The beauty of research is that it allows you to take control of your own path.
“We are very lucky to be in the position to decide what we love to do and do it,” says Tai-ping Sun, a Duke biology professor studying the plant hormone GA. Researchers get to take control of their own path, she said. Every day is an opportunity to learn something new, design and analyze experiments and decide what direction to take.
Tai-ping Sun is a professor of Biology at Duke
Sun studies the GA signaling pathway because it regulates plant growth and development. She got interested in GA when she was a post-doctoral fellow at Harvard University in 1988. At the time, a lot of tools needed to be developed. As she was developing new tools to clone plant genes, she came across a GA mutant that was different. Her research is very important to understanding how the mutations in the GA signaling pathways can control the height of a plant. In fact, she says, GA mutations were one of the reasons for the success of the “Green Revolution” in the 1960s.
Sun’s current research revolves around identifying the mechanisms of the cell that make GA hormones and identifying how GA mutations have affected this pathway. Her team has identified important facets of the pathway, such as the structure and function of the nuclear receptors that allow for transcription that drives the GA response. Her team has also identified transcription factors that control the rate of the signaling pathway such as the DELLA proteins that act as master growth repressors to inhibit GA response. In fact one of her favorite discoveries is that GA triggers destruction of the DELLA proteins to activate the GA signaling pathway.
A figure from a 2004 paper by Sun on plant growth. All three of the mutants grew less well than wild type plants.
“As a scientist, the most exciting thing is to discuss experimental data, and then trying to deduce hypothesis or modify models and then come up with new experiments for testing,” she said.
But research is not without its challenges, Sun says “not everything that you do works out the first time.” That’s why she says that as a researcher the most important thing is to have an interest in your field as well as perseverance.
Guest post by Anika Jain, Class of 2021, NC School of Science and Math
We are all born with defining physical characteristics. Whether it be piercing blue eyes or jet black hair, these traits distinguish us throughout our entire lives. However, there is something that all of our attributes have in common, a shared origin: genes.
Beyond dictating our individual features, genes instruct cells to create proteins that are essential for a variety of processes, from controlling muscle function to managing digestive systems. Despite their importance in the workings of our body, genes can also code for detrimental diseases, such as Huntington’s disease or Duchenne muscular dystrophy.
Raluca Gordân, Ph.D.
These types of diseases are exactly what Raluca Gordân, Ph.D. is battling through her research. She and her group are trying to figure out how to decode the non-coding genome, the DNA apart from protein-coding genes. They are deepening their understanding of the role non-coding areas of the genome play in the expression of the coding genes and the production of proteins.
Gordân, an associate professor in biostatistics and bioinformatics at Duke, said a majority of disease-causing genetic mutations derive from the genome outside of genes.
“That is a huge search space,” she says, chuckling. “Genes only make up about 2% of the genome. If we don’t understand what those non-coding regions are doing, it’s hard to make predictions about what the mutation in those regions would be doing and how to connect that to the development of a disease.”
Gordân recently published a paper, entitled “DNA mismatches reveal conformational penalties in protein–DNA recognition,” which focuses on transcription factors and their exceptional ability to bind to mispaired DNA, misspellings that occur as DNA is copied. During regular replication, nucleotide bases (the building blocks of our DNA) are paired correctly, where adenine pairs with thymine and cytosine goes with guanine. However, when an error occurs during replication, mispairs start to appear, as adenine may pair with guanine instead.
“Normally, those are mistakes that get repaired by specific mismatch repair pathways but that repair might not happen if one of these transcription factors sits on the replication error and doesn’t allow the repair mechanism to see it,” Gordân explains. “Normally, one would expect the transcription factors not to bind to those errors. But we found that they can bind way better than their actual genomic targets.”
Modeling of the binding between mismatched DNA and transcription factors.
To expand on her computational discovery, Gordân is now following up with a study of transcription factor binding to mismatches in living cells, observing whether they adopt their usual role of regulating gene expression or contribute to the development of mutations.
Gordân’s research is a product of her passion and desire to make change. It also can be attributed to a series of realizations she made during college and inspirational mentors who guided her along the way.
While pursuing her undergraduate degree, Gordân was a purely computer science major, concentrating on cryptography. However, as she was nearing the end of her four years of college, she soon found herself yearning for the opportunity to do more. She began looking into machine learning applications and enrolled in a course based around genetic algorithms which she credits for launching her career path.
At that point, she attained what she describes as her “first taste of genetics” and her interest in bioinformatics was irrevocably piqued. Thereafter, Gordân applied for a PhD at Duke, where she worked with advisor Alex Hartemink investigating transcription factor proteins in regulatory genomics. At Duke, her work was primarily computational. But with her postdoctoral advisor Martha Bulyk of Harvard Medical School, Gordan was exposed to the more experimental aspects of biology.
Today, she recognizes these experiences as integral to her ongoing research, which requires her to frequently iterate between observational approaches and computational work.
Gordân is acclimating to the newly quarantined world. While she strives to continue her research, in the pandemic, it has changed her routine.
“I think what was affected a lot since the pandemic started is the fact that we don’t meet in person,” she says. “A lot of the quick progress was being made when we were in the same physical space and were able to get feedback immediately, with students learning about each other’s results in the lab, in real time. That was replaced with Zoom meetings, where students get to see the other students’ results mainly at lab meetings, weeks or months later. Those continuous discussions that were going on in the lab all the time. We’re missing that.”
Gordân offered some thoughtful parting advice to aspiring computational biologists, like me.
“I was trained as a computer scientist, so I wasn’t really sure about experimental work. But after actually doing the experimental work, I realized how much value there is in doing both,” she said. “You have to pick what you’re strongest at, either the computational or experimental part, but you should not be afraid of the other side.”
Guest Post by Akshra Paimagam, Class of 2021, NC School of Science and Math
Meet Claire Engstrom, a Senior from Pasadena California. Claire is a Biology major who works in the Gersbach Lab at Duke.
Claire first got involved with on-campus research through her pre-orientation program, PSearch that introduces incoming first-years to undergraduate research. Following her experience in PSearch, Claire got her first work-study research position in the Tung Lab where she worked closely with Jenny Tung, an Associate Professor in the Departments of Evolutionary Anthropology and Biology at Duke and a Faculty Associate of the Duke University Population Research Institute.
In the Tung Lab, Claire’s research focused on how DNA methylation is passed through generations. Essentially looking at the inheritance of DNA whose methylation was impacted by environmental factors and how that affects future generations.
Duke has research opportunities available in all disciplines as well as across departments. Approximately 53% of undergraduates graduate with research experience. Not only can students participate in groundbreaking research, but they can receive funding from the university as well to support the work they are doing.
Within the Biology department, there is a fellowship called B-SURF, the Biological Sciences Undergraduate Research Fellowship, an 8-week summer research program for rising sophomores. Claire applied for and was accepted to the fellowship and placed in one of Duke’s biomedical science laboratories. She also received a $4,000 stipend for her summer research.
Claire was placed in Charles Gersbach’s Lab focused on researching Genome Editing for Gene and Cell Therapy. Dr, Gersbach is a Rooney Family Associate Professor of Biomedical Engineering and has conducted groundbreaking work in genome editing.
Members of the Gersbach Lab in Fall 2019
Gersbach is doing research in several different domains of biomedical engineering. Claire’s project focuses on using CRISPR-Cas9, a technology that allows scientists to change an organism’s DNA using clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9. faster, cheaper, more accurate, and more efficient than other existing genome editing methods.
Prior to joining his lab, Claire had already heard a lot about Gersbach in her course Biology 201 as well as through reading his papers. The project she would spend the next two and a half years working on focused on using and optimizing CRISPR-Cas9 to treat Duchenne’s Muscular Dystrophy and lessen the severity of the symptoms.
Duchenne’s Muscular Dystrophy is a muscle wasting disease that affects one in every five thousand male births.
“People are diagnosed when they are around five and then they lose the ability to walk and their heart can’t pump blood because of the lack of muscles.” Claire explained.
“CRISPR-based genome editing restores dystrophin expression in mouse models of Duchenne muscular dystrophy. Cross-sections of muscle tissue where the dystrophin protein has been labeled green, including normal, healthy tissue (left), tissue from a mouse model of Duchenne muscular dystrophy (middle), and tissue from the same mouse model that has been treated with the CRISPR gene editing system (right). Nelson et al., Science (2016)”
Thus, those affected often die in early adulthood despite current advances in cardiovascular and respiratory treatments. Duchenne’s Muscular Dystrophy generally occurs as a result of a frameshift mutation of the dystrophin gene. As a result, one’s muscles can no longer connect to anything making it nearly impossible to contract and function properly. In the Gersbach lab they are trying to treat the mutation by using CRISPR-Cas9 to remove an exon or coding region of the gene in order to shift the reading frame back into its normal place.
This shift produces a less severe phenotype that lessens the effects of Duchenne’s Muscular Dystrophy. The result will significantly improve the quality of life and life spans for affected patients.
Claire will be continuing her work in the Gersbach lab full time in Spring 2021 as she graduated early, with distinction in the Fall. Her thesis on the work she did in the Gersbach lab was recently approved and her results will be published in a larger paper in the future. After this year she plans to take a gap year an then return to California to hopefully attend grad school and pursue a Ph.D. in Biology.
America is getting both older and Blacker. The proportion of non-white older adults is increasing, and by 2050 the majority of elderly people will be racial minorities. In his Langford Lecture “Who gets sick and why? How racial inequality gets under the skin” on November 10, Professor Tyson H. Brown discussed the importance of studying older minorities when learning about human health. His current project aims to address gaps in research by quantifying effects of structural racism on health.
Health disparities result in unnecessary fatalities. Dr. Brown estimates that if we took away racial disparities in health, we could avoid 229 premature deaths per day. Health disparities also have substantial economic costs that add up to about 200 billion dollars annually. Dr. Brown explained that the effects of structural racism are so deadly because it is complex and not the same as the overt, intentional, interpersonal racism that most people think of. Thus, it is easier to ignore or to halt attempts to fix structural racism. Dr. Brown’s study posits that structural racism has five key tenets: it is multifaceted, interconnected, an institutionalized system, involves relational subordination and manifests in racial inequalities in life chances.
A motivator for Brown’s research was that less than 1% of studies of the effects of race on health have focused on structural racism, even though macro level structural racism has deleterious effects on health of Black people. When thinking about inequalities, the traditional mode of thinking is the group that dominates (in this case, white people) receives all benefits and the subordinates (in Dr. Brown’s study, Black people) receive all of the negative effects of racism. In this mode of thinking, whites actively benefit from social inequality. However, Dr. Brown discussed another theory: that structural racism and its effects on health undermines the fabric of our entire society and has negative impacts on both whites and Blacks. It is possible for whites to be harmed by structural racism, but not to the same extent as Black people.
Dr. Brown identified states as “important institutional actors that affect population health.” As a part of his research, he made a state level index of structural racism based off of data from 2010. The index was composed of nine indicators of structural racism, which combine to make an overall index of structural racism in states. In mapping out structural racism across the domains, the results were not what most people might expect. According to Dr. Brown’s study, structural racism tends to be highest in the midwest of the United States, rather than the south. These higher levels of structural racism were associated with worse self-rated health: one standard deviation increase in level of structural racism correlated with the equivalent of two standard deviation increases in age. In other words, a person who is affected by structural racism has similar self-rated health to people two age categories above them who do not experience negative effects of structural racism.
As the structural racism index increases, the Black-white difference in COVID-19 related deaths also increases. Overall, Dr. Brown found that structural racism is a key driver of inequalities in COVID-19 deaths between whites and Blacks. Looking forward, Dr. Brown is interested in learning more about how contemporary forms of racism contribute to inequality—such as searching racial slurs on Google and implicit bias, both of which are high in the southern United States.
After his discussion, colleagues raised questions about what can be done to eliminate negative effects of structural racism. Dr. Brown listed options such as rent protection, COVID-19 test sites in lower income communities and another stimulus bill. He also explained that the distribution of a COVID-19 vaccine needs to be done in an ethical manner and not exclude those who are less fortunate who really need the vaccine. We also need better data collection in general—the more we know about the effects of structural racism, the better we will be able to adapt equity practices to mitigate harm on Black communities.
Two Covid vaccines have been approved via Emergency Use Authorizations. But, many scientists, health professionals, and regulatory members alike are left wondering how to best ensure the American and global public opt-in to getting vaccinated.
Dr. Fauci has become a household name this year as a member of the White House Coronavirus Task Force but is more widely regarded as one of the most trusted U.S. medical figures and has been director of the National Institute of Allergy and Infectious Disease since 1984.
Mr. Alda, though popularized through his acting career, has been a life-long advocate for science. He hosted PBS show “Scientific American Frontiers,” founded the Alan Alda Center for Communicating Science at SUNY Stony Brook, and recently released a podcast titled “Soldiers of Science.” At Stanford, Mr. Greely is director for the Center for Law and Biosciences and the Program in Neuroscience and Society, as well as a Professor of Law.
Anthony Fauci (M.D.) left, Alan Alda center, and Hank Greely (J.D.) right
Greely asked about the public’s current level of trust for science and what must be done to get it “where it should be.” Alda said that there “seems to be this awful fall off of trust in science … at the worst possible time.” But Dr. Fauci pointed out that we have seen the evolution of lack of trust in science over the previous couple of years. The pandemic fell in the middle of extreme American divisiveness, he said, leading to individuals “developing their own set of facts instead of interpreting [actual] data that exists.”
Alda and Fauci both emphasized the need for transparent and clear scientific communication as a main tactic for increasing public faith in science. This includes use of the words “I don’t know,” particularly in response to the question of vaccine longevity, a question Dr. Fauci said will be answered “in due time.”
Alda said scientific communicators should “communicate with audience[s] with respect … with personal contact where trust builds up more quickly.” He pointed out that this means communicators must become more familiar with their audiences, what terms would be best to use, and what their audiences are “ready to hear.” Dr. Fauci added that when someone is “speaking science” to any group, the objective should not be to “impress the [audience] as to how smart [they] are.” The two major objectives laid out by Fauci: 1) Know the audience and 2) know your message, avoiding granularity and inaccessible language.
Greely interjected that the though all three panelists agree on trust in science, they were three white guys “of mature years.” He continued to say that, “One of the saddest ironies [is that] people getting hammered hardest by [Covid] tend to be people from racial and ethnic minorities … those are also [the same] groups of people that have understandable historic reasons to have less trust [in scientific agencies].” How do we reach these groups?
To do this, Dr. Fauci proposed that we need to get messengers for vaccination to “to look like and understand to whom [we] we are delivering the message.” Leaning into an idea by Alda – that we should get celebrities and widely-respected and admired individuals to get vaccinated on television – Fauci described how Surgeon General Jerome Adams got publicly vaccinated Friday morning.
Adams also delivered a message to his “Black and Brown sisters and brothers” in support of vaccination. Dr. Fauci believes more positive messaging like this will be effective. Alda reinforced that “we can’t guess about the people we’re trying to talk to.” We have to know about their biases and cause for hesitancy in order to meet them where they are, as well as address their concerns in genuine, non-condescending ways.
Alda also proposed that individuals snap a quick shot of themselves getting vaccinated and post it to social media as a #vaccie – a play on the #selfie sensation – which Greely said was “brilliant.”
Alda and Fauci concurred that the most powerful proponents of restoring faith in science may lie in the impact of individual civilians who share their trust in and compliance with vaccination amongst family and friends. Fauci said individuals should not “underestimate the impact that they have in their own immediate environment.”
Sandra Lindsay, an Intensive Care Unit nurse in New York, was one of the first people in the U.S. to receive the Pfizer Covid vaccine.
This impact could be either positive or negative, though, as Alda pointed out the problem with social media algorithms. While working on “Soldiers of Science,” he learned that social media sites are designed to “keep your eyeballs on the screen” as long as possible. This means that social media sites keep “showing you what you want to see,” which is your own bias and affirmation that your ideas are correct. If #vaccie starts trending, this might provide necessary momentum for widescale vaccine uptake.
However, because we have become “addicted to [our] bias” and convinced “over and over again that only our view is right,” according to Alda, we must work intentionally to see commonalities across seemingly alienating lines. Reflecting on his work with AIDS, Dr. Fauci suggested that we take what scientific communicators and regulatory bodies learned during that time. “What do we all want?” Fauci said, ”And how do we get there in a way that is synergistic [instead of] opposing?”
In his parting thoughts, Alda stated simply that “science will save us.” It has and will continue to allow us to “counterattack the attacks we get from our mother nature.” Dr. Fauci said that in dealing with the current pandemic, “biomedical research and science has given us something that just a decade ago would have seemed unimaginable.”
“When this is over, and it’s going to be over,” Fauci said, “We’re [going to] look back and say, ‘It was science that got us out of this, pure science.’”
Greely said we have learned a lot about science communication this year – invaluable information that we must carry forward with us.
I, like so many others around the world, can’t wait for my turn to get the Covid vaccine and to kiss 2020 and the pandemic goodbye.
The sudden need for contact-tracing technologies to address the Covid-19 pandemic is inspiring some miraculous human ingenuity.
Wednesday, December 16th, Rodney Jenkins, Praudman Jain, and Kartik Nayak discussed Covid-19 contact tracing and the role of new technologies in a forum organized by the Duke Mobile App Gateway team.
Jenkins is the Health Director of Durham County’s Department of Public Health, Jain is CEO and founder of Vibrent Health. And Nayak is an Assistant Professor in Duke’s Computer Science department. The panel was hosted by Leatrice Martin (M.B.A.), Senior Program Coordinator for Duke’s Mobile App Gateway with Duke’s Clinical and Translational Science Institute.
Panelists, left to right: Rodney Jenkins (M.P.H.), Praudman Jain (M.S.), and Kartik Nayak (Ph.D.)
Contact tracing is critical to slowing the spread of Covid, and Jenkins says it’s not going away anytime soon. Jenkins, who only began his position with Durham County Public Health in January 2020, said Durham County’s contact tracing has been… interesting. As the virus approached Durham, “Durham County suffered a severe malware attack that really rendered platforms…useless.”
Eventually, though, the department developed its own method of tracing through trial and error. North Carolina’s Department of Health and Human Services (NC HHS), like many other health departments across the nation in March, was scrambling to adjust. NC HHS was not able to provide support for Durham’s contact tracing until July, when Jenkins identified a serious need for reinforcement due to disproportionate Covid cases amongst Latinx community members. In the meantime, Durham county received help from Duke’s Physician Assistant students and the Blue Cross Blue Shield Foundation. They expanded their team of five to 95 individuals investigating and tracing Durham County’s positive cases.
Rodney Jenkins MPH is the health director of the Durham County Public Health Department.
Jenkins proclaimed contact tracing as “sacred to public health” and a necessary element to “boxing in” Covid-19 – along with widespread testing.
Durham’s tracing tool is conducted through a HIPPA-compliant, secure online portal. Data about individuals is loaded into the system, transmitted to the contact tracing team, and then the team calls close contacts to enable a quick quarantine response. The department had to “make a huge jump very quickly,” said Jenkins. It was this speedy development and integration of new technology that has helped Durham County Public Health better manage the pandemic.
Jain, along with colleague Rachele Peterson, spoke about his company, Vibrent Health. Vibrent, which was recently awarded a five-year grant from the National Institutes of Health’s ‘ll of Us Research Program, is focused on creating and dispersing digital and mobile platforms for public health.
Naturally, this includes a new focus on Covid. With renewed interest in and dependency on contact tracing, Jain says there is a need for different tools to help various stakeholders – from researchers to citizens to government. He believes technology can “become the underlying infrastructure for accelerating science.”
Vibrent identified needs for a national tracing model, including the labor intensity of manual processes, disparate tools, and lack of automation.
Peterson said that as we “are all painfully aware,” the U.S. was not prepared for Covid, resulting in no national tracing solution. She offered that the success of tracing has been mostly due to efforts of “local heroes” like Jenkins. Through their five-year award, Vibrent is developing a next-generation tracing solution that they hope will better target infectious spread, optimize response time, reduce labor burden in managing spread, and increase public trust.
On left, Jain provided background information on his company, Vibrent Health. On right, Peterson outlined the current state of contact tracing in the U.S. and identified needs for a national tracing system.
Along with an online digital interface, the company is partnering with Virginia Commonwealth University to work on a statistical modeling system. Peterson likened their idea to the Waze navigation app, which relies on users to add important, real-time data. They hope to offer a visualization tool to identify individuals in close contact with infected or high-risk persons and identify places or routes where users are at higher risk.
Nayak closed the panel by discussing his work on a project complementary to contact tracing, dubbed Poirot. Poirot will use aggregated private contact summary data. Because physical distancing is key to preventing Covid spread, Nayak said it is both important and difficult to measure physical interactions through contact events due to privacy concerns over sensitive data. Using Duke as the case study, Poirot will help decision makers answer questions about which buildings have the most contact events or which populations – faculty versus students – are at higher risk. The technology can also help individuals identify how many daily contacts they have or the safest time of day to visit a particular building.
On left, Poirot’s design. On right, examples of Poirot’s uses by decision makers and individuals.
Nayak said users will only be able to learn about their own contact events, as well as aggregate stats, while decision makers can only access aggregate statistics and have no ability to link data to individuals.
Users will log into a Duke server and then privately upload their data using a technology called blinded tokens. Contact events will be discovered with the help of continuously changing, random identifiers with data summation at intermittent intervals. Data processing will use multiparty computation and differential privacy to ensure information is delinked from individuals. The tool is expected for release in the spring.
Screenshot of Duke’s Mobile App Gateway site.
Although we are just starting vaccination, the need for nationwide resources “will be ongoing,” Martin said.
We should continue to embrace contact tracing because widespread vaccination will take time, Jenkins said.
Jenkins, Jain, and Nayak are but a few who have stepped up to respond innovatively to Covid. It becomes increasingly apparent that we will continue to need individuals like them, as well as their technological tools, to ease the burden of an overworked and unprepared health system as the pandemic prevails in America.
New study casts doubt on links between personality and brain structure. MRI scan courtesy of Annchen Knodt, Duke University
We know personality comes from the brain, but does that mean the brain’s shape and composition affect personality as well?
Previous studies have attempted to find links between brain structure and personality types, but new data indicates otherwise. A new study, the largest of its kind, suggests these links may not be so strong after all. In fact, they may not even exist.
Recently Duke researchers, led by Reut Avinun Ph.D., a postdoctoral associate at Professor Ahmad Hariri’s lab, analyzed the MRI scans of over a thousand people to determine potential links between personality and brain shape.
Although there are many personality neuroscience studies, consistent and reliable findings have not been established. While most previous studies used less than 300 individuals, this study has a large sample of 1,107 individuals. Additionally, this research comprehensively measures personality with 240 items.
“When I got into the field, people were collecting data sets with only 10 people and doing analysis with only 20 participants,” said Avram Holmes, an asssociate professor of psychology at Yale who was not involved in the study.
Personality studies such as this typically use the “Big Five” personality traits: neuroticism, extraversion, agreeableness, conscientiousness, and openness-to-experience. Extraverted people tend to be outgoing and social and those with high openness-to-experience are imaginative, curious, and enjoy trying new things. High neuroticism and low conscientiousness have been associated with negative health behaviors such as smoking. These were even connected to negative life outcomes, such as depression, anxiety, and poor sleep. By understanding what underlies these behaviors, scientists may be able to better treat them.
For brain shape, Avinun and her colleagues examined brain morphometry, cortical thickness, cortical surface area, subcortical volume, and white matter microstructural integrity. She used a univariate approach, looking at the relationship between one phenotype and one behavior. Statistical analysis also accounted for the factors of race/ethnicity, sex, and age.
Last year, researchers published a paper finding 15 correlations between specific personality traits and neuroanatomical structures. However, Avinun’s new research found that none of these connections held true in the large Duke Neurogenetics Study sample.
When scientists analyze an MRI dataset, there is a lot of freedom in the phenotypes collected and the types of analyses. “With so many degrees of investigative freedom and the expectation that you should see something there, researchers may accidentally find false positives. It’s easy to fall into the trap of making a story about why the effect has this particular brain pattern and see an association that doesn’t exist,” Holmes explained.
Ultimately, Avinun found no links between the Big Five personality traits and multiple features of brain structure.
While this may seem anticlimactic, even null findings are incredibly useful and could lead to recommendations to future research in this area. By showing that links between brain morphometry and personality tend to be small, this research may push the field toward studies with larger samples and guidelines for higher replication rates.
“The brain is plastic and it is affected every day by our experiences, so expecting to find straightforward associations between brain morphometry and personality traits may be too naïve,” Avinun said. “We are beginning to realize that large samples and multivariate methods are needed in neuroscience. Trying to understand what makes us who we are is exciting. Research is really challenging as the field is constantly changing, but it is constantly improving as well.”
Niba Nirmal is a multimedia science communicator based in San Francisco, CA. She graduated in the Duke class of 2020, with a Master’s degree in Genetics. Find samples of her work at www.notesbyniba.com
Five of the ten Duke women included in the most highly-cited list this year. Their scholarly publications are viewed as important and influential by their peers. (Clockwise from upper left: Costello, Curtis, Dawson, Bernhardt, Moffitt)
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.
Barton Haynes
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.
Michael Pencina
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.
Clinical Medicine:
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.
Geosciences:
Drew T. Shindell
Immunology:
Barton F. Haynes, Edward A. Miao
Microbiology:
Barton F. Haynes
Plant and Animal Science:
Sheng Yang He
Psychiatry and Psychology:
Avshalom Caspi, E. Jane Costello, Renate M. Houts, Terrie E. Moffitt
Social Sciences:
Michael J. Pencina
Cross-Field:
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.
As multiple drug companies in the United States speed towards Phase 3 trials for Covid-19 vaccinations, there remain many unanswered questions about these vaccines.
Moderated by Professor of Law and Philosophy, Nita Farahany (J.D., Ph.D), principal investigators Cynthia Gay (M.D., M.P.H) and Emmanuel (Chip) Walter (M.D.) explored these lingering anxieties in a Science and Society hosted Coronavirus Conversation Thursday, November 6th. Dr. Gay is an Associate Professor of Medicine at the University of North Carolia Chapel Hill (UNC) and Medical Director of the UNC HIV Cure Center. Dr. Walter is a professor of Pediatrics with Duke’s Global Health Institute, as well as a member in the Duke Clinical Research Institute and Duke Human Vaccine Institute. Both Gay and Walter are currently overseeing trials for SARS-COV-2 vaccines.
Moderator Nita Farahany (left) and panelists Cynthia Gay (middle) and Emmanuel (Chip) Walter (right)
Farahany began the conversation by pointing out that though the previous ideal of a vaccine by the US presidential election did not come to fruition, Phizer and Moderna just reached full enrollment for their Phase 3 trials. “[The timeline question] is a million-dollar question,” said Dr. Gay, who is overseeing the Moderna trials at UNC. She said that soon statisticians who have no conflicts of interest with the trials will have a look at the unblinded trial data to see if there are any differences between those who received placebo injections and those who received vaccines. Gay believes this first “peek” may be too early to see a significant signal indicating success of the vaccines. Dr. Walter weighed in, saying that though he hopes “we’ll see something,” he concurs that Dr. Gay’s estimate that no significant signal will be present until January is an accurate one.
As Gay and Walter explained, probed for clarification from Farahany, drug companies undertaking vaccine development enrolled portions of the population at higher risk for contracting Covid — typically on the basis of their form of employment. For example, someone working in healthcare statistically has a higher likelihood of contracting Covid because of increased exposure to environments where Covid-infected persons may be. Vaccine trial groups were either assigned to a placebo or to a vaccine. The drug companies will be able to test the success of the vaccines by evaluating whether those who received the vaccine contract Covid at some statistically significant lower amount than those who received the placebo.
But as Farahany pointed out, a drug company could receive an Emergency Use Authorization (EUA) for their vaccine before trials are complete, prompting the question: Will Phase 3 trial placebo participants receive the vaccine if their company receives an EUA? Dr. Walter offered that this could be problematic because there would be a lack of long-term data on vaccines and Dr. Gay suggested that because blinding is the best sort of study design, there is tension around this question. However, Walter and Gay both agreed that study participants should be honored for the role they stepped into for these trials. Thus, the timing for the EUA may be the biggest determinant on whether or not placebo-receiving Phase 3 participants will receive the vaccines as soon as they are available or not.
Other concerns focus on the overall safety of the vaccines. All of the current Covid vaccines in development are mRNA vaccines, which have never before been approved for use in humans. Dr. Walter offered that before Covid, some companies were actually poised to start an mRNA vaccine in children for other respiratory pathogens and that mRNA vaccines are “pretty well studied.” Dr. Gay reinforced these notions by stating that she doesn’t have concerns about the vaccine safety, but rather whether or not the vaccines will actually work for the particular strand of virus and “produce enough effective antibodies to have an impact.” If Covid vaccines are successful, they may actually change the direction of vaccinology in a promising way.
Walter and Gay also addressed the concerns of side effects and generally conceded that most of the side effects seen, such as low-grade fevers and injection-site tenderness, are merely side effects seen with any sort of vaccine. As Farahany pointed out, these sorts of symptoms are actually often just a signal that the immune system is working and responding to the vaccine. Dr. Gay said that a lot of the concerns over vaccine side-effects can be thought about as cost-benefit analysis. She says we make these sorts of analyses all day, every day — whether we realize it or not. For Gay, one day of muscle soreness and a slight fever is highly preferential to weeks of potential immobilization from contracting Coronavirus.
The concluding question: How do we ensure trials are met with public trust? “We have to remember we’re in the middle of a pandemic where things really have to move quickly,” Dr. Walter said. He also offered that though this has been the fastest vaccine development he’s ever seen – aside from H1N1 – all of the safety mechanisms in place have provided safety comparable to that we would normally see.
“This is a global tragedy we’re dealing with,” Dr. Gay said. “There is a time to step back and think, ‘Isn’t it amazing that all these [amazing, talented, expert] people are working day and night’ …They’re making it happen to try to get us an answer and some effective vaccines.”
Nikki Mahendru’s mother didn’t go to the gynecologist for 45 years — and when she did, she regretted it. Ms. Mahendru felt “decades of anxieties and hesitancy reduced to five minutes of brisk interaction with her provider,” and left convinced that the “realm of women’s health was just not for her.” According to Nikki, a Duke University undergraduate, her mother’s “trust in the system was lost.”
Mahendru joined Dr. Megan Huchko, the director of the Duke Center for Global Reproductive Health, and Dr. Chemtai Mungo, a Fogarty Global Health Fellow and OB-GYN doctor, on the Center for Global Women’s Health Technologies’ October 20 panel “Impact of Race and Socioeconomic Status in Women’s Health and Gynecology.” The panel was moderated by Ashley Deans and Alexandria Da Ponte.
Mahendru went on to detail an experience she had in the clinic with Carmen, a patient who spoke only Spanish and was also new to the gynecologist. The medical translator and Mahendru learned her story: she had been in pain for a year but had kept quiet due to money problems, had worked most of her life to send her kids to college, and was learning English via Rosetta Stone. With the details of Carmen’s story and an “equitable working relationship,” Mahendru and the translator could relay Carmen’s previous history to her provider. But Carmen’s provider knew only of her condition.
Mahendru thinks gynecology done right has the potential to help women love their bodies and take care of their health, but gynecologists must earn the trust of their patients: “Acts of listening help bridge disparities.”
Dr. Huchko stated that throughout history, a male-dominated healthcare landscape saw the depiction of menses as ‘dirty,’ terms like ‘hysteria,’ and an overall lack of female control. The “father of gynecology” James Marion Sims exploited Black women in his development of the field, using unanesthetized slaves as subjects of experimentation. In general, Dr. Huchko sees a trend: “The lessening or decentering of women in women’s health corresponds to more discrimination.” In addition to the decentering of women, Dr. Huchko said that structural and individual factors “produce outcomes that prevent women from getting the care they need.” Like Mahendru, she identified trust as a central issue.
Dr. Megan Huchko, MD, MPH, is the director of the Duke Center for Global Reproductive Health
Dr. Huchko cited an experience in which she bore witness to the unattended consequences of racial bias in medicine. In Niger to repair women’s fistulas, which occur due to lack of postpartum care, Dr. Huchko felt she was attending to the downstream symptom of a much broader issue. She felt uncomfortable when the urogynecologist on her team ignorantly praised Sims without acknowledging his problematic history. Then, she saw this ignorance firsthand.
Making a false assumption about the nature of the case, Dr. Huchko’s team chose to operate on a woman with a mass in her bladder. During the surgery, they realized the mass was a malignant tumor. With an unbiased eye and a complete exam and workup, this would have been clear. But because the team was looking at these women as “one-dimensional,” a woman with stage 4 cancer was subjected to a very invasive surgery that worsened her quality of life.
Dr. Huchko experienced a similar lack of structural competency during her residency, where colleagues openly racially profiled people and overtly discussed disparities in pain tolerances among different ethnicities. Since then, “things have changed,” and she embraces this new culture of “being patient centered, exploring our own biases, and [having] zero tolerance for racial profiling.” She stresses the need for personal education and accountability alongside systemic change. Eventually, this will lead to women feeling “respected, seen, and heard.”
Coming to the US from Kenya, Dr. Mungo quickly came to appreciate the “sheer magnitude” of structural racism and its impact on health and healthcare. Dr. Mungo explained that “mutually reinforcing systems of disadvantage” for people of color, such as food deserts, are both the result and cause of healthcare disparities and result in enduring legacies of disadvantage.
Dr. Chemtai Mungo, MD, MPH, is a Fogarty Global Health Fellow and OB-GYN doctor
Dr. Mungo also observed that with healthcare in the US being so economically driven, the best care is often directed at those with racial and socioeconomic privilege. When she worked in a high resourced (read: white, wealthy) hospital, access to uterus-saving equipment such as interventional radiology meant that she only did one hysterectomy in four years. Doctors at the hospital also came in on weekends to get a person with cancer into the OR immediately.
Now, working with a “safety net hospital,” Dr. Mungo sees a stark difference. With non-existent interventional radiology and more part-time, “less invested” employees, Dr. Mungo has done three hysterectomies (for obstetric hemorrhage) in three years — a 75% increase — and sees patients with time-sensitive conditions wait much longer before surgery. This “separate and unequal access to resources” is a cause for concern.
Dr. Mungo also stressed the need to make practices “safe places” for patients of color by increasing minority representation. Dr. Mungo explained that while Black physicians make up only 5% of doctors and 3% of faculty, there is strong evidence that patients who are cared for by someone of their own race or ethnicity have better outcomes. “We live in a racist society,” Dr. Mungo stated, “so we need specific anti-racist policies.”
Dr. Mungo also acknowledged that healthcare providers work within “templates” like 15 minute appointments, and posed the closing question, how can we make patients feel safe and heard within the constraints of modern medicine?
Dr. Mungo indicted these algorithms as “an example of how institutionalized some [racial] biases are.” There is “no concrete evidence” on why these corrections for race — which typically act to reduce the probability of success for a procedure or favorability of an outcome — exist. Dr. Mungo would urge providers “not to stop at, ‘well, African Americans have an increased risk of diabetes.’ Ask why. Have them explain food deserts… and structural and environmental racism.”
Dr. Huchko stated that giving aspirin throughout pregnancy reduces preeclampsia, and is thus traditionally offered based on risk factors for preeclampsia, like low socioeconomic status and African American race. Sometimes, healthcare providers may not be able to address these risks without the acknowledgement of race as a risk factor. Dr. Huchko is right, African American women are at a higher risk for preeclampsia, and ignoring this correlation would probably do more harm than good.
But per Dr. Mungo’s appeal, providers must interrogate these associations more deeply — and be ever anti-racist in their efforts — if they are to create the safe spaces and trusting relationships that Mahendru, Dr. Huchko, and Dr. Mungo each hope to see.
By Anna Gotskind
