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

Category: Chemistry Page 1 of 7

Materials For a Changing World… What is That?

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.

Written by Skylar Hughes
Class of 2025

Finding the Tipping Point for Coastal Wetlands

Cypress swamp, eastern North Carolina. Photo by Steve Anderson, Duke

DURHAM, N.C. — The Albemarle-Pamlico Peninsula covers more than 2,000 square miles on the North Carolina coastal plain, a vast expanse of forested swamps and tea-colored creeks. Many people would probably avoid this place, whose dense thickets of cane and shrubs and waterlogged soils can slow a hike to a crawl.

“It’s hard fieldwork,” says Duke researcher Steve Anderson. “It gets really dense and scratchy. That, plus the heat and humidity mixed with the smell of sulfur and the ticks and the poison ivy; it just kind of adds up.”

But to Anderson and colleagues from Duke and North Carolina State University, these bottomlands are more than impenetrable marsh and muck and mosquitoes. They’re also a barometer of change.

Researchers surveying plants in Alligator River National Wildlife Refuge in 2016. Photo by Mathew Stillwagon, North Carolina State University

Most of the area they study lies a mere two to three feet above sea level, which exposes it to surges of ocean water — 400 times saltier than freshwater — driven inland by storms and rising seas. The salt deposits left behind when these waters recede build up year after year, until eventually they become too much for some plants to cope with.

Trudging in hip waders through stunted shrubs and rotting tree stumps, Anderson snaps a picture with his phone of a carpet of partridge berry trailing along the forest floor. In some parts of the peninsula, he says, the soils are becoming so salty that plants like these can no longer reproduce or are dying off entirely.

Along the North Carolina coast, understory plants such as this partridge berry (left) are quickly ceding ground to species such as this bigleaf marsh-elder (right) as the soils become too salty for them to thrive. Credit: Steve Anderson

In a recent study the team, led by professors Justin Wright and Emily Bernhardt of Duke, and Marcelo Ardón of NC State, surveyed some 112 understory plants in the region, making note of where they were found and how abundant they were in relation to salt levels in the soil.

The researchers identified a ‘tipping point,’ around 265 parts per million sodium, where even tiny changes in salinity can set off disproportionately large changes in the plants that live there.

Above this critical threshold, the makeup of the marsh floor suddenly shifts, as plants such as wax myrtle, swamp bay and pennywort are taken over by rushes, reeds and other plants that can better tolerate salty soils.

Certain dwindling plants could be an early warning sign that salt is poisoning inland waters, researchers say. Credit: Steve Anderson

The hope is that monitoring indicator species like these could help researchers spot the early warning signs of salt stress, Anderson says.

This research was supported by grants from the National Science Foundation (DEB1713435, DEB 1713502, and Coastal SEES Collaborative Research Award Grant No. 1426802).

CITATION: “Salinity Thresholds for Understory Plants in Coastal Wetlands,” Anderson, S. M., E. A. Ury, P. J. Taillie, E. A. Ungberg, C. E. Moorman, B. Poulter, M. Ardón, E. S. Bernhardt, and J. P. Wright. Plant Ecology, Nov. 24, 2021. DOI: 10.1007/s11258-021-01209-2.

Salt is poisoning the soils past a point of no return for some marsh plants; one team is trying to pinpoint the early warning signs. By Steve Anderson.

Nobel Laureate Dr. Jennifer Doudna and Groundbreaking Applications of CRISPR

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. 

By Anna Gotskind, Class of 2022

For Undergraduate Student Tiffany Yen, Sustainability is More Than Just a Buzzword

Tiffany Yen, a Duke junior majoring in chemistry, grew up in the sunny suburbs of Los Angeles, never too far from the coastline. She’s always loved being outside, especially in California where there is no shortage of trails to hike and beaches to go to. Friends know her as a Patagonia aficionado, going so far as to buy her a book profiling the company’s business model for her birthday. In fact, from Yen, I learned that every Patagonia store gives out city-specific stickers, so if you feel so inclined, you can collect them (as Yen obviously does). All this is to say: Tiffany Yen has always been interested in sustainability.

“I never understood why what we do has to come at the cost of the planet,” Yen said, in discussing how her years in school learning about climate change fueled her passion for sustainable science. “The environment is so important. Without it, we wouldn’t be here.”

Tiffany Yen

Unsure of what she wanted to study at Duke and where she wanted to go post-graduation, she decided to take her two interests – sustainability and chemistry, particularly polymer chemistry – and see what she could do to combine them. She knew coming into college that she wanted to do research, so that landed her at the Becker Lab for Functional Materials.

The Becker Lab is a multidisciplinary organic materials lab focused on biomedical applications – specifically, things like adhesives and drug delivery. Yen works on improvements to intercranial pressure sensors. Traditionally, after head trauma, doctors need to measure the intercranial space to see if the brain is damaged. The sensor that is used is wired and tends to be a very invasive procedure – the probe is connected to a machine outside, and there’s a high risk of infection.

Collaborators at Northwestern developed a biodegradable wireless device that, after implantation, doesn’t require a secondary procedure to take out. The problem is that it degrades a little too fast – and so measurements can’t be taken. Yen, with her mentor, is working on building a film encapsulation to make it possible for the device to take good measurements.

Right now, they’re trying out azelaic acid instead of succinic acid. Azelaic acid has favorable anti-inflammatory properties and is commonly used in acne medications. It could also potentially increase the bioresorbability of the polymer. Their hope is that the film not only helps the body metabolize more of the polymer, but actually helps in healing.

Snapshots from Yen’s life at the lab

So why medical research? Yen explains that while her work may not seem obviously linked to sustainability, the push for finding materials that can degrade is extremely relevant. And while she’s not all that interested in medicine specifically, she likes things that are practical and applicable.

“When I did research in the past,” Yen said, “there wasn’t always an application. It sometimes was about synthesizing something, just for the sake of science.” And while there’s certainly value in strengthening science fundamentals, she admits that research in that vein doesn’t really appeal to her. “I want to work on things that I directly see adding value to society.”

After college, Yen sees herself going to graduate school and working towards a PhD in “some physical science related to chemistry.”  Ultimately, her goal is to work at the interface of venture capital and scientific research, using her science background to find and fund promising innovations in sustainability. “There are so many incredible things being researched out there,” Yen says, “but the biggest problem in research is funding and commercializing.” She continues, “I think there are other people out there who can do better research than I can, so I want to go out there, find the stuff, and fund it.”

Yen has come to believe that just because she dedicated her time at Duke to science, it doesn’t mean she needs to stay in science forever. There’s value in scientific knowledge no matter where you go. And as businesses realize that public interest in sustainability is growing, she’s crossing her fingers that her skillset will poise her to be a valuable asset in seeking out new innovations. 

Snapshots from Yen’s life at the lab

She said that when she came into college, she felt a pressure to pursue a more traditional path, like being pre-med. “I value stability, and I’m very risk-averse,” she laughs.

But when she asked herself what she’d be happiest doing, she knew it would be trying to save the planet in some way. But she clarifies: “At this point, I can’t save the planet. I think that’s a very far-fetched thing for one person to do.” Instead, “I’d rather try and maybe fail than not try at all.”

Post by Meghna Datta, Class of 2023

New Blogger Olivia Ares: Building Bridges

My name is Olivia Ares (she/her), and I’d like to provide the opportunity for you to get to know me better. In true blog post fashion, here are some quick facts at the outset:

  1. I’m from Johnson City, TN, which probably doesn’t mean anything to you unless you’re a fan of Mountain Dew or Logan from Gilmore Girls.
  2. I’m a freshman here at Duke, and I plan on majoring in Evolutionary Anthropology. For now.
  3. My party trick is knowing way too much about celebrities.
  4. I’m half-Cuban, but I’m also a vegetarian, which is a tragedy in seven words. At least I’ll always have moros y christianos.
  5. I play the fiddle; not the violin. What’s the difference, you ask?
  6. Those close to me claim I have a “cardigan problem.” (By that, they mean that I own an obscene amount of cardigans. If you ask me, that sounds like the exact opposite of a problem.)
Pictured here is my green three-quarter sleeve cardigan with flower-shaped buttons, which provides a colorful accent.

You may be asking yourself what interest I could possibly have in being a research blogger, since I’m clearly destined for a future in comedy (or cardigan connoisseurship). And especially since, as you’ll soon learn, I’m not a science person.

Like a lot of people during our year of virtual school, I went through a lifetime of hobby phases in a matter of months. I started with baking, which only lasted until the bread flour ran out. I watched a lot of movies that I had always wanted to see (which often disappointed), and I rewatched a lot of movies I loved (which never disappointed). I tried learning the guitar, but I never practiced enough to build up the right callouses, so I never practiced at all. I discovered a love for puzzles and an utter lack of skill for them. I downloaded The Sims 4 on a free trial, spent months building a super cool house, then deleted the whole game.

My three favorite things in one picture: lavender cold brew, Taylor Swift, and my blue wool cardigan.

The only thing that’s stuck so far has been reading. In middle school, we used to stay up late with a flashlight under our covers to finish books, then abruptly lost all motivation somewhere between The Giver and The Scarlet Letter. I think we forgot along the way that there are no rules to reading; there’s no one to impress. There’s no one to sample your sourdough or judge your twangy, painful acoustic cover of “Three Blind Mice.” Reading is something you do purely for yourself.

Reading makes information and ideas universally accessible; it connects worlds using only ink on a page. There’s this myth that analytical minds are not creative minds and vice versa, and it alienates people: people who would bring such great perspectives to the table if they hadn’t been defined by a checklist of abilities. Reading is for everyone to find what they love and to love what they find (or hate it; one of the great things about doing things for yourself is that you can just quit whenever you want to).

Scientific research, on the other hand, is something produced for everyone. Humans exploring more and more about the world is something that affects all of us, despite the research being conducted only by a select few of us.

My black long-sleeve cardigan is a personal favorite, as it goes with pretty much everything.

Freshman year of high school, I finished chemistry with a B, which was a miracle considering I was rocking a D around November. I had to change my way of looking at the material; I couldn’t remember the makeup of an atom, but I could remember it if I thought about the stories of individuals who built off of each model in succession. I didn’t understand stoichiometry, but I did understand you have to balance equations just like weights on a scale or kids on a see-saw.

My point is: everyone sees things differently. Exclusivity in different fields is fabricated to make information and education elitist, and it is not reflective of individuals’ ability to understand the world. If you want to read about cool science stuff, you shouldn’t feel left out because you’re more of an art history person. If you want to read about cool art history stuff, you shouldn’t feel left out because you’re an aerospace engineer.


So I like to think that I can be that bridge for some people; at the very least, I can do it for myself.

Post by Olivia Ares, Class of 2025

Introducing: The Duke Space Initiative

NASA

Engineers, medical students, ecologists, political scientists, ethicists, policymakers — come one, come all to the Duke Space Initiative (DSI), “the interdisciplinary home for all things space at Duke.”

At Duke Polis’ “Perspectives on Space: Introducing the Duke Space Initiative” on Sept. 9, DSI co-founder and undergraduate student Ritika Saligram introduced the initiative and moderated a discussion on the current landscape of space studies both at Duke and beyond.

William R. & Thomas L. Perkins Professor of Law Jonathan Wiener began by expressing his excitement in the amount of interest he’s observed in space at Duke. 

One of these interested students was Spencer Kaplan. Kaplan, an undergraduate student studying public policy, couldn’t attend Wiener’s Science & Society Dinner Dialogue about policy and risk in the settlement of Mars. Unwilling to miss the learning opportunity, Kaplan set up a one-on-one conversation with Wiener. One thing led to another: the two created a readings course on space law — Wiener hired Kaplan as a research assistant and they worked together to compile materials for the syllabus — then thought, “Why stop there?” 

Wiener and Kaplan, together with Chase Hamilton, Jory Weintraub, Tyler Felgenhauer, Dan Buckland, and Somia Youssef, created the Bass Connections project “Going to Mars: Science, Society, and Sustainability,” through which a highly interdisciplinary team of faculty and students discussed problems ranging from the science and technology of getting to Mars, to the social and political reality of living on another planet. 

The team produced a website, research papers, policy memos and recommendations, and a policy report for stakeholders including NASA and some prestigious actors in the private sector. According to Saligram, through their work, the team realized the need for a concerted “space for space” at Duke, and the DSI was born. The Initiative seeks to serve more immediately as a resource center for higher education on space, and eventually as the home of a space studies certificate program for undergraduates at Duke. 

Wiener sees space as an “opportunity to reflect on what we’ve learned from being on Earth” — to consider how we could avoid mistakes made here and “try to do better if we settle another planet.” He listed a few of the many problems that the Bass Connections examined. 

The economics of space exploration have changed: once, national governments funded space exploration; now, private companies like SpaceX, Blue Origin, and Virgin Galactic seek to run the show. Space debris, satellite and launch junk that could impair future launches, is the tragedy of the commons at work — in space. How would we resolve international disputes on other planets and avoid conflict, especially when settlements have different missions? Can we develop technology to ward off asteroids? What if we unintentionally brought microorganisms from one planet to another? How will we make the rules for the settlement of other planets?

These questions are vast — thereby reflecting the vastness of space, commented Saligram — and weren’t answerable within the hour. However, cutting edge research and thinking around them can be found on the Bass Connections’ website.

Earth and Climate Sciences Senior Lecturer Alexander Glass added to Wiener’s list of problems: “terraforming” — or creating a human habitat — on Mars. According to Glass, oxygen “isn’t a huge issue”: MOXIE can buzz Co2 with electricity to produce it. A greater concern is radiation. Without Earth’s magnetosphere, shielding of some sort will be necessary; it takes sixteen feet of rock to produce the same protection. Humans on Mars might have to live underground. 

Glass noted that although “we have the science to solve a lot of these problems, the science we’re lagging in is the human aspects of it: the psychological, of humanity living in conditions like isolation.” The engineering could be rock solid. But the mission “will fail because there will be a sociopath we couldn’t predict beforehand.”

Bass Connections project leader and PhD candidate in political science Somia Youssef discussed the need to examine deeply our laws, systems, and culture. Youssef emphasized that we humans have been on Earth for six million years. Like Wiener, she asked how we will “apply what we’ve learned to space” and what changes we should make. How, she mused, do prevailing ideas about humanity “transform in the confines, the harsh environment of space?” Youssef urged the balancing of unity with protection of the things that make us different, as well as consideration for voices that aren’t being represented.

Material Science Professor, Assistant Professor of Surgery, and NASA Human System Risk Manager Dr. Dan Buckland explained that automation has exciting potential in improving medical care in space. If robots can do the “most dangerous aspects” of mission medical care, humans won’t have to. Offloading onto “repeatable devices” will reduce the amount of accidents and medical capabilities needed in space. 

Multiple panelists also discussed the “false dichotomy” between spending resources on space and back home on Earth. Youssef pointed out that many innovations which have benefited (or will benefit) earthly humanity have come from the excitement and passion that comes from investing in space. Saligram stated that space is an “extension of the same social and policy issues as the ones we face on Earth, just in a different context.” This means that solutions we find in our attempt to settle Mars and explore the universe can be “reverse engineered” to help Earth-dwelling humans everywhere.

Saligram opened up the panel for discussion, and one guest asked Buckland how he ended up working for NASA. Buckland said his advice was to “be in rooms you’re not really supposed to be in, and eventually people will start thinking you’re supposed to be there.” 

Youssef echoed this view, expressing the need for diverse perspectives in space exploration. She’s most excited by all the people “who are interested in space, but don’t know if there’s enough space for them.”

If this sounds like you, check out the Duke Space Initiative. They’ve got space.

Post by Zella Hanson

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

DAVIDE BONAZZI / SALZMANART

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

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

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

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

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

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

Marc Lipsitch

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

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

Cameron Wolfe

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

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

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

Nir Eyal

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Post By Zella Hanson

Tracking Tiny Moving Targets

This squiggly line shows the path taken by a snippet of DNA as it might move around within the soupy interior of a cell. Duke’s Kevin Welsher and colleagues have developed a technique that turns a microscope into a ‘flight tracker’ for molecules, making it possible to follow the paths of viruses and other particles thousands of times smaller than the period at the end of this sentence. Until now, such techniques have required particles to be tethered to make sure they stay within the field of view. But the Welsher lab has developed a way to lock on to freely moving targets and track them for minutes at a time.

Researchers created a tiny circuit through a single water molecule, and here’s what they found

Graphic by Limin Xiang, Arizona State University

Many university labs may have gone quiet amid coronavirus shutdowns, but faculty continue to analyze data, publish papers and write grants. In this guest post from Duke chemistry professor David Beratan and colleagues, the researchers describe a new study showing how water’s ability to shepherd electrons can change with subtle shifts in a water molecule’s 3-D structure:

Water, the humble combination of hydrogen and oxygen, is essential for life. Despite its central place in nature, relatively little is known about the role that single water molecules play in biology.

Researchers at Duke University, in collaboration with Arizona State University, Pennsylvania State University and University of California-Davis have studied how electrons flow though water molecules, a process crucial for the energy-generating machinery of living systems. The team discovered that the way that water molecules cluster on solid surfaces enables the molecules to be either strong or weak mediators of electron transfer, depending on their orientation. The team’s experiments show that water is able to adopt a higher- or a lower-conducting form, much like the electrical switch on your wall. They were able to shift between the two structures using large electric fields.

In a previous paper published fifteen years ago in the journal Science, Duke chemistry professor David Beratan predicted that water’s mediation properties in living systems would depend on how the water molecules are oriented.

Water assemblies and chains occur throughout biological systems. “If you know the conducting properties of the two forms for a single water molecule, then you can predict the conducting properties of a water chain,” said Limin Xiang, a postdoctoral scholar at University of California, Berkeley, and the first author of the paper.

“Just like the piling up of Lego bricks, you could also pile up a water chain with the two forms of water as the building blocks,” Xiang said.

In addition to discovering the two forms of water, the authors also found that water can change its structure at high voltages. Indeed, when the voltage is large, water switches from a high- to a low-conductive form. In fact, it is may be possible that this switching could gate the flow of electron charge in living systems.

This study marks an important first step in establishing water synthetic structures that could assist in making electrical contact between biomolecules and electrodes. In addition, the research may help reveal nature’s strategies for maintaining appropriate electron transport through water molecules and could shed light on diseases linked to oxidative damage processes.

The researchers dedicate this study to the memory of Prof. Nongjian (NJ) Tao.

CITATION: “Conductance and Configuration of Molecular Gold-Water-Gold Junctions Under Electric Fields,” Limin Xiang, Peng Zhang, Chaoren Liu, Xin He, Haipeng B. Li, Yueqi Li, Zixiao Wang, Joshua Hihath, Seong H. Kim, David N. Beratan and Nongjian Tao. Matter, April 20, 2020. DOI: 10.1016/j.matt.2020.03.023

Guest post by David Beratan and Limin Xiang

Big SMILES All Around for Polymer Chemists at Duke, MIT and Northwestern

Science is increasingly asking artificial intelligence machines to help us search and interpret huge collections of data, and it’s making a difference.

But unfortunately, polymer chemistry — the study of large, complex molecules — has been hampered in this effort because it lacks a crisp, coherent language to describe molecules that are not tidy and orderly.

Think nylon. Teflon. Silicone. Polyester. These and other polymers are what the chemists call “stochastic,” they’re assembled from predictable building blocks and follow a finite set of attachment rules, but can be very different in the details from one strand to the next, even within the same polymer formulation.

Plastics, love ’em or hate ’em, they’re here to stay.
Foto: Mathias Cramer/temporealfoto.com

Chemistry’s old stick and ball models and shorthand chemical notations aren’t adequate for a long molecule that can best be described as a series of probabilities that one kind of piece might be in a given spot, or not.

Polymer chemists searching for new materials for medical treatments or plastics that won’t become an environmental burden have been somewhat hampered by using a written language that looks like long strings of consonants, equal signs, brackets, carets and parentheses. It’s also somewhat equivocal, so the polymer Nylon-6-6 ends up written like this: 

{<C(=O)CCCCC(=O)<,>NCCCCCCN>}

Or this,

{<C(=O)CCCCC(=O)NCCCCCCN>}

And when we get to something called ‘concatenation syntax,’ matters only get worse.  

Stephen Craig, the William T. Miller Professor of Chemistry, has been a polymer chemist for almost two decades and he says the notation language above has some utility for polymers. But Craig, who now heads the National Science Foundation’s Center for the Chemistry of Molecularly Optimized Networks (MONET), and his MONET colleagues thought they could do better.

Stephen Craig

“Once you have that insight about how a polymer is grown, you need to define some symbols that say there’s a probability of this kind of structure occurring here, or some other structure occurring at that spot,” Craig says. “And then it’s reducing that to practice and sort of defining a set of symbols.”

Now he and his MONET colleagues at MIT and Northwestern University have done just that, resulting in a new language – BigSMILES – that’s an adaptation of the existing language called SMILES (simplified molecular-input line-entry system). They they think it can reduce this hugely combinatorial problem of describing polymers down to something even a dumb computer can understand.

And that, Craig says, should enable computers to do all the stuff they’re good at – searching huge datasets for patterns and finding needles in haystacks.

The initial heavy lifting was done by MONET members Prof. Brad Olsen and his co-worker Tzyy-Shyang Lin at MIT who conceived of the idea and developed the set of symbols and the syntax together. Now polymers and their constituent building blocks and variety of linkages might be described like this:

Examples of bigSMILES symbols from the recent paper

It’s certainly not the best reading material for us and it would be terribly difficult to read aloud, but it becomes child’s play for a computer.

Members of MONET spent a couple of weeks trying to stump the new language with the weirdest polymers they could imagine, which turned up the need for a few more parts to the ‘alphabet.’ But by and large, it holds up, Craig says. They also threw a huge database of polymers at it and it translated them with ease.

“One of the things I’m excited about is how the data entry might eventually be tied directly to the synthetic methods used to make a particular polymer,” Craig says. “There’s an opportunity to actually capture and process more information about the molecules than is typically available from standard characterizations. If that can be done, it will enable all sorts of discoveries.”

BigSMILES was introduced to the polymer community by an article in ACS Central Science last week, and the MONET team is eager to see the response.

“Can other people use it and does it work for everything?” Craig asks. “Because polymer structure space is effectively infinite.” Which is just the kind of thing you need Big Data and machine learning to address. “This is an area where the intersection of chemistry and data science can have a huge impact,” Craig says.

Page 1 of 7

Powered by WordPress & Theme by Anders Norén