Following the people and events that make up the research community at Duke

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We Are Not All Living The COVID Moment Equally

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Diagram of telomere from a study conducted by Dr. Pearson

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

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

Post by Cydney Livingston

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

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DAVIDE BONAZZI / SALZMANART

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

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

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

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

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

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

Marc Lipsitch

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

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

Cameron Wolfe

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

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

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

Nir Eyal

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Post By Zella Hanson

COVID-19, and the Costs of Big Data

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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. 

Health data from smartphones and fitness trackers may help predict and identify disease.

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. 

Left: Jessilyn Dunn, PhD, a professor at Duke University and CovIdentify Researcher
Right: Marielle Gross, MD, MBE, a bioethicist and professor at the University of Pittsburgh

“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.”

Post by Jeremy Jacobs

Duke Scientists Studying the Shape of COVID Things to Come

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Duke’s Fundamental Research Can Turn Viruses Into Marvels

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.

Gregory Gray, MD MPH
Gregory Gray, MD MPH

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.

Barton Haynes,MD
Barton Haynes, MD

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. 

David Ashley, Ph.D.
David Ashley, Ph.D.

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

Medicine’s ‘Digital Health’ Future

“How often do we get to see a new field [of medicine] grow?” asked Satasuk “Joy” Bhosai (MD MPH), the chief of digital health and strategy for the Duke Clinical Research Institute.

Bhosai offered insights to the rapidly emerging and expanding field of digital health in her talk “Digital Health: How Do We Scale?” at Duke’s School of Nursing on Wednesday, March 4th.

Joy Bhosai, MD MPH

Digital health is a blanketing term that refers to a wide – and growing – array of services and products that merge digital technologies with healthcare to improve its quality, efficiency, and personalization. To put it simply: Digital health is the computerization of healthcare. Some of the largest, current digital trends of health care, according to Bhosai, are Artificial Intelligence (AI)/Machine Learning (ML), digital therapeutics, and innovations in delivery models. However, she presented a graphic (shown below) that shows the reach of the field.

Digital health is an expansive field that encompasses many types of products and services in the field of healthcare.

Bhosai focused on the challenges to digital health’s progress and the role that academia and research play in addressing these issues. “Having an idea and the technology are only the beginning,” Bhosai said.

To prove her point, Bhosai highlighted the company Proteus. Once valued at $1.5 billion, they are now struggling to stay afloat because they haven’t provided the data on effectiveness that investors needed.

She also pointed out the collaboration between Google and Ascension.  The duo teamed up with great technological potential to work on digital healthcare, but they received major pushback because Ascension released patients’ medical records to Google without patient knowledge or consent.

In the life cycle of developing and implementing digital health tools, Bhosai said that most companies falter or fail between beta testing and scaling. “To reach scale, evidence, and the right partners are needed.”

She proposed three main challenges as current limiters to breaking through the difficult transition that crushes so many digital health companies: 1) translating ideas to action, 2) evaluation and validation, and 3) adoption and scale.

Bhosai believes that there are many ways that academia and research could play a role in addressing these issues. Academics and researchers could give insight to the applicability of products, offer guidance on clinical utility, provide networks of contacts and support, materialize solutions, and build innovations at the front of business and growth models.

Bhosai’s proposed life cycle of digital health innovations.

This could help with things such as workflow, which may not be actualized in the product design of digital health products. One venture-backed attempt at putting information into a wearable, glasses-like device caused physicians to become very dizzy and disoriented – a problem that could have been avoided if medical specialists were integrated in the design process.

One success story is the company Akili, a digital therapeutic company that addresses cognitive impairments. A team at Duke, led by Scott Kollins, PhD, conducted a controlled clinical trial using the therapeutics and proved that the software led to improvements in treatment groups. The results of the study were submitted to the Federal Drug Administration (FDA) so that Akili can make claims around these findings in support of their service. Many other digital health products could benefit from these types of trials that provide evidence of their potential impacts in healthcare.

“Providers and academics are needed in health tech,” said Bhosai. This is a crucial connection to make for the future of the digital health field. Bhosai also pointed out that digital health tool users are not always a customer. For example, hospital systems are often the intended users of digital health services, but most hospitals have technical requirements that must be met in order to adopt a service. A product may be amazing but be barred from consideration for use because it would fail system security audits.

Products that are directly consumed by customers also must integrate into a patient’s lifestyle. “When products are high-touch, you may lose engagement,” Bhosai stated, “Patients don’t want to log onto three different apps when they could just log onto one.”

As digital health grows rapidly, companies in the field should work to navigate the health policies in place, understand the landscape of healthcare, and collaborate with academics and researchers to be successful and provide the best services for this new field of medicine.

Polymath Mae Jemison encourages bolder exploration, collaboration

Photo from Biography.com

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

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

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

Photo courtesy of Elizabeth Roy

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

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

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

Photo courtesy of Elizabeth Roy

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

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

By Victoria Priester

Man’s Best Friend, Our Relationship to Dogs

The average dog costs its human owner $10,000-20,000 over the course of its lifetime, from vet care and grooming to treats and toys to the new fad of doggie DNA testing. But what’s in it for us? Researcher Kerri Rodriguez – a Duke alum of evolutionary anthropology and current grad student with Purdue University’s College of Veterinary Medicine – explores just that.

Rodriguez is a member of the OHAIRE Lab at Purdue, which stands for the Organization for Human-Animal Interaction Research and Education. Continuing her work from undergrad, Rodriguez researches the dynamic duo between humans and dogs – a relationship some 15,000 to 40,000 years in the evolutionary making. Rodriguez returned to Duke to speak on February 12th, honoring both Darwin Day and Duke’s second annual Dog Day.

It’s well-known that dogs are man’s best friend, but they do much more than just hang out with us. Dogs provide emotional support when we are stressed or anxious and are highly attentive to us and our emotional states.

In a study of 975 adult dog owners, dogs ranked closely to romantic partners and above best friends, children, parents, and siblings when their owners were asked who they turn to when feeling a variety of ways. Dogs provide non-judgmental support in a unique way. They have also been found to reduce levels of the stress hormone cortisol, lower perceived stress in individuals, improve mood, and improve energy up to 10 hours after interactions. Therapy dogs are prevalent on many college campuses now due to these impacts and are found in hospitals for the same reasons, having been found to reduce subjective pain, increase good hormones and dampen bad ones, causing some patients to require less pain medications.

(Creative Commons)

 Along with reduced stress, dogs make us healthier in other ways, from making us exercise to reducing risk of cardiovascular disease. A study of 424 heart attack survivors found that non-dog owners were four times more likely to be deceased one year after the attack than victims who owned dogs.

The increased social interaction that dogs offer their human companions is also quite amazing due to the social facilitation effect they provide by offering a neutral way to start conversations. One study with people who have intellectual disabilities found that they received 30% more smiles along with increased social interactions when out in public with a dog. Similar studies with people who use wheelchairs have produced similar results, offering that dogs decreased their loneliness in public spaces and led to more social engagements.

Rodriguez also shared results from a study dubbed Pet Wingman. Using dating platforms Tinder and Bumble, researchers found that after one month, simulated profiles containing pictures with dogs received 38% more matches, 58% more messages, and 46% more interactions than simulated profiles without. Even just having a dog in photos makes you appear more likable, happier, relaxed, and approachable – it’s science!

 A large bulk of Rodriguez’s own work is focused on dogs in working roles, particularly the roles of a service dog. She explained that unlike therapy or emotional support dogs, service dogs are trained for one person, to do work and perform tasks to help with a disability, and are the only dogs granted public access by the American Disability Association. Rodriguez is particularly interested in the work of dogs who help American veterans with post-traumatic stress disorder (PTSD).

(Creative Commons)

 Around one out of five post-9/11 military veterans have PTSD and the disorder is difficult to treat. Service dogs are becoming increasingly popular to help combat effects of PTSD, ranking at the third highest placed type of service dog in the United States. PTSD service dogs are able to use their body weight as a grounding method, provide tactile interruption, reduce hypervigilance, and prevent crowding of their veterans. However, because of the lack of research for the practice, the Veterans Association doesn’t support the use of the dogs as a therapy option. This is an issue Rodriguez is currently trying to address.           

 Working with a group called K9s for Warriors, Rodriguez’s research evaluated the mental health, social health, quality of life, and cortisol levels of veterans who have received service dogs and those who were on the wait list for dogs. Veterans with service dogs had lower PTSD symptoms, better mental health, and better social health. Rodriguez is now working on a modification to this study using both veterans and their spouses that will be able to measure these changes to their well-being and health over time, as well as assessing the dog’s health too. Unlike other organizations, K9s for Warriors uses 90% shelter dogs, most of which are mutts. Each dog is as unique as the human it is placed with, but no bond is any less special.

By Cydney Livingston

The evolution of a tumor

The results of evolution are often awe-inspiring — from the long neck of the giraffe to the majestic colors of a peacock — but evolution does not always create structures of function and beauty.

In the case of cancer, the growth of a population of malignant cells from a single cell reflects a process of evolution too, but with much more harrowing results.

Johannes Reiter uses mathematical models to understand the evolution of cancer

Researchers like Johannes Reiter, PhD, of Stanford University’s Translational Cancer Evolution Laboratory, are examining the path of cancer from a single sell to many metastatic tumors. By using this perspective and simple mathematical models, Reiter interrogates the current practices in cancer treatment. He spoke at Duke’s mathematical biology seminar on Jan. 17.

 The evolutionary process of cancer begins with a single cell. At each division, a cell acquires a few mutations to its genetic code, most of which are inconsequential. However, if the mutations occur in certain genes called driver genes, the cell lineage can follow a different path of rapid growth. If these mutations can survive, cells continue to divide at a rate faster than normal, and the result is a tumor.

As cells divide, they acquire mutations that can drive abnormal growth and form tumors. Tumors and their metastases can consist of diverse cell populations, complicating treatment plans out patient outcomes. Image courtesy of Reiter Lab

With each additional division, the cell continues to acquire mutations. The result is that a single tumor can consist of a variety of unique cell populations; this diversity is called intratumoral heterogeneity (ITH). As tumors metastasize, or spread to other locations throughout the body, the possibility for diversity grows.

Intratumoral heterogeneity can exist within primary tumors, within metastases, or between metastases. Vogelstein et al., Science, 2013

Reiter describes three flavors of ITH. Intra-primary heterogeneity describes the diversity of cell types within the initial tumor. Intrametastatic heterogeneity describes the diversity of cell types within a single metastasis. Finally, inter-metastatic heterogeneity describes diversity between metastases from the same primary tumor.

For Reiter, inter-metastatic heterogeneity presents a particularly compelling problem. If treatment plans are made based on biopsy of the primary tumor but the metastases differ from each other and from the primary tumor, the efficacy of treatment will be greatly limited.

With this in mind, Reiter developed a mathematical model to predict whether a cell sample collected by biopsy of just the primary tumor would provide adequate information for treatment.

Using genetic sequence data from patients who had at least two untreated metastases and a primary tumor, Reiter found that metastases and primary tumors overwhelmingly share a single driver gene. Reiter said this confirmed that a biopsy of the primary tumor should be sufficient to plan targeted therapies, because the risk of missing driver genes that are functional in the metastases proved to be negligible.

 In his next endeavors as a new member of the Canary Center for Cancer Early Detection, Reiter plans to use his knack for mathematical modeling to tackle problems of identifying cancer while still in its most treatable stage.  

Post by undergraduate blogger Sarah Haurin

Post by Sarah Haurin

Inventing New Ways to Do Brain Surgery

This is the sixth and final 2019 post written by students at the North Carolina School of Science and Math as part of an elective about science communication with Dean Amy Sheck.

Dr. Patrick Codd is the Director of the Duke Brain Tool Laboratory and an Assistant Professor of Neurosurgery at Duke. Working as a neurosurgeon and helping with the research and development of various neurosurgical devices is “a delicate balance,” he said.

Patrick Codd

Codd currently runs a minimally invasive neurosurgery group. However, at Massachusetts General Hospital, he used to run the trauma section. When asked about which role was more stressful, he stated “they were both pretty stressful” but for different reasons. At Mass General, he was on call for most hours of the day and had to pull long shifts in the operating room. At Duke, he has to juggle surgery, teaching, and research and the development of new technology.

“I didn’t know I was going to be a neurosurgeon until I was in college,” Codd said. Despite all of the interesting specialties he learned about in medical school, he said “it was always neurosurgery that brought me back.”

Currently, he is exclusively conducting cranial surgery.

 Neurosurgeon U.S. Air Force Maj Jonathan Forbes,looks through loupes as he performs brain surgery at the Bagram Air Field in Afghanistan, Oct. 10, 2014. 

Though Dr. Codd has earned many leadership positions in his career, he said he was never focused on advancement. He simply enjoys working on topics which he loves, such as improving minimally invasive surgical techniques. But being in leadership lets him unite other people who are interested in working towards a common goal in research and development. He has been able to skillfully bring people together from various specialties and help guide them. However, it is difficult to meet everyone’s needs all of the time. What is important for him is to be a leader when he needs to be.

Dr. Codd said there are typically five to eight research papers necessary in to lay the groundwork for every device that is developed. However, some technologies are based on the development of a single paper. He has worked on devices that make surgery more efficient and less minimally invasive and those that help the surgical team work together better. When developing technologies, he tries to keep the original purpose of the devices the same. However, many revisions are made to the initial design plans as requirements from the FDA and other institutions must be met. Ironically, Dr. Codd can’t use the devices he develops in his own operating room because it would be a conflict of interest. Typically other neurosurgeons from across the country will use them instead.

Post by Andrew Bahhouth, NCSSM 2020

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