( 20 to 50 miles per hour ) , she says .
But slingshot spiders are using an external tool , a web , to snare their prey , and they ’ re working at speeds faster than their nervous systems can monitor , so they have to plan ahead and essentially let their spring and latch system control what happens @ @ @ @ @ @ @ thread .
“ It ’ s superpower-type stuff , ” Patek says .
Theridiosomatidae aren ’ t completely unique in this respect , however .
Spiders in the Hyptiotes genus also use orb webs to actively hunt .
Hyptiotes spiders move at slower accelerations—a mere 772.85 m/s2 , compared with the Theridiosomatidae ’ s 1300 m/s2—yet they load energy in their webs similarly , then rocket toward prey , unleashing additional silk threads onto their victims to finalize the capture .
When the spider stops itself suddenly by clamping down on its tension @ @ @ @ @ @ @ jerk on the web wraps the capture threads around its prey from all directions .
What ’ s fascinating is the amount of energy the spiders can store in their web and then unleash to catch their prey , says Sarah Han , a graduate student in biologist Todd Blackledge ’ s lab at the University of Akron .
With Blackledge , she wants to investigate how the webbing material , typically thought to disperse energy , can , in fact , store energy , a characteristic that might inform the design of @ @ @ @ @ @ @ collaborating with Alexander , who will be starting her own lab at Auburn University in 2021 , and Bhamla on Theridiosomatidae , to look at how those spiders have evolved their slingshot systems .
Now that high-speed camera footage can offer scientists a frame-by-frame view of what the arachnids are doing , Patek says , “ it just opens up a myriad of areas of research in evolution , neuroscience , materials science , and human engineering .
”

ABOVE: A slingshot spider prepares to launch its cone-shaped web at a flying insect. To do so, the spider will release a bundle of silk, catapulting both the spider and the web.
LAWRENCE E. REEVES
Leg over leg, a furry brownish-black spider tugs on a single silk thread, tightening the frame of its web. It pulls and pulls, as if removing slack from a slingshot, and then it waits. Minutes pass, sometimes hours. Then, when an unsuspecting insect flies by, the spider releases the thread, springing itself and its satellite dish–shaped web toward its prey. All of this happens in the blink of an eye, with the spider and its web hurtling through the air at more than 4 meters per second (9 miles per hour) with accelerations exceeding 130 g. That’s 130 times the acceleration experienced in freefall, and an order of magnitude greater than that of a sprinting cheetah.
The spider can usually slingshot itself several times before the web is destroyed.
Those eye-watering numbers led Georgia Tech chemical engineer Saad Bhamla to wonder: How the heck are these tiny spiders achieving such fast movements? Bhamla’s lab is “obsessed with ultra-fast motions in biology,” he says, so when he spotted one of these spiders flying past his face a few years ago while he was hiking through the Peruvian rainforest, he knew he had to investigate. He checked the literature and found only a few papers on Theridiosomatidae, the arachnid family comprising spider species that use their webs as slingshots. The papers were decades old and only described the slingshot motion, not the speeds or g-forces the spiders experienced. So Bhamla enlisted the help of his postdoc, Symone Alexander, and together they “went out hunting for spiders in the Amazon rainforest,” Alexander says.
After locating one of the spiders, which measure roughly 2 millimeters in length, the researchers would set up portable high-speed cameras with magnifying lenses to zoom in on and record their motions. Then, either Alexander or Bhamla would snap their fingers to get the spider to catapult itself through the air. Only later did the pair learn that a human finger-snap closely matches the frequency of a buzzing mosquito—and that seemed to be the only frequency that set the spiders’ spring off. “It’s just amazing that we can snap our fingers and get this magical thing,” Bhamla says.
ANDRZEJ KRAUZE
Analyzing the footage, Alexander and Bhamla could watch exactly how the spiders oriented themselves on the tension line at the front of their webs. Facing away from the web, the spider grips its silk net with its four back legs and pulls itself up the tension line with its four front legs, bundling it up in two front appendages called pedipalps as it goes. On sensing the sounds of prey nearby-—most likely via its web, which appears to act like a small antenna—the spider releases the tension line. Although researchers had previously assumed it let go of the silk thread altogether, Alexander and Bhamla’s videos show that the spider in fact only releases some of the line while keeping hold of a part of it with its pedipalps, making it easier to reset its slingshot to trap its next victim. Again and again, the spider captures an insect, wraps it in silk for later, then “comes right back to that tension line and bundles it up again. That allows it to reset and reload pretty quickly,” Alexander says. The spider can usually slingshot itself several times before the web is destroyed.
The speeds and accelerations of this spider are impressive, but so is the fact that, unlike most web-building spiders, it’s actively hunting, Bhamla says. “It’s changed the function of its web,” he says. “Instead of waiting for something to collide with it, the spider is going after things . . . actually catching flying insects in midair.”
SETTING UP: Chemical engineer Saad Bhamla (left), postdoctoral researcher Symone Alexander (center), and Peruvian field guide Jaime Navarro adjust an ultrafast camera in preparation for imaging a slingshot spider. GEOFF GALLICE
To see the video of this little spider pull on its line, load its web, sense its prey, and then fly through the air to trap it is humbling, says Sheila Patek, a biologist at Duke University who studies tiny spring mechanisms across the natural world but was not involved in this work. “We humans always think we’re the best at everything, and in the natural world, those spiders are doing something that’s pretty difficult.” Other critters, including trap-jaw spiders and mantis shrimp, can move certain appendages such as claws or mouthparts at speeds of 30 to 80 kilometers per hour (20 to 50 miles per hour), she says. But slingshot spiders are using an external tool, a web, to snare their prey, and they’re working at speeds faster than their nervous systems can monitor, so they have to plan ahead and essentially let their spring and latch system control what happens after they let go of the tension thread. “It’s superpower-type stuff,” Patek says.
Instead of waiting for something to collide with it, the spider is going after things . . . actually catching flying insects in midair. —Saad Bhamla, Georgia Tech
Theridiosomatidae aren’t completely unique in this respect, however. Spiders in the Hyptiotes genus also use orb webs to actively hunt. Hyptiotes spiders move at slower accelerations—a mere 772.85 m/s2, compared with the Theridiosomatidae’s 1300 m/s2—yet they load energy in their webs similarly, then rocket toward prey, unleashing additional silk threads onto their victims to finalize the capture. When the spider stops itself suddenly by clamping down on its tension thread with its legs, the resulting jerk on the web wraps the capture threads around its prey from all directions.
What’s fascinating is the amount of energy the spiders can store in their web and then unleash to catch their prey, says Sarah Han, a graduate student in biologist Todd Blackledge’s lab at the University of Akron. With Blackledge, she wants to investigate how the webbing material, typically thought to disperse energy, can, in fact, store energy, a characteristic that might inform the design of synthetic silk. Han also recently began collaborating with Alexander, who will be starting her own lab at Auburn University in 2021, and Bhamla on Theridiosomatidae, to look at how those spiders have evolved their slingshot systems. Now that high-speed camera footage can offer scientists a frame-by-frame view of what the arachnids are doing, Patek says, “it just opens up a myriad of areas of research in evolution, neuroscience, materials science, and human engineering.”