The Web of Science ranking of the world’s most highly-cited scientists was released this morning, telling us who makes up the top 1 percent of the world’s scientists. These are the authors of influential papers that other scientists point to when making their arguments.
EDITOR’S NOTE! — Web of Science shared last year’s data! We apologize. List below is now corrected, changes to copy in bold. We’re so sorry.
Twenty-three of the citation laureates are Duke scholars or had a Duke affiliation when the landmark works were created over the last decade.
A couple of these Duke people disappeared from this year’s list, but we’re still proud of them.
Dan Scolnic of Physics returns as our lone entry in Space Science, which just makes Duke sound cooler all around, don’t you think?
This is a big deal for the named faculty and an impressive line on their CVs. But the selection process weeds out “hyper-authorship, excessive self-citation and anomalous citation patterns,” so don’t even think about gaming it.
Fifty-nine nations are represented by the 6,636 individual researchers on this year’s list. About half of the citation champions are in specific fields and half in ‘cross-field’ — where interdisciplinary Duke typically dominates. The U.S. is still the most-cited nation with 36 percent of the world’s share, but shrinking slightly. Mainland China continues to rise, claiming second place with 20 percent of the cohort, up 2.5 percent from just last year. Then, in order, the UK, Germany and Australia round out the top five.
In fact, five Duke NUS faculty made this year’s list: Antonio Bertoletti, Derek Hausenloy and Jenny Guek-Hong Low for cross-field; Carolyn S. P. Lam for clinical medicine, and the world famous “Bat Man,” Lin-Fa Wang, for microbiology.
It’s that most wonderful time of the year: The official list of Clarivate’s Most Highly Cited Scientists came out this morning. Scientists all over the world came racing down the stairs in their PJs to see if Clarivate had left a treat under the tree for them.
L-R: Odgers, Scolnic, Dong, Hernandez, Harrington, Smith, Ostrom and Lopes.
Good news – there are 30 Duke names on the list!
Being highly cited is a point of pride for researchers. To make the cut, a paper has to be ranked in the top 1 percent for its field for the last decade. Clarivate’s “Institute for Scientific Information” crunches all the numbers.
Mostly, the names on this year’s list of Duke authors are the usual titans. Oddly, some returning names have changed categories since last year — but that’s okay, they’re still important.
And there are three fresh faces: Cardiologist Renato Delascio Lopes, MD Ph.D., who studies atrial fibrillation; David R. Smith Ph.D. of physics and electrical engineering, who’s a leading light in the field of metamaterials; and Dan Scolnic Ph.D. of physics, who’s measuring the expansion of the universe and trying to figure out the dark energy that apparently drives it.
Five of the Duke names on the list this year are co-authors in the Terrie Moffit and Avshalom Caspi lab, a hugely influential group of psychologists and social scientists. Honnalee Harrington, Renate Houts, Caspi, Moffitt, and UC Irvine professor and Duke adjunct Candice Odgers are studying human development from cradle to grave using two cohorts of life-long study participants in New Zealand and England.
Two other longitudinal scientists, Jane Costello and William Copeland of the Great Smoky Mountains Study, are also on the list.
There are 6,938 highly cited scientists this year, from 69 countries and regions. Several appear in more than one division. The United States still dominates with 38 percent of the honorees, but Chinese scientists are on the rise at 16 percent.
The most highly cited Duke authors are:
Biology and Biochemistry
Charles A. Gersbach
Clinical Medicine
Christopher Bull Granger
Adrian F. Hernandez
Renato D. Lopes
Cross-Field
Stefano Curtarolo
Xinnian Dong
HonaLee Harrington
Renate Houts
Tony Jun Huang
Ru-Rong Ji
Robert Lefkowitz
Jason Locasale
David B. Mitzi
Christopher B. Newgard
Michael J. Pencina
Bryce B. Reeve
Pratiksha I. Thakore
Mark R. Wiesner
Microbiology
Barton F. Haynes
Neuroscience and Behavior
Quinn T. Ostrom
Pharmacology and Toxicology
Evan D. Kharasch
Physics
David R. Smith
Plant and Animal Science
Sheng Yang He
Psychiatry and Psychology
Avshalom Caspi
E. Jane Costello
Terrie E. Moffitt
Space Science
Dan Scolnic
Duke Affiliated:
Cross Field
Po-Chun Hsu – University of Chicago, Adjunct Assistant Professor in Mechanical Engineering and Materials Science at Pratt School of Engineering
Candice Odgers, UC Irvine, Adjunct at Duke
Environment and Ecology
Robert B. Jackson, Stanford University, Adjunct Professor of Earth and Ocean Science at Nicholas School of the Environment
William E. Copeland, University of Vermont, adjunct in psychiatry and behavioral sciences, School of Medicine.
I recently had the pleasure of attending Professor Janet Malek’s lecture: Only Mostly Dead? The Evolving Ethical Evaluation of Death by Neurologic Criteria, a lecture sponsored by the Trent Center for Bioethics, Humanities & History of Medicine.
Dr. Malek is an associate professor in the Duke Initiative for Science & Society, and at the Baylor College of Medicine Center for Medical Ethics and Health Policy.
Janet Malek Ph.D.
We don’t often talk about death. On the surface, it seems like it would be a straight-forward concept. You’re either dead, or you’re not dead. Right? It turns out that clinically defining death is not so simple.
Popular media has some grasp on the ambiguity of the definition of death. Remember this scene from the popular movie, The Princess Bride? Suspecting that the protagonist is dead, his friends bring him to a miracle-worker and have the following conversation.
Miracle Max: “Whoo-hoo-hoo, look who knows so much. It just so happens that your friend here is only MOSTLY dead. There’s a big difference between mostly dead and all dead. Mostly dead is slightly alive. With all dead, well, with all dead there’s usually only one thing you can do.
Inigo Montoya: What’s that?
Miracle Max: Go through his clothes and look for loose change.
In real life, death used to be determined by cardiopulmonary criteria – when the heart and lungs stop working. In recent decades the idea that death can be determined using neurologic criteria – when the brain stops working – has gained acceptance. As neuroscience and technology has evolved, so too have our definitions. Now that we know more about how the brain works, we know that there may be some brain activity even after a person has met the criteria for death by neurologic criteria (DNC). This leads to philosophically rich and practically relevant questions of ethics – for example, when do we stop providing life-sustaining care? In the field of bioethics and beyond, there is high demand for discussion on this topic.
There has been controversy over defining death since the 1650’s — when a woman named Anne Greene woke up after being hanged. It wasn’t until the 1980’s that a consensus definition of death was first identified. Here is a brief history:
1950s
Widespread availability of ventilators led to the identification of a state described as death of the neurological system.
1960s
Advances in organ transplantation foster discussion on the ethics of defining death.
A committee at Harvard Medical School examined the definition of Brain Death. They created a definition of “Irreversible Coma,” which focused on loss of neurological function.
1980s
The 1980 Uniform Determination of Death Act (UDDA) provided a legal basis for clinically determining death as: an individual who has sustained either 1) irreversible cessation of circulatory and respiratory functions OR 2) irreversible cessation of functions of the entire brain.
1981: President’s Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research report. Findings are centered on questions of functioning of the organism as a whole and the brain’s role in coordinating it.
1990s-2000s
Clinicians arrive at general agreement that a patient in a state of coma or unresponsiveness, without brainstem reflexes and who fails an apnea test is dead by neurologic criteria. Largely it is accepted that “brain death is death” but there is not complete consensus.
2010-late
2013: Case of Jahi McMath. A 13-year old girl was declared “brain dead” in California, and a death certificate was issued. However, the family fought to have her maintained on life support. They moved to New Jersey, the only state which recognized objections to brain death, and the “brain dead” declaration was reversed. Jahi lived there for 4 years before passing away. This famous case caused people to reconsider the concept of brain death.
2020s:
Recent innovations in heart transplantation technology will likely challenge the acceptance of the Dead Donor Rule (DDR) which requires that an individual is clinically declared dead before vital organs are removed for transplantation.
2021: Assembly of the Determination of Death Committee, tasked with updating the Uniform Determination of Death Act (UDDA). Duke faculty (and founding director of Science & Society) Nita Farahany, is involved with this process.
What ethical issues and practical questions challenging Death by Neurologic Criteria (DNC) today? Dr. Malek shared the following case.
Following a tragic car accident, Ms. Jones, a 20-year-old college student, was brought to the hospital, having suffered significant anoxic brain injury. The medical team determined that she met criteria for DNC. However, her family refused to allow for further testing. Several days passed. Ms. Jones was maintained on life support, during which she did not show signs of improvement. After several difficult conversations, the family consented for assessment and Ms. Jones was declared dead — using the criteria associated with DNC.
What is the proper amount of time to continue life-sustaining treatment if a physician suspects the patient will never recover?
Although this may sound like an uncommon occurrence, nearly half of neurologists have been asked to continue neurologic support for patients that may meet criteria for DNC.
Obligating life support for patients suspected of meeting DNC, either through the family’s refusal for testing or by direct request, would likely result in ethical harms such as violation of the dignity of decedent, unjustly using scarce resources, or causing moral distress in caregivers.
However, it may be permissible to maintain life support in these situations. Dr. Malek says that we do not yet have a good ethical framework for this. Reasonable accommodations that are in line with professional guidelines probably have minimal impact, and might provide some psychosocial benefits to families.
Is consent required to test for DNC? Should it be?
These are extremely difficult questions, and there is continuing controversy over what the correct answers should be. Dr. Malek advises medical experts to work with healthcare administrators to develop clear institutional policies.
Post by Victoria Wilson, 2023 MA student in Bioethics & Science Policy
From shot-putting, to helping conduct two research studies, to being selected for a cardiology conference, meet: Kinsie Huggins. She is from Houston, Texas, currently majoring in Biology and minoring in Psychology with a Pre-Med track here at Duke. With such a simple description, one can already see how bright her future is!
“I want to be a pediatrician and work with kids,” Huggins says. “When I was younger, I lived in Kansas, and in my area, there were no black pediatricians. My mother decided to go far to find one and I really bonded with my pediatrician. One day, I made a pact with her in that I would become a pediatrician too so that I can also inspire other little girls like me of my color and other minority groups.”
Having such a passion to let African-American and minority voices be heard, Huggins is also part of the United Black Athletes, using her shot-put platform to make sure these voices are heard in the athletics department.
And while she may be a top-notch sportswoman, she is also just as impressive when it comes to her studies and research. One of her projects focuses on the field of nephrology – the study of kidneys and kidney disease. She and a pediatric nephrologist are currently working on studying rare kidney diseases and the differences in DNA correlating to these diseases.
Kinsie is also a researcher at GRID (Genomics Race Identity Difference), which studies the sickle cell trait in the NCAA. With the sudden deaths of college athletes from periods of over-exhaustion during conditioning, there has been a rise in attention of sickle cell trait and its impact on athletes. At first, the NCAA implemented a policy that made it mandatory for college athletes to get tested for sickle cell in 2010, but some were wary about the lack of scientific validity in such claims. Now, the NCAA has funded GRID to conduct such research.
The difference of Normal red blood cell and sickle cell (CDC).
“We are analyzing the policy (athletes need to be tested for sickle cell), interviewing athletes in check-ups, and looking at data to see if the policy is working out for athletes and their performance/health,” Huggins explains.
With such an impressive profile, it doesn’t go without saying that Huggins didn’t go unnoticed. The American College of Cardiology (ACC) select high school and college students interested in the field of medicine and have them attend a conference in Washington D.C. to hear about research presentations, groundbreaking results of late-breaking clinical trials, and lectures in the field. Having worked hard, Huggins was selected to be part of the Youth Scholars program from the ACC and was invited to the conference on April 2-4.
Let’s wish Kinsie the best of luck at the conference and on her future research!
Peak achievement in the sciences isn’t measured by stopwatches or goals scored, it goes by citations – the number of times other scientists have referenced your findings in their own academic papers. A high number of citations is an indication that a particular work was influential in moving the field forward.
Nobel laureate Bob Lefkowitz made the list in two categories this year.
And the peak of this peak is the annual “Highly Cited Researchers” list produced each year by the folks at Clarivate, who run the Institute for Scientific Information. The names on this list are drawn from publications that rank in the top 1% by citations for field and publication year in the Web of Science™ citation index – the most-cited of the cited.
Duke has 38 names on the highly cited list this year — including Bob Lefkowitz twice because he’s just that good — and two colleagues at the Duke NUS Medical School in Singapore. In all, the 2021 list includes 6,602 researchers from more than 70 countries.
The ISI says that US scientists are a little less than 40 percent of the highly cited list this year – and dropping. Chinese researchers are gaining, having nearly doubled their presence on the roster in the last four years.
“The headline story is one of sizeable gains for Mainland China and a decline for the United States, particularly when you look at the trends over the last four years,” said a statement from David Pendlebury, Senior Citation Analyst at the Institute for Scientific Information. “(This reflects) a transformational rebalancing of scientific and scholarly contributions at the top level through the globalization of the research enterprise.”
Without further ado, let’s see who our champions are!
Hey everyone! My name is Vibhav Nandagiri, I use he/him/his pronouns, and I’m currently a first-year student at Duke. Amidst the sea of continuous transition brought upon by college, one area of my identity that has stayed fairly constant is my geography. I’ve lived in North Carolina for sixteen of my eighteen years, and my current home lies just twenty minutes from campus in sunny, suburban Cary, NC.
The two missing years are accounted for through my adventures in my parents’ hometown–Hyderabad, India–as a toddler. Spending some of my earliest years surrounded by a large and loving family impacted my life profoundly, forever cementing a strong connection to my emotional, cultural, and linguistic roots.
The latter had a secondary impact on me, one I wouldn’t discover until my parents enrolled me in preschool after returning to the States. With hubris, I marched into my first day of class, ready to seize the day, until I soon discovered an uncomfortable fact: I couldn’t speak English. I am told through some unfortunate stories that I struggled considerably during my first month in a new, Anglicized environment; however, I soon learned the quirks of this language, and two-year-old me, perhaps realizing that he had some catching up to do, fully immersed himself in the English language.
Nowadays, I read quite a bit. Fiction and journalism, academic and satire, I firmly believe that all styles of literature play a role in educating people on the ebbs and flows of our world. In recent years, I’ve developed a thematic fascination with the future. The genre of far-future science fiction, with its rich exploration of hypothetical advanced societies, has led me to ask pressing questions about the future of the human species. How will society organize itself politically? What are the ethical implications of future medical advancements? Will we achieve a healthy symbiosis with technology? As a Duke Research Blogger, I hope to find answers to these questions while getting a front-row, multidisciplinary seat to what the future has to offer. It’s an invigorating opportunity to grow as a writer and communicator, to have my curiosity piqued on a weekly basis, to understand the futuristic visions of innovators at the top of their field.
Prior to Duke, I had the opportunity to conduct research at the Appalachian State University Pediatric Exercise and Physiology Lab, where I co-authored a published paper about adolescent fat metabolism. Not only was I introduced to the academic research process, but I also learned the importance of communicating my findings clearly through writing and presentations. I intend to bring these valuable lessons and perspectives to the Duke Research Blog.
Beyond exercise science, I am intrigued by a diverse range of research areas, from Public Health to Climate Change to Business to Neuroscience, the latter of which I hope to explore further through the Cognitive Neuroscience and Law FOCUS. I was drawn to the program for the opportunity to build strong relationships with professors and investigators; I intend to approach my work at the Duke Research Blog with a similar keenness to listen and connect with researchers and readers alike. When I’m not reading or typing away furiously at my computer, you can find me hitting on the tennis courts, singing Choral or Indian Classical music, or convincing my friends that my music taste is better than theirs.
Dr. Bryan Batch, a Duke endocrinologist and researcher, studies treating metabolic disorders (like diabetes) with non-pharmacological approaches. But, she says, her parents’ medical professions, and the hard work that went into them, resulted in her not wanting to pursue science at all as a child.
Bryan Batch MD
When she took biology in middle school however, it clicked. It didn’t feel like “the slog of math,” she says, because she enjoyed studying life in its different forms. This infatuation with science combined with a love for other people pushed her to pursue medicine.
Now, Dr. Batch focuses on racial disparities. She says that a huge issue with disparities, whether they involve race, poverty, food insecurity, educational opportunity, or health insurance, is that they are often driven by policy. “We are not trained to know how to affect change in policy in medical school — it’s not something we are taught. But I do think if physicians got more involved in politics and policy we would be able to make significant positive impact.”
What she does try to do is adapt to individual patient needs in the moment. Her work at Duke signifies what she, as a healthcare provider, can do within the time spent with patients to interact in the best way possible. For example, she can understand if someone has a literacy issue and adapt her methods of explanation so that their literacy doesn’t hinder their understanding. While it can be challenging for one person to change systemic issues or share lived experiences with people of different backgrounds, Dr. Batch makes every effort to create a comfortable environment where she is able to leave a positive impact.
These impacts have no doubt been affected by COVID-19, which Dr. Batch describes as one of the most challenging experiences in her twenty years of practicing medicine. Although telephone and video conferencing have been available for years, Dr. Batch explains that only now is there a drive to put them to use. “It was like someone came up behind you and just whacked you on the head,” she says — no warning, no time to get organized.
Dr. Batch feels lucky to be in endocrinology, where there is flexibility for remote visits. Yet, even when patients do have the chance to have an in-person visit, some don’t want to. If they do, the physical separation, masks, and face shields create a feeling of distance. Dr. Batch spends much of her clinical time at the Durham Veteran Affairs Hospital, across the street from Duke Hospital, where many hearing-impaired patients have difficulty understanding her words because her mask takes away the ability to read lips.
Dr. Batch says that even after the pandemic has passed, more than 30% of visits may remain over the telephone, which can give patients increased access to their doctors.
The challenges have infiltrated her research too, where now the only people she can bring in are those who need to visit the VA Medical Center for another reason anyway, like going to the eye doctor. Overall, she says, she has been surrounded by phenomenal people who rolled up their sleeves and said “let’s get it done.” Still, it has been exhausting.
The Durham Veterans Administration Medical Center, where Dr. Batch conducts most of her practice.
To her, family is everything, and she tries her best to stay in touch with the people who matter most as a way to get through it all.
Even before COVID-19, Dr. Batch has been intentional about living her life to the fullest and staying true to her core values. If that means rescheduling things at work to be with her kids, she is unapologetic. She chose endocrinology as a specialty in part because it’s very family-oriented, and she feels lucky to have colleagues who understand the flexibility she values. Her ultimate goal is to leave a mark on the world but she also wants her happiness to come from what matters, so she stays close to her big family and lots of friends.
While sacrifices are inevitable in any career, Dr. Batch tries not to make large ones on the homefront. She takes it day by day, week by week, she says, to make it such that “work” and “life” are in harmony as much as possible. It is easy to get caught up and have the years go by, one day realizing that the important people have pulled away. Dr. Batch is deliberate about making the time for these people, including her two children and husband.
Dr. Batch is a role model for young people, particularly for women of color. She shared an anecdote about her inattentive high school counselor, to whom she went for a signature on her college application list. Seeing Yale, Harvard, and Brown, he told her that she was “reaching too high.” Batch responded, “I’m not here for your opinion on this list. I’m here for you to sign this form..
She ended up at Yale.
She says she had the courage to talk back to the counselor because her parents instilled the idea of working hard and pushing higher. What matters, she says, is believing in yourself and surrounding yourself with people who believe in you.
Unfortunately, Batch said, underestimation by others resonated throughout her college, medical school, residency, and fellowship, because she is a woman or because she is Black.
At the end of the day, Dr. Bryan Batch never let other people define her experience but instead allowed her hard work to prove her value and propel her to always reach higher.
Guest Post by Viha Patel, Class of 2021, NC School of Science and Math
Imagine a live, health-focused version Shark Tank open to the public: presentations
from real health professionals,
presenting real innovations they developed
to address real health care issues.
And yes, there are real money awards
at stake.
At ten minutes ‘til show time, people gather in small groups
clothed in suits, business attire, and white coats. They chat in low voices. The
hum of comfortable conversation buzzes through the room. The sixth floor of the
Trent
Semans Center is quite the setting. Three sides of the room are
encapsulated in glass and you can easily see an expansive view of both Duke’s
West and Medical campuses, as well as luscious green trees comprising parts of
Duke’s Forest. Naturally, there is a glorious view of the Chapel, basked in
sunlight.
This light finds its way into the room to shine on various
research posters at the back displayed on a few rows of mobile walls. Though a
few strays meander through the stationary arrangements – stopping to look more
closely at particular findings – most people make their way into the room and
find a seat as the minutes dwindle away. The hum grows and there is a bit of anticipatory
energy among those readying themselves to present.
At three minutes after 10, the program director of the Duke
Institute for Health Innovation, Suresh Balu,
takes position at the front of the room, standing before the small stage at
center that is surrounded by lots of TV monitors. No seat in the room is a bad
one. Balu indicates that it is time to begin and the hum immediately
dissipates. He explains the general format of the event: six pitches total,
five minutes to present, eight minutes to answer questions from investors, a
show-of-hand interest from investors, and transition to the next pitch,
followed by deliberation and presentation of awards.
After a round of thanks, introduction of the emcee – Duke’s
Chief of Cardiology, Dr. Manesh Patel – the curtains opened – figuratively – on
Duke’s fifth annual Innovation
Jam.
Groups presented on the problems they were addressing, their
proposed innovations, and how the innovations worked. There was also
information about getting products into the market, varying economic analysis,
next steps or detailed goals for the projection of the projects, and analysis
of the investment they are currently seeking and for what purposes.
The first group pitched an idea about patient-centric blood
draw and suggest a device to plug into existing peripheral draws to reduce the frequent
poking and prodding that hospital patients often experience during their hospital
stay when blood is needed for lab tests. Next up was a group who designed an
intelligent microscope for automated pathology that has a programmable system and
uses machine learning to automate pathological blood analysis that is currently
highly time consuming. Third at bat was a group that made a UV light bag to
clean surgical drain bags that frequently become colonized with bacteria and
are quite frankly “nasty” – according to the presenter.
Batting cleanup was PILVAS – Peripherally Inserted Left
Ventricular Vent Anticoagulation System – which is a device that would be
accessory to VA
ECMO support to reduce thromboembolism and
stroke that are risks of ECMO. Fifth was the ReadyView and ReadyLift, a laparoscopic
tool set that is much cheaper than current laparoscopic tools and methods, and
because of its ability to be used with any USB compatible laptop, it would
increase access to laparoscopic surgery in countries that have a high need for
it. Last, but not least, was an innovation that is the first synthetic
biometric osteochondral
graft for knee cartilage repair that hopes to improve knee osteoarthritis surgical
care as the first hydrogel
with the same mechanical properties of cartilage.
Following a quick ten-minute break for investors to huddle
around and discuss who should win the awards – $15,000 for Best Innovation and
$15,000 for Best Presentation – the winners were announced. Drumroll, please.
ReadyView won Best Presentation and the synthetic
osteochondral graft won Best Innovation. A pair of representatives from
Microsoft were also in attendance – a first for the Innovation Jam – and
awarded SalineAI, the group who designed the intelligent microscope with an
independent award package.
Patel, the emcee, says we are in the midst of a fourth
industrial revolution.
“What is the biggest cinema in the world?” Patel asked.
“Netflix,” he says. Industries are reimagining themselves and healthcare is no
exception.
What is the best healthcare system of the future going to
look like? Of course, we really don’t know, but there are certainly people who
are already doing more than just think about it.
Experiencing cardiac arrest can be compared to being in a hot air balloon in a room that is rapidly filling with water. You are trapped, desperately aware of the danger you are in, and running out of time.
Andrew Landstrom, PHD, MD, shared this metaphor with his audience in the Duke Medicine Pavilion last Thursday, and a wave of empathy flooded through his listeners. He works as an Assistant Professor of Pediatrics in Duke University’s School of Medicine, and devotes his time and energy to studying the genetic and molecular causes of sudden cardiac death in the young.
Andrew Landstrom, PHD, MD (Photo from Duke Center for Applied Genomics and Precision Medicine)
For families of children who have died suddenly and unexpectedly, the worst thing of all is hearing their doctors say, “we have no idea why.” A third of sudden death cases in children have negative autopsies, which means these children die with no explanation.
When faced with an inconclusive autopsy, everyone wants answers. Why did these children die? How do we know it’s a problem with the heart? What can be done about it? What does it mean for the siblings of the child who died?
It has since been discovered that many of these unexplained deaths are actually the result of cardiac channelopathies, which are DNA mutations that cause ion channel defects in heart cell proteins. These mutations can mess up the electrical activity of the heart and cause a heart to beat in an irregular rhythm, which can have fatal consequences. Since this is a molecular problem, and not a structural one, it cannot be identified with a conventional autopsy, and requires a deeper level of genetic and molecular analysis.
One type of channelopathy is a condition known as CPVT, which is short for catecholaminergic polymorphic ventricular tachycardia. This potentially life-threatening genetic disorder is the result of a point mutation in the genome, which means that one tiny nucleotide being changed in the DNA can lead to the single most fatal arrhythmia (irregular heart rhythm) known.
Sixty percent of children suffering from CPVT have a mutation in their RYR2 gene. This gene encodes for a protein that is found in cardiac muscle, and is a key player in how calcium is processed in heart cells. The mutated version of this gene results in proteins that let way too much calcium flood the cell, which can cause fatal changes in heart rhythm.
Dr. Landstrom has been using genome research to identify and explain sudden cardiac death in children, but the human genome doesn’t always provide straightforward answers. The problem is, a mutation in the RYR2 gene doesn’t always mean a person will have CPVT, and having an incidental RYR2 gene is much more common than being diagnosed with CPVT. Dr. Landstrom is studying this gene to try to figure out which variants are pathologic, and which are physiological.
“The human genome is a lot more confusing than I think I gave it credit for, and we’re just learning to deal with that confusion now,” he admitted to his audience Feb. 14.
The Components of the Human Genome (photo from NHS National Genetics and Genomics Education Centre)
If a variant is falsely identified as pathologic, a patient will be given incorrect therapies, and suffer through unnecessary procedures. However, if a variant is falsely identified as physiological, and the patient isn’t given the necessary treatment, there will be no mitigation of the patient’s life threatening disease. Neither of these are good outcomes, so it’s very important to get it right. The current models for predicting pathogenicity are poor, and Dr. Landstrom is looking to design new model that will be able to avoid the personal, subjective opinions of human doctors and determine if a variant is pathologic or not.
Could serotonin levels be used to predict an infant’s vulnerability to SIDS? (photo from Elmedir, Wikimedia Commons)
Another area that is of interest to Dr. Landstrom is the problem of Sudden Infant Death Syndrome (SIDS), which affects about six in every 10,000 infants, and cannot be diagnosed before death. He is on the search for a biomarker that would be able to predict an infant’s vulnerability to SIDS, and thinks that these deaths may be related to elevated levels of serotonin. Finding a marker like this would allow doctors to save many healthy infants from unexplained death. Dr. Landstrom knows its not easy research and admitted “we have to fail — we are meant to fail,” on the path to success. He is very aware of both the ethical complexity and the exciting implications of genome research at Duke, and committed to converting his research into patient care.
X-ray vision just got cooler. A technique developed in recent years boosts researchers’ ability to see through the body and capture high-resolution images of animals inside and out.
This special type of 3-D scanning reveals not only bones, teeth and other hard tissues, but also muscles, blood vessels and other soft structures that are difficult to see using conventional X-ray techniques.
There, the specimens are stained with an iodine solution that helps soft tissues absorb X-rays, then placed in a micro-CT scanner, which takes thousands of X-ray images from different angles while the specimen spins around. A computer then stitches the scans into digital cross sections and stacks them, like slices of bread, to create a virtual 3-D model that can be rotated, dissected and measured as if by hand.
Here’s a look at some of the images they’ve taken:
See-through shrimp
If you get flushed after a workout, you’re not alone — the Caribbean anemone shrimp does too.
Recent Duke Ph.D. Laura Bagge was scuba diving off the coast of Belize when she noticed the transparent shrimp Ancylomenes pedersoni turn from clear to cloudy after rapidly flipping its tail.
To find out why exercise changes the shrimp’s complexion, Bagge and Duke professor Sönke Johnsen and colleagues compared their internal anatomy before and after physical exertion using diceCT.
In the shrimp cross sections in this video, blood vessels are colored blue-green, and muscle is orange-red. The researchers found that more blood flowed to the tail after exercise, presumably to deliver more oxygen-rich blood to working muscles. The increased blood flow between muscle fibers causes light to scatter or bounce in different directions, which is why the normally see-through shrimp lose their transparency.
Peer inside the leg of a mouse
Duke cardiologist Christopher Kontos, M.D., and MD/PhD student Hasan Abbas have been using the technique to visualize the inside of a mouse’s leg.
The researchers hope the images will shed light on changes in blood vessels in people, particularly those with peripheral artery disease, in which plaque buildup in the arteries reduces blood flow to the extremities such as the legs and feet.
The micro-CT scanner at Duke’s Shared Materials Instrumentation Facility made it possible for Abbas and Kontos to see structures as small as 13 microns, or a fraction of the width of a human hair, including muscle fibers and even small arteries and veins in 3-D.
Take a tour through a tree shrew
DiceCT imaging allows Heather Kristjanson at the Johns Hopkins School of Medicine to digitally dissect the chewing muscles of animals such as this tree shrew, a small mammal from Southeast Asia that looks like a cross between a mouse and a squirrel. By virtually zooming in and measuring muscle volume and the length of muscle fibers, she hopes to see how strong they were. Studying such clues in modern mammals helps Kristjanson and colleagues reconstruct similar features in the earliest primates that lived millions of years ago.
Try it for yourself
Students and instructors who are interested in trying the technique in their research are eligible to apply for vouchers to cover SMIF fees. People at Duke University and elsewhere are encouraged to apply. For more information visit https://smif.pratt.duke.edu/Funding_Opportunities, or contact Dr. Mark Walters, Director of SMIF, via email at mark.walters@duke.edu.
Located on Duke’s West Campus in the Fitzpatrick Building, the SMIF is a shared use facility available to Duke researchers and educators as well as external users from other universities, government laboratories or industry through a partnership called the Research Triangle Nanotechnology Network. For more info visit http://smif.pratt.duke.edu/.
