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We Are Not All Living The COVID Moment Equally

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We are all living within the Covid moment, but we are not living within the Covid moment equally. The pandemic has exposed a recurrent rift in the United States’ healthcare system: Black Americans and other people of color (POC) are both disproportionately impacted by health issues and disproportionately lack access to care.

In a recent study on North Carolina conditions, Duke researchers found that the “odds of testing positive for [Covid] were higher for both Black and Hispanic individuals as well as within neighborhoods with a higher proportion of Black or Hispanic residents – confirming that Black and Hispanic communities are disproportionately affected.”

In a Coronavirus Conversation sponsored last week by the Science & Society Initiative, Thomas Williams J.D. discussed this and related issues with Duke scholars Keisha L. Bentley-Edwards, Ph.D. of medicine and Jay A. Pearson, M.P.H., Ph.D of public policy.

Williams opened the panel by emphasizing the relevance of this moment: Current Covid impacts are directly informed by historical inequities and intricately span into the future. This is but one system of plaguing racism.

To speak about the intimate intersection of race and healthcare in America, Pearson offered grounding insight to systemic and structural racism. The United States is a country filled with patterns that produce and reproduce systematic advantages for those who are white while simultaneously disadvantaging people of color, most often Black and indigenous populations. Racism in America greatly transcends personal acts of racialized discrimination and harassment, he said. Racism in America is multiplex, foundational, and rooted within our society’s core.

“The U.S. national identity is tied to structural racism. …This is who we are, this is who we’ve been since the beginning of this country,” Pearson said, “The racialized inequities of Covid are simply the latest [manifestations]. We shouldn’t be surprised.”

A recently circulating figure states that 96% of people with severe outcomes or death from Covid had comorbidities, the presence of health conditions in addition to Covid. But Bentley-Edwards cautioned against misuse of this claim: “Many of these people would be alive if not for Covid.”

Though many who have died from the virus had underlying conditions, it is ultimately the virus that killed them. Communities of color often have disproportionate prevalence of underlying conditions, making them more susceptible to complications from Covid. But even when the prevalence of underlying conditions is the same among white and non-white populations, people of color are more likely to be more negatively affected by them.

For example, cardiovascular disease is similarly distributed between white and Black people, yet Black people are more likely to die of it, and at a younger age, compared to white people. Similarly, Black and other POC populations who contract Covid are more likely to die despite similar rates of contracting the virus in certain regions of the country.

Dr. Bentley-Edwards speaking during Friday’s virtual Coronavirus Conversation

Pearson and Bentley-Edwards also offered their insights on who is seen as essential and who is seen as dispensable in the United States.

Those who have been on the front lines with the most exposure and risks have been laborers who are most often under-valued Black and Brown peoples, Bentley-Edwards said. Though Covid terminology has come to dub them essential, it is undeniable that our society continues to see these types of workers as dispensable or replacable, and thus does not protect the people responsible for protecting us. Because many people of color live in multi-generational households as a culturally protective factor, increased chance of contracting Covid has led to uncertainties on the safety of returning home to young and elderly family members, she said. Further, the disproportionate unemployment rate of 13% for Black Americans compared to the 8.4% national rate is a staggering one. Since insurance is tied to employment, Black and Brown communities often avoid treatments due to the financial burden of unaffordable and inaccessible care.

Within the pandemic, we have seen the ever-present epidemiological impacts of police brutality and murder in the U.S with fresh eyes, the panelists said. In many ways, Black peoples’ experiences with healthcare mirrors that of their experiences with police – likely because both systems are anchored by an unjust nucleus.

“[Covid and police brutality] are slightly different manifestations of the same phenomenon,” Pearson said. We are able to easily identify the murders of individuals such as Breonna Taylor, George Floyd, and Ahmaud Arbery as stolen lives due to racist actions, however the slow burn of a racist health care system is less easily conceptualized or reconciled with, he said. Either way, the cause is one and the same.

Racism within systems that are meant to protect have generated a deep mistrust from Black and Brown people. Williams brought up the issue of a potential Covid vaccination amongst communities of color. “You have to know the history and why they would hesitate,” Bentley-Edwards said, bringing up the Tuskegee experiments and the work of J. Marion Sims. These accounts offer grim revelation of a heinous, racist history of exploiting vulnerable people for scientific and medical explorations.

Bentley-Edwards said that governments and healthcare institutions must address the rightful apprehensions of Black and Brown people in order to decrease vaccine hesitancy and serve at-risk communities. “What are they going to do differently?”

Williams also proposed the notion of data collection as a source of bias: In what ways are the data informatics that are collected reflections of an inequitable system? Bentley-Edwards and Pearson both suggest that to understand the current moment, as well as the healthcare system more largely, there needs to be collection and analysis of racial data. Additionally, there simply needs to be measurements for indicators beyond conventional ones which do not properly account for impacts on communities of color.

The push for new and different kind of data is supported by a growing evidence for the manifestations of inequality within biological bodies. For example, Pearson spoke about his own research on telomeres, a protective structure on the ends of chromosomes that protect DNA from degradation. Telomeres are telling both of stress and aging. Pearson’s work found that the average Black American woman is six to seven biological years older than a white American woman of the same age by evaluating telomere lengths, controlling for income, education, and other important socioeconomic factors. This indicates physiological affects linked to the stresses and disproportionalities of race down to the cellular level. Through genetics, mental health, and other physical degradations, the impacts of racism and racist healthcare quite literally last a lifetime and are even intergenerational.

Diagram of telomere from a study conducted by Dr. Pearson

Pearson closed the panel by urging attendees to take action where they find themselves. Though the need for animated policy which reflects recent discussions and protests is dire, the local spaces we find ourselves in need to be reshaped as well – including our universities.

In this moment, our responsibilities to one another have become more obvious than ever before. We must become more adept in thinking about and taking action for the communities in which we live and are connected to, whether they are comprised of people who look like us or not.

Post by Cydney Livingston

“Do No Harm to Whom?” Challenge Trials & COVID-19

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DAVIDE BONAZZI / SALZMANART

Imagine: you wake on a chilly November morning, alarm blaring, for your 8:30 am class. You toss aside the blankets and grab your phone. Shutting the alarm off reveals a Washington Post notification. But this isn’t your standard election headline. You almost drop your phone in shock. It can’t be, you think. This is too good to be true. It’s not — a second later, you get a text from the SymMon app, notifying you of your upcoming appointment in the Bryan Center.

A vaccine for COVID-19 is finally available, and you’re getting one.

This scenario could be less far-fetched than one might think: the Centers for Disease Control and Prevention has told officials to prepare for a vaccine as soon as November 1st. To a country foundering due to the economic and social effects of COVID-19, this comes as incredible news — a bright spot on a bleak horizon. But to make a vaccine a reality, traditional phase 3 clinical trials may not be enough. What are challenge trials? Should they be used? What’s at stake, and what are the ethical implications of the path we choose?

At Duke Science and Society’s “Coronavirus Conversations: The Science and Ethics of Human Challenge Trials for COVID-19” on Aug. 24, Kim Krawiec of the Duke School of Law posed these and other questions to three experts in health.

Dr. Marc Lipsitch, Director of the Center for Communicable Disease Dynamics at the Harvard School of Public Health, began by comparing traditional phase 3 trials and challenge trials. 

In both kinds of trials, vaccines are tested for their “safety and ability to provoke an immune response” in phases 1 and 2. In phase 3 trials, large numbers (typically thousands or tens of thousands) of individuals are randomly assigned either the vaccine being tested or a placebo. Scientists observe how many vaccinated individuals become infected compared to participants who received a placebo. This information enables scientists to assess the efficacy — as well as rarer side effects — of the vaccine. 

Marc Lipsitch

In challenge trials, instead of random assignment, small numbers of low-risk individuals are deliberately infected in order to more directly study the efficacy of vaccine and treatment candidates. Though none are underway yet, the advocacy group 1Day Sooner has built a list of more than 35,000 volunteers willing to participate.

Dr. Cameron Wolfe, an Infectious Disease Specialist, Associate Professor of Medicine, and Clinical Expert In Respiratory and Infectious Disease at the Duke Medical School, provided an overview of the current vaccine landscape.

Cameron Wolfe

There are currently at least 150 potential vaccine candidates, from preclinical to approved stages of development. Two vaccines, developed by Russia’s Gamelaya Research Institute and China’s CanSinoBIO, have skipped phase 3, but are little more than an idiosyncrasy to Dr. Wolfe, as there is “minimal clarity about their safety and efficacy.” Three more vaccines of interest — Moderna’s mRNA vaccine, Pfizer’s mRNA vaccine, and Oxford and AstraZeneca’s adenovirus vaccine — are all in phase 3 trials with around 30,000 enrollees. Scientists will be watching for a “meaningful infection and a durable immune response.”

Dr. Nir Eyal, the Henry Rutgers Professor of Bioethics and Director of The Center for Population-Level Bioethics at Rutgers University, explained how challenge trials could fit into the vaccine roadmap.

According to Dr. Eyal, challenge trials would most likely be combined with phase 3 trials. One way this could look is the use of challenge trials to weed out vaccine candidates before undergoing more expensive phase 3 trials. Additionally, if phase 3 trials fail to produce meaningful results about efficacy, a challenge trial could be used to obtain information while still collecting safety data from the more comprehensive phase 3 trial.

Nir Eyal

Dr. Eyal emphasized the importance of challenge trials for expediting the arrival of the vaccine. According to his own calculations, getting a vaccine — and making it widely available — just one month sooner would avert the loss of 720,000 years of life and 40 million years of poverty, mostly concentrated in the developing world. (Dr. Eyal stressed that his estimate is extremely conservative as it neglects many factors, including loss of life from avoidance of child vaccines, cancer care, malaria treatment, etc.) Therefore, speed is of “great humanitarian value.”

Dr. Wolfe added that because phase 3 trials rely on a lot of transmission, if the US gets better at mitigating the virus, “the distinction between protective efficacy and simple placebo will take longer to see.” A challenge study, however, is “always a well defined time period… you can anticipate when you’ll get results.” 

The panelists then discussed the ethics of challenge trials in the absence of effective treatment — as Krawiec put it, “making people sick without knowing if we can make them better.”

Dr. Wolfe pointed to the flu, citing challenge trials that have been conducted even though current treatments are not uniformly effective (“tamiflu is no panacea”). He then conceded that the biggest challenge is not a lack of effective therapies, but the current inability to “say to a patient, ‘you will not have a severe outcome.’ It varies so much from person to person, I guess.” (See one troubling example of that variance.)

Dr. Eyal acknowledged the trouble of informed consent when the implications are scarcely known, but argued that “in extraordinary times, business as usual is no longer the standard.” He asserted that if people volunteer with full understanding of what they are committing to, there is no reason to assume they are less informed than when making other decisions where the outcome is as yet unknown. 

Dr. Lipsitch compared this to the military: “we are not cheating if we cannot provide a roadmap of future wars because they are not yet known to us.” Rather, we commend brave soldiers (and hope they come home safe). 

Furthermore, Dr. Eyal asserted that “informed consent is not a comprehensive understanding of the disease,” lest much of the epidemiological research from the 1970s be called into question too. Instead, volunteers should be considered informed as long as they comprehend questions like, “‘we can’t give you an exact figure yet; do you understand?’”

Agreeing, Dr. Wolfe stated that when critics of challenge trials ask, isn’t your mission to do no harm?, he asks, “Do no harm in regards to whom?” “Who is in front of you matters,” Dr. Wolfe confirmed, “that’s why we put up safeguards. But as clinicians it can be problematic [to stop there]. It’s not just about the patient, but to do no harm in regards to the broader community.”

The experts then discussed what they’d like to see in challenge trials.

Dr. Wolfe said he’d like to see challenge trials carried out with a focus on immunology components, side effect profiles, and a “barrage” of biological safety and health standards for hospitals and facilities. 

Dr. Eyal stated the need for exclusion criteria (young adults, perhaps age 20-25, with no risk factors), a “high high high” quality of informed consent ideally involving a third party, and access to therapies and critical care for all volunteers, even those without insurance. 

Dr. Lipsitch stressed the scientific importance of assessing participants from a “virological, not symptom bent.” He mused that the issue of viral inoculum was a thorny one — should scientists “titrate down” to where many participants won’t get infected and more volunteers will be needed overall? Or should scientists keep it concentrated, and contend with the increased risk? 

Like many questions pondered during the hour — from the ideal viral strain to use to the safest way to collect information about high risk patients — this one remained unanswered. 

So don’t mark November 1st on your calendar just yet. But if you do get that life-changing notification, there’s a chance you’ll have human challenge trials to thank.

Post By Zella Hanson

Why Ruffed Lemurs (and Their Gut Microbes) Need to Eat Greens

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We offered fruit-eating ruffed lemurs at the Duke Lemur Center fresh lettuce each afternoon for 10 days. They happily ate it and their gut microbiomes shifted, suggesting that leafy greens could be incorporated into the lemurs’ standard dietary regimen to boost foraging opportunity and fiber intake.

Red-ruffed lemurs and black-and-white ruffed lemurs are some of Madagascar’s most iconic wildlife. Sporting a long snout and a neck ruff to rival those of the Elizabethan court, these primates naturally live in the rainforests, where they mostly eat fruits and flowers, and make their living as seed dispersers and pollinators.

Ruffed lemurs really like romaine lettuce and their gut bugs do too! (Lydia Greene)

Ruffed lemurs also live in zoos worldwide, where they are given fruit-rich diets to match those foraged by their wild peers. But scientists are starting to realize that the fruit eaten by wild lemurs is quite different from the domesticated fruit provided at zoos. Wild fruits are seedy, pulpy, and thick-skinned, whereas orchard fruits are fleshy, plump, and sweet. From a nutritional standpoint, wild fruits contain more fiber, whereas orchard fruits contain more sugar. 

Our team wondered if a fiber boost might benefit Duke’s ruffed lemur colony. But would these fruit-loving lemurs eat their veggies?  

Cue the salad bar.

To test this idea, we offered ruffed lemurs at the Duke Lemur Center a lot of lettuce. Lettuce seemed like a pretty palatable way to stimulate foraging behavior, while boosting fiber intake.

With help from the research department, we offered 19 ruffed lemurs 150-200 grams of romaine lettuce each day, which is about double the weight of their standard diet. We repeated this regimen every day for 10 days, while recording the lemurs’ feeding behavior and collecting fecal samples for gut microbiome analysis. Because gut microbes are chiefly responsible for converting plant fiber into energy for the lemurs, measuring changes to the lemurs’ microbiomes offered a way to ‘see’ the impact of lettuce consumption.

It turns out that ruffed lemurs really like lettuce. They consistently ate lettuce every day and showed no decline in consumption across the study. Younger animals ate more lettuce than did geriatric lemurs, but all lemurs spent more time crunching on lettuce stalks than the leaves.

And their gut microbiomes responded. We noted two microbes that were more abundant on the lettuce diet: a known fiber digester from the Ruminococcaceae family, and a microbe known for its positive association with host health in other animals called Akkermansia.

Despite their classification as fruit eaters, ruffed lemurs readily eat lettuce. We think lettuce can be used to extend the lemurs’ foraging time while boosting dietary fiber. And it might just help replicate the lifestyles experienced by wild ruffed lemurs in their native Malagasy rainforests.     At the Duke Lemur Center, lettuce is now a routine item offered to ruffed lemurs (and other species too!). Next time you come out for a tour (once it’s safe to do so), you might get to see them crunching away on their new favorite snack!

( Read our paper here: https://onlinelibrary.wiley.com/doi/abs/10.1002/zoo.21555 )

Guest Post by Lydia Greene Ph.D., an NSF-sponsored postdoctoral fellow in biology working at the Duke Lemur Center.

Saving Africa’s Biggest Trees to Help Earth Breathe

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Like wine, cheese, and savvy financial investments, many tropical trees become more valuable with age. This is particularly true when it comes to carbon storage, because old trees are often the biggest trees and the larger the tree, the more carbon it stores.

The value of big, old trees in combating climate change was underscored in a recent study of Gabon’s forests, led by the Nicholas School of the Environment’s John Poulsen. The team’s striking finding — that half of Gabon’s wealth of carbon is found in the largest 5% of trees — has implications that reach far beyond the sparsely populated Central African country’s borders.

Nicholas School Ph.D. student Graden Froese admires a forest giant in Ivindo National Park, Gabon.

Tropical forests play a key role in the global carbon cycle by keeping carbon out of the atmosphere. Trees take in CO2 — one of the infamous, heat-trapping greenhouse gases — during photosynthesis and use the carbon to grow, making new leaves, thicker and taller trunks, and more expansive root systems.

Scientists can estimate how much carbon a tree holds by measuring its trunk. So, like rainforest tailors, trained technicians traveled to all corners of the country to measure the girth and height of tens of thousands of trees.

This extraordinary two-year long effort was one of the first nationwide forest inventories in the tropics, making Gabon a leader in comprehensive forest monitoring.

John Poulsen is an associate professor of tropical ecology.

Poulsen and collaborators used the tree measurements to estimate the amount of carbon stored in Gabon’s forests and to determine why some forests hold more carbon than others.

“The field techs deserve all the credit”, Poulsen explained, “as they often walked for days through thick forest, traversing swamps and enduring humid, buggy conditions to measure trees. We turned their sweat and toil into information that could be used by Gabon’s government to prioritize areas for conservation.”

Who needs ladders, when you have colleagues? The field team collaborates to measure a forest giant.

The team analyzed a suite of environmental factors to see their effects on carbon storage. Of the natural factors, only soil fertility had a noticeable positive effect on tree biomass. Much more important was the impact of humans. As human activities such as agriculture and logging tend to target large trees, more heavily human-disturbed forests had a much different structure than pristine forests. The farther a study area was from human settlements, the more likely it was to host large trees and consequently, higher amounts of carbon.

The paper notes that Gabon stands out as a country with “one of the highest densities of aboveground forest carbon.” In fact, Gabon’s undisturbed forests store more carbon than those in the Amazon, which have been referred to as the lungs of the planet.

According to Poulsen, “Gabon is the second most forested country in the world with 87% forest cover, a deforestation rate near zero…” Because of its impressive forest cover and its location straddling the equator, Gabon’s forests host an incredibly diverse array of plants and animals, including many threatened and endangered species. Rural communities depend on these forests for their livelihoods.

Unfortunately, even Gabon’s ‘small’ trees make for spectacular felled logs.

However, Gabon’s impressive forests are valuable to more than just wildlife, climate researchers, and local communities. The logging industry also sees these forests as a chance for profit. More than half (about 67%) of Gabon’s forests are under contract with logging companies to harvest timber, putting them at risk of losing many of their carbon-storing giants.

Poulsen’s study highlights the importance of a more nuanced approach to forest conservation in Gabon. One that doesn’t simply focus on stopping deforestation or promoting restoration, as is prescribed in many international climate change plans, but an approach that recognizes the necessity of preserving high conservation value, old growth forests.

Anna Nordseth

Guest Post by Anna Nordseth, a graduate student in the Nicholas School of the Environment.

Following In The Footsteps of Elephants

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Imagine for a moment that you’re 6,000 pounds, living in one of the wildest places on Earth, with no schedule, nowhere to be. How do you decide where to spend your time? Where to go next? Do you move where food is most plentiful? Is water your main priority?

Amelia Meier in the field.

These are some of the questions addressed by Duke Ph.D. candidate Amelia Meier and former postdoctoral researcher Dr. Chris Beirne in Dr. John Poulsen’s lab. Their recent study published in Trends in Ecology and Evolution focused on the African forest elephant–the slightly smaller yet still undeniably huge cousin of the savanna elephant.  

The team wanted to know what influences certain aspects of elephant behavior. Specifically, how much climate and resource availability drives elephant movement and influences their diet. To do this, the team looked at fruit abundance (a high-energy staple of elephants’ diets), water availability from rainfall, and elephant identity and how those factors affect how an individual moves and eats.

One might think that such a massive animal is easy to spot in the forest. However, the dense vegetation of Central African rainforests can be an impenetrable wall, allowing the massive animals to move unseen through the forest, leaving broken branches and steaming dung piles in their wake.

To better track them, the researchers fitted individual elephants with GPS collars that turn an iPhone into an elephant-tracking tool. This also allowed trackers to follow the elephants at a distance and avoid conflict with the sometimes temperamental animals.

Collared elephant, Marijo, (left) enjoying the rich minerals found at the Langoue Bai forest clearing.

Meier, Beirne, and colleagues also wanted to know more about the diets of the tracked elephants to see if what they ate changed with how much fruit is available. This less-than-glamorous job was done by dissecting fresh dung piles, estimating the proportions of leafy and woody material, and counting the number of seeds in each one.

Tropical rainforests are lush, yet have patchy resources, making it important for many frugivores to have flexible diets. Some trees only produce fruit in the wet season. Others fruit every other year. To gauge fruit availability, the research team conducted “fruit-walks” at the beginning and end of each day of following an elephant, in which trackers counted all of the ripe fruit on the ground.

A key finding of the study was that the most important factor driving movement was an elephant’s individuality; some respond to food or water availability differently and some simply move around more than others.

Field researcher Marius Edang getting the straight poop on elephant diets.

Interestingly, elephants appear to be affected by resources differently depending on the timescale the authors looked at. Water was important on both a day-to-day and month-to-month basis. Yet on a daily basis, fruit and water were more equally matched, with water still maintaining a slight lead.

Fruit availability was also critical in determining how much elephants moved and what they ate. When there was more fruit available, the elephants ate more fruit, as evidenced by the proportion of seeds in dissected dung piles.

Aside from being an awe-inspiring species, forest elephants are important to the health of their native ecosystems. They are unwitting gardeners, planting seeds of the fruits they consume in piles of dung and giving those seeds a better chance of survival. That’s part of why understanding what motivates forest elephant movement is more than the satisfaction of an elephant enthusiast’s curiosity; it is critical to managing and conserving a species that is vulnerable to multiple threats from humans.

Meier’s dissertation research focuses on elephant social behavior and the effects of human disturbance on elephant social groups, allowing her to pursue her long-term interest in animal behavior with a practical conservation application.

“I was living in Congo and I knew I wanted to keep working in the region. There, you have elephants–this amazing, highly intelligent, social species that is surrounded by conflict.”

Poachers seek elephants for their ivory tusks, which are valuable on the black market. The pachyderms are also prone to conflict with humans when they start foraging in village plantations, destroying crops and damaging livelihoods.

The team’s findings open the way for new questions about why different elephants exhibit different patterns of movement. What underlying factors affect behavior, and why? Does it have to do with age? Sex? Their social environment?

These questions remain unanswered for now, but the work of Meier and colleagues represents a critical step in understanding elephant behavior to improve forest elephant management and conservation strategies.

Guest Post by Anna Nordseth, a Ph.D. Candidate in the Nicholas School of the Environment

Duke Scientists Studying the Shape of COVID Things to Come

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The novel coronavirus pandemic has now resulted in more than 3 million confirmed cases globally and is pushing scientists to share ideas quickly and figure out the best ways to collaborate and contribute to solutions.

SARS-CoV-2 surface proteins illustrated by We Are Covert, via Wikimedia Commons

Recently, Duke researchers across the School of Medicine came together for an online symposium consisting of several short presentations to summarize the latest of what is known about the novel coronavirus, SARS-CoV-2.

This daylong event was organized by faculty in the Department of Molecular Genetics and Microbiology and researchers from different fields to share what they know about the virus and immunity to guide vaccine design. This conference highlighted the myriad new research pathways that Duke researchers are launching to better understand this pandemic virus.

One neat area of research is understanding viral processes within cells to identify steps at which antivirals may block the virus. Stacy Horner’s Laboratory studies how RNA viruses replicate inside human cells. By figuring out how viruses and cells interact at the molecular level, Horner can inform development of antivirals and strategies to block viral replication. Antivirals stop infections by preventing the virus from generating more of copies of itself and spreading to other cells. This controls damage to our cells and allows the immune system to catch up and clear the infection.

At the symposium, Horner explained how the SARS-CoV viral genome consists of 29,891 ribonucleotides, which are the building blocks of the RNA strand. The viral genome contains 14 areas where the RNA code can be transcribed into shorter RNA sequences for viral protein production. Though each RNA transcript generally contains the code for a single protein, this virus is intriguing in that it uses RNA tricks to code for up to 27 proteins. Horner highlighted two interesting ways that SARS-CoV packs in additional proteins to produce all the necessary components for its replication and assembly into new viral progeny.

The first way is through slippery sequences on the RNA genome of the virus. A ribosome is a machine inside the cell that runs along a string of RNA to translate its code into proteins that have various functions. Each set of 3 ribonucleotides forms one amino acid, a building block of proteins. In turn, a string of amino acids assembles into a distinct structure that gives rise to a functional protein.

One way that SARS-CoV-2 packs in additional proteins is with regions of its RNA genome that make the ribosome machinery slip back by one ribonucleotide. Once the ribosome gets offset it reads a new grouping of 3 ribonucleotides and creates a different amino acid for the same RNA sequence. In this way, SARS-CoV-2 makes multiple proteins from the same piece of RNA and maximizes space on its genome for additional viral proteins.

An example of an RNA ‘hairpin’ structure, which might fool a ribosome to jump across the sequence rather than reading around the little cul de sac. (Ben Moore, via Wikimedia Commons)

Secondly, the RNA genome of SARS-CoV-2 has regions where the single strand of RNA twists over itself and connects with another segment of RNA farther along the code to form a new protein. These folds create structures that look like diverse trees made of repetitive hairpin-like shapes. If the ribosome runs into a fold, it can hop from one spot in the RNA to another disjoint piece and attach a new string of amino acids instead of the ones directly ahead of it on the linear RNA sequence. This is another way the SARS-CoV-2 packs in extra proteins with the same piece of RNA.

Horner said a step-by-step understanding of what the virus needs to survive at each step of its replication cycle will allow us to design molecules that are able to block these crucial steps.

Indeed, shapes of molecules can determine their function inside the cell. Three Duke teams are pursuing detailed investigation of SARS-CoV-2 protein structures that might guide development of complementarily shaped molecules that can serve as drugs by interfering with viral processes inside cells.

Some Duke faculty who participated in the virtual viral conference. (L-R from, top) Stacy Horner, Nick Heaton, Micah Luftig, Sallie Permar, Ed Miao and Georgia Tomaras. (image: Tulika Singh)

For example the laboratory of Hashim Al-Hashimi, develops computational models to predict the diversity of structures produced by these tree-like RNA folds to identify possible targets for new therapeutics. Currently, the Laboratories of Nicholas Heaton and Claire Smith are teaming up to identify novel restriction factors inside cells that can stop SARS-CoV-2.

However, it is not just the structures of viral components expressed inside the cells that matter, but also those on the outside of a virus particle. In Latin, corona means a crown or garland, and coronaviruses have been named for their distinctive crown-like spikes that envelop each virus particle. The viral protein that forms this corona is aptly named the “Spike” protein.

This Spike protein on the viral surface connects with a human cell surface protein (Angiotensin-converting enzyme 2, abbreviated as ACE2) to allow the virus to enter our cells and cause an infection. Heaton proposed that molecules designed to block this contact, by blocking either the human cell surface protein or the viral Spike protein, should also be tested as possible therapies.

One promising type of molecule to block this interaction is an antibody. Antibodies are “Y” shaped molecules that are developed as part of the immune response in the body by the second week of coronavirus infection. These molecules can detect viral proteins, bind with them, and prevent viruses from entering cells. Unlike several other components on our immune defense, antibodies are shaped to specifically latch on to one type of virus. Teams of scientists at Duke led by Dr. Sallie Permar, Dr. Georgia Tomaras, and Dr. Genevieve Fouda are working to characterize this antibody response to SARS-CoV-2 infection and identify the types of antibodies that confer protection.

Infectious disease specialist Dr. Chris Woods is leading an effort to test whether plasma with antibodies from people who have recovered can prevent severe coronavirus disease in acutely infected patients.

Indeed, there are several intriguing research questions to resolve in the months ahead. Duke scientists are forging new plans for research and actively launching new projects to unravel the mysteries of SARS-CoV-2. With Duke laboratory scientists rolling up their sleeves and gowning up to conduct research on the novel coronavirus, there will be soon be many more vaccine and therapeutic interventions to test.

Guest post by Tulika Singh, MPH, PhD Candidate in the Department of Molecular Genetics and Microbiology (T: @Singh_Tulika)

Researchers created a tiny circuit through a single water molecule, and here’s what they found

Graphic by Limin Xiang, Arizona State University

Many university labs may have gone quiet amid coronavirus shutdowns, but faculty continue to analyze data, publish papers and write grants. In this guest post from Duke chemistry professor David Beratan and colleagues, the researchers describe a new study showing how water’s ability to shepherd electrons can change with subtle shifts in a water molecule’s 3-D structure:

Water, the humble combination of hydrogen and oxygen, is essential for life. Despite its central place in nature, relatively little is known about the role that single water molecules play in biology.

Researchers at Duke University, in collaboration with Arizona State University, Pennsylvania State University and University of California-Davis have studied how electrons flow though water molecules, a process crucial for the energy-generating machinery of living systems. The team discovered that the way that water molecules cluster on solid surfaces enables the molecules to be either strong or weak mediators of electron transfer, depending on their orientation. The team’s experiments show that water is able to adopt a higher- or a lower-conducting form, much like the electrical switch on your wall. They were able to shift between the two structures using large electric fields.

In a previous paper published fifteen years ago in the journal Science, Duke chemistry professor David Beratan predicted that water’s mediation properties in living systems would depend on how the water molecules are oriented.

Water assemblies and chains occur throughout biological systems. “If you know the conducting properties of the two forms for a single water molecule, then you can predict the conducting properties of a water chain,” said Limin Xiang, a postdoctoral scholar at University of California, Berkeley, and the first author of the paper.

“Just like the piling up of Lego bricks, you could also pile up a water chain with the two forms of water as the building blocks,” Xiang said.

In addition to discovering the two forms of water, the authors also found that water can change its structure at high voltages. Indeed, when the voltage is large, water switches from a high- to a low-conductive form. In fact, it is may be possible that this switching could gate the flow of electron charge in living systems.

This study marks an important first step in establishing water synthetic structures that could assist in making electrical contact between biomolecules and electrodes. In addition, the research may help reveal nature’s strategies for maintaining appropriate electron transport through water molecules and could shed light on diseases linked to oxidative damage processes.

The researchers dedicate this study to the memory of Prof. Nongjian (NJ) Tao.

CITATION: “Conductance and Configuration of Molecular Gold-Water-Gold Junctions Under Electric Fields,” Limin Xiang, Peng Zhang, Chaoren Liu, Xin He, Haipeng B. Li, Yueqi Li, Zixiao Wang, Joshua Hihath, Seong H. Kim, David N. Beratan and Nongjian Tao. Matter, April 20, 2020. DOI: 10.1016/j.matt.2020.03.023

Guest post by David Beratan and Limin Xiang

A Day of STEM for Girls

On any average weekday at Duke University, a walk through the Engineering Quad and down Science Drive would yield the vibrant and exciting sight of bleary-eyed, caffeine-dependent college students heading to labs or lectures, most definitely with Airpods stuck in their ears.

But on Saturday, February 22nd, a glance towards this side of campus would have shown you nearly 200 energetic and chatty female and female-identifying 4th to 6th graders from the Durham area. As part of Capstone, an event organized by Duke FEMMES, these students spent the day in a series of four hands-on STEM activities designed to give them exposure to different science, technology, engineering, and math disciplines.

Nina MacLeod, 10, gets grossed out when viewing fruit fly larvae through a microscope while her guide, Duke first-year Sweta Kafle, waits patiently. (Jared Lazarus)

FEMMES, which stands for Females Excelling More in Math, Engineering, and Science, is an organization comprised of Duke students with the aim of improving female participation in STEM subjects. Their focus starts young: FEMMES uses hands-on programming for young girls and hosts various events throughout the year, including after-school activities at nearby schools and summer camps. 

Capstone was a day of fun STEM exposure divided into four events stationed along Science Drive and E-Quad — two in the morning, and two in the afternoon, with a break for lunch. Students were separated into groups of around eight, and were led by two to three Duke undergraduates and a high school student. The day started bright and early at 8:45 A.M with keynote speaker Stacy Bilbo, Duke professor of Psychology and Neuroscience. 

Staci Bilbo

Bilbo explained that her work centers around microglial cells, a type of brain cell. A series of slides about her journey into a science career sparked awe, especially as she remarked that microglial cells are significant players in our immune system, but scientists used to know nearly nothing about them. Perhaps most impactful, however, was a particular slide depicting microglial cells as macrophages, because they literally eat cellular debris and dead neurons.

A cartoon depiction of this phenomenon generated a variety of reactions from the young audience, including but not limited to: “I’m NEVER being a doctor!”, “I wish I was a microglial cell!”, “Ew, why are brains so gross?”, and “I’m so glad I’m not a brain because that’s SO weird.”

Even in 2020, while fields like medicine and veterinary science see more women than men, only 20% of students that earn bachelor’s degrees in physical sciences, math, and engineering disciplines are female. What accounts for the dramatic lack of female participation in STEM disciplines? The reasons are nuanced and varied. For example, according to a 2010 research report by the American Association of University Women, girls tend to have more difficulty acquiring spatial thinking and reasoning skills – all because of the type of play young female children are more likely to engage in. 

Durham area students learned how to perform a blood pressure check during a FEMMES session taught by Duke EMS, an all-volunteer, student-run division of the police department and Duke Life Flight. Duke senior Kayla Corredera-Wells (center) put the blood pressure cuff on sophomore Pallavi Avasarala. (Jared Lazarus)

This creates a chicken-and-egg story: girls don’t enter STEM at the same rate as their male counterparts, and as a result, future generations of girls are discouraged from pursuing STEM because they don’t see as many accomplished, visibly female scientists to look up to. Spaces like Capstone which encourage hands-on activity are key to exposing girls to the same activities that their male counterparts engage in on a regular basis – and to exposing girls to a world of incredible science and discovery led by other females. 

After Bilbo’s talk, it was off to the activities, led by distinguished female professors at Duke — a nod to the importance of representation when encouraging female participation in science. For example, one of the computer science activities, led by Susan Rodger, taught girls how to use basic CS skills to create 3-D interactive animation.

An introduction to categorizing different minerals based on appearance was led by Emily Klein, while one of the medicine-centered activities involved Duke EMS imparting first aid skills onto the students. 

For one of the biology-themed activities, Nina Sherwood and Emily Ozdowski (dubbed “The Fly Ladies”) showed students fruit flies under a microscope. The activity clearly split the group: girls who stared in glee at unconscious flies, shrieking “It’s SO BIG, look at it!” and girls who exchanged disgusted looks, edging their swivel chairs as far as physically possible from the lab benches. Elizabeth Bucholz, a Biomedical Engineering professor, led one of the engineering activities, showing students how CT scans generate images using paper, a keychain light and a block (meant to represent the body). In math, meanwhile, Shira Viel used the activity of jump-roping to show how fractions can untangle the inevitable and ensuing snarls.

The day definitely wasn’t all science. During lunch in LSRC’s Love Auditorium, most groups spread out after scarfing down pizza and spent intense focus over learning (and recording) TikTok dances, and when walking down Science Drive under blue and sunny skies, conversations ranged from the sequins on someone’s Ugg boots to how to properly bathe one’s dog, to yelling erupting over someone confidently proclaiming that they were a die-hard Tar Heel.

Nina Sherwood, Associate Professor of Biology, showed Emma Zhang, 9, some fruit flies, which we study because they share 75% of their genes with humans. (Jared Lazarus)

A raffle at the end of the day for the chance to win Duke merchandise inspired many closed eyes and crossed fingers (“I want a waterbottle so bad, you have no idea!”) And as newfound friends said goodbye to each other and wistfully bonded over how much fun they had at the end of the day, one thing was clear: events like Capstone are crucial to instilling confidence and a love of STEM in girls. 

By Meghna Datta

Paleo Fact and Fiction: the Key to Being Healthy

Humans have conquered smallpox and drastically reduced child mortality rates, yet we now face problems never seen before. Conditions like heart disease, obesity, cancer, and diabetes pose serious threats to our health. How can we overcome them? The answer may lie in our past.

Herman Pontzer, an associate professor of evolutionary anthropology at Duke, thinks we have something to learn by looking at hunter gatherers.

For most of human evolution, we had to work for our food. Recent developments like supermarkets and cities are strange and have flipped the script on daily life. Pontzer believes if we could live more like our ancestors, maybe we wouldn’t get sick.

Pontzer started off by studying a hunter gatherer group in Tanzania known as the Hadza. The Hadza cling tight to cultural traditions and live off the land in the African savannah. There are no domesticated animals, no guns, and no vehicles. Women spend their days digging for fibrous tubers and gathering berries and baobab fruits. When men aren’t hunting game, they collect honey. Honey plays a major role in the Hadza diet — around 15-20% of their caloric intake.

The Hadza live a very active lifestyle. They walk between 13,000 and 20,000 steps a day, compared to the generic Fitbit goal of 10,000 steps (which most of us don’t even meet, if we’re being honest).

Curious to see if the Hadza’s vigorous activity levels had something to do with their superior health, Pontzer used the doubly labeled water technique to measure total energy expenditure. Shockingly, he found that Hadza and Americans burn the same amount of calories on average.

All our lives we’ve been told exercise converts to burned calories. But evidence from the Hadza tells us this is not the case. What really happens is natural systems in our body adjust to suppress other activity, keeping total expenditure constant. This means that exercise alone is an ineffective tool for weight loss. But don’t quit the gym quite yet — while the Hadza spend most of their total energy being active, an inactive body will spend it on unhealthy things such as inflammation and stress reactivity. This constrained energy mechanism makes exercise essential for overall health. But in the words of Pontzer, “in order to end obesity, we need to fix our diet.”

Image result for paleo diet

The idea that the “paleo diet” is necessarily low-carb is a myth, Pontzer says. Hadza rely heavily on starches and fructose for sustenance. Furthermore, what you eat as a hunter gatherer is entirely dependent on geographical location. Hunter gatherer diets do things in common, though: they eat no processed foods, and energy dense foods are hard to come by. 

Never before have we had so much food high in energy available at such a low effort. In supermarkets, the cheapest food is the most rich in energy. In the wild, it’s the complete opposite. Pontzer says, “traditional diets are diverse, modern diets are perverse.”

Image result for supermarket cereal aisle

He calculated that an American can get twenty times as much food energy in an hour’s work as a Hadza could with the same effort. Plus, the Hadza don’t have irresistible Doritos they can’t stop eating. When the Hadza are full, they’re full.

The Hadza are naturally protected from the same “diseases of civilization” that we are likely to die from. A beautiful combination of diet and how they expend energy provides a shield that modernization seems to have taken from us. Energy has become too available. But staying healthy is still in our control. It’s about finding the right balance of exercise and eating right.  

There is still a lot to be learned from hunter gatherer societies. For now, let the Hadza inspire you to get outside, get active, and cut out processed foods!

Polymath Mae Jemison encourages bolder exploration, collaboration

Photo from Biography.com

“I don’t believe that [going to] Mars pushes us hard enough.” This was just one of the bold, thought-provoking statements made by Dr. Mae Jemison, who came to speak at Duke on Monday, February 24 as part of the 15th annual Jean Fox O’Barr Distinguished Speaker Series, presented by Baldwin Scholars.

Dr. Jemison is at the pinnacle of interdisciplinary engagement—though she is most famous for serving as a NASA astronaut and being the first African American woman to go into space, she is also trained as an engineer, social scientist and dancer. Dr. Jemison always knew that she was going to space—even though there were no women or people or color participating in space exploration as she was growing up.

Dr. Jemison says that simply “looking up” brought her here. As a child, she would look up at the sky, see the stars and wonder if other children in other places in the world were looking at the same view that she had. Growing up in the 1960’s instilled into Dr. Jemison at an early age that our potential is limitless, and the political culture of civil rights, changing art and music and decolonization were all about “people declaring that they had a right to participate.” 

Photo courtesy of Elizabeth Roy

One of the biggest pieces of advice that Dr. Jemison wanted to impart on her audience was the value of confidence, and how to build confidence in situations where people are tempted to feel incapable or forget the strengths they already possess. “They told me if I wanted to lead projects I needed an M.D.,” Dr. Jemison explained. “I went to medical school because I know myself and I knew I would want to be in charge one day.” 

At 26 years old, Dr. Jemison was on call 24 hours a day, 7 days a week, 365 days a year as the Area Peace Corps Medical Officer for Sierra Leone and Liberia. She described a case where a man came back with a diagnosis of malaria from Senegal. When Dr. Jemison first took a look, the diagnosis seemed more likely to be meningitis. After making an “antibiotic cocktail,” from what she had on site, she realized this man might lose his life if they didn’t get him to a better hospital. At this point, Dr. Jemison wanted to call a military medical evacuation, and she had the authority to do it. However, another man working with her suggested calling a doctor in Ivory Coast, or a doctor at the hospital in Germany to see what he thought before making the evacuation. Dr. Jemison knew what the patient needed in this situation was to be flown to Germany regardless of the cost of the evacuation. In reflecting on this experience, she says that she could have given someone else her authority, but letting her confidence in herself and what she knew was the right thing to do would have negatively impacted her patient. 

So, how do you maintain confidence? According to Dr. Jemison, you come prepared. She knew her job was to save people’s lives, not to listen to someone else. Dr. Jemison also admonished the audience to “value, corral and protect your energy.” She couldn’t afford to always make herself available for non-emergency situations, because she needed her energy for when a patient’s life would depend on it. 

Photo courtesy of Elizabeth Roy

Dr. Jemison’s current project, 100 Year Starship, is about  trying to ensure we have the capabilities to travel to interstellar space. “The extreme nature of interstellar hurdles requires we re-evaluate what we think we know,” Dr. Jemison explained. Alpha Centauri, the next closest star, is more than 25 trillion miles away. Even if we go 10% the speed of light, it will still take us 50 years to get there. We need to be able to travel faster, the vehicle has to be self-replenishing, and we have to think about space-time changes. What Dr. Jemison calls the “long pole in the tent” is human behavior. We need to know how humans will act and interact in a small spaceship setting for possibly decades of space travel. Dr. Jemison is thinking deeply about how we can apply the knowledge we already possess to fix world problems, and how we can start preparing now for problems we may face in the future. For example, how would health infrastructure in deep space look different? How would we act on a starship that contains 5,000 people when we can’t figure out how to interact with each other on the “starship” we’re on now?

Returning to the childhood love for stargazing that brought her here, Dr. Jemison discussed towards the end of her talk that a stumbling block for the majority of people is insufficient appreciation of our connection across time and space. She has worked with a team to develop Skyfie, an app that allows you to upload photos and videos of your sky to the Sky Tapestry and explore images other people in different parts of the world are posting of their sky. Dr. Jemison’s hope is this app will help people realize that we are interconnected with the rest of the universe, and we won’t be able to figure out how to survive as a species on this planet alone. 

By Victoria Priester

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