Category: Biomedical Engineering Page 1 of 7

Only Mostly Dead? The Evolving Ethics of Evaluating Death

On March 31, 2023

In Behavior/Psychology, Biology, Biomedical Engineering, Cardiology, Lecture, Medicine, Religion, Responsible Conduct

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.

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?

Legal and professional standards favor the idea that testing for DNC likely falls under the category of implied consent, which assumes that a person would want reasonable medical care in the event of unconsciousness. In fact, 80% of neurologists think that getting consent for these evaluations is unnecessary.

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

What is it like to Direct a Large, Externally-Funded Research Center?

By Meghna Datta

On January 30, 2023

In Artificial Intelligence, Biomedical Engineering, Chemistry, Faculty, Science Communication & Education

What are the trials and tribulations one can expect? And conversely, what are the highlights? To answer these questions, Duke Research & Innovation Week kicked off with a panel discussion on Monday, January 23.

The panel

Moderated by George A. Truskey, Ph.D, the Associate Vice President for Research & Innovation and a professor in the Department of Biomedical Engineering, the panelists included…

Claudia K. Gunsch, Ph.D., a professor in the Departments of Civil & Environmental Engineering, Biomedical Engineering, and Environmental Science & Policy. Dr. Gunsch is the director of the NSF Engineering Research Center for Microbiome Engineering (PreMiEr) and is also the Associate Dean for Duke Engineering Research & Infrastructure.

Yiran Chen, Ph.D., a professor in the Department of Electrical & Computer Engineering. Dr. Chen is the director of the NSF AI Institute for Edge Computing (Athena).

Stephen Craig, Ph.D., a professor in the Department of Chemistry. Dr. Craig is the director of the Center for the Chemistry of Molecularly Optimized Networks (MONET).

The centers

As the panelists joked, a catchy acronym for a research center is almost an unspoken requirement. Case in point: PreMiEr, Athena, and MONET were the centers discussed on Monday. As evidenced by the diversity of research explored by the three centers, large externally-funded centers run the gamut of academic fields.

PreMiEr, which is led by Gunsch, is looking to answer the question of microbiome acquisition. Globally, inflammatory diseases are connected to the microbiome, and studies suggest that our built environment is the problem, given that Americans spend on average less than 8% of time outdoors. It’s atypical for an Engineering Research Center (ERC) to be concentrated in one state but uniquely, PreMieR is. The center is a joint venture between Duke University, North Carolina A&T State University, North Carolina State University, the University of North Carolina – Chapel Hill and the University of North Carolina – Charlotte.

PreMiEr – not to be confused with the English Premier League

Dr. Chen’s Athena is the first funded AI institute for edge computing. Edge computing is all about improving a computer’s ability to process data faster and at greater volumes by processing data closer to where it’s being generated. AI is a relatively new branch of research, but it is growing in prevalence and in funding. In 2020, 7 institutes looking at AI were funded by the National Science Foundation (NSF), with total funding equaling 140 million. By 2021, 11 institutes were funded at 220 million – including Athena. All of these institutes span over 48 U.S states.

Athena, or the Greek goddess of wisdom, is a fitting name for a research center

MONET is innovating in polymer chemistry with Stephen Craig leading. Conceptualizing polymers as operating in a network, the center aims to connect the behaviors of a single chemical molecule in that network to the behavior of the network as a whole. The goal of the center is to transform polymer and materials chemistry by “developing the knowledge and methods to enable molecular-level, chemical control of polymer network properties for the betterment of humankind.” The center has nine partner institutions in the U.S and one internationally.

Key takeaways

Research that matters

Dr. Gunsch talked at length about how PreMiEr aspires to pursue convergent research. She describes this as identifying a large, societal challenge, then determining what individual fields can “converge” to solve the problem.

Because these centers aspire to solve large, societal problems, market research and industry involvement is common and often required in the form of an industry advisory group. At PreMiEr, the advisory group performs market analyses to assess the relevance and importance of their research. Dr. Chen also remarked that there is an advisory group at Athena, and in addition to academic institutions the center also boasts collaborators in the form of companies like Microsoft, Motorola, and AT&T.

Dr. Chen presenting on Athena’s partner institutions at Monday’s talk.

Commonalities in structure

Most research centers, like PreMiEr, Athena, and MONET, organize their work around pillars or “thrusts.” This can help to make research goals understandable to a lay audience but also clarifies the purpose of these centers to the NSF, other funding bodies, host and collaborating institutions, and the researchers themselves.

How exactly these goals are organized and presented is up to the center in question. For example, MONET conceptualizes its vision into three fronts – “fundamental chemical advances,” “conceptual advances,” and “technological advances.”

At Athena, the research is organized into four “thrusts” – “AI for Edge Computing,” “AI-Powered Computer Systems,” “AI-Powered Networking Systems,” and “AI-Enabled Services and Applications.”

Meanwhile, at PreMiEr, the three “thrusts” have a more procedural slant. The first “thrust” is “Measure,” involving the development of tracking tools and the exploration of microbial “dark matter.” Then there’s “Modify,” or the modification of target delivery methods based on measurements. Finally, “Modeling” involves predictive microbiome monitoring to generate models that can help analyze built environment microbiomes.

A center is about the people

“Collaborators who change what you can do are a gift. Collaborators who change how you think are a blessing.”
Dr. stephen craig

All three panelists emphasized that their centers would be nowhere without the people that make the work possible. But of course, humans complicate every equation, and when working with a team, it is important to anticipate and address tensions that may arise.

Dr. Craig spoke to the fact that successful people are also busy people, so what may be one person’s highest priority may not necessarily be another person’s priority. This makes it important to assemble a team of researchers that are united in a common vision. But, if you choose wisely, it’s worth it. As Dr. Craig quipped on one of his slides, “Collaborators who change what you can do are a gift. Collaborators who change how you think are a blessing.”

In academia, there is a loud push for diversity, and research centers are no exception. Dr. Chen spoke about Athena’s goals to continue to increase their proportions of female and underrepresented minority (URM) researchers. At PreMiEr, comprised of 42 scholars, the ratio of non-URM to URM researchers is 83-17, and the ratio of male to female researchers is approximately 50-50.

In conclusion, cutting-edge research is often equal parts thrilling and mundane, as the realities of applying for funding, organizing manpower, pushing through failures, and working out tensions with others sets in. But the opportunity to receive funding in order to start and run an externally-funded center is the chance to put together some of the brightest minds to solve some of the most pressing problems the world faces. And this imperative is summarized well by the words of Dr. Craig: “Remember: if you get it, you have to do it!”

Post by Megna Datta, Class of 2023

The Need for Title IX in STEM

By Jakaiyah Franklin

On October 10, 2022

In Behavior/Psychology, Biology, Biomedical Engineering, Engineering, Faculty, Science Communication & Education, Statistics, Students

The Panel:

In recognition of the 50th anniversary of Title IX, which was intended to make sex discrimination in education illegal, a panel of Duke women met on Thursday, September 29 to talk about whether Title IX could change STEM, (Science Technology, Engineering and Math). Unfortunately, the answer was not simple.

But just through the sharing of the statistics relevant to this problem, the stories, and their solutions, one could start to understand the depth of this problem. One takeaway was that all women in STEM, whether they be student, professor, or director, have faced gender discrimination.

The student panelists after a successful forum

Down to the Statistics:

Dr. Sherryl Broverman, a Duke professor of the practice in biology and global health, gave the audience an overview. Of all of Duke’s regular ranked, tenured-track faculty, only 30% are women. In contrast, women make up 60% of the non-tenure track faculty. Dr. Broverman said men are promoted in Duke at a higher frequency. This is especially seen with the associate professor title because, on average, men are associate professors for 4 to 5 years; whereas women are associate professors for up to 9 years.

To give an example, senior Nasya Bernard-Lucien, a student panelist who studied Biomedical Engineering and then Neuroscience informed me that she has had a total of two women professors in her entire STEM career. This is a common pattern here at Duke because taking a STEM class that has a woman professor is as rare as finding a non-stressed Duke student.

Dr. Kisha Daniels (left) and Dr. Whitney McCoy (right)

The Beginning of a Girl’s Career in STEM

This disproportionate demographic of women professors in STEM is not a new occurrence with Duke or the rest of the world because the disproportion of women in STEM can be seen as early as middle school. Two of the student panelists noted that during their middle school career, they were not chosen to join an honors STEM program and had to push their school’s administration when they asked to take more advanced STEM classes.

Dr. Kisha Daniels, an associate professor of the practice in education said on a faculty panel that one of her daughters was asked by her male peers, “what are you doing here?” when she attended her middle school’s honors math class. Gender discrimination in STEM begins in early childhood, and it extends its reach as long as women continue to be in a STEM field, and that is particularly evident here at Duke.

Women in STEM at Duke

The last panel of the Title IX @ 50 event was the student panel which consisted of undergraduate and graduate students. Even though they were all from different backgrounds, all acknowledged the gender disparity within STEM classes.

Student Bentley Choi said she was introduced to this experience of gender discrimination when she first arrived at Duke from South Korea. She noted how she was uncomfortable and how it was hard to ask for help while being one of the few women in her physics class. One would have hoped that Duke would provide a more welcoming environment to her, but that is not the case, and it is also not an isolated incident. Across the panel, all of the women have experienced discomfort in their STEM classes due to being one of the few girls in there.

The Future of Title IX

How can Title IX change these issues? Right now, Title IX and STEM are not as connected as they need to be; in fact, Title IX, in the past, has been used to attack programs created to remedy the gender disparity in STEM. So, before Title IX can change STEM, it needs to change itself.

Title IX needs to address that this problem is a systemic issue and not a standalone occurrence. However, for this change to happen, Dr. Whitney McCoy, a research scientist in Child and Family Policy, said it perfectly, “we need people of all backgrounds to voice the same opinion to create policy change.”

So, talk to your peers about this issue because the more people who understand this situation, the chances of creating a change increases. The last thing that needs to occur is that 50 years in the future, there will be similar panels like this one that talk about this very issue, and there are no panels that talk about how we, in the present, fixed it.

Post by Jakaiyah Franklin, Class of 2025

Jason Dinh Once Collected Cicadas, Now He Researches Snapping Shrimp

By Cydney Livingston

On March 14, 2022

In Animals, Biology, Biomedical Engineering, Students

Jason Dinh’s research career began unintentionally with a semester at Duke’s Marine Lab. A current fourth-year PhD candidate in Duke’s Biology Department, Dinh ventured to the Marine Lab for a mental reset in the spring of his sophomore year as a Duke undergraduate. “While I was there, I realized that people can just get paid to ask questions about how the world works,” Dinh told me, “And I really didn’t know that was a thing that you could do.” Maybe this is what I want to do, he thought.

Jason Dinh, fourth-year PhD candidate in Duke Biology Department

Dinh spent his remaining undergraduate summers investigating the impacts of soundscapes on oyster and fish larvae development. Now, he studies snapping shrimp – a small oceanic species that is “one of the biggest sound producers in the ocean,” bested only by toothed whales.

Dinh first became aware of snapping shrimp during his undergraduate research. He told me that you can find snapping shrimp “basically anywhere, from the equator up to Virginia or maybe North Carolina.” While conducting research on ocean sounds and oyster and fish larvae, Dinh noticed the frequent snapping sounds of the snapping shrimp when he placed underwater microphones. “We didn’t really know what they were doing,” Dinh said.

An image of a species of snapping shrimp like Dinh works with.

The male snapping shrimp is asymmetrical with one very large claw and one that is regular-sized. The large claw has a tiny hook on the end and when the shrimp clamps down or “snaps” the claw, the top half latches into the bottom, shooting out an air bubble at sixty miles per hour that “essentially boils the water behind it,” producing the loud snapping noise in its wake. When many shrimp are snapping at once, it sounds almost like the frying grease when cooking bacon, Dinh tells me. (Click here to watch a video of the snapping shrimp in action.)

At first, researchers suspected the bubble from the snap was a means of stunning prey, but “It turns out that snapping shrimp also fight each other,” Dinh said. And when fighting, male snapping shrimp shoot the air bubbles at one another. The bigger the shrimp’s body size, the larger the snapping claw and the louder the snapping sound.

An image of two snapping shrimp facing off.

Going into his PhD, Dinh wanted to continue his undergraduate work in acoustics and figure out novel ways animals were producing sounds. His investigation of the snapping shrimp took him in new directions, however. Through his projects, Dinh has conducted work on the costs and benefits that keep the claw size as an honest indicator of shrimp size in competitions and approached a plethora of questions from the physiological and physical mechanisms of sending and assessing snaps, up to the evolutionary implications of the sexual selection for claw size.

“I don’t think I really knew I wanted to do research until right before I applied for grad school,” Dinh said at the beginning of our conversation. He remembers being a child curious about nature and bringing in “hundreds of cicadas” and “random critters into the house.” A few decades later and his research is centered on living creatures, which is both a rewarding and tricky process.

“Live animals are going to do what live animals want to do,” Dinh stated simply. “One thing my advisor always tells us is that you don’t get to tell the animal what to do, it tells you what you are going to do.” This has certainly held true for Dinh. While he has had many detailed and well-planned experimental ideas, he says he’s ultimately ended up doing what the “animals told him they were willing and happy to do in the lab.” However, along the way Dinh basks in the “joys in tiny discoveries in the process of research.”

I asked Dinh how he ended up at Duke in the first place and why he chose to stick around for his PhD. “So I ended up at Duke for undergrad because I really liked basketball, which is a really bad reason to choose a school.” But ultimately, this choice “paid off really well because my first year was the last year we won the National Championship,” Dinh said. He traveled to Indianapolis for the event which he says was the “best basketball game of [his] life.”

Dinh decided to do his PhD at Duke because of how deeply he admires his advisor, Sheila Patek (PhD), as a scientist. “I think she’s just a wonderful, passionate, passionate defender of basic science and just doing science because more knowledge is good for society,” Dinh elaborated, “Sheila’s also a staunch and fearless advocate for her students.” Though Dinh considers himself an “outlier” in the lab – primarily a behavioral ecologist in a lab of researchers investigating biomechanics – the way that Patek approaches science is the way that he wants to approach science as well.

Like Alice falling down the rabbit hole in *Alice in Wonderland,* Dinh compares the diving explorations of science as being a “professional rabbit holer.” Science consists of picking questions further and further apart and leaning into research findings to tunnel into topics.

“I feel like science is being a professional rabbit holer,” Dinh stated. While Dinh is on the pursuit of the weapon size and fighting strategies of snapping shrimp, he doesn’t know exactly where he wants to head next, following the completion of his PhD. Like the snapping shrimp that collect information about their opponents to make an informed decision about engaging in fights, Dinh says he is conducting a sort of Bayesian method of his own. He’s assessing his experiences as he goes and sorting out the right next step for him.

A fan of the meditative art of writing, long morning walks with his dog, and reality TV, Dinh appreciates being “on the frontier of what we know” and is sure to let his deep-rooted curiosity about the natural world continue to guide him.

Materials For a Changing World… What is That?

By Skylar Hughes

On February 10, 2022

In Biology, Biomedical Engineering, Chemistry, Faculty

Everything in our world is made from materials, meaning life is enabled by material development and efficiency. In today’s society, from constant technological revolution to the global pandemic, life as we know it is always evolving. But as the world around us evolves, the materials around us also need to evolve to keep up with current demands. But how? As a part of Duke University’s annual Research Week on Feb. 3, researchers from a multitude of practices offered their wisdom and research.

Moderated by Dr. Catherine L. Brinson, Ph.D., the panel hosted three Duke Scholars and their research on ‘Materials for a Changing World’. “The development of new materials can really be key in solving some of the more critical challenges of our time,” Brinson maintained.

Dr. David Beratan explaining his research on bio-machines and their material efficiency.

The first scholar to present was R.J Reynolds distinguished professor of chemistry, Dr. David N Beratan, Ph.D. His research concerns the transition from soft, wet, and tiny research machines to more durable, long-term research machines in the science field. “The machines of biology tend to be stochastic and floppy rather than deterministic and hard,” Beratan began. “They’re messy and there are lots of moving parts. They’re intrinsically noisy and error-prone, etc…They’re very different from the kinds of things you see under the hood of your car, and we’d really like to understand how they work and what lessons we might derive from them for our world.” His complex research and research group have aided in bridging the gap in knowledge regarding the transition of biological functional machines to synthetic ones.

Dr.Rubinstein presenting his research on materials at Duke’s Pratt School of Engineering in 2019.

The panel continued with Aleksandar S. Vesic Distinguished Professor in mechanical engineering, Dr. Michael Rubinstein, Ph.D. His research involves the development of self-healing materials across multiple spectrums. “What you want to think about is materials that can heal themselves,” he stated. “If there’s a crack or a failure in a material, we would like the material to heal itself without external perturbation involvement. So it could be done by the other diffusion of molecules across some physical approaches, or by a chemical approach where you have bonds that were broken to the form.” His research on this possibility has made strides in the scientific field, especially in a time of such ecological stress and demand for materials.

Dr. Segura talking with Dr. Brinson on her research involving self-healing materials.

The panel concluded with biomedical engineering professor Dr. Tatiana Segura, Ph.D. Segura talked about work they are doing at their lab regarding materials that can be used to heal the human body after damage or injury. She began by mentioning that “we are a materials lab and that’s what we’re interested in designing. So what are we inspired by? Well, we are really inspired by the ability of our body to heal.” At her lab, a primary motivation is healing disabilities after a stroke. “Sometimes you have something that you deal with for a long time no matter how your body healed. And that inspires us to consider how do we actually engage this process with materials to make it go better and actually make our body heal in a way that we can promote repair and regeneration.” Understanding this process is a complex one, she explained, but one that she believes is crucial in understanding the design of the material.

‘Materials for a Changing World’ was yet another extremely powerful speaker series offered this year during Duke Research Week. Our world is changing, and our materials need to keep up. With the help of these experts, material innovation has a bright future.

LowCostomy: the Low-Cost Colostomy Bag for Africa

By Camila Cordero

On January 11, 2022

In Biology, Biomedical Engineering, Cancer, Engineering, Environment/Sustainability, Global Health, Medicine, Students

It’s common for a Pratt engineering student like me to be surrounded by incredible individuals who work hard on their revolutionary projects. I am always in awe when I speak to my peers about their designs and processes.

So, I couldn’t help but talk to sophomore Joanna Peng about her project: LowCostomy.

Rising from the EGR101 class during her freshman year, the project is about building a low-cost colostomy bag — a device that collects excrement outside the patient after they’ve had their colon removed in surgery. Her device is intended for use in under-resourced Sub-Saharan Africa.

“The rates in colorectal cancer are rising in Africa, making this a global health issue,” Peng says. “This is a project to promote health care equality.”

The solution? Multiple plastic bags with recycled cloth and water bottles attached, and a beeswax buffer.

“We had to meet two criteria: it had to be low cost; our max being five cents. And the second criteria was that it had to be environmentally friendly. We decided to make this bag out of recycled materials,” Peng says.

For now, the team’s device has succeeded in all of their testing phases. From using their professor’s dog feces for odor testing, to running around Duke with the device wrapped around them for stability testing, the team now look forward to improving their device and testing procedures.

“We are now looking into clinical testing with the beeswax buffer to see whether or not it truly is comfortable and doesn’t cause other health problems,” Peng explains.

_{Poster with details of the team’s testing and procedures}

Peng’s group have worked long hours on their design, which didn’t go unnoticed by the National Institutes of Health (NIH). Out of the five prizes they give to university students to continue their research, the NIH awarded Peng and her peers a $15,000 prize for cancer device building. She is planning to use the money on clinical testing to take a step closer to their goal of bringing their device to Africa.

Peng shows an example of the beeswax port buffer (above). The design team of Amy Guan, Alanna Manfredini, Joanna Peng, and Darienne Rogers (L-R).

“All of us are still fiercely passionate about this project, so I’m excited,” Peng says. “There have been very few teams that have gotten this far, so we are in this no-man’s land where we are on our own.”

She and her team continue with their research in their EGR102 class, working diligently so that their ideas can become a reality and help those in need.

Post by Camila Cordero, Class of 2025

Nobel Laureate Dr. Jennifer Doudna and Groundbreaking Applications of CRISPR

By Anna Gotskind

On November 29, 2021

In Biology, Biomedical Engineering, Chemistry, Genetics/Genomics, Global Health, Lecture, Medicine

In 2011, Dr. Jennifer Doudna began studying an enzyme called Cas9. Little did she know, in 2020 she would go on to win the Nobel Prize in Chemistry along with Emmanuelle Charpentier for discovering the powerful gene-editing tool, CRISPR-Cas9. Today, Doudna is a decorated researcher, the Li Ka Shing Chancellors Chair, a Professor in the Department of Chemistry and Molecular as well as Cell Biology at the University of California Berkeley, and the founder of the Innovative Genomics Institute.

Doudna was also this year’s speaker for the MEDx Distinguished Lecture in October where she delivered presented on “CRISPR: Rewriting DNA and the Future of Humanity.”

“CRISPR is a system that originated in bacteria as an adaptive immune system” Doudna explained.

Dr. Jennifer Doudna holding the Nobel Prize in Chemistry

When bacterial cells are infected by viruses those viruses inject their genetic material into the cell. This discovery, a couple decades ago, was the first indication that there may be ways to apply bacteria’s ability to acquire genetic information from viruses.

CRISPR itself was discovered in 1987 and stands for “Clustered Regularly Interspaced Short Palindromic Repeats.” Doudna was initially studying RNA when she discovered Cas-9, a bacterial RNA-guided endonuclease and one of the enzymes produced by the CRISPR system. In 2012, Doudna and her colleagues found that Cas9 used base pairing to locate and splice target DNAs when combined with a guide RNA.

Essentially, they designed guide RNA to target specific cells. If those cells had a CRISPR system encoded in their genome, the cell is able to make an RNA copy of the CRISPR locus. Those RNA molecules are then processed into units that each include a sequence derived from a virus and then assemble with proteins. This RNA protein then looks for DNA sequences that match the sequence in the RNA guide. Once a match occurs, Cas9 is able to bind to and cut the DNA, leading to the destruction of the viral genome. The cutting of DNA then triggers DNA repair allowing gene editing to occur.

“This system has been harnessed as a technology for genome editing because of the ability of these proteins, these CRISPR Cas-p proteins, to be programmed by RNA molecules to cut any desired DNA sequence,” Doudna said.

Jennifer Doudna holding a Model of CRISPR-cas9

While continuing to conduct research, Doudna has also been focused on applying CRISPR in agriculture and medicine. For agriculture, researchers are looking to make changes to the genomes of plants in order to improve drought resistance and crop protection.

CRISPR-cas9 is also being applied in many clinical settings. In fact, when the COVID-19 pandemic hit, Doudna along with several colleagues organized a five-lab consortium including the labs of Dan Fletcher, Patrick Hsu, Melanie Ott, and David Savage. The focus was on developing the Cas13 system to detect COVID-19. Cas13 is a class of proteins, that are RNA guided, RNA targeting, CRISPR enzymes. This research was initially done by one of Doudna’s former graduate students, Alexandra East-Seletsky. They discovered that if the reporter RNA is is paired with enzymes that have a quenched fluorophore pair on the ends, when the target is activated, the reporter is cleaved and a fluorescent signal is released.

One study out of the Melanie Ott group demonstrated that Cas13 can be used to detect viral RNA. They are hoping to apply this as a point-of-care diagnostic by using a detector as well as a microfluidic chip which would allow for the conduction of these chemical reactions in much smaller volumes that can then be read out by a laser. Currently, the detection limit is similar to what one can get with a PCR reaction however it is significantly easier to run.

Graphical Abstract of Cas13 Research by the Melanie Ott lab

“And this is again, not fantasy, we’ve actually had just fabricated devices that will be sitting on a benchtop, and are able to use fabricated chips that will allow us to run the Cas13 chemistry with either nasal swab samples or saliva samples for detection of the virus,” Doudna added.

Another exciting development is the use of genome editing in somatic cells. This involves making changes in the cells of an individual as opposed to the germline. One example is sickle cell disease which is caused by a single base pair defect in a gene. Soon, clinicians will be able to target and correct this defect at the source of the mutation alleviating people from this devastating illness. Currently, there are multiple ongoing clinical trials including one at the Innovative Genomics Institute run by Doudna. In fact, one patient, Victoria Gray, has already been treated for her sickle cell disease using CRISPR.

Victoria Gray being treated for Sickle Cell Anemia
*Meredith Rizzo/NPR*

“The results of these trials are incredibly exciting and encouraging to all of us in the field, with the knowledge that this technology is being deployed to have a positive impact on patient’s lives,” Doudna said.

Another important advancement was made last summer involving the use of CRISPR-based therapy to treat ATR, a rare genetic disease that primarily affects the liver. This is also the first time CRISPR molecules will be delivered in vivo.

In just 10 years CRISPR-cas9 has gone from an exciting discovery to being applied in several medical and agricultural settings.

“This powerful technology enables scientists to change DNA with precision only dreamed of a few years ago,” said MEDx director Geoffrey Ginsburg, a Professor of Medicine at Duke. “Labs worldwide have redirected the course of research programs to incorporate this new tool, creating a CRISPR revolution with huge implications across biology and medicine.”

Examples of further CRISPR-Cas9 research can also be found in the Charles Gersbach lab here at Duke.

Duke has 38 of the World’s Most Highly-Cited Scientists

By Karl Bates

On November 16, 2021

In Behavior/Psychology, Biology, Biomedical Engineering, Cardiology, Climate/Global Change, Engineering, Environment/Sustainability, Faculty, Immunology, Medicine, Neuroscience, Physics

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!

Biology and Biochemistry

Charles A. Gersbach

Robert J. Lefkowitz

Clinical Medicine

Pamela S. Douglas

Christopher Bull Granger

Adrian F. Hernandez

Manesh R.Patel

Eric D. Peterson

Cross-Field

Richard Becker

Antonio Bertoletti (NUS)

Yiran Chen

Stefano Curtarolo

Derek J. Hausenloy (NUS)

Ru-Rong Ji

Jie Liu

Jason W. Locasale

David B. Mitzi

Christopher B. Newgard

Ram Oren

David R. Smith

Heather M. Stapleton

Avner Vengosh

Mark R. Wiesner

Environment and Ecology

Emily S. Bernhardt

Geosciences

Drew T. Shindell

Immunology

Edward A. Miao

Microbiology

Barton F. Haynes

Neuroscience and Behavior

Quinn T. Ostrom

Pharmacology and Toxicology

Robert J. Lefkowitz

Plant and Animal Science

Xinnian Dong

Sheng Yang He

Philip N. Benfey

Psychiatry and Psychology

Avshalom Caspi

E. Jane Costello

Honalee Harrington

Renate M. Houts

Terrie E. Moffitt

Social Sciences

Michael J. Pencina

Bryce B. Reeve

John W. Williams

Post by Karl Bates

How Freshman Engineers Solve Real-World Problems in EGR 101

By Camila Cordero

On November 2, 2021

In Biomedical Engineering, Computers/Technology, Engineering, Lecture, Students

The sound of drills whirring, the smell of heated plastic from the 3D printers, and trying to see through foggy goggles. As distracting as it may sound, this is a normal day for a first-year engineering student (including myself) in class.

During these past few weeks, freshmen engineers have been brainstorming and building projects that have piqued their interest in their EGR101 class. Wanting to know more, I couldn’t help but approach Amanda Smith, Jaden Fisher, Myers Murphy, and Christopher Cosby, and ask about their goal to make an assistive device to help people with limited mobility take trash cans up an inclined driveway that is slippery and wet.

“Our client noticed the problem in his neighborhood in Chapel Hill with its mainly-elderly population, and asked for a solution to help them,” Fisher says. “We thought it would be cool to give back to the community.” Their solution: a spool with a motor.

Coming from a mechanical engineering mindset, the team came up with the idea to create a spool-like object that has ropes that connect to the trash can, and with a motor, it would twist, pull up the trash can, and then slowly unroll it back down the driveway. As of now, they are currently in the prototyping phase, but they are continuing to work hard nonetheless.

“For now, our goal is to slowly begin to scale up and hopefully be able to make it carry a full trash can. Maybe one day, our clients can implement it in real life and help the people that need it,” says Smith.

All of this planning and building is part of the Engineering Design & Communication class, also known as EGR 101, which all Pratt students have to take in their first year. Students are taught about the engineering design process, and then assigned a project to implement what they learned in a real life situation by the end of the semester.

“This is a very active learning type of class, with an emphasis on the design process,” says Chip Bobbert, one of the EGR 101 professors. “We think early exposure will be something that will carry forward with student’s careers.”

Not only do the students deal with local clients, but some take on problems from nationwide companies, like Vivek Tarapara, Will Denton, Del Cudjoe, Ken Kalin, Desmond Decker, and their client, SKANSKA, a global construction company.

“They have an issue scheduling deliveries of materials to their subcontractors, which causes many issues like getting things late, dropped in the wrong areas, etc.,” Tarapara explains. “There is a white board in these construction sites, but with people erasing things and illegible handwriting, we want to make a software-based organizational tool so that everyone involved in the construction is on the same page.”

Watching the team test their code and explain to me each part of their software, I see they have successfully developed an online form that can be accessed with a QR code at the construction site or through a website. It would input the information on a calendar so that users can see everything at any time, where anyone can access it, and a text bot to help facilitate the details.

“We are currently still working on making it look better and more fluid, and make a final solution that SKANSKA will be satisfied with,” Denton says, as he continues to type away at his code.

_{Vivek Tarapara (left) and Will Denton (right) working on their code and text bot}

One final project, brought up by Duke oral surgeon Katharine Ciarrocca, consists of students Abigail Paris, Fernando Rodriguez, Konur Nordberg, and Camila Cordero (hey, that’s me!), and their mouth prop design project.

After many trials and errors, my team has created a solution that we are currently in the works of printing with liquid silicone rubber. “We have made a bite block pair, connected by a horizontal prism with a gap to clip on, as well as elevated it to give space for the tongue to rest naturally,” Paris elaborates.

The motivation behind this project comes from COVID-19. With the increase of ICU patients, many receiving endotracheal intubations, doctors have come to realize that these intubations are causing other health issues such as pressure necrosis, biting on the tongue, and bruising from the lip. Dr. Ciarrocca decided to ask the EGR 101 class to come up with a device to help reduce such injuries.

_{Medium-fidelity prototype of mouth prop inside of mouth model with an endotracheal intubation tube}

Being part of this class and having first-hand look at all the upcoming projects, it’s surprising to see freshman students already working on such real-world problems.

“One of the things I love about engineering and this course is that we’re governed by physics and power, and it all comes to bear,” says Steven McClelland, another EGR 101 professor. “So this reckoning of using the real world and beginning to take theory and take everything into consideration, it’s fascinating to see the students finally step into reality.”

Not only does it push freshmen to test their creativity, but it also creates a sense of teamwork and bonding between classmates, even in the most unordinary class setting.

“I look around the room and there’s someone wearing a pool noodle, another boiling alcohol, and another trying to measure the inside of their mouth,” says Bobberts as he scans the area quickly. “I’m excited to see people going and doing stuff together.”

Post by Camila Codero, Class of 2025

New Blogger Nidhi Srivaths: Attracted by Words

By Nidhi Srivaths

On October 7, 2021

In Biomedical Engineering, Science Communication & Education, Students

Before I moved to the U.S, the concept of a “Starbucks name” was foreign to me, but after six cups of coffee that read everything from “Nemo” to just an unintelligible scrawl, I understood the need for it. Back home in India, my name was quite common, but having to repeat myself multiple times only to still be misheard made suddenly made feel unusually unique.

Speech can often be tricky, and growing up in a family that speaks four languages interchangeably, I’ve always been acutely aware of that. Missing a tongue roll on the word for “tell” in Kannada makes it dinner-table inappropriate, and a small vowel slip in Telugu can completely alter conversational context. I lived in India’s objectively best city, Hyderabad, that has its special version of Hindi, which was unacceptable in conversation with my mother’s own dialect. Language was thus the most unique part of my upbringing, and the unconventionally twisted sentences that combined the vocabulary of two languages and the grammar of another are characteristic of my childhood.

Raised amidst the chaotic storm of my family’s polyglotism, I found my shelter under the pages of books. Writing soon became a beautiful structure of stability for me, and the decisiveness of ink on paper drew me to it. At first, I began to read simply because I loved dragging my finger across the smooth finish of my brother’s gigantic encyclopedia but soon my childish captivation with the book turned to fascination with its contents. I loved hunting for and sounding out difficult words, and my favorite ones would always be the scientific terms.

So, the world of science was the logical next destination.

My strange love for the word “bioluminescence” led me to the ocean, and for months, I dreamed of glowing plankton and starfish. When “constellation” caught my fancy, I spent years imagining myself flying through the vast expanse of outer space, journeying to the very ends of the universe as an astronaut. From the cozy confines of my bedroom, I traversed through Egyptian ruins with “pharaoh”, Norse myths with “valkyrie” and dinosaur dig sites with “paleontology.” Finally, it was an anatomy book that bound me to the world of healthcare and the human body, and my brother’s weekly technology magazine that pulled me towards automation, before I settled on the middle ground I now love – biomedical engineering. Now a sophomore majoring in BME and ECE, I learn new words every day!

Scientific innovations and advancements are often looked at as difficult to understand, discouraging many from learning more about them. But science is embedded in every facet of our daily lives, and I believe it is essential (now, more than ever!) that its literature and progress become more accessible and understandable. As a child, it was the simple, clear and concise language of informal blogs and books that convinced me that I belonged in the fields I read about, and as a blogger, I want to convince many more that the world of science is well within their reach! Fancy terms like glycolysis may seem daunting, but everything can be broken down and made simpler (in this case, quite literally!). Blogging for Duke Research, I hope to meet trailblazers, learn and write about research that fascinates me, and make it accessible to more people. Along the way, I want to introduce the next inquisitive little girl to the exotic word that feeds her imagination, propelling her into the world of science!

However, beyond my selfless mission of spreading the good word of science and technology far and wide, I recently found a new, far more relatable reason to love writing – I don’t need a Starbucks name! It’s a lot easier to just tell you my name is Nidhi.

Post by Nidhi Srivaths, Class of 2024