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Power of 3

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Nancy Reich. Photo from SBU

By Daniel Dunaief

Even as pharmaceutical companies are working furiously to produce a vaccine for COVID-19, scientists are taking other approaches that might lead to treatment for this disease or for other viruses that might threaten public health.

Nancy Reich, a Professor in the Department of Microbiology and Immunology at the Renaissance School of Medicine at Stony Brook University, and several colleagues at SBU recently received a $450,000 grant from the G. Harold and Leila Y. Mathers Foundation to pursue the laboratory study of two possible interventions.

Reich and her colleagues plan to investigate the use of interferon-lambda, which is in clinical trials for Hepatitis D virus, and an inhibitor for bradykinin called icatibant, which is approved for angioedema.

“Although we are very hopeful for a vaccine in the near future, vaccines can take months or years” to develop and use, Reich said. “The likelihood is that there will be more emerging diseases” which increases the need for broad spectrum first line defense therapeutics that might provide relief and save lives.

A few months ago, several faculty in microbiology and immunology got together on a Zoom call to discuss what they could do to combat COVID-19. The group was “very enthusiastic” about interferon, which is a natural hormone and is the only cytokine that’s antiviral. It has the ability to prevent the spread of the virus by reducing replication.

Reich will work with Patrick Hearing and Erich Mackow, who are both professors in the Department of Microbiology and Immunology, on the molecular aspects of COVID-19. Associate Professor Janet Hearing and Assistant Professor Hwan Kim are certified to work in high containment biosafety laboratories.

COVID-19 seems to have figured out how to block the action or production of interferon, Reich said, although the lower levels of the hormone haven’t been confirmed yet.

Other researchers are testing how the virus that has caused the pandemic has blocked the production of this defense mechanism. The Reich-led group is also planning to test this process.

To get protection from interferon, people would likely need an increased amount of the antiviral molecule early in the infection process, Reich said. She and her team are focusing on interferon lambda, which is a specific type that primarily affect epithelial cells, which are the type of cells that line the respiratory and digestive systems.

Interferon alpha and beta cause systemic problems, which can trigger an overactive immune system to cause a cytokine storm. This can lead to severe symptoms, if the body’s reaction is strong enough.

“Because interferon lambda is more specialized in the targets it hits, it doesn’t cause this crazy, global effect in your body,” Reich said.

At this point, Reich is looking to use a pre-clinical animal model of COVID-19 to understand the processes involved with the virus and its reaction to different concentrations of this hormone at different times after infection.

Reich has reached out to a company called EIGR Pharmaceuticals, which is the only company that produces a pegylated version of interferon lambda. By adding polyethlylene glycol, or PEG, EIGR can extend the time that the drug remains in the body, reducing the need for new doses.

The interferon lambda receptors are prevalent in hepatocytes, or liver cells. The liver is particularly important in capturing bacteria, viruses and macromolecules that might otherwise cause harm in the human body. The interest in the liver and interferon is mainly because of hepatitis viruses.

Interferon lambda’s higher specificity reduces potential side effects that other interferons trigger in the blood or in the central nervous system. EIGR has created this interferon to treat Hepatitis D.

“I have contacted [EIGR] to do some COVID work and now they are,” Reich said. “They have some clinical trials going on in the United States, Israel and Australia.” In addition to their research work with interferon lambda, the group will also study the effects of bradykinin, which is a small peptide hormone that the angiotensin-converting enzyme 2 (or ACE2) receptor inactivates.

The group is exploring the use of inhibitors for bradykinin, hoping to reduce a molecular trigger that exacerbates symptoms of the disease.

“We are taking two approaches; one is more about the symptoms, through bradykinin inhibition, and the other is trying to block virus replication,” said Reich.

In their research with interferon and inhibitors to bradykinin, Reich is hoping to generate data that will be ready within several months.

If both of the approaches proves effective independently, Reich said the next steps could involve combining them.

If the combination works better than either of the treatments alone, the researchers, and, down the road, the doctors, who might use this approach could use a lower dose of both drugs, which could reduce any potential side effects.

Reich said this research is possible at Stony Brook because it has a Biosafety Level 3.“We are able to do these experiments that others may not be able to do,” she said.

The animal facility that will house the mice for her studies is still not accepting new animals. Reich hopes they start to accept them in June.

Reich appreciated the speed at which the Mathers Charitable Foundation reacted to their request for funds.

The Foundation, which was created by a Santa Barbara, California couple who donated their wealth to research in 1983, made a decision within weeks, reflecting the urgency that the public health crisis triggered by COVID-19 has created.

Many foundations typically take six to eight months to decide on funding.

Reich appreciates that she and her colleagues will have a chance to contribute to a growing body of research about a virus that has caused close to 100,000 deaths in the United States and has disrupted billions of lives around the world.

“Everybody realizes the urgency,” Reich said.

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Jennifer Keluskar. Photo from SBU

By Daniel Dunaief

In the second of a two-part series, Times Beacon Record News Media describes the clinical and research work of Jennifer Keluskar, a Clinical Professor in the Department of Psychiatry at Stony Brook University.

Keluskar and Matthew Lerner, an Associate Professor of Psychology, Psychiatry & Pediatrics (see last week’s paper), recently received a grant from the Office of the Vice President for Research & the Institute for Engineering-Driven Medicine to study the effects of COVID-19-induced social isolation on people with Autism Spectrum Disorder. 

Keluskar spends half her time working at the Outpatient Department of Psychiatry, Child and Adolescent Services, where she provides cognitive behavioral intervention and ASD diagnostic evaluations for youth with autism, and the other half working on the SB Autism Initiative.

The pandemic has challenged young people with autism, as they manage through social isolation and worry about an uncertain future. Many of Jennifer Keluskar’s patients are struggling, with some dreading the return to school in the fall and others grappling with the removal or change in a routine or structure.

Some of her clients have felt increased pressure to organize their time and be productive amid a lack of peer support and without the opportunities to model their performance based on interacting with other students at school.

Through modeling, some students take notes when they notice their classmates writing down concepts or ideas a teacher is sharing or gaining some measure of reassurance when they see that everyone is struggling with the work load.

“This latter point is particularly relevant given the novelty of this situation for teachers as well as the consequent likelihood that they will have trouble knowing how much work to give, especially given the wide variety” of circumstances at home, Keluskar explained in an email.

For some students with autism who have a measure of social-anxiety disorder, the remote learning environment has provided some measure of relief, reducing the difficulty in reading nonverbal cues from their classmates and teachers.

Now that these students are learning remotely, these “social stressors have been lifted,” Keluskar said.

Nonetheless, even the patients who have felt relieved about fewer anxiety-inducing social interactions are starting to develop concerns about a potential resumption of classes in the fall.

Keluskar has already seen some patients who are perseverating on that future upcoming transition. “We are going to see more of it in my clientele as we get closer to reopening schools,” she said, adding that she has some patients who are afraid of not being able to advance in life, to college or to jobs, but who, at the same time, are afraid of taking the next step after getting used to quarantine.

Jennifer Keluskar with her husband Raja, 5-year-old daughter Skylar and three-year-old son Colby.

Working with Alan Gerber, a graduate student in Matthew Lerner’s lab at SBU, Keluskar will assess responses to COVID-19. They have sent out two questionnaires. One, which was released by other researchers, examines how the pandemic has affected circumstances and behaviors, from employment changes to junk food consumption. The other is an evidence-based measure of parental stress that is not specific to the virus. She is going to measure anxiety and depression to see how they change during quarantine. 

Keluskar appreciates how the Initiative offers programs such as a homework club, which students can attend virtually for an hour each day. “I have connected some of my clients in the clinic to undergraduate mentors and so far this has been quite successful” although the scale of these connections has been small so far.

The Initiative currently has a mentoring program geared towards older adolescents. She is planning to offer this program to younger individuals.

Deborah Gross, the Initiative’s coordinator, runs a program called the Sidekicks Squad, which is for older adolescents and young adults with special needs.

“Some of my patients would benefit from pairing with a mentor,” Keluskar said. “Through these mentoring sessions, people with autism hang out with their mentors.”

Child-directed interpersonal time is “so important for people’s well being and development,” Keluskar explained, referring to both the mentor and the mentee.

She appreciates that this mentoring program is laid back and fun and believes that mentors benefit just as much from it as mentees.

Through the Initiative, the group has also done eight weekly, Facebook livestream events. The organizers discuss a topic and add three tips at the end. The tips have provided suggestions, including: using creativity to engage children by adding special interests into activities; taking a collaborative problem solving approach when running into difficulties getting a child to cooperate; and understanding emotional underpinnings to children’s behavioral difficulties.

Keluskar recognizes the challenge that come from having self-directed resources available to children and their parents. Even when people have access to many resources, they do not always know where to begin or what to prioritize, she said.

She advises a parents to try to get enough rest for themselves. “You need to take care of yourself so you can model [appropriate behavior] to your children,” she said.

Through the pandemic challenges, Keluskar also urges parents to be creative in their responses to the stressors that are affecting them and their children. She suggests people to take chances in how they approach their interactions with anxious children.

“You can’t be creative if you’re afraid of being wrong,” she said. “Being able to move past little mistakes shows flexible control. Set limits and be structured, but also be flexible at the same time.”

A resident of Commack, Keluskar lives with her husband Raja Keluskar, who is an engineer, their five-year old daughter Skylar and their three-year old son Colby.

Keluskar said she has been anxious about public speaking since she was young and can empathize with others who struggle with this. Through Facebook groups and other efforts, she said she can “personally attest to the value of multiple exposures and say that it can even become enjoyable with time and practice.”

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On Zoom screen, clockwise from top left, Committee member Hoi-Chung Leung; Committee Member Matthew Lerner; Eve Rosen; Committee Member Nicholas Eaton; Tamara Rosen; graduate student Cara Keifer; and Shira Yudkoff.

By Daniel Dunaief

On April 17, Tamara Rosen did something she had been anticipating for six years: she defended her graduate thesis.

Working in the lab of Matthew Lerner, who is an Associate Professor of Psychology, Psychiatry & Pediatrics in the Department of Psychology at Stony Brook University, Rosen had focused her efforts on the symptoms people with autism exhibit when they are anxious or depressed.

While the questions in her graduate thesis defense followed a pattern she anticipated, with professors asking her about the way she compiled her data and the conclusions she drew, the format wasn’t what she had expected.

Like so many other gatherings that had formerly been public events, Rosen’s thesis defense was broadcast by Zoom. The downside was that she wasn’t in the room with everyone, where she could have a discussion one on one. The upside was that her friends and family could tune in as easily as they do to work calls or other family gatherings. Indeed, Rosen’s mother, Marna; her step-mother Eve; and her father Dennis, all of whom share an appreciation for the work Tammy did for her thesis, watched the defense from start to finish, exulting in a landmark achievement.

“This was a really important day in our family’s history,” Dennis Rosen told his daughter, sharing the pride he felt for her.

“I always knew you were smart, but now I know you are brilliant,” her mother beamed.

After the call, Rosen saw her mother and stepmother overwhelmed with emotions, shedding tears for an achievement she sometimes needs to reassure herself really happened.

Rosen’s work focused on how anxiety and depression, two conditions that mental health professionals are concerned are becoming more prevalent amid the viral pandemic, have different symptoms in the population of people with autism spectrum disorder than they do for those who are not on the spectrum.

Based on prior research, Rosen wanted to account for the different symptoms in her follow-up analysis.

Prior studies have found that the traditional models of anxiety and depression do not adequately fit youth with autism. Others had suggested, but not tested, the notion that the Diagnostic and Statistical Manual model of these symptoms provides an ineffective model of anxiety and/or depression symptoms because of the influence of autism symptoms.

That is why Rosen specifically examined the influence of autism on these conditions in one of her analyses.

Among other findings, Rosen said that autism influences anxiety and depression. The prevalence of anxiety and depression is higher compared to the general population.

There are a range of clinical implications for her work, Rosen said.

Her work validates what clinicians are doing, which is to take the profile of autism into account when they treat anxiety.

Rosen moved to Colorado last July to start her internship year at JFK Partners at the University of Colorado School of Medicine, where she is also starting her post-doctoral clinical fellowship. She is treating clients with autism and anxiety and depression, which she said is in her “wheel house” of expertise.

Rosen is grateful for the support she received from Lerner and the program at Stony Brook. “It was great training,” she said.

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Matthew Lerner. Photo from SBU

By Daniel Dunaief

Though hampered by the pandemic in their direct contact with people who have autism, the founder of The Autism Initiative and research director Matthew Lerner along with the Head of Autism Clinical Education Jennifer Keluskar at Stony Brook University are managing to continue to reach out to members of the community through remote efforts. In a two-part series, Times Beacon Record News Media will feature Lerner’s efforts this week and Keluskar’s work next week.

Through several approaches, including improvisational theater, Matthew Lerner works with people who are on and off the autism spectrum on ways to improve social competence, including by being flexible in their approach to life.

In the midst of the ongoing pandemic, he has had to apply the same approach to his own work.

Lerner, who is an Associate Professor of Psychology, Psychiatry & Pediatrics in the Department of Psychology at Stony Brook University, recognizes that it’s difficult to continue a project called SENSE ® Theatre (for Social Emotional NeuroScience Endocrinology), where the whole function of the process is to provide in-person social intervention.

The SENSE Theater study is a multisite National Institute of Mental Health-funded project focused on assessing and improving interventions to improve social competence among adolescents with autism. The core involves in person intervention through group social interaction.

Matthew Lerner with his sons Everett,6, and Sawyer,2. Photo by Chelsea Finn

That, however, is not where the effort ends.“There are arms of that study that are more educational and didactic,” Lerner said. “We’re starting to think about how we could capitalize on that.”

In the ongoing SENSE effort, Lerner is coordinating with Vanderbilt University, which is the lead site for the study, and the University of Alabama.

Stony Brook is in active contact with the families who are participating in that effort, making sure they know “we are doing our best to get things up and running as quickly as possible,” Lerner said.

The staff is reaching out to local school districts as well, including the Three Village School District, with whom Lerner is collaborating on the project, to ensure that people know the effort will restart as soon as it’s “safe to be together again.”

Lerner is also the founder and Research Director of The Autism Initiative at SBU, which launched last year before the pandemic altered the possibilities for in-person contact and forced many people to remain at or close to home for much of the time. The initiative provides programs and services for the community to support research, social and recreational activities and other therapeutic efforts.

The Stony Brook effort initially involved video game nights, adult socials and book clubs. The organizers and participants in the initiative, however, have “stepped up in a huge way and have created, in a couple of weeks, an entirely new set of programming,” Lerner said.

This includes a homework support club, guidance, webinars and support from clinicians for parents, which address fundamental questions about how to support and adapt programs for people with autism. The group is keeping the book club active. The initiative at least doubled if not tripled the number of offerings, Lerner suggested.

Additionally, SBU has two grants to study a single session intervention adapted for teens with autism. The project has been running for about nine months. Lerner said they are looking to adapt it for online applications. For many families, such remote therapy would be a “real boon to have access to free treatment remotely,” he said.

Lerner had been preparing to conduct a study of social connections versus loneliness in teens or young adults with autism. Since COVID-19 hit, “we have reformulated that and are just about to launch” a longitudinal a study that explores the effects of the lockdown on well-being and stress for people who have autism and their families.

Lerner is looking at how the pandemic has enhanced the importance of resilience. He said these kinds of studies can perhaps “give us some insight when we return to something like normalcy about how to best help and support” people in the autism community. “We can learn” from the stresses for the community of people with autism during the pandemic.

To be sure, the pandemic and the lockdown through New York Pause that followed hasn’t affected the entire community of people with autism the same way. Indeed, for some people, the new norms are more consistent with their behavioral patterns.  “Some autistic teens and young adults have said things to me like, ‘I was social distancing before it was cool,’” Lerner said.

Another teenager Lerner interacted with regularly went to the bathroom several times to wash his hands. When Lerner checked in on him to see how he was doing amid the pandemic, he said, “I was made for this.”

Lerner also said people who aren’t on the spectrum may also gain greater empathy through the changes and challenges of their new routines. People find the zoom calls that involve looking at boxes of people on a full screen exhausting. After hours of shifting our attention from one box to another, some people develop “zoom fatigue.”

Lerner said someone with autism noted that this experience “may be giving the rest of us a taste of what it’s like for folks on the spectrum,” which could provide insights “we might not otherwise have.”

Even though some people with autism may feel like the rest of the world is mirroring their behavioral patterns, many people in and outside the autism community have struggled with the stresses of the public health crisis and with the interruption in the familiar structure of life.

The loss of that structure for many with autism is “really profound,” which is the much more frequent response, Lerner said. “More kids are telling us they are stressed out, while parents are saying the same thing.” In some sense, the crisis has revealed the urgency of work in the mental health field for people who are on and off the spectrum, Lerner said.

The studies in autism and other mental health fields that come out of an analysis of the challenges people face and the possible mental health solutions will likely include the equivalent of an asterisk, to capture a modern reality that differs so markedly from conditions prior to the pandemic. There may be a new reporting requirement in which researchers break down their studies by gender, age, race, ethnicity, income and “another variable we put in there: recruited during social isolation.”

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Life-like reconstruction of Adalatherium hui from the Late Cretaceous of Madagascar. ©Denver Museum of Nature & Science/Andrey Atuchin
Mounted cast skeleton of Adalatherium hui from the Late Cretaceous of Madagascar (left lateral view). Courtesy of Triebold Paleontology
Mounted cast skeleton of Adalatherium hui from the Late Cretaceous of Madagascar (front view). Courtesy of Triebold Paleontology
View of fossil site at which the skeleton of Adalatherium hui was discovered. Co-author Lydia Rahantarisoa is seated at the excavation spot. ©Denver Museum of Nature & Science/David Krause.
View of plaster jacket containing skeleton of Adalatherium hui being carried from excavation site to road. Author David Krause at left front. Photo courtesy of National Geographic Society/Maria Stenzel
Madagascar field study area where skeleton of Adalatherium hui was discovered. Photo courtesy Macalester College/Raymond Rogers
Skeleton of Adalatherium hui from the Late Cretaceous of Madagascar (left lateral view). ©Denver Museum of Nature & Science/Scott Hartman
Author David Krause with skeleton of Adalatherium hui. Photo courtesy of Story Brook University/John Griffin
James Rossie studies CT scan of the Adalatherium cranium. Photo by Helen Cullyer

By Daniel Dunaief

It’s not exactly a Rembrandt hidden in the basement until someone discovers it in a garage sale, but it’s pretty close.

More than two decades ago, a Malagasy graduate student named Augustin Rabarison spotted crocodile bones in northwestern Madagascar, so he and a colleague encased them in a plaster jacket for further study.

David Krause, who was then a Professor at Stony Brook University and is now the Senior Curator of Vertebrate Paleontology at the Denver Museum of Nature & Science, didn’t think the crocodile was particularly significant, so he didn’t open the jacket until three years later, in 2002.

When he unwrapped it, however, he immediately recognized a mammalian elbow joint further down in the encased block of rock. That elbow bone, as it turned out, was connected to a new species that is a singular evolutionary masterpiece that has taken close to 18 years to explore. 

Recently, Krause, James Rossie (an Associate Professor in the Department of Anthropology at Stony Brook University) and 11 other scientists published the results of their extensive analysis in the journal Nature.

The creature, which they have named Adalatherium hui, has numerous distinctive features, including an inexplicable and unique hole on the top of its snout, and an unusually large body for a mammal of its era. The fossil is the most complete for any Mesozoic mammal discovered in the southern hemisphere.

“The fossil record from the northern continents, called Laurasia, is about an order of magnitude better than that from Gondwana,” which is an ancient supercontinent in the south that included Africa, South America, Australia and Antarctica, Krause explained in an email. “We know precious little about the evolution of early mammals in the southern hemisphere.”

This finding provides a missing piece to the puzzle of mammalian evolution in southern continents during the Mesozoic Era, Krause wrote.

The Adalatherium, whose name means “crazy beast” from a combination of words in Malagasy and Greek, helps to broaden the understanding of early mammals called gondwanatherians, which had been known from isolated teeth and lower jaws and from the cranium of a new genus and species, Vintana sertichi, that Krause also described in 2014.

The closest living relatives of gondwanatherians were a group that is well known from the northern hemisphere, called multituberculates, Krause explained.

The body of Adalatherium resembled a badger, although its trunk was likely longer, suggested Krause, who is a Distinguished Service Professor Emeritus at Stony Brook. 

Krause called its teeth “bizarre,” as the molars are constructed differently from any other known mammal, living or extinct. The front teeth were likely used for gnawing, while the back teeth likely sliced up vegetation, which made probably made this unique species a herbivore.

The fossil, which probably died before it became an adult, had powerful hind limbs and a short, stubby tail, which meant it was probably a digger and might have made burrows.

Rossie, who is an expert in studying the inside of the face of fossils with the help of CT scans, explored this unusually large hole in the snout. “We didn’t know what to make of it,” he said. “We can’t find any living mammal that has one.”

Indeed, the interpretation of fossils involves the search for structural and functional analogs that might suggest more about how it functions in a living system. The challenge with this hole, however, is that no living mammal has it.

Gathering together with other cranial fossil experts, Rossie said they agreed that the presence of the hole doesn’t necessarily indicate that there was an opening between the inside of the nose and the outside world. It was likely plugged up by cartilage or other soft tissue or skin.

“If we had to guess conservatively, it would probably be an enlarged hole that allowed the passage of a cluster of nerves and blood vessels,” Rossie said. 

That begs the question: why would the animal need that?

Rossie suggests that there might have been a soft tissue structure on the outside of the nose but, at this point, it’s impossible to say the nature of that structure.

The Associate Professor, who has been a part of the research team exploring this particular fossil since 2012, described the excitement as being akin to opening up a Christmas present.

“You’re excited to see what’s in there,” he said. “Sometimes, you open up the box and see what you were hoping for. Other times, you open the box and say, ‘Oh, I don’t know what to say about this [or] I don’t know what I’m looking at.’”

For Rossie, one of the biggest surprises from exploring this fossil was seeing the position of the maxillary sinus, which is in a space that is similar across all mammals except this one. When he first saw the maxillary sinus, he believed he was looking at a certain part of the nasal cavity, where it usually resides. When he studied it more carefully, he realized it was in a different place.

“All cars have some things in common,” said Rossie, who is interested in old cars and likes to fix them. The common structural elements of cars include front and back seats, a steering wheel, and dashboard. With the maxillary sinus “what we found is that the steering wheel was in the back seat instead of the front.” 

A native of upstate Canton, which is on the border with Canada, Rossie enjoyed camping growing up, which was one of the initial appeals of paleontology. Another was that he saw an overlap between the structures nature had included in anatomy with the ones people put together in cars.

A resident of Centerport, Rossie lives with his wife Helen Cullyer, who is the Executive Director of the Society for Classical Studies, and their seven-year-old son.

As for the Adalatherium, it would have had to avoid a wide range of predators, Krause explained, which would have included two meat-eating theropod dinosaurs, two or three large crocodiles and a 20-foot-long constrictor snake.

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Centre ValBio staff members distribute face masks to the Malagasy people.

By Daniel Dunaief

Long Islanders are pitching in to protect the people of Madagascar, called the Malagasy, from COVID-19. They are also trying to ensure the survival of the endangered lemurs that have become an important local attraction and a central driver of the economy around Ranomofana National Park.

Patricia Wright, a Distinguished Service Professor at Stony Brook University and founder and executive director of the research station Centre ValBio (CVB), is working with BeLocal to coordinate the creation and distribution of masks. They have also donated soap, created hand washing stations at the local market, and encouraged social distancing.

BeLocal, an organization founded by Laurel Hollow residents Mickie and Jeff Nagel, along with Jeff’s Carnegie Mellon roommate Eric Bergerson, is working with CVB to fund and support the creation of 200 to 250 masks per day. BeLocal also purchased over 1,800 bars of soap that they are distributing at hand washing stations.

Wildlife artist Jessie Jordan is volunteering her time to help the Malagasy people.

All administrators for regional government in the national park area near CVB, which is in the southeastern part of the island nation, have received masks. The groups have also given them to restaurant owners and anybody that handles food, including vendors in the market.

At the same time, CVB has received permission to become a testing site for people who might have contracted COVID-19. At this point, Wright is still hoping to raise enough money to buy a polymerase chain reaction machine, which would enable CVB to perform as many as 96 tests each day.

The non-governmental organization PIVOT, which was founded by Jim and Robin Hernstein, has also helped create screening stations to test residents for fever and other symptoms of the virus. As for the masks, BeLocal and CVB are supporting the efforts of seamstresses, who are working 7 days a week.

Jessie Jordan, a wildlife artist based in Madagascar who has been living at CVB for several weeks amid limited opportunities to return to the United States, has been “busy collaborating with local authorities and contributing masks, soap and hand washing stations to the community.”

At this point, Jordan said people were concerned about the economy, but not as afraid of the virus. “The local health centers are less busy right now because of confinement measures and people are scared of testing positive,” she explained in an email.

The Malagasy who benefit from the national park economically through tours and the sale of local artwork have suffered financially. Social distancing in the cities is “nearly impossible,” while Jordan said she has heard that some people in the countryside don’t have access to TV or radio and are not aware of the situation.

As of last week, Madagascar had 132 confirmed positive cases of the virus. Through contact tracing, the government determined that three people brought COVID-19 to the nation when they arrived on different planes. The country had 10 ventilators earlier this month for a population that is well over 23 million.

BeLocal researched the best material to create masks that would protect people who worked in the villages around Ranomafana. “We researched templates and materials and worked together with CVB to choose the best material that would be available,” Leila Esmailzada, the Executive Director of BeLocal, explained in an email.

BeLocal organized a team that reached out to Chris Coulter, who had started making soap several years ago. Coulter has worked with local officials to make soap.

“We knew Coulter from a few years ago” from an effort called the Madagascar Soap Initiative to get soap into every home and make it accessible, explained Mickie Nagel, the Executive Director of BeLocal. “We hope the people making it right now will consider turning this into a business.” Before Madagascar instituted restrictions on travel, BeLocal and CVB had purchased several sewing machines.

Representatives from BeLocal and CVB have been conducting hand washing and social distance education efforts to encourage practices that will limit the spread of COVID-19.  Government officials have also shared instructions on the radio and TV, Wright said. When the mayor of Ranomofana Victor Ramiandrisoa has meetings, everybody stands at least six feet apart.

CVB has produced picture drawings in Malagasy that are plastered on the sides of cars that describe hand washing procedures and social distancing. “We also have educational signs in the post offices, restaurants and in the mayor’s offices that we paid for,” Wright explained. She said the government, CVB and BeLocal are all educating people about practices that can limit the spread of the deadly virus.

“Organizations in Ranofamana are collaborating with the local government on efforts to prevent the spread of COVID-19,” Esmailzada wrote. “The local government recently began conducting PSA’s along the road and in main markets about hand washing, mask wearing and social distancing and CVB staff are leading by example.”

As for the lemurs Wright, whose work was the subject of the Imax film “Island of Lemurs: Madagascar,” said the country has taken critical steps to protect these primates.

“The government of Madagascar is assuming the worst and is not allowing anybody into the park,” Wright said. The president of Madagascar, Andry Rajoelina, has closed national parks to protect the lemurs, Wright said.

The lemurs have the support of conservation leader Jonah Ratsimbazafy, who earned his PhD while working with Wright at Stony Brook University. Ratsimbazafy is one of the founding members of the Groupe d’Etude et de Research sur les Primates, which is a community based conservation organization that protects lemurs. 

Wright and others are concerned the virus may spread to lemurs. Several lemurs species have the angiotensin converting enzyme, or ACE2, that forms the primary point of attachment for the virus in humans.

Indeed, scientists around the world are working to find those species which might be vulnerable to the virus. According to recent research preprinted in bioRxiv from a multi-national effort led by scientists at the University of California in Davis, several species of lemur have high overlap in their ACE2 inhibitors. This includes the endangered aye-aye lemur, which is the world’s largest nocturnal primate, and the critically endangered indri and sifaka.

“We are worried that lemurs might get the virus,” Wright said.

Photos courtesy of Jessie Jordan

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Photo from SBU (copyright ©2013 Warner Bros. Entertainment Inc.) by Drew Fellman

By Daniel Dunaief

Small primates on an island nation off the southeastern coast of the African continent need about a million dollars.

That’s how much it might take to keep Ranofamana National Park, where Centre ValBio is located, afloat financially until people develop a vaccine.

Patricia Wright, who founded CVB, has spent the last 36 years studying a wide range of lemurs, even as she has integrated her efforts into the life of the Malagasy.

While she won conservation awards in the United States, including the 2014 Indianapolis Prize for Conservation from the Indianapolis Zoo, Wright has also won three medals of honor from the government of Madagascar as she has taken steps to improve the economic and physical health of the people who live around Ranomofana.

Now, with tourists who might be carriers of COVID-19 excluded from the national parks, lemur conservation, the tour guides who provide colorful commentary about the world-renowned primates, and the artists who provide local flavor and collectibles for visitors are all under duress.

The tour guides are “local residents and are incredible,” Wright said. “They are locally trained.” Indeed, many of those who share the natural riches of the region used to be loggers when they were younger. 

“We’re talking about people and about critically endangered lemurs,” she added.

Wright often highlights the positive feedback loop between conservation and the local economy, which has created job opportunities even as it has enabled the country to attract tourists from around the world who celebrate the land of the lemur. 

Building on her experience with delivering medicine to people around the national park, Wright plans to bring a polymerase chain reaction machine to Centre ValBio to test people for COVID-19.

Wright is seeking financial support from those who would like to ensure that the sifaka lemur, named after the “shi-fa” alarm call it makes when it feels threatened; the aye-aye lemur, which is the largest nocturnal primate in the world; and the indri lemur outlast the devastating effects of a virus that threatens the lives of people throughout the world.

Someday, when the smoke has cleared and people can look at what’s left in the world, Wright hopes Ranomafana Park and its lemurs are not only one of the survivors, but are also a rare, ecological site that calls to visitors from all over the world eager to celebrate the cultural richness of the Malagasy as well as the lemurs and other rare creates calling to each other from the rainforest.

Those interested in donating to this effort may visit the CVB web site at Welcome to Centre ValBio at Stony Brook University. 

 

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SBU Professor Malcolm Bowman teaches an online course from his 'office' in a camper in New Zealand during the coronavirus pandemic.
The ultimate in remote teaching: 9,000 miles from the classroom

By Daniel Dunaief

Halfway between where they grew up and their home in Stony Brook, Malcolm and Waveney Bowman had a choice to make: venture back northeast to New York, which was in the midst of a growing coronavirus crisis or return southwest to New Zealand, where the borders were quickly closing.

The couple chose New Zealand, where their extended family told them not to dare visit. The Do Not Enter sign wasn’t as inhospitable as it sounded.

Malcolm Bowman, a Distinguished Service Professor at Stony Brook University’s School of Marine and Atmospheric Sciences, recognized that he could continue to teach three courses from a great distance, even a camper on a small stretch of land in the northwest part of the Coromandel Peninsula in New Zealand.

“We could be anywhere on the planet,” Malcolm suggested to his wife. “Why don’t we see if we can set up camp?”

Climbing aboard the last plane out of Honolulu before New Zealand closed its borders, the Bowmans didn’t have much of a welcoming party when they arrived at the airport. Their family told them, “We love you, but you can’t come anywhere near us,” Malcolm recalled. “Coming from the states, you could be infected.”

If his family took the American couple in, they would have had to report the contact, which would have forced Waveney’s brother and his wife, Derek and Judy Olsson, into personal isolation for two weeks.

Derek filled the trunk of an old car with food and left the key under the front tire. The Stony Brook couple set up a temporary living space in two campers on a small piece of land in the middle of the night, where they have been living for over a month. All told, their 235 square feet of living space is about 12% of the size of their Long Island home.

The country has been in lockdown, where people are practicing social distancing and are limiting their non-essential outings.

Malcolm realized he had to “rise to the challenge” which, in his case, literally meant climbing out of his bed at all hours of the morning. New Zealand is 16 hours ahead of New York, which means that he had to be awake and coherent at 2 a.m. on Tuesday morning in New Zealand to teach a course that meets at 10 a.m. on Monday morning on Long Island.

With a cell tower up the hill behind their camper, the Bowmans could access the internet. While they had shelter, they still needed electricity. Fortunately, Malcolm’s brother Chris, who is an engineer, provided solar panels to generate electricity.

Living south of the equator means the Bowmans are heading into winter in New Zealand, where the days are shorter and the sun is lower in the sky, which makes the solar panels that provide electricity less effective. Malcolm describes the biggest challenges as the “time difference and mosquitoes.”

In a typical day, the professor rises at 4 a.m. or earlier local time to teach his classes, participate in online seminars, attend University Senate and other committee meetings, continue his research and take care of his students, all through Google Meet and Zoom. He co-teaches Physics for Environmental Studies, Contemporary Environmental Issues and Polices and Advanced Coastal Physical Oceanography.

Malcolm’s favorite part of the day occurs at sunrise, when the cloud formations over Mercury Bay serve as a canvas for the colorful red and orange rays of the sun that herald the start of another day down under.

He recognizes that he and his wife’s current indefinite time in New Zealand provides them with a comfortable connection to the land of his youth, where he can enjoy some of the beaches that have made the country famous and hear the sounds of flightless birds near his camper home.

Given the focus on work early in the day, Malcolm can choose his activities in the afternoon, which include catching up on emails, reading the New York Times, cleaning up the campsite and fishing for the evening’s meal.

Even from a distance of almost 9,000 miles from New York, the Bowmans agonize with their neighbors and community members in the Empire State.

“It’s very difficult watching all the suffering, sickness, death, inadequate availability of life-saving equipment, the enormous stress health care workers are under and the loss of income for many families,” Bowman explained in an email. “Our eldest daughter Gail is a medical worker at the Peconic Bay Medical Center in Riverhead so she is fighting at the front line. Very exhausting work.”

The Bowmans, who are naturalized American citizens, have no idea when international flights will resume from New Zealand.

A retired elementary school teacher who taught at the Laurel Hill School in Setauket for 34 years, Waveney wears a mask when she visits a large supermarket that is 12 miles away once a week. Malcolm, who also goes to the supermarket, said the store only allows one family member per visit.

As New Zealand natives, the Bowmans can live in the country indefinitely, but their intention is to return to Stony Brook as soon as possible.

Even though the shorter daylight hours and rainy days lower the amount of power the Bowmans can collect from their solar panels, the couple loves the outdoors. They have camped with their four children during summers in the hills of New Hampshire and Vermont and have both been involved with scouting activities, which emphasizes self sufficiency and living close to nature.

As a former amateur radio enthusiast, Malcolm is also adept at setting up communication systems in remote settings. He offers a message of hope to Long Islanders, “You can weather this storm. If possible, work and stay home and stay isolated.”

The Bowmans have followed the advice of the 37-year old Prime Minister of New Zealand, Jacinda Ardern, who urges people to “be especially kind to each other.”

All photos courtesy of Malcolm Bowman

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Mikala Egeblad with a blown-up image of a neutrophil extracellular trap, or NET. Photo from CSHL

By Daniel Dunaief

Mikala Egeblad couldn’t shake the feeling that the work she was doing with cancer might somehow have a link to coronavirus.

Egeblad, who is an Associate Professor and cancer biologist at Cold Spring Harbor Laboratory, recently saw ways to apply her expertise to the fight against the global pandemic.

She studies something called neutrophil extracellular traps, which are spider webs that develop when a part of the immune system triggered by neutrophil is trying to fight off a bacteria. When these NETs, as they are known, are abundant enough in the blood stream, they may contribute to the spread of cancers to other organs and may also cause blood clots, which are also a symptom of more severe versions of COVID-19, the disease caused by the coronavirus, which has now infected over two million people worldwide.

“I always felt an urgency about cancer, but this has an urgency on steroids,” Egeblad said.

Cold Spring Harbor Laboratory reached out to numerous other scientists who specialize in the study of NETs, sometimes picking up on the tweets of colleagues who wondered in the social networking world whether NETs could contribute or exacerbate the progression of Covid19.

Egeblad started by reaching out to two scientists who tweeted, “Nothing about NETs and Covid-19?” She then started reaching out to other researchers.

“A lot of us had come to this conclusion independently,” she said. “Being able to talk together validated that this was something worth studying as a group.”

Indeed, the group, which Egeblad is leading and includes scientists at the Feinstein Institutes for Medical Research and the Research Institute of the McGill University Health Centre, published a paper last week in the Journal of Experimental Medicine, in which they proposed a potential role for NETs.

“We are putting this out so the field doesn’t overlook NETs,” said Egeblad, who appreciated the support from Andrew Whiteley, who is the Vice President of Business Development and Technology Transfer at CSHL.

With a range of responses to the coronavirus infection, from people who have it but are asymptomatic all the way to those who are battling for their survival in the intensive care units of hospitals around the world, the biologist said the disease may involve vastly different levels of NETs. “The hypothesis is that in mild or asymptomatic cases, the NETs probably play little if any role,” she said.

In more severe cases, Egeblad and her colleagues would like to determine if NETs contribute or exacerbate the condition. If they do, the NETs could become a diagnostic tool or a target for therapies.

At this point, the researchers in this field have ways of measuring the NETs, but haven’t been able to do so through clinical grade assays. “That has to be developed,” Egeblad explained. “As a group, we are looking into whether the NETs could come up before or after symptoms and whether the symptoms would track” with their presence, she added.

To conduct the lab work at Cold Spring Harbor, Egeblad said her team is preparing to develop special procedures to handle blood samples that contain the virus. 

As the lead investigator on this project, Egeblad said she is organizing weekly conference calls and writing up the summaries of those discussions. She and the first author on the paper Betsy J. Barnes, who is a Professor at the Feinstein Institute, wrote much of the text for the paper. Some specific paragraphs were written by experts in those areas.

At this point, doctors are conducting clinical trials with drugs that would also likely limit NET formation. In the specific sub field of working with this immune-system related challenge, researchers haven’t found a drug that specifically targets these NETs. 

If the study of patient samples indicates that NETs play an important role in the progression of the disease, particularly among the most severe cases, the scientists will look for drugs that have been tried in humans and are already approved for other diseases. This would create the shortest path for clinical use.

Suppressing NETs might require careful management of potential bacterial infections. Egeblad suggested any bacterial invaders might be manageable with other antibiotics.

NETs forming in airways may make it easier to get bacterial infections because the bacteria likes to grow on the DNA.

Thus far, laboratory research studies on NETs in COVID-19 patients have involved taking samples from routine care that have been discarded from their daily routine analysis. While those are not as reliable as samples taken specifically for an analysis of the presence of these specific markers, researchers don’t want to burden a hospital system already stretched thin with a deluge of sick patients to provide samples for a hypothetical pathway.

Egeblad and her colleagues anticipate the NETs will likely be more prevalent among the sicker patients. As more information comes in, the researchers also hope to link comorbidities, or other medical conditions, to the severity of COVID-19, which may implicate specific mechanisms in the progression of the disease.

“There are so many different efforts” to understand what might cause the progression of the disease, Egeblad said. “Everybody’s attention is laser focused.” A measure that is easy to study, such as this hypothesis, could have an impact and “it wouldn’t take long to find out,” she added. Indeed, she expects the results of this analysis should be available within a matter of weeks.

Egeblad believes the NETs may drive mucus production in the lungs, which could make it harder to ventilate in severe cases. They also may activate platelets, which are part of the clotting process. If they did play such a role, they could contribute to the blood clotting some patients with coronavirus experience.

Egeblad recognizes that NETs, which she has been studying in the context of cancer, may not be involved in COVID-19, which researchers should know soon. “We need to know whether this is important.”

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From left, Kerstin Kleese van Dam, Brand Development Manager at BNL Diana Murphy, and John Hill at the Practical Quantum Computing Conference (Q2B) in San Jose, CA, Dec. 2019. Photo courtesy of Kerstin Kleese van Dam

By Daniel Dunaief

Brookhaven National Laboratory is putting its considerable human and technical resources behind the global effort to combat the coronavirus.

John Hill, the director of the National Synchrotron Lightsource II, is leading a working group to coordinate the lab’s COVID-19 science and technology initiatives. He is also working on a team to coordinate COVID-19 research across all the Department of Energy labs.

“We are proud that the tools we built at BNL, which include the NSLS II, which took 10 years to build and cost about a billion dollars,” will contribute to the public health effort, Hill said. “We feel that science will solve this problem, and hopefully soon. It’s great that BNL is a part of that fight.”

In addition to using high-technology equipment like the NSLS II to study the atomic structure of the virus and any possible treatments or vaccines, BNL is also engaging a team led by Kerstin Kleese van Dam, who is the director of BNL’s Computational Science Initiative.

According to Hill, the combination of the physical experiments and the computing expertise will provide a feedback loop that informs the efforts with each team. Kleese van Dam’s team is using supercomputers to run simulated experiments, matching up the atomic structure of the viral proteins with any potential drugs or small molecules that might interfere with its self-copying and life-destroying efforts.

The computer simulations will enable researchers to narrow down the list of potential drug candidates to a more manageable number. Experimental scientists can then test the most likely  treatments the computer helped select.

Across the world, the scale of the science to which BNL is contributing is even larger than the Manhattan Project that led to the creation of the atomic bomb during World War II, said Hill.

In just three months since scientists in China produced the genetic sequence of the coronavirus, researchers around the world have produced over 15,000 research articles, some of which have been published in scientific journals, while researchers have self-published others to share their findings in real time.

Working with computer scientists from different fields at BNL, Kleese van Dam is helping researchers screen through the abundant current research on COVID-19. The number of papers is “accelerating at a rate no one can read,” Hill explained. 

Kleese van Dam and four of her scientists are setting up a natural language processing interface so scientists can type in what they want to find, such as a protein binding with a specific complex, and put it into a search engine. She is working on an initial service that she hopes to expand. Additionally, the computer science team is planning to start a project to look at epidemiological data to determine how various people might react to different treatment.

Kleese van Dam and her team are also working to build an archive in the United States that they hope will host at least the results of the Department of Energy funded projects in medical therapeutics. “[We are] convinced that this would provide a much better starting point for future outbreaks, as well as providing a near term clearing house of results,” she explained in an email.

As for the work at the synchrotron, Hill said that the high-energy x-rays can determine the specific atomic configuration of proteins in the virus.

The NSLS II, which was designed to study the structure of batteries, geology and plant cells, among other objects, can look at “small protein crystals better than anywhere else in the world.”

The virus relies on a docking mechanism that allows it to enter a cell and then insert its malevolent RNA to disrupt the cell’s normal function. Understanding how the pieces come together physically can allow researchers to look for small molecules or approved drugs that could interfere with the virus.

One of the many advantages of the synchrotron over protein crystallography is that the NSLS II doesn’t need as many copies of proteins to determine their atomic structure. Hill said protein crystallography needs samples that are about 100 to 200 microns in size, which is about the width of a human hair, which can take weeks to months to years to grow. This is a “bottleneck in the whole process” of solving protein structure, he said.

On the other hand, the NSLS II only requires samples of about a micron in size. This “greatly speeds up the process,” he added. Two different groups of researchers, from the pharmaceutical industry and from academia and national labs, are conducting experiments on the NSLS II.

Hill said he was receiving viral proteins scientists believe will bind with the virus from collaborators in the United Kingdom. The scientific process is as quick and collaborative as it’s ever been among researchers, he said. The proteins arrived recently.

That collaborative process would have “taken months to set up under normal circumstances,” Hill said. Instead, it only took a few days.

At the same time, BNL is constructing a cryo-electron microscope, which doesn’t have the same resolution as the NSLS II, but does not need crystals and can study individual proteins. Researchers need about 10,000 of them and can average the images together. The resolution is five to 10 times worse than x-rays.

BNL is accelerating the construction of the cryo EM and hope to have the first beam in mid-May. Commissioning will take some extra time, Hill said. The first structure of the coronavirus spike protein was determined by using an electron microscope.

For Hill and Kleese van Dam, who each have dedicated much of their time to these efforts, the opportunity to contribute to a project that could have implications for a public that is battling this disease is rewarding and offers reasons for optimism. 

“To be able to help at such a scale is indeed humbling and gratifying,” said Kleese van Dam. “Science is going to solve this problem,” added Hill. “That gives me comfort.”

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