The discovery of a signaling pathway in the brain that could make mice into ‘superlearners’ understandably touched off a lot of excitement a few years back.
But new work led by Duke neurologist and neuroscientist Nicole Calakos MD PhD suggests there’s more to the story of the superlearner chemical pathway than anybody realized.
In a study led by postdoctoral researchers Ashley Helseth and Ricardo Hernandez-Martinez, the Calakos lab developed a new tool to visualize activity of this Integrated Stress Response (ISR) signaling pathway because it contributes to synaptic plasticity – the brain’s ability to rewire circuits – as well as to learning and memory.
What they didn’t expect to see is that a population of cells called cholinergic interneurons, which comprise only 1 or 2 percent of the whole basal ganglia structure, seem to have the ISR pathway working all the time. The basal ganglia, which is the focus of much of Calakos’ work, plays a role in Parkinson’s and Huntington’s diseases, Tourette’s syndrome, obsessive compulsive disorder and more.
“This totally changes how you think about the pathway,” Calakos said. “Everybody thought this pathway used an on-demand response type of mechanism, but what if some cells needed it for their everyday activities?”
To answer this, they blocked the ISR in just those rare interneurons in mice and it actually reproduced the enhanced performance on learned tasks that the earlier studies had shown when the pathway was blocked universally throughout the brain. This finding focuses attention on this select subset of brain cells, the cholinergic interneurons that release the chemical signal acetylcholine, as being responsible for at least some of the ‘superlearner’ behavior.
Since the integrated stress response pathway and its potential to enhance learning and memory was identified, drugs for dementia and traumatic brain injury are being designed to manipulate it and help the brain recover. But there may be more to the story than anyone realized, Calakos said.
“Our results show that the ISR plays a major role in acetylcholine-releasing cells, and our current best dementia drugs boost acetylcholine,” she said.
Acetylcholine, the chemical that these rare cholinergic interneurons use to signal in the brain, is well known for its powerful effects on influencing brain states for attention and learning. This finding suggests that at least some of the ‘superlearner’ properties of inhibiting the ISR occur by influencing brain state, rather than acting directly in the cells that are being rewired during learning.
Chances are, you’ve heard about survival of the fittest. But what about survival of the friendliest? While we often think that the strongest, meanest, and most powerful organisms often prevail as the most fit, it seems that friendship bears the real evolutionary winners.
In the history of evolution, friendliness often proceeds unusual evolutionary success, meaning that friendly species prevail over time. Hare and Woods are uncovering critical factors for why this pattern emerges in their research. For the context of their work, Woods defined friendliness as anything that is mutually beneficial between organisms. Their questions and investigation were first centered around dogs.
“Where did dogs come from?” Hare said. This poses a really “fascinating evolutionary problem.” Prior research shows that dogs first originated 15,000-25,000 years ago, delineated from wolves. But why? Dogs have become one of the “top two or three most successful animals,” while wolves have nearly gone extinct.
The answer to their evolution and their success is found in friendliness. “Dogs have remarkable social genius,” Hare said, they are able to understand communicative gestures and in return communicate with humans in a way that not even one of our closet genetic relatives, the Bonobo, can. This evolutionary selection for friendliness drove the stark contrasts seen between dogs and wolves today, fundamentally changing dogs’ physical shapes and forms along with their psychology. The same pattern of genetic inheritance encoding for inclination to cooperate also changes much of a species morphology in signature ways.
Hare and Woods ventured to Siberia to analyze the findings of an experiment pertaining to fox behavior that has been ongoing since it was first set up by a Russian geneticist in 1959. One group of foxes has experienced randomly selected mating, while the other group of foxes has been artificially shaped by manmade selection for the friendliest foxes.
When they compared the long-term results of decades separate population changes, Hare and Woods found the friendlier foxes had shorter faces, different colorations, curlier tails, and smaller canines. These are the same factors used by archaeologists to distinguish dogs from wolves. The morphological and physiological changes for niceness are synonymous across the two species.
They have also found a similar pattern in humans. Our species as not alone on the planet when it first evolved, said Hare: We shared the planet with approximately four other Hominids who also had big brains, cultural artifacts, and linguistic abilities like we do. “There had to be something in addition to those traits that allowed our species to survive while others went extinct.” He proposes survival of the friendliness and the development of different physical characteristics.
In a study comparing modern humans to archaic ones, Hare and Woods found that modern humans have traits like much smaller brow ridges and narrower, shorter faces – what you would expect to see, based on the fox model from their work in Siberia that also helped explain the evolution of dogs. Our white sclera – the white part of your eye – acts as our “curly tail.” The white tissue likely has been selected for with the development of our other friendly features, as we are the only primate whose sclera is light, which makes communication by glance easier.
If we are the friendliest, Woods asked, then why are we capable of such cruelty and malice? Even though we are extremely friendly to in-group strangers, when our in-group is threatened, we are prepared to defend them against out-group strangers.
“We are all capable of dehumanization when we feel that the group that we love … is threatened,” Woods said. This is a model they are referring to as the mother bear hypothesis: A mother bear is most patient when she is dealing with her cubs, but most angry when another organism threatens her offspring.
The number one predictor of dehumanization is the feeling that your own group or identity is being dehumanized, and in those moments, the same part of the brain that enables cooperative communication shuts down and is dampened.
The duo cited cross-group friendships, democracy, and our perception of other animals as important factors for offsetting dehumanization in the human species. Cross-group friendships provide a bridge of empathy, democracy contributes to collective group identity and decisions, and our perceptions of other animals limit dehumanization when we have an ecological view of our relation to other species rather than a top-down, human-centric approach.
“You have to understand what was wrong about the past but not blind yourself to what you do find,” Woods said when asked about the dark history of morphology-based pseudo-sciences that prompted racial persecutions. This is something that the pair reckons with for a whole chapter in their book.
“You can see in our faces the faces of friendliness,” Hare said.
May we all lean into this niceness after encountering Hare and Woods work. It’s gotten us this far, and it seems particularly vital for our collective future.
Posters, presentations, and formalwear: despite the challenge of a virtual environment, this year’s annual Fortin Foundation Bass Connections Showcase still represented the same exciting scholarship and collegiality as it has in years past.
While individuals could no longer walk around to see each of this year’s 70+ teams present in person, they were instead able to navigate a virtual hall with “floors” designated for certain teams. With labels on each virtual table, it almost mimicked the freedom of leisurely strolls down a hall lined with posters, stopping at what catches your eye. Three sessions were held over Thursday, April 15 and Friday, April 16.
The beginning of each session featured five-minute “lightning” presentations by a diverse set of teams, representing the range of research that students and faculty participated in. One such presentation was lead by Juhi Dattani ’22 (NCSU) and Annie Roberts ’21, who covered research generated by their team, “Regenerative Grazing to Mitigate Climate Change.” The team was an inter-institutional project bringing together UNC, NCCU, NCSU, and Duke. And as they aptly summarized, “It’s not the cow, but how.” Cows can help fight instead of contribute to the climate crisis, through utilizing regenerative grazing – which is an indigenous practice that has been around for hundreds of years – to improve soil health and boost plant growth.
One of the most remarkable parts of Bass Connections is how it opens doors for students to pursue avenues and opportunities that they may have never been exposed to otherwise. Hurewitz said that “Being a part of this team led me and a team member to apply for the 2021 Bass Connections Student Research Award, which we were ultimately awarded to study the barriers and facilitators to early childhood diagnosis of Autism Spectrum Disorder (ASD) among Black and Latinx children in North Carolina.” In addition to the award, Hurewitz and fellow team member Ainsley Buck were able to present their team’s research at the APA Region IV Annual Meeting.
From gene therapy for Alzheimer’s disease to power grids on the African continent, this year’s teams represented a wide range of research and collaboration. Erica Langan ’22, a member of the team “REGAIN: Roadmap for Evaluating Goals in Advanced Illness Navigation”, said that “For me, Bass Connections has been an extraordinary way to dive into interdisciplinary research. It’s an environment where I can bring my existing skills and knowledge to the table and also learn and grow in new ways.” This interdisciplinary thinking is a hallmark of not just Bass Connections, but Duke as a research institution, and it’s clear that this spirit is alive and well, even virtually.
Collaborating with a colleague in Shanghai, we recently published an article that explains the mathematical concept of ‘in-betweening,’in images – calculating intermediate stages of changes in appearance from one image to the next.
Our equilibrium-driven deformation algorithm (EDDA) was used to demonstrate three difficult tasks of ‘in-betweening’ images: Facial aging, coronavirus spread in the lungs, and continental drift.
Part I. Understanding Pneumonia Invasion and Retreat in COVID-19
The pandemic has influenced the entire world and taken away nearly 3 million lives to date. If a person were unlucky enough to contract the virus and COVID-19, one way to diagnose them is to carry out CT scans of their lungs to visualize the damage caused by pneumonia.
However, it is impossible to monitor the patient all the time using CT scans. Thus, the invading process is usually invisible for doctors and researchers.
To solve this difficulty, we developed a mathematical algorithm which relies on only two CT scans to simulate the pneumonia invasion process caused by COVID-19.
We compared a series of CT scans of a Chinese patient taken at different times. This patient had severe pneumonia caused by COVID-19 but recovered after a successful treatment. Our simulation clearly revealed the pneumonia invasion process in the patient’s lungs and the fading away process after the treatment.
Our simulation results also identify several significant areas in which the patient’s lungs are more vulnerable to the virus and other areas in which the lungs have better response to the treatment. Those areas were perfectly consistent with the medical analysis based on this patient’s actual, real-time CT scan images. The consistency of our results indicates the value of the method.
Part II. Solving the Puzzle of Continental Drift
It has always been mysterious how the continents we know evolved and formed from the ancient single supercontinent, Pangaea. But then German polar researcher Alfred Wegener proposed the continental drift hypothesis in the early 20th century. Although many geologists argued about his hypothesis initially, more sound evidence such as continental structures, fossils and the magnetic polarity of rocks has supported Wegener’s proposition.
Our data-driven algorithm has been applied to simulate the possible evolution process of continents from Pangaea period.
The underlying forces driving continental drift were determined by the equilibrium status of the continents on the current planet. In order to describe the edges that divide the land to create oceans, we proposed a delicate thresholding scheme.
The formation and deformation for different continents is clearly revealed in our simulation. For example, the ‘drift’ of the Antarctic continent from Africa can be seen happening. This exciting simulation presents a quick and obvious way for geologists to establish more possible lines of inquiry about how continents can drift from one status to another, just based on the initial and equilibrium continental status. Combined with other technological advances, this data-driven method may provide a path to solve Wegener’s puzzle of continental drift.
The study was supported by the Department of Mathematics and Physics, Duke University.
On Saturday, April 10th, Duke Postdoc Comedy Club hosted Are We There Yet?, a virtual comedy showcase featuring Triangle-based comedians. The show was moderated by Bo Ma and featured six comics: Tori Grace Nichols, Amy Mora, Josh Rosenstein, Nat Davis, Yutian Feng, and headliner Isatu Kamara (in order of appearance).
The virtual comedy club was sponsored by the Duke Office of Research, The Graduate School, and the Division of Student Affairs, who collectively scraped together a whopping $15 to pay each of the up-and-coming comedians, giving the audience their first laugh of the night. Let’s see $8 billion endowment… subtract the product of 15 times 6… carry the one… wait, how many zeroes is that again? Good one, Duke.
Given that the show was free, I definitely felt like I got a lot more than I paid for.
I was shocked at how many of the performers had prior comedy experience in the community; almost all of the comics had extensive performance resumes both in Durham and outside of the Triangle area. Prevalent themes of the night included jokes related to gender and racial identity, COVID-induced weight gains (dubbed by Amy Mora as the “quarantine fifteen”), and the less than prolific employment prospects currently awaiting postdoctoral students.
One of the highlights of the show was radiology postdoc Yutian Feng’s set. A self-described PhD, which he clarified stood for “permanent head damage,” his hobbies included identifying as a straight white male “because it’s the only way to get elected in this country,” and conversing with Siri on his Apple Watch, which he has programmed to congratulate him with a salty profanity every time he finishes exercising. After watching his set, all I can think to say is congratulations (salty profanity) — being that funny must’ve been quite the workout!
The show’s headliner was Isatu Kamara, an up-and-coming Durham-based comedian who tuned in alongside her cat, Jimmy Carter.
Kamara’s set revolved around her identities, particularly as a “stay-at-home daughter” and non-rich person, lamenting about the recent invasion of “gentrification scooters” and the sunroom epidemic in Durham.
Future plans? Kamara hopes to upgrade from the shopping cart that they have at the grocery store specifically for single people. You know, the one that’s “half of the size of the Happy Family™ shopping cart” and only has room for “a pack of White Claws, a bottle of wine, and some cat food?” A very ambitious goal but, hey, we’re rooting for you, Isatu.
Though the fruits of their research careers remain unknown, the comedic future seems promising for the Postdoc Comedy Club’s self-described “two to three” members. After all, as Yutian aptly pointed out during his set, they all have the opportunity to move “from the most underpaid job to the second most underpaid job” — a drop in the bucket when compared to their masses of student debt and cure their similarly high degrees of self-loathing, but hey, at least they got fifteen bucks?
Creighton, who has an MS in exercise physiology and has spent her career involved in clinical research and community health at both UNC-Chapel Hill and Duke, has spinocerebellar ataxia, a hereditary neurodegenerative condition characterized by a lack of muscle coordination. The illness is commonly visible through slurred speech, stumbling, falling, and incoordination due to damage to the cerebellum – the part of the brain that controls muscle coordination.
As Creighton described, prior to writing her book in her late forties, she hadn’t successfully communicated to anyone the impact of ataxia on her life. And so, her memoir was organically born, but as Creighton says, “it was hard for me to type as fast as I was thinking, and that lasted for several months.”
It took Creighton a couple of years just to write the foundation of the book, which draws on neuroplasticity research, personal memories, and medical records to highlight the importance of storytelling in deriving meaning from illness. She spent the next two years after that re-shaping the arc, drawing on a wealth of her own experiences as well as decades of journaling that had left her with a meticulous set of notes.
As both Creighton and Dr. Mantri emphasized, writing is a deeply cathartic exercise as well as a way to share significant personal narratives. This is especially true in a field such as medicine, where people are so often treated as an illness or statistic rather than a human being.
While the recognition of patient and doctor narratives has been around for many years, it was not until fairly recently that narrative medicine emerged as a field of knowledge that doctors could educate themselves in.
Dr. Mantri is familiar with the benefits of narrative medicine from a clinical perspective, holding an M.S in Narrative Medicine from Columbia University and being a leader of various narrative medicine initiatives at Duke, both with doctors and medical students.
According to Dr. Mantri, elucidating these narratives is crucial to understanding that at the end of the day, doctors and patients work to navigate challenges of illnesses with different perspectives. It’s necessary to hear the story of a patient as well as understand the story of a clinician. Only then can doctors work to find moments of alignment between these two perspectives, resulting in care that is more patient-centered.
From the patient perspective, Creighton remarks that a chapter in her book delves into narrative medicine, even though at the time she had no idea what it was. As she learned more about the field, though, it became clear just how integral narrative medicine was to her experience processing and coming to terms with her ataxia. Prior to taking a class on narrative medicine, she assumed that it wouldn’t be a positive experience. But years later, she credits the process of writing her memoir with allowing her to move on, in many ways, from the hold her illness had on her.
Creighton also pointed out that as humans, “we want the same things – to feel heard and to make meaningful connections with others who can potentially help us navigate whatever condition we’re going through.”
To that end, Dr. Mantri and Creighton both referred to several resources that can help people with illnesses find communities of other individuals with the same illness, in order to find the type of solidarity and understanding promoted by sharing experiences. One such resource is PatientsLikeMe, where individuals can ask questions and exchange tips on their specific illness with others going through similar struggles.
Finally, Creighton was asked about the things she’d like clinicians to know from her perspective as a patient. She described the disconnect that she had often felt, not only with doctors but with therapists and counselors, stemming from a feeling that the help she was offered often did not meet her where she was. In brainstorming ways to mitigate this gap, both Dr. Mantri and Creighton pointed to a need for doctors to focus on a patients’ needs and desires, and a need for patients to advocate for themselves.
As the conversation concluded, Creighton emphasized the importance of being seen as a human rather than a victim of a disease. Spinocerebellar ataxia is neurodegenerative, meaning that symptoms progressively get worse. But as Creighton remarked: “Losing my abilities is going to happen. Losing my abilities doesn’t change the human that I am.”
Autism Spectrum Disorder can be detected as early as six to twelve months old and the American Academy of Pediatrics recommends all children be screened between twelve and eighteen months of age.
But most diagnoses happen after the age of 4, and later detection makes it more difficult and expensive to treat.
One in 40 children is diagnosed with Autism Spectrum Disorder and Duke currently serves about 3,000 ASD patients per year. To improve care for patients with ASD, Duke researchers have been working to develop a data science approach to early detection.
Geraldine Dawson, the William Cleland Distinguished Professor in the Department of Psychiatry & Behavioral Sciences and Director of the Duke Center for Autism and Brain Development, and Dr. Matthew Engelhard, a Conners Fellow in Digital Health in Psychiatry & Behavioral Sciences, recently presented on the advances being made to improve ASD detection and better understand symptoms.
The earlier ASD is detected, the easier and less expensive it is to treat. Children with ASD face challenges in learning and social environments.
ASD differs widely from case to case, however. For most people, ASD makes it difficult to navigate the social world, and those with the diagnosis often struggle to understand facial expressions, maintain eye contact, and develop strong peer relations.
However, ASD also has many positive traits associated with it and autistic children often show unique skills and talents. Receiving a diagnosis is important for those with ASD so that they can receive learning accommodations and ensure that their environment helps promote growth.
Because early detection is so helpful researchers began to ask:
“Can digital behavioral assessments improve our ability to screen for neurodevelopmental disorders and monitor treatment outcomes?”
Dr. geraldine DawsoN
The current approach for ASD detection is questionnaires given to parents. However, there are many issues in this method of detection such as literacy and language barriers as well as requiring caregivers to have some knowledge of child development. Recent studies have demonstrated that digital assessments could potentially address these challenges by allowing for direct observation of the child’s behavior as well as the ability to capture the dynamic nature of behavior, and collect more data surrounding autism.
“Our goal is to reduce disparities in access to screening and enable earlier detection of ASD by developing digital behavioral screening tools that are scalable, feasible, and more accurate than current paper-and-pencil questionnaires that are standard of care.”
Dr. Geraldine Dawson
Guillermo Sapiro, a James B. Duke Distinguished Professor of Electrical and Computer Engineering, and his team have developed an app to do just this.
On the app, videos are shown to the child on an iPad or iPhone that prompt the child’s reaction through various stimuli. These are the same games and stimuli typically used in ASD diagnostic evaluations in the clinic. As they watch and interact, the child’s behavior is measured with the iPhone/iPad’s selfie camera. Some behavioral symptoms can be detected as early as six months of age are, such as: not paying as much attention to people, reduced affective expression, early motor differences, and failure to orient to name.
In the proof-of-concept study, computers were programmed to detect a child’s response to hearing their name called. The child’s name was called out by the examiner three times while movies were shown. Toddlers with ASD demonstrated about a second of latency in their responses.
Another study used gaze monitoring on an iPhone. Nearly a thousand toddlers were presented with a split screen where a person was on one side of the screen and toys were on the other. Typical toddlers shifted their gaze between the person and toy, whereas the autistic toddlers focused more on the toys. Forty of the toddlers involved in the study received an ASD diagnosis. Using eye gaze, researchers were also able to look at how toddlers responded to speech sounds as well as to observe early motor differences because toddlers with ASD frequently show postural sway (a type of head movement).
“The idea behind the app is to begin to combine all of these behaviors to develop a much more robust ASD algorithm. We do believe no one feature will allow us to detect ASD in developing children because there is so much variation”
DR. GERALDINE DAWSON
The app has multiple features and will allow ASD detection to be done in the home. Duke researchers are now one step away from launching an at-home study. Other benefits of this method include the ability to observe over time with parents collecting data once a month. In the future, this could be used in a treatment study to see if symptoms are improving.
Duke’s ASD researchers are also working to integrate information from the app with electronic health records (EHR) to see if information collected from routine medical care before age 1 can help with detection.
What do you get when you mix double majors in Philosophy and Psychology with a certificate in Philosophy, Politics, and Economics? You get someone like Kelis Johnson, a junior from Lithonia, Georgia in suburban Atlanta, who works in not one research lab at Duke, but two.
“Managing two research assistant positions while working as an embedded writing consultant with the Thompson Writing Studio, on top of my academics, can definitely be a challenge,” Kelis says. But, she said, “The way that I have been able to manage these positions along with the rest of my busy schedule is cohesion: Although working in a lab provides a different context than the material from my classes, I think my lab work and classwork supplement one another in a profound way.”
After taking a class with Elizabeth Marsh, the lab’s Principal Investigator, Kelis found herself “interested in deepening [her] knowledge of and experience with memory research,” so she reached out to get involved in the summer of 2020. The lab has provided her a means to explore her interests in the “intersections between memory and personal identity, education and the law.”
Simultaneously, in the midst of the (first) Covid-19 summer, Kelis worked with the Microworlds Lab. She conducted historical research that profiled Black female activists. “I felt like my interests and passions began to converge on activism and bringing about change while also exploring empirical research,” she said, “This passion aligned with the work being done at the Wilson Center who use research to advance civil rights.” She joined her second lab in the fall of 2020.
In both positions, Kelis meets weekly with her fellow colleagues to discuss an overview of the labs work or the current research in the field. She finds this fulfilling, knowing that the work she and fellow research assistants have contributed to is providing “concrete advancements … in the labs and the world more broadly.” Kelis’ work consists mostly of coding or scoring data. This means reading study participants’ responses and using a codebook (like a grading rubric) to determine how each response compares to the standard established in the experimental protocol. Kelis also participates in literature reviews and stimuli creation, where she generates relevant material such as questions, statements, or images that will be used in experiments to test research questions.
This work has enabled Kelis to meet fellow undergraduates, along with graduate students and faculty mentors, who have similar interests to her own. She has learned more about grant writing, research ethics, and statistical tools. Along with providing her invaluable research experience, strengthening her passions for criminal justice reform, and reinforcing her plans to go to law school following graduation from Duke, through her work with the Wilson Center, Kelis has been able to learn more about Durham and North Carolina. This prompted her to think deeper about her role in the larger communities around her.
Kelis’ research is valuable outside of the lab. “Memory research is essential to how we learn, how we structure our life and personal identity, and how we form relationships with others,” Kelis said. She also stated that, “Learning about and reforming our criminal justice system is something we must all care about. In order to attack the systematic oppression of marginalized groups, we have to understand it.”
Unfortunately, due to Covid-19, Kelis has been unable to participate in person with either of her labs. This is something she is emphatically looking forward to. However, the virtual realm has enabled other forms of meaningful interactions and experiences through digital platforms. Kelis says she really appreciates “the events hosted by the [Wilson Center] Lab that often feature exonerated individuals who speak about their experience within the criminal justice system.”
Kelis’ contributions to projects from memory difference in older and younger adults to autobiographical memory are surely only the first steps in a planned lifetime of standing at the intersection between memory, identity, and the structures of our society.
Herman Pontzer explains where our calories really go, and what studying humanity’s past can teach us about staying healthy today.
Duke professor Herman Pontzer has spent his career counting calories. Not because he’s watching his waistline, exactly. But because, as he sees it, “in the economics of life, calories are the currency.” Every minute, everything the body does — growing, moving, fighting infection, even just existing — “all of it takes energy,” Pontzer says.
In his new book, “Burn,” the evolutionary anthropologist recounts the 10-plus years he and his colleagues have spent measuring the metabolisms of people ranging from ultra-athletes to office workers, as well as those of our closest animal relatives, and some of the surprising insights the research has revealed along the way.
Much of his work takes him to Tanzania, where members of the Hadza tribe still get their food the way our ancestors did — by hunting and gathering. By setting out on foot each day to hunt zebra and antelope or forage for berries and tubers, without guns or electricity or domesticated animals to lighten the load, the Hadza get more physical activity each day than most Westerners get in a week.
So they must burn more calories, right? Wrong.
Pontzer and his colleagues have found that, despite their high activity levels, the Hadza don’t burn more energy per day than sedentary people in the U.S. and Europe.
These and other recent findings are changing the way we understand the links between energy expenditure, exercise and diet. For example, we’ve all been told that if we want to burn more calories and fight fat, we need to work out to boost our metabolism. But Pontzer says it’s not so simple.
“Our metabolic engines were not crafted by millions of years of evolution to guarantee a beach-ready bikini body,” Pontzer says. But rather, our metabolism has been primed “to pack on more fat than any other ape.” What’s more, our metabolism responds to changes in exercise and diet in ways that thwart our efforts to shed pounds.
What this means, Pontzer says, is you can walk 16,000 steps each day like the Hadza and you won’t lose weight. Sure, if you run a marathon tomorrow you’ll burn more energy than you did today. But over time, metabolism responds to changes in activity to keep the total energy you spend in check.
Pontzer’s book is more than a romp through the Krebs cycle. For anyone suffering pandemic-induced pangs of frustrated wanderlust, it’s also filled with adventure. He takes readers on an hours-long trek to watch a Hadza man track a wounded giraffe across the savannah, to the rainforests of Uganda to study climbing chimpanzees, and to the foothills of the Caucasus Mountains to unearth the 1.8 million-year-old remains of some of the first people who trekked out of Africa.
His humor shines through along the way. Even when awoken by a chorus of 300-pound lions just a few hundred yards from his tent, he stops to ponder whether his own stench gives him away, and what he might do if they come for his “soft American carcass, the warm triple crème brie of human flesh.”
Pontzer spoke via email with Duke Today about his book:
Q: What’s the lesson the Hadza and other hunter-gatherers teach us about managing weight and staying healthy?
A: The Hadza stay incredibly fit and healthy throughout their lives, even into their older ages (60’s, 70’s, even 80’s). They don’t develop heart disease, diabetes, obesity, or the other diseases that we in the industrialized world are most likely to suffer from. They also have an incredibly active lifestyle, getting more physical activity in a typical day than most Americans get in a week.
My work with the Hadza showed that, surprisingly, even though they are so physically active, Hadza men and women burn the same number of calories each day as men and women in the U.S. and other industrialized countries. Instead of increasing the calories burned per day, the Hadza physical activity was changing the way they spend their calories — more on activity, less on other, unseen tasks in the body.
The takeaway for us here in the industrialized world is that we need to stay active to stay healthy, but we can’t count on exercise to increase our daily calorie burn. Our bodies adjust, keeping energy expenditure in a narrow range regardless of lifestyle. And that means that we need to focus on diet and the calories we consume in order to manage our weight. At the end of the day, our weight is a matter of calories eaten versus calories burned — and it’s really hard to change the calories we burn!
Q: You’re saying that exercise doesn’t matter? What’s the point, if we can’t eat that donut?
A: All those adjustments our bodies make responding to exercise are really important for our health! When we burn more calories on exercise, our bodies spend less energy on inflammation, stress reactivity (like cortisol), and other things that make us sick.
Q: What’s the biggest misunderstanding about human metabolism?
A: We’re told — through fitness magazines, diet fads, online calorie counters — that the energy we burn each day is under our control: if we exercise more, we’ll burn more calories and burn off fat. It’s not that simple! Your body is a clever, dynamic product of evolution, shifting and adapting to changes in our lifestyle.
Q: In your book you say we’re driven to magical thinking when it comes to calories. What do you mean by that?
A: Because our body is so clever and dynamic, and because humans are just bad at keeping track of what we eat, it’s awfully hard to keep track of the calories we consume and burn each day. That, along with the proliferation of fad diets and get-thin-quick schemes, has led to this idea that “calories don’t matter.” That’s magical thinking. Every ounce of your body — including every calorie of fat you carry — is food you consumed and didn’t burn off. If we want to lose weight, we must eat fewer calories than we burn. It really comes down to that.
Q: Some people say that if the cavemen didn’t eat it, we shouldn’t either. What does research show about what foods are “natural” for humans to eat?
A: There’s no singular, natural human diet. Hunter-gatherers like the Hadza eat a diverse mix of plant and animal foods that varies day to day, month to month, and year to year. There’s even more dietary diversity when we look across populations. Humans are built to thrive on a wide variety of diets — just about everything is on the menu.
That said, the ultra-processed foods we’re inundated with in our modern industrialized world really are unnatural. There are no Twinkies to forage in the wild. Those foods are literally engineered to be overconsumed, with a mix of flavors that overwhelm our brain’s ability to regulate our appetites. Now, it is still possible to lose weight on a Twinkie diet (I’m not recommending it!), if you’re very strict about the calories eaten per day. But we need to be really careful about how we incorporate ultra-processed foods into our daily diets, because they are calorie bombs that drive us to overconsume.
Q: If we could time travel, what would our hunter-gatherer ancestors make of our industrialized diet today?
A: We don’t even need to imagine — We are those hunter-gatherers! Biologically, genetically, we are the same species that we were a hundred thousand years ago, when hunting and gathering were the only game in town. When we’re confronted with modern ultra-processed foods, we struggle. They are engineered to be delicious, and we tend to overconsume.
Q: Has the COVID-19 pandemic brought any of these lessons home for you? What can we do to keep active and watch what we eat, even while working from home?
The pandemic has been a tragedy on so many levels — the loss of life, those suffering with long-term effects, the social and economic impacts. The impact on diet and exercise have been bad as well, for many of us. Stress eating is a real phenomenon, and the stress and emotional toll of the pandemic — along with having easy access to the snacks in our kitchen — have led many to gain weight. Physical activity seems to have declined for many. There aren’t easy answers, but we should try to make a point to get active every day. And we can help ourselves make better decisions about food by keeping ultra-processed foods out of our houses. You can’t plow through a bag of chips if you don’t have chips in your cupboard.
Q: You’ve measured the energy costs of activities ranging from taking a breath to doing an Ironman. What is one of the more extreme or surprising calorie-burning activities that you’ve measured, or would like to measure, in humans or some other animal?
A: With colleagues from Japan, I measured the energy cost of a heartbeat – a tricky bit of metabolic measurement! Turns out each beat of your heart burns about 1/300th of a kilocalorie! Amazing how efficient our bodies can be.
Q: What is something people have questions about that we just don’t know the answer to yet? What would it take to find out?
A: Right now we’re excited about measuring the adjustments our bodies make when we increase our exercise: how exactly does burning more energy on physical activity impact our immune system, our stress response, our reproductive system? It will take a long-term study of exercise to see how these systems change over time.
As Daniel Sprague ‘21 prepares to graduate from Duke this Spring with a double major in Computer Science and Neuroscience, I had the opportunity to interview him on his undergraduate research experience. In his final semester, Sprague reflects on what he accomplished and learned in the three research labs he was a part of over his four years at Duke.
Outside of the lab, Sprague is also active in the arts community at Duke. He has been a member of Hoof ‘n’ Horn since his freshman year and has performed in four student-run musical theater productions. He is also a part of Speak of the Devil, one of Duke’s acapella groups that he was the president of during his Junior year. Recently, a video they uploaded more than two years ago has picked up speed and acquired over 150,000 views on YouTube. I think it’s fair to say Sprague is even more than a triple threat.
Sprague was interested in neuroscience and biology before he came to Duke and knew he wanted to participate in undergraduate research when he arrived. His first year, planning on pursuing pre-med, he joined Rima Fathi Kaddurah-Daouk’s lab where he worked with metabolomics, the large-scale study of small molecules within cells, biofluids, tissues, or organisms as it relates to neuropsychiatric disorders. While he learned a lot and enjoyed working in this lab, Sprague was eager to explore more.
The summer after his first year, Sprague was accepted to the Huang Fellows Program run by Duke’s Science & Society initiative.
Sprague described their focus as, “The way that research, science, communication, and medicine interact with social issues and ethics.”
As a part of the program, Sprague was matched and placed in Ornit Chiba-Falek’s lab. There he conducted work in genomics and neuroscience, centered around neurodegenerative diseases, specifically, Parkinson’s and Alzheimer’s. His job involved processing mouse brains to extract neurons for genomic sequencing. From there, the lab would conduct genome-wide association studies to correlate specific human or animal genotypes with genetic markers.
“We were trying to identify SNPs (Single-nucleotide polymorphism) which are single base pair variations in a genome that correlated with Alzheimer’s” Sprague explained
Along with working in a lab, Sprague also attended research seminars, learned about how science publishing works, and participated in a science symposium at the culmination of the summer experience.
“Research is a slow iterative process and it rarely ever works how you expect it to.”
Junior year brought Sprague to the John Pearson’s Lab where they build modeling and analysis tools for brain data.
He also began taking courses in machine learning which he brought into his lab work. His role involved working on the lab’s code base and aiding in the development of a software system for analyzing the brain. He was specifically looking at calcium imaging data. Sprague explained that there are a lot of different ways to do neuroimaging and visualize brain cell function. His work involved using fluorescent calcium.
“When brain cells spike, they release a fluorescent calcium trace that we can visualize with a camera to detect brian cell function with a high degree of temporal and spatial specificity,” Sprague said. “This allows us to accurately detect brain cell function on a millisecond and single cell scale.”
In many neuroscience studies, a stimulus is presented to an organism and the response is observed. The Pearson lab wants to be able to dynamically adjust which stimulus they present based on the intermediary results during the experiment.
“A big limitation in neuroscience research is it just has an absurd amount of data, even for a very small organism,” Sprague said. “Even a couple thousand brain cells will provide so much data that it can’t be visualized or analyzed quick enough to adjust the experiment in ways that would improve it.”
As a result of this limitation, they are trying to adapt conventional computational neuroscience methods to be used in an “online fashion,” which means working with the data as it comes in. Ultimately, they are developing methods to analyze data that traditionally would take hours due to computational time and trying to condense it to a millisecond.
“There are a lot of similar problems that computer scientists work on, but they focus on theoretical analyses of types of functions and how mathematical functions work. What’s cool about this is that it’s very applied with the constraints of a biological system and also requires knowledge of multiple disciplines.”
Sprague will continue to apply these skills as he begins working next year as an associate consultant at Bain & Company in San Francisco. He is very interested in the connection between science, tech, and society.
Additionally, he is hoping to learn more about how artificial intelligence and machine learning are used in industry as well as their future directions, ethical dilemmas, and legal considerations. Consulting is becoming an increasingly data-driven industry and Sprague hopes to continue developing his domain knowledge and work with these ideas in an applied setting.
As Sprague prepares to leave Duke he reflects on his time here and the research he has had the opportunity to participate in.
“One thing I’m grateful for is having the chance to have different experiences but still settle into one lab for two years. Don’t be afraid to get involved early, and don’t feel like you have to stay in the same lab for four years.”
Covid-19 is considered a “general pandemic,” but its impacts have been disproportionate along the lines of race and ethnicity. Though vaccines may serve as our best chance to put an end to Covid, the problem of vaccine hesitancy amongst Black people in the U.S. is particularly pervasive and grounded by more than simple mistrust.
Gary Bennett (Ph.D.) discussed the issue of complex determinants of vaccine hesitancy among Black Americans Monday, April 5. Bennett is a Professor of Psychology, Neuroscience, Global Health, and Medicine at Duke, as well as director of Duke Digital Health and Vice Provost for Undergraduate Education.
“At the end of the day, we are dealing with an issue that demands pragmatic attention,” Bennett said, “How do we get shots in arms?” It turns out, the answer is quite complex and historically confounded.
While Black people have experienced much higher burdens from Covid-19 despite contracting the disease at a similar rate to whites, they have been disproportionately vaccinated at lower rates than white people.
“Access matters and it matters a lot,” Bennett said. One clear example of decreased access for Black Americans is that fewer vaccination sites are located in areas with high concentrations of Black people.
However, Bennett said, access does not simply equal place. “How much friction are you creating in this process?” he prompted, pointing to examples of complicated registration systems, inadequate public transportation to vaccine sites, or overall distance from a location. All of these factors already limit who is able to access vaccinations without the added influences of reduced vaccine uptake due to vaccine hesitancy.
Bennett said that many claims around hesitancy blame communities for their inability to access vaccines, but this fails to consider or to change the underlying behaviors that drive hesitancy. Bennett outlined these underlying drivers as 1) mistrust, 2) social norms, and 3) understandable uncertainties.
“It’s not just mistrust of the medical system, it’s mistrust of institutions,” Bennett said, “There’s a lot of reasons for [Black people] to mistrust institutions.” The murder of George Floyd stands as one poignant contemporary example, but “Tuskegee [still] looms large in the minds of Black Americans.” The Tuskegee experiment exploited 600 Black men working as sharecroppers who had syphilis by knowingly withholding treatment and simply seeing what happened to their bodies as a result of the disease for over 40 years.
Our social networks are also vitally important to influencing our feelings about receiving the Covid vaccine. In Black communities, Bennett said, fewer people in their networks have gotten vaccinations and those who have received vaccines are less vocal about it leading to a collective lack of interest in receiving vaccinations.
These two factors, paired with understandable uncertainties about the side effects of the vaccine or potentially getting Covid itself, generate the need to change our approaches to vaccine hesitancy and increased uptake amongst Black communities in the U.S.
To do this we need to lead with empathy and appreciate the fact that changing attitudes towards vaccines is a process. “Shaming people is bad,” Bennett said. “Stigmatizing people will actually lead to the converse of what we expect.”
Over time, we can work to correct misconceptions, contextualized uncertainties, and share stories rather than statistics to push people further from vaccine refusal and closer to vaccine demand.
And when more Black Americans are ready, “vaccination should be an easy choice.” By implementing opt-out policies, rather than opt-in and by taking more direct actions like making vaccination appointments for people, Covid vaccines may indeed be the key to ending the pandemic – in an equitable and proportionate way.