Thirty-seven Duke faculty were named to the list this year, based on the number of highly cited papers they produced over an 11-year period from January 2009 to December 2019. Citation rate, as tracked by Clarivate’s Web of Science, is an approximate measure of a study’s influence and importance.
Two Duke researchers appear in two categories: Human Vaccine Institute Director Barton Haynes, and Michael Pencina, vice dean of data science and information technology in the School of Medicine.
And two of the Duke names listed are new faculty, recruited as part of the Science & Technology initiative: Edward Miao in Immunology and Sheng Yang He in Biology.
This year, 6,127 researchers from 60 countries are being recognized by the listing. The United States still dominates, with 41 percent of the names on the list, but China continues to grow its influence, with 12 percent of the names.
Robert M. Califf, Lesley H. Curtis, Pamela S. Douglas, Christopher Bull Granger, Adrian F. Hernandez, L. Kristen Newby, Erik Magnus Ohman, Manesh R. Patel, Michael J. Pencina, Eric D. Peterson.
Environment and Ecology:
Emily S. Bernhardt, Stuart L. Pimm, Mark R. Weisner.
Drew T. Shindell
Barton F. Haynes, Edward A. Miao
Barton F. Haynes
Plant and Animal Science:
Sheng Yang He
Psychiatry and Psychology:
Avshalom Caspi, E. Jane Costello, Renate M. Houts, Terrie E. Moffitt
Michael J. Pencina
Dan Ariely, Geraldine Dawson, Xinnian Dong, Charles A. Gersbach, Ru-Rong Ji, Robert J. Lefkowitz, Sarah H. Lisanby, Jie Liu, Jason W. Locasale, David B. Mitzi, Christopher B. Newgard, Ram Oren, David R. Smith, Avner Vengosh.
We’ve all heard the term “survival of the fittest,” which scientist Charles Darwin famously coined to explain how organisms with heritable traits that give them an advantage — such as avoiding predators or beating out others for the chance to mate — are able to survive and pass on these advantageous traits to their offspring.
In his talk with ClubEvMed last Tuesday, Brian Hare of Duke Evolutionary Anthropology explained key points from his new book that he co-authored with his wife and research partner, Vanessa Woods, entitled Survival of the Friendliest: Understanding Our Origins and Rediscovering Our Common Humanity.
The term “fittest” is often associated with animals who are physically stronger or of more value than others, but being “fit” can also include an organism’s ability to communicate well with others in its group, which can provide an evolutionary advantage. For example, more social animals can form alliances with each other and protect each others’ young, so the whole population stays stronger in terms of number.
Hare cited a comparison between chimpanzees and bonobos, both of which have the potential for infanticide by aggressive males in a group. However, bonobos have zero cases of infanticide because female bonobos are able to communicate well and form alliances to protect each others’ young from aggressive males. Since the high cost of aggression for males outweighs the benefit, the males are friendlier, and the young bonobos survive. While this is a specific case with wild animals, other species have adopted social skills as a method of survival through domestication or self-domestication.
Hare referred to dogs as “exhibit A” of survival of the friendliest via domestication, because humans have bred dogs that are more playful, approachable and patient for centuries. Dogs are exceptionally good at understanding, responding to and communicating with humans as a result of domestication. Hare also explained one Russian study in which they began selecting foxes based on their friendliness towards people. They bred the most friendly foxes together and then compared the friendliness of their offspring to the offspring of randomly bred foxes. The results showed that friendlier foxes differed in physiology in addition to behavior, and were better at cooperating and communicating with humans. This is an example of self-domestication, which changes development patterns and has increased fitness via friendliness. Friendliness in this case means skill in cooperating and communication.
Survival of the Friendliest argues that humans today are the friendliest species of human, which may be why we have lasted so long evolutionarily. However, with the new type of friendliness also comes a new type of aggression. Mother bears are kind and nurturing to their cubs, but also have the most potential for aggression when they feel their cubs are threatened. Similarly in humans, when we feel people who share our identity are threatened, we want to protect those individuals.
Hare and Woods reason that this desire to protect also reduces our ability to cooperate or communicate with those who we feel threaten us or threaten our “group”— whether this be our family, our race or another trait. When our ability to communicate is reduced, we begin to dehumanize those who we feel threaten the people who share our identity. This then becomes a cycle, where people dehumanize those who they believe are dehumanizing them.
In order to stop this cycle, Hare and Woods argue that humans will need to alter their view of who they believe “belongs” to their group to include more people. We need to communicate openly and build a desire to protect other humans, rather than dehumanize them.
Conversations on and actions toward making American medicine less racist continue to grow. At Duke, that includes looking at our own history as a hospital and medical center serving a diverse community.
The career of Dr. Baker, who is a professor of both pediatrics and history, has taken him around the globe, right back to his hometown of Durham –where he said he has found the most interesting story of all.
After becoming Director for the Trent Center in 2016, he was approached with “hunger” by Durham natives to know their hometown’s story. Through oral and archival sources, Dr. Baker has broached Duke hospital’s history with humility in hopes of uncovering and contextualizing the historical roles of race in Duke medicine and Durham.
Dr. Tweedy, author of Black Man in a White Coat, attended Duke for medical school in the 1990s. He was warned that it was a plantation and an institution built on tobacco and slave money.
Though Dr. Baker proposed that in many ways the hospital structure often reflects plantation hierarchies in which there is racialization of who holds what jobs and power, he said Duke’s endowment money actually came from technological progress within tobacco production rather than slavery or plantations directly.
The Duke family’s vision for the hospital was quite different from actual outcomes in practice, Dr. Baker said. The Dukes were considered racial progressives in their time and the endowment they provided to launch the Duke Medical School and Hospital in 1930 was meant to improve health and education in North Carolina and train primary care doctors for the state.
“However,” Dr. Baker said, “there were two realities: Jim Crow and the Great Depression.”
During the era of Jim Crow segregation, Duke’s primary care doctors were all white, and nearly all male. Though the hospital cared for both Black and white patients, they were segregated by race. Black patients had separate wards, and waiting areas for pediatric care were separated racially by days of the week. Waiting areas for adult patients functioned without appointments, but only white people were seen before noon. It’s likely that the care granted to white people in the first half of the day was superior to that of Black people receiving care at 4 pm or told to return the next day, he said.
The Great Depression also generated a diversion from plans in the 1940s. When the Duke Hospital came close to bankruptcy, it chose to open private clinics on the side for revenue – which had an unintended consequence. The clinics brought a lot of money into Duke, Dr. Baker said, but it also reinforced distinctions between those who could pay for treatment and those who couldn’t. Over time, the disparities expanded with shifts towards hospital beds for insured and private patients.
In one terrible example, Maltheus “Sunny” Avery, a North Carolina A & T graduate who got into a car wreck in Burlington, NC in 1950, was diagnosed with an epidermal hematoma — a clot near his brain — and sent to Duke for emergency brain surgery. But he was refused treatment due to inadequate room in the “colored” ward.
Avery was redirected to Lincoln Hospital, Durham’s Black hospital, where he died shortly after admission. Though Dr. Baker said this story quickly faded from white memory, it is something that has retained severe importance in the popular memory of Black Durhamites. This narrative is also often conflated with a similar story about Dr. Charles Drew, the Black inventor of blood banking, who died despite attempts at rescue at a white hospital in Alamance, NC. He is often misremembered as having died from the refusal of care in a racially divided South, even though he was not.
Duke’s first Black medical student, Delano “Dale” Meriwether, arrived the same year the hospital began desegregation, 1963, and he was the first Black M.D. in 1967. Meriwether was the only Black medical student for four years before other brave pioneers joined the school.
Dr. Tweedy reflected on his own medical school experiences at Duke during clinical rotations just a little more than 20 years ago.
“I was asked to help suture a deep gash on a Black patient’s forehead,” he said, “The patient asked if we were experimenting on him since I was still a student.” In the private clinics, he once “couldn’t go anywhere near” a white patent with a minor lesion on their arm, let alone suture that patient.
Dr. Baker said there are two narratives surrounding Duke Hospital’s desegregation. One assumes that desegregation was quick and easy and uneventful, while the other proposes that systems of racial segregation were simply transformed rather than eradicated. The latter narrative better applies to the public and private clinics that had become nearly completely racialized over time, Baker said.
Even though segregation was no longer legal, Black patients received care from less experienced medical residents in the public clinics, while white patients received care from attending physicians in the nicer, private environments.
Dr. Baker said that Duke has a complicated relationship with the community of Durham. He said the merger of Durham Regional Hospital with Duke Health in the late 1990s tapped into some long-term tensions and distrust between Duke and other medical facilities of Durham.
Dr. Tweedy pointed out that Duke researchers always have trouble recruiting Black patients for clinical studies, despite the fact that Durham County is about half Black and Hispanic. There is some distrust to overcome, but a diverse patient population is essential to creating robust study data that ensures that treatments will work for everyone, he said.
Medical professionals “need more than just science,” Baker concluded. He said that being trained as scientists often inclines doctors to think that they are above the larger contexts and histories they exist within, and that they can somehow remain objective.
“We have come out of specific stories and backgrounds,” Dr. Baker said. “[When we treat patients], we have to think about what story we are walking into.”
“We all carry our bags of ‘stuff'” that complicate patient prognosis and care, Dr. Tweedy concurred.
As Ann Brown (M.D., M.H.S), Vice Dean for Faculty, stated at the beginning of the conversation, “In order to move forward, we must understand where we come from.”
This is true of our nation as a whole, and Duke is certainly no exception.
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.”
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.
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.
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.
Like nearly all other aspects of life, the normal routines of Duke research labs came to a grinding halt due to COVID-19. Duke researchers shared their reflections on the struggles and insights the process of research shutdown and reboot has had within their labs during a Virtual Research Town Hall on Thursday, September 3rd.
The Town Hall, titled “The Impact of COVID 19 on Research at Duke, Overcoming Challenges and Pressures” was moderated by Duke Vice President for Research, Larry Carin (Ph.D.). Dr. Carin mentioned that discussion of shutting down the research enterprise began in February, and at that point in time it seemed nearly hysterical. However, by mid-March shut-down plans were fully in progress, leaving labs out of commission until mid-June. To get research at Duke back underway, labs were forced to significantly reduce the density of people in facilities and no undergraduate students were allowed to participate.
Though most of the basic science labs are back in operation now, human subjects research trials have had a slower return. In no way is it business as usual. Detailed planning and scheduling, a focus on social distancing, and daily health surveys are all part of the new normal. “There is almost a Big Brother feel to this,” Dr. Carin said, comparing the moderated tracking of who enters facilities through their DukeCard swipes to George Orwell’s 1984 dystopian society.
Associate Professor Debra Silver Ph.D. spoke about her neurodevelopmental lab in molecular genetics and microbiology (MGM). In the three-month shutdown, lab members focused on writing reviews, grants, manuscripts, and took online classes to improve skills. Since re-opening, Silver’s lab has implemented lab shifts, pre-scheduled experiments, and coordinated use of shared equipment. Some of the biggest issues are the trainees missing out on critical networking and undergraduates forced to transition to nearly exclusively online work. Silver also voiced serious concern for the mental and physical health of lab members, logistical coordination of childcare and homeschooling, challenges faced by international trainees, and the need for flexibility. However, there were some silver linings as well. The Silver Lab engaged with lots of seminars, had joint lab meetings, and the mutual support for one another grew immensely under the unique circumstances.
Both Silver’s lab and the West Lab, led by professor Anne West Ph.D. in neurobiology, are heavily reliant on mice for wet lab work. The mandates to reduce their mouse colonies by more than 50% was a large task and now that the labs are up and running, re-expanding the colonies has been a primary focus. West said that, similar to the Silver Lab members, half of her team picked up writing or a computational project while the other half attended online classes or meetings during shutdown. Undergraduates read and presented research papers – which turned out to be a very fruitful training experience.
One major roadblock for the West Lab’s reopening were the murders of George Floyd, Breonna Taylor, and Ahmoud Arbery. The civic unrest surrounding these deaths and the revivalism of the Black Lives Matter movement became a frequent point of discussion in lab meetings. Some members of the West Lab were unable to work during this time. West emphasized the importance of lowered expectations. She asked everyone to focus on one core experiment and to try to come into the lab for at least a few hours a day, a few days a week. The lab has been gaining traction with new data and research papers nearing completion. Like other panelists, West discussed prevailing issues including anxiety and depression, continued societal uncertainties, and the questionable financial future for research.
Assistant professor of anesthesiology Jamie R. Privratsky MD, Ph.D. highlighted COVID’s impact on clinical and critical care research. Among the positive impacts are the Society of Critical Care Medicine’s COVID-19 registry database, the abilities to do observational and database research work, and research opportunities for working with COVID patients. However, the rest of critical care research has been completely sidelined, clinician-scientists have been moved to mostly clinical duties, and there have been lots of administrative hurdles for conducting COVID related research.
Many colleagues share Dr. Privratsky’s mixed thoughts on the gains and losses during the halt of critical care research. For those who were able to conduct some research, the risks to personal health also posed looming anxiety and danger. Dr. Privratsky chose to do what he could being physically away from his lab and worked to update protocols, maintain electronic lab notebooks, write methods sections of papers, and care for his mouse colony. He also submitted three grant proposals and said that he left the shutdown with a clearer vision and direction for his research.
The School of Medicine’s Vice Dean for Basic Science, Colin S. Duckett Ph.D. closed the town hall with encouraging reflections. Out of 17,000 Duke administered COVID tests, there have been very few positives. Duckett emphasized how seriously the Duke community and its recently returned students are taking the continued threat of Coronavirus. Though communications persist as a challenge and many argue that life right now just doesn’t feel right, Duckett called attendees’ attention to the fact that the research enterprise was successfully ramped down, ramped back up, and lab activities have made a nearly completely return. This was and continues to be no small feat and is possible due to highly collaborative efforts, he said.
Further, there were large insights gleaned from this collective experience; those of researchers’ resiliency, the importance of community, and the need to look beyond work and check in on each other as human beings. Research and the people who make it possible do not exist in a vacuum away from society. Their work and their well-being are subject to the pandemic just like everyone else. Yet, similar to the broader global public, researchers and their research are emerging stronger than before in the face of COVID-19.
TikTok’s illicit collection of user data recently drew fire from US officials. But TikTok’s base—largely young adults under 25—was unfazed. In viral videos posted in July and August, users expressed little concern about their digital privacy.
“If china wants to know how obsessed i am with hockey,” wrote one user, “then just let them its not a secret.” “#Takemydata,” captioned another, in a video racking up 6,000 likes and over 42,000 views.
As digital technologies become ever more pervasive – or even invasive – concerns for privacy should be a concern, a pair of experts said in a Duke Science & Society webinar earlier this month.
TikTok and digital marketing aside, data collection can have real, tangible benefits. Case in point: COVID-19. Researchers at Duke and elsewhere are using peoples’ fitness trackers and smart watches to try to understand and predict the pandemic’s spread by monitoring a variety of health metrics, producing real-time snapshots of heart rate, blood pressure, sleep quality, and more. Webinar speaker Jessilyn Dunn of Duke biomedical engineering and her team have tapped into this data for CovIdentify, a Duke-funded effort to predict COVID infections using data collected by smartphones and wearable devices.
For several years, Dunn’s lab has researched digital biomarkers of disease—that is, how health data collected by tech we carry every day can predict anything from heart disease to cognitive decline.
It’s a potential goldmine: One recent poll suggests that 40 million Americans own some kind of smartwatch or fitness tracker. And the wearables market is rapidly expanding—by 2022, it may be worth upwards of 25 billion dollars.
As coronavirus cases began to rise in the US, Dunn’s lab quickly pivoted to develop COVID-specific biomarkers. “We have these devices … that perform physiologic monitoring,” Dunn said, “This is a method of taking vitals continuously to try to monitor what’s going on with people.”
Say you’re a participant in Dr. Dunn’s study. You download the CovIdentify app, which analyzes health data collected by your phone or smartwatch. Short daily surveys then assess your exposure to COVID-19 and whether you’ve developed any symptoms. Dunn and her team hope to find a link, some specific change in vitals that corresponds to COVID-19 infection.
There are some challenges. CovIdentify must account for variability between devices—data collected from a Fitbit, for example, might differ dramatically from an Apple Watch. And because COVID-19 manifests in unique ways across populations, a truly universal biomarker may not exist.
However, panelist Marielle Gross—a bioethicist at the University of Pittsburgh—said projects like Dunn’s raise questions of digital privacy. Gross emphasized how easily our health data can be abused.
“Digital specimen is the digital representation of the human body,” she said. “Disrespecting it disrespects the body it represents.”
Dr. Gross cited South Korea’s efforts to curb COVID-19 as a cautionary tale. As part of the government’s response, which quickly minimized cases early in the pandemic, exposed or infected South Koreans were expected to stay home and isolate, tracked using GPS-enabled devices.
But many South Koreans chose to leave their devices at home, rather than be tracked by their government. In response, the government required its citizens to carry their devices, 24/7. In a pandemic, desperate measures may be called for. But, Gross suggests, it isn’t hard to imagine a grimmer future—where the government requires all citizens to share their location, all the time.
Gross argues that we must fundamentally shift how we think about our personal data. “There’s this broad assumption that we have to give up privacy to reap the benefits of collective data.” Gross noted. “And that’s false.”
Most ‘digital natives’ aren’t naive. They’re well aware that internet companies collect, analyze, and sell their data, sometimes to malicious effect. But many view data collection as a necessary tradeoff for an intuitive and tailored web experience.
So where do we go from here? Dr. Gross points to new developments like zero knowledge proofs, which use complex algorithms to verify data without actually seeing it. This technique promises anonymity without compromising the value of collective data. And as computing power increases, it may also be possible to perform real-time analysis without ever transmitting or storing collected health data.
And for future tech? In Dr. Gross’s opinion, ethical implications must be considered from day one. “Those sorts of considerations are not the kind of thing that you can tack on later. They have to be built into devices…at the ground floor.”
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.
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.
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.
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)
The COVID-19 epidemic has impacted the Duke research enterprise in profound ways. Nearly all laboratory-based research has been temporarily halted, except for research directly connected to the fight against COVID-19. It will take much time to return to normal, and that process of renewal will be gradual and will be implemented carefully.
Trying to put this situation into a broader perspective, I thought of the 1939 essay by Abraham Flexner published in Harper’s magazine, entitled “The Usefulness of Useless Knowledge.” Flexner was the founding Director of the Institute for Advanced Study at Princeton, and in that essay, he ruminated on much of the type of knowledge acquired at research universities — knowledge motivated by no objective other than the basic human desire to understand. As Flexner said, the pursuit of this type of knowledge sometimes leads to surprises that transform the way we see that which was previously taken for granted, or for which we had previously given up hope. Such knowledge is sometimes very useful, in highly unintended ways.
The 1918 influenza pandemic led to 500 million confirmed cases, and 50 million deaths. In the Century since, consider how far we have come in our understanding of epidemics, and how that knowledge has impacted our ability to respond. People like Greg Gray, a professor of medicine and member of the Duke Global Health Institute (DGHI), have been quietly studying viruses for many years, including how viruses at domestic animal farms and food markets can leap from animals to humans. Many believe the COVID-19 virus started from a bat and was transferred to a human. Dr. Gray has been a global leader in studying this mechanism of a potential viral pandemic, doing much of his work in Asia, and that experience makes him uniquely positioned to provide understanding of our current predicament.
From the health-policy perspective, Mark McClellan, Director of the Duke Margolis Center for Health Policy, has been a leading voice in understanding viruses and the best policy responses to an epidemic. As a former FDA director, he has experience bringing policy to life, and his voice carries weight in the halls of Washington. Drawing on faculty from across Duke and its extensive applied policy research capacity, the Margolis Center has been at the forefront in guiding policymakers in responding to COVID-19.
Through knowledge accrued by academic leaders like Drs. Gray and McClellan, one notes with awe the difference in how the world has responded to a viral threat today, relative to 100 years ago. While there has been significant turmoil in many people’s lives today, as well as significant hardship, the number of global deaths caused by COVID-19 has been reduced substantially relative to 1918.
One of the seemingly unusual aspects of COVID-19 is that a substantial fraction of the population infected by the virus has no symptoms. However, those asymptomatic individuals shed the virus and infect others. While most people have no or mild symptoms, other people have very adverse effects to COVID-19, some dying quickly.
This heterogeneous response to COVID-19 is a characteristic of viruses studied by Chris Woods, a professor medicine in infectious diseases. Dr. Woods, and his colleagues in the Schools of Medicine and Engineering, have investigated this phenomenon for years, long before the current crisis, focusing their studies on the genomic response of the human host to a virus. This knowledge of viruses has made Dr. Woods and his colleagues leading voices in understanding COVID-19, and guiding the clinical response.
A team led by Greg Sempowski, a professor of pathology in the Human Vaccine Institute is working to isolate protective antibodies from SARS-CoV-2-infected individuals to see if they may be used as drugs to prevent or treat COVID-19. They’re seeking antibodies that can neutralize or kill the virus, which are called neutralizing antibodies.
Many believe that only a vaccine for COVID-19 can truly return life to normal. Human Vaccine Institute Director Barton Haynes, and his colleagues are at the forefront of developing that vaccine to provide human resistance to COVID-19. Dr. Haynes has been focusing on vaccine research for numerous years, and now that work is at the forefront in the fight against COVID-19.
Engineering and materials science have also advanced significantly since 1918. Ken Gall, a professor of mechanical engineering and materials science has led Duke’s novel application of 3D printing to develop methods for creatively designing personal protective equipment (PPE). These PPE are being used in the Duke hospital, and throughout the world to protect healthcare providers in the fight against COVID-19.
Much of the work discussed above, in addition to being motivated by the desire to understand and adapt to viruses, is motivated from the perspective that viruses must be fought to extend human life.
In contrast, several years ago Jennifer Doudna and Emmanuelle Charpentier, academics at Berkeley and the Max Planck Institute, respectively, asked a seemingly useless question. They wanted to understand how bacteria defended themselves against a virus. What may have made this work seem even more useless is that the specific class of viruses (called phage) that infect bacteria do not cause human disease. Useless stuff! The kind of work that can only take place at a university. That basic research led to the discovery of clustered regularly interspaced short palindromic repeats (CRISPR), a bacterial defense system against viruses, as a tool for manipulating genome sequences. Unexpectedly, CRISPR manifested an almost unbelievable ability to edit the genome, with the potential to cure previously incurable genetic diseases.
Charles Gersbach, a professor of Biomedical Engineering, and his colleagues at Duke are at the forefront of CRISPR research for gene and cell therapy. In fact, he is working with Duke surgery professor and gene therapy expert Aravind Asokan to engineer another class of viruses, recently approved by the FDA for other gene therapies, to deliver CRISPR to diseased tissues. Far from a killer, the modified virus is essential to getting CRISPR to the right tissues to perform gene editing in a manner that was previously thought impossible. There is hope that CRISPR technology can lead to cures for sickle cell and other genetic blood disorders. It is also being used to fight cancer and muscular dystrophy, among many other diseases and it is being used at Duke by Dr. Gersbach in the fight against COVID-19.
In another seemingly bizarre use of a virus, a modified form of the polio virus is being used at Duke to fight glioblastoma, a brain tumor. That work is being pursued within the Preston Robert Tisch Brain Tumor Center, for which David Ashley is the Director. The use of modified polio virus excites the innate human immune system to fight glioblastoma, and extends life in ways that were previously unimaginable. But there are still many basic-science questions that must be overcome. The remarkable extension of life with polio-based immunotherapy occurs for only 20% of glioblastoma patients. Why? Recall from the work of Dr. Woods discussed above, and from our own observation of COVID-19, not all people respond to viruses in the same way. Could this explain the mixed effectiveness of immunotherapy for glioblastoma? It is not known at this time, although Dr. Ashley feels it is likely to be a key factor. Much research is required, to better understand the diversity in the host response to viruses, and to further improve immunotherapy.
The COVID-19 pandemic is a challenge that is disrupting all aspects of life. Through fundamental research being done at Duke, our understanding of such a pandemic has advanced markedly, speeding and improving our capacity to respond. By innovative partnerships between Duke engineers and clinicians, novel methods are being developed to protect frontline medical professionals. Further, via innovative technologies like CRISPR and immunotherapy — that could only seem like science fiction in 1918 (and as recently as 2010!) — viruses are being used to save lives for previously intractable diseases.
Viruses can be killers, but they are also scientific marvels. This is the promise of fundamental research; this is the impact of Duke research.
“We shall not cease from exploration And the end of all our exploring Will be to arrive where we started And know the place for the first time.”
T.S. Eliot, Four Quartets
Post by Lawrence Carin, Vice President for Research
About 70% of the human body is made up of water. Water is something we consume on a daily basis. Therefore, when a community’s water source is threatened or contaminated it can be extremely detrimental.
In 2017, it became apparent that there was water contamination in eastern North Carolina. Specifically, PFAS or per- and polyfluoroalkyl Alkyl chemicals were found in the water supply. As a result, several legislative mandates were issued in 2018 establishing a PFAS Testing Network to investigate the contamination.
Lee Ferguson, an Associate Professor of Civil and Environmental Engineering at Duke and Kathleen Gray, a professor at UNC’s Institute for the Environment, are testing PFAS water contamination and communicating any risks to the public.
Gray is part of the network’s risk communication team. She explained that PFASs are hard to address because the health effects are unknown and they have yet to determine a standard or guideline for these substances. However, because this water contamination affects the lives of everyone connected to the water supply it is extremely important to communicate risk to the affected community but without eliciting panic.
Gray explained that people often ask, “Are my family and I safe?” “What can I do to protect myself and my family?” “Why did this happen?” and “Why wasn’t it prevented?”
In the last year Ferguson and his research team have tested 409 sites in North Carolina for PFAS compounds.
He explained that PFAS substances are particularly dangerous because they are non-degradable, potentially toxic and constantly changing. Long-chain PFASs are being replaced by fluorinated alternatives.
Ferguson described this phenomenon as “playing environmental ‘whack-a-mole’ with different substances.”
Ferguson and his testing team have found two contaminated water supply sites in North Carolina. Dangerous contamination is based on the EPA health advisory level of 70ng/Liter. The exceedances were found in Maysville and Orange Water and Sewer Authority. Maysville was able to switch to the Jones County water source once the problem was identified.
New data that came in within the last couple weeks found high month-to-month variability in PFAS in the Haw River near Pittsboro. Ferguson and his team predict that it is coming downstream from a waste treatment plant.
While all of this information may seem very alarming, Gray and Ferguson both reiterated that it is not necessary to panic. Instead, people should make sure they are drinking filtered water or invest in a water filter.
Ferguson added, “The best choice is reverse osmosis.”
Gray and Ferguson presented their work at a SciComm Lunch-and-Learn, a monthly event sponsored by Duke Science & Society Initiative that explores interesting and innovative aspects of science communication. The event is free and open to anyone in the Duke community.
On Friday, January 17, Duke’s From Slavery to Freedom Lab hosted a panel in conjunction with the Franklin Humanities Institute on the topic of contemporary Black arts and icons. The panel, “New Black Aesthetics,” featured speakers Rhea L. Combs, curator at the National Museum of African American & Culture, and Richard J. Powell, John Spencer Bassett Professor of Art & Art History at Duke, and was one half of a two-panel conference titled “Black Images, Black Histories.”
According to Combs and Powell, the reason for the unprecedented popularity of works like the NMAAHC by contemporary Black artists is likely because they do something that other pieces and people rarely do: allow African Americans to tell the African American story.
As a museum curator, Combs doesn’t simply curate cohesive mixed-media exhibitions that shed light on the Black experience. In order to create those exhibitions, she must also dig through and analyze a wide range of old archival materials.
However, these archival materials at the NMAAHC aren’t necessarily just historical artifacts and records associated with figures like Rosa Parks or the Obamas; the Museum wants people to shuffle through their own attics to find things to donate. It demystifies the question of who belongs in a museum, according to Combs. “We create agency in terms of who gets to tell everyday stories,” she said.
She’s especially interested in the role of photography and film in African American studies. “We use cameras to culturally agitate the ways in which African Americans are understood,” she explained; the camera is a pathway into self-representation.
Captured in the Museum’s photos and moving images are stories of duplicity, or “celebrations that happened in the midst of tragedies.” Combs often finds themes of faith and activism as well as education and uplift, but she says that there’s plenty of variety within those overarching ideas. A photo of boys playing basketball on unicycles, for example.
“Art creates social understanding of who we are,” Combs said. Like hip-hop remixes and re-envisions things that are already understood in one way, so too does the NMAAHC.
On a similar vein, Powell’s presentation focused on the famous Obama portraits, and I’m guessing you might already know which ones I’m referring to. A fully-suited Barack Obama, seated in a wooden chair against a lush green background of flora and fauna; Michelle Obama in a flowing black-and-white colorblock dress, her chin resting on the back of her hand.
While the portraits are visually exceptional, Powell said their context is what envelops. These images of the first Black U.S. president and first lady do allude to the old, white traditions of portraiture, “but they dismantle the genre’s conventional outcomes” for something new, he explained.
The portrait of Barack Obama is, visually, extremely similar to those of Abraham Lincoln and Franklin Delano Roosevelt. Likewise, Michelle Obama’s portrait quite closely resembles that of Madame Moitessier, for example. But unlike these representations of pre-21st-century white men and women, the Obama portraits finally depict people of color. According to Powell, portraits elevate status, and it isn’t very often that you see Black individuals portrayed.
And yet there’s also a sad irony involved, Powell explained. Especially for other similar contemporary works of portraiture that depict Black people, there’s a decorative, incongruous grandeur that highlights the tension between social realities and the manner of portrayal. For instance, “saintly” portraits exist of Black men wearing urban clothing, but despite whatever “saintliness” might be visually depicted, the realities of Blackness in the inner cities of America is often far from positive.
One of the most striking features of the Barack Obama portrait is the blooming greenery behind the former president. It’s a metaphor of sorts, Powell said: social and historical context isn’t absent from art. Or, in other words, “The world can never be left out of the garden.”