In a Duke-led study appearing Nov. 17 in Science Advances, the researchers report that the findings create a foundation for a new area of investigation, fueled by the timely impact of environmental factors on human biology.

“Parkinson’s disease has been called the fastest growing neurological disorder in the world,” said principal investigator, Andrew West, Ph.D., professor in the Department of Pharmacology and Cancer Biology at Duke University School of Medicine. “Numerous lines of data suggest environmental factors might play a prominent role in Parkinson’s disease, but such factors have for the most part not been identified.”

Improperly disposed plastics have been shown to break into very small pieces and accumulate in water and food supplies, and were found in the blood of most adults in a recent study.

“Our study suggests that the emergence of micro and nanoplastics in the environment might represent a new toxin challenge with respect to Parkinson’s disease risk and progression,” West said. “This is especially concerning given the predicted increase in concentrations of these contaminants in our water and food supplies.”

West and colleagues in Duke’s Nicholas School of the Environment and the Department of Chemistry at Trinity College of Arts and Sciences found that nanoparticles of the plastic polystyrene — typically found in single use items such as disposable drinking cups and cutlery — attract the accumulation of the protein known as alpha-synuclein. West said the study’s most surprising findings are the tight bonds formed between the plastic and the protein within the area of the neuron where these accumulations are congregating, the lysosome.

Researchers said the plastic-protein accumulations happened across three different models performed in the study — in test tubes, cultured neurons, and mouse models of Parkinson’s disease. West said questions remain about how such interactions might be happening within humans and whether the type of plastic might play a role.

“While microplastic and nanoplastic contaminants are being closely evaluated for their potential impact in cancer and autoimmune diseases, the striking nature of the interactions we could observe in our models suggest a need for evaluating increasing nanoplastic contaminants on Parkinson’s disease and dementia risk and progression,” West said.

“The technology needed to monitor nanoplastics is still at the earliest possible stages and not ready yet to answer all the questions we have,” he said. “But hopefully efforts in this area will increase rapidly, as we see what these particles can do in our models. If we know what to look out for, we can take the necessary steps to protect ourselves, without compromising all the benefits we reap every day from plastics.”

The study was funded by in part by The Michael J. Fox Foundation for Parkinson’s Research and the Aligning Science Across Parkinson’s initiative (ASAP-020527).

In addition to West, study authors include Zhiyong Liu, Arpine Sokratian, Addison M. Duda, Enquan Xu, Christina Stanhope, Amber Fu, Samuel Strader, Huizhong Li, Yuan Yuan, Benjamin G. Bobay, Joana Sipe, Ketty Bai, Iben Lundgaard, Na Liu, Belinda Hernandez, Catherine Bowes Rickman, and Sara E. Miller.

Despite this headline finding, the environmental scientists behind the research are quick to underline that this should in no way be taken to mean the world’s governments can take their foot off the brake in their obligations to reduce carbon emissions as fast as possible. Simply planting more trees and protecting existing vegetation is not a golden-bullet solution but the research does underline the multiple benefits to conserving such vegetation.

“Plants take up a substantial amount of carbon dioxide (CO₂) every year, thereby slowing down the detrimental effects of climate change, but the extent to which they will continue this CO₂ uptake into the future has been uncertain,” explains Dr Jürgen Knauer, who headed the research team led by the Hawkesbury Institute for the Environment at Western Sydney University.

“What we found is that a well-established climate model that is used to feed into global climate predictions made by the likes of the IPCC predicts stronger and sustained carbon uptake until the end of the 21^st century when it accounts for the impact of some critical physiological processes that govern how plants conduct photosynthesis.

“We accounted for aspects like how efficiently carbon dioxide can move through the interior of the leaf, how plants adjust to changes in temperatures, and how plants most economically distribute nutrients in their canopy. These are three really important mechanisms that affect a plant’s ability to ‘fix’ carbon, yet they are commonly ignored in most global models” said Dr Knauer.

Photosynthesis is the scientific term for the process in which plants convert — or “fix” — CO₂ into the sugars they use for growth and metabolism. This carbon fixing serves as a natural climate change mitigator by reducing the amount of carbon in the atmosphere; it is this increased uptake of CO₂ by vegetation that is the primary driver of an increasing land carbon sink reported over the last few decades.

However, the beneficial effect of climate change on vegetation carbon uptake might not last forever and it has long been unclear how vegetation will respond to CO₂, temperature and changes in rainfall that are significantly different from what is observed today. Scientists have thought that intense climate change such as more intense droughts and severe heat could significantly weaken the sink capacity of terrestrial ecosystems, for example.

In the study published this week, however, Knauer and colleagues present results from their modelling study set to assess a high-emission climate scenario, to test how vegetation carbon uptake would respond to global climate change until the end of the 21^st century.

The authors tested different versions of the model that varied in their complexity and realism of how plant physiological processes are accounted for. The simplest version ignored the three critical physiological mechanisms associated with photosynthesis while the most complex version accounted for all three mechanisms.

The results were clear: the more complex models that incorporated more of our current plant physiological understanding consistently projected stronger increases of vegetation carbon uptake globally. The processes accounted for re-enforced each other, so that effects were even stronger when accounted for in combination, which is what would happen in a real-world scenario.

Silvia Caldararu, Assistant Professor in Trinity’s School of Natural Sciences, was involved in the study. Contextualising the findings and their relevance, she said:

“Because the majority of terrestrial biosphere models used to assess the global carbon sink are located at the lower end of this complexity range, accounting only partially for these mechanisms or ignoring them altogether, it is likely that we are currently underestimating climate change effects on vegetation as well as its resilience to changes in climate. We often think about climate models as being all about physics, but biology plays a huge role and it is something that we really need to account for.

“These kinds of predictions have implications for nature-based solutions to climate change such as reforestation and afforestation and how much carbon such initiatives can take up. Our findings suggest these approaches could have a larger impact in mitigating climate change and over a longer time period than we thought.

“However, simply planting trees will not solve all our problems. We absolutely need to cut down emissions from all sectors. Trees alone cannot offer humanity a get out of jail free card.”

The team has found that adding small quantities of liquid soap to some classes of pesticides can boost their potency by more than ten-fold.

The discovery is promising news as malaria-carrying mosquitoes display an increasing resistance to current insecticides, said Colince Kamdem, Ph.D., lead author of the study and assistant professor in UTEP’s Department of Biological Sciences.

“Over the past two decades, mosquitoes have become strongly resistant to most insecticides,” Kamdem said. “It’s a race now to develop alternative compounds with new modes of action.”

Both laboratory tests and field trials have shown that neonicotinoids, a special class of insecticide, are a promising alternative to target populations showing resistance to existing insecticides, said UTEP Research Assistant Professor Caroline Fouet, Ph.D., second author of the study. Neonicotinoids, however, do not kill some mosquito species unless their potency is boosted. In this case, Fouet said, soap is the boosting substance.

Malaria is a devastating mosquito-borne disease that is prevalent in sub-Saharan Africa, Asia and Latin America, causing fever, fatigue, headaches and chills; the disease can be fatal. In 2020, there were an estimated 241 million cases of malaria worldwide, according to the Centers for Disease Control, resulting in 627,000 deaths.

Prior to joining UTEP, Kamdem worked at Cameroon’s Centre for Research in Infectious Diseases (CRID); it was there that he first caught on to soap’s potency while conducting routine insecticide testing.

Current protocols from the World Health Organization (WHO) for testing mosquitoes’ susceptibility to some insecticides recommend adding a seed oil-based product to insecticide concoctions. Kamdem noticed when the compound was added, mosquito mortality increased from when the insecticide was used on its own.

“That compound belongs to the same class of substances as kitchen soap,” Kamdem said. “We thought, ‘Why don’t we test products that have same properties?’

He and his team selected three low-cost, linseed-oil based soaps that are prevalent in sub-Saharan Africa — Maître Savon de Marseille, Carolin Savon Noir and La Perdrix Savon — and added them to four different neonicotinoids, acetamiprid, clothianidin, imidacloprid and thiamethoxam.

The hunch paid off. In all cases, the insecticides drastically enhanced potency, the team wrote in the study. “All three brands of soap increase mortality from 30 percent to 100 percent compared to when the insecticides were used on their own,” said Ashu Fred, first author of the study and Ph.D. student at Cameroon’s University of Yaoundé 1.

The team also tested the addition of soap to a class of insecticides known as pyrethroids. In those cases, however, they saw no benefits.

The team hopes to conduct additional testing to establish exactly how much soap is needed to enhance insecticides.

“We would love to make a soap-insecticide formulation that can be used indoors in Africa and be healthy for users,” Kamdem said. “There are unknowns as to whether such a formulation will stick to materials like mosquito nets, but the challenge is both promising and very exciting.”

Additional authors on the study are doctoral student Marilene M. Ambadiang of CRID and the University of Yaoundé 1; and Professor Veronique Penlap-Beng, Ph.D., of the University of Yaoundé 1.

The project was supported by a grant from the National Institutes of Health.

Research from the lab of cancer biologist Tuomas Tammela, MD, PhD shows that some lung cancer cells retain a “memory” of the healthy cell where they came from — one that might be exploited to make an emerging type of lung cancer treatment called KRAS inhibition more effective.

The study looked specifically at lung adenocarcinoma, a type of non-small cell lung cancer that is the most common type of lung cancer in the U.S. and responsible for 7% of all cancer deaths. This cancer is frequently driven by mutations in the KRAS gene.

“For a long time, cancer-driving KRAS proteins were considered ‘undruggable,'” says study co-first author Zhuxuan “Zoe” Li, a doctoral student in the Tammela Lab at MSK’s Sloan Kettering Institute. “Within the last few years, however, the U.S. Food and Drug Administration approved the first KRAS inhibitors, with quite a few more in clinical trials. But they don’t work for everyone, and most patients’ cancers eventually acquire resistance to the drugs and come back.”

The team’s findings — co-led by postdoctoral fellow Xueqian Zhuang, PhD — shed important light on lung cancer cells that linger after treatment with a KRAS inhibitor. Importantly, they suggest that separately targeting these cells alongside treatment with a KRAS inhibitor could help prevent recurrence. The study was recently published in Cancer Discovery, a leading journal for biological insights that have important implications for clinical care.

Stem Cells With a Day Job’

To understand the MSK discovery and its implications, it’s helpful to know a little lung biology.

Within the lungs, oxygen is absorbed and carbon dioxide released via air sacs called alveoli. The lining of the alveoli is made of two distinct types of cells — alveolar type 1 (AT1) and alveolar type 2 (AT2).

And while they’re similarly named, these two cells couldn’t be more different.

AT1 cells are long and thin, with a large surface to facilitate gas exchange between the lungs and the bloodstream.

AT2 cells, meanwhile, play a caretaking role, secreting compounds that are important for the health and function of the lungs, as well as helping maintain and repair the lungs by dividing to create replacement AT1 cells.

“You can think of them as stem cells with a day job,” Dr. Tammela says.

The big problem comes when lung cancer cells — which typically develop from AT2 cells — take on some “remembered” properties of the AT1 cells that AT2 cells differentiate into when they’re playing their stem cell role. Scientists call these cancer cells “AT1-like” cells.

Eliminating AT1-Like Cells Improves Response to KRAS Inhibition

In healthy cells, KRAS plays a key role in regulating cell growth and division. But when the gene becomes mutated, it can lead to runaway cell proliferation.

KRAS inhibitors can switch off this explosive growth, greatly diminishing tumors, but they still leave behind pockets of cancer cells that aren’t sensitive to the drug, and that also give the cancer a chance to develop new mutations to resist the drugs’ effects.

The research team painstakingly studied these residual cancer cells to uncover the mechanisms of this resistance using genetically engineered mouse models, mice implanted with patient-derived tumors, and tumor samples from patients.

They discovered that the cancer cells that remained after treatment were these AT1-like cells. They also found these cells have the capacity to reignite the cancer’s runaway growth.

“Importantly, we found that if you get rid of these AT1-like cells, it greatly improves the treatment response to KRAS inhibitors,” Dr. Tammela says.

Eliminating those cells in experimental models is relatively easy, but doing so in the clinic will require further research.

“We actually live in a very exciting time with fantastic pharmacology,” Dr. Tammela says. “We can engineer molecules to bind to a certain cell type and kill them — this is how CAR T cell therapy and antibody drug conjugates work.

“Now that we’ve done these proof-of-concept experiments, the next step would be to find surface proteins that are unique to these AT1-like cells and then develop a therapeutic that can bind to them and kill them,” he adds.

Thanks to the extensive network of cameras, GPS collars and other instruments, park staff and wildlife ecologists had an “unprecedented opportunity” to assemble a minute-by-minute view of how the storm affected the park and how the animals responded, said Hallie Brown, a postdoctoral research associate in Princeton’s Department of Ecology and Environmental Biology and the first author of a new paper in Nature about the hurricane’s impact.

“This is the first study that has ever been able to track the real-time responses of a large-mammal community to a natural disaster,” said Robert Pringle, an EEB professor who has worked with Gorongosa National Park since its inception.

Brown, now a postdoctoral research associate in Pringle’s lab, was a graduate student at the time with Ryan Long, an associate professor of wildlife sciences at the University of Idaho and a former Princeton postdoc. Long and Pringle shared senior author credits on the new Nature paper.

“We watched the waters rise,” Brown recalled. “We watched the animals’ reactions in the hours, days, weeks after the cyclone: how some of them escaped the floodwaters, and some of them didn’t. We used the data we had from before, during and after the storm to create, not just a description of this one event, but a broader set of expectations, so managers can better anticipate the effects of increasingly severe weather events.”

The research team found that the best predictor of survival was size. The tiny oribi, about the size of a greyhound, saw its population plummet by 50%. About half of the slightly larger reedbucks died as well. The bushbucks, which are the smallest species that can wear a GPS collar, saw three of its eight collared animals die — the smallest male and the two smallest females — but only lost 4% of their population overall.

GPS data revealed that the bushbucks looked for hills to climb, including termite mound hillocks that reach up to 16 feet tall (5 meters) and 65 feet long (20 meters), which became islands in the flood. The researchers saw that one survivor hopscotched from mound to mound, passing quickly through the floodwaters in between, before finding safety in the woods at higher elevations. The four largest herbivores wearing GPS collars — nyala, kudu, sable and elephant — had no fatalities.

Body size also offered a secondary protection, the researchers found.

“Not only could the smaller-sized animals not outpace the waters, they were also not able to buffer the nutritional limitation afterwards,” said Brown. “Because the flood was so high for so long, it killed a lot of the grasses and low-lying vegetation. Smaller animals can’t withstand those nutritionally limited periods like larger animals, who have more fat to rely on.”

The only previous study of hurricane effects on island populations looked at lizards and spiders in the Bahamas and found very similar patterns. “It’s incredible how the patterns we found cross taxonomic and geographic lines,” said Brown. “They seem to play out the same ways in our terrestrial ecosystem, with the largest mammals on earth, and with these tiny little invertebrates and reptiles in the Bahamas.”

The researchers have two primary recommendations for other wildlife managers: evacuate the smallest and most ecologically vulnerable creatures to safer areas before storms come, and provide supplementary feed after the storm. Once all of the grasses have drowned, animals will turn to foraging on less-nutritious shrubs and bark, and many small creatures can’t survive that dietary shift.

The few carnivores in the park weathered the storm just fine, Brown said. The wild dogs and leopards benefited from having their prey animals concentrated in the upland areas, and the lions’ primary food source — warthogs — stayed in the uplands for several months but were otherwise largely unaffected by the cyclone.

The research team included institutions from five countries: Princeton University; the University of Idaho-Moscow; the University of California-Merced; Montana State University-Bozeman;Yale University; Archbold Biological Station in Venus, Florida; the University of British Columbia-Vancouver; Gorongosa National Park; the University of Kent; the University of the Witwatersrand-Johannesburg; Associac?a?o Azul Moc?ambique in Maputo, Mozambique.

Other Princeton authors on the paper are then-graduate students Matt Hutchinson, Ph.D. 2021; Justine Atkins Becker, Ph.D. 2020; Arjun Potter, Ph.D. 2022; and then-NSF postdoctoral fellow Meredith Palmer.

“For me, the most exciting thing about this paper is the incredible collaboration between so many groups of researchers, from hydrology to large animal ecology, to create this really integrated piece of science,” Brown said. “The best work happens in collaborative projects.”

By analyzing measurements of the cranial vault — the part of the skull that forms the rounded top of the head and protects the brain — the team identified 30 regions of the genome associated with different aspects of head shape, 29 of which have not been reported previously.

“Anthropologists have speculated and debated the genetics of cranial vault shape since the early 20^th century,” said co-senior author Seth Weinberg, Ph.D., professor of oral and craniofacial sciences in the Pitt School of Dental Medicine and co-director of the Center for Craniofacial and Dental Genetics. “We knew from certain rare human conditions and animal experiments that genes play an important role in vault size and shape, but very little was known about the genetic basis for typical features we see in the general population, such as what makes someone’s head long and narrow versus short and wide. This study reveals some of the key genes driving variation in this part of the human body.”

According to the researchers, one application of better understanding the factors that drive natural variation in human head shape is informing paleoanthropology studies, potentially shedding light on the early development of modern humans.

Weinberg and colleagues used magnetic resonance (MR) scans from more than 6,000 adolescents to extract 3D surfaces corresponding to the cranial vault. After dividing the 3D vault surfaces into incrementally smaller anatomical subparts and quantifying the shape of these subparts, they tested more than 10 million genetic variants for evidence of statistical association with measures of vault shape.

“Previous genetic studies of the cranial vault involved a small number of relatively simple measures,” added Weinberg. “While such measures are often easy to obtain, they may fail to capture features that are biologically relevant. Our analysis used an innovative approach capable of describing 3D vault shape in much more comprehensive and nuanced ways. This approach increased our ability to find genetic associations.”

An important discovery was that many of the strong associations are near genes that play key roles in the early formation of the head and face and regulation of bone development. For example, variants in and near the gene RUNX2, a major player in coordinating development of the skull, were associated with multiple aspects of vault shape.

While some genes, including RUNX2, had global effects involving the entire vault, others showed more localized effects that only impacted a specific portion of the vault, such as the central forehead.

When the researchers compared the 30 genomic regions associated with head shape across participants with European, African and Indigenous American ancestry, they found that the majority of genetic associations were shared across these different ancestral groups.

Although the study focused on healthy participants, the findings may reveal important clues about the biological basis of diseases involving the cranial vault, according to Weinberg.

One of these conditions is craniosynostosis, which occurs when the bones of the skull fuse too early while the brain is still growing rapidly. Without neurosurgery, craniosynostosis can cause permanent disfigurement, brain damage, blindness and even death. The team showed that variants near three genes associated with vault shape, BMP2, BBS9 and ZIC2, were also associated with craniosynostosis, suggesting that these genes could play a role in the development of the disease.

“This kind of study is possible due to the availability of publicly funded resources,” said Weinberg. “The original study that generated these MR scans is focused on understanding brain development and behavior. By creatively leveraging these resources, we have managed to advance discovery beyond that original scope.”

Other authors on the study were Seppe Goovaerts, Hanne Hoskens, Ph.D., Meng Yuan, Dirk Vandermeulen, Ph.D., all of KU Leuven; Ryan J. Eller, Ph.D., Noah Herrick, Ph.D., and Susan Walsh, Ph.D., all of Indiana University-Purdue University Indianapolis; Anthony M. Musolf, Ph.D., and Cristina M. Justice, Ph.D., both of the National Human Genome Research Institute; Sahin Naqvi, Ph.D., and Joanna Wysocka, Ph.D., both of Stanford University; Myoung Keun Lee, Heather L. Szabo-Rogers, Ph.D., Mary L. Marazita, Ph.D., and John R. Shaffer, Ph.D., all of Pitt; Paul A. Romitti, Ph.D., of the University of Iowa; Simeon A. Boyadjiev, M.D., of the University of California, Davis; Mark D. Shriver, Ph.D., of Penn State University; and Peter Claes, Ph.D., of KU Leuven and Murdoch Children’s Research Institute.

This research was supported by the National Institute of Dental and Craniofacial Research (R01DE027023, R01DE016886, R03DE031061 and X01HL14053) and the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health

Scientists at Lawrence Berkeley National Laboratory (Berkeley Lab) and the Joint BioEnergy Institute (JBEI) are collaborating with X — the moonshot incubator led by Alphabet, Google’s parent company — to not only skip the problematic separation step, but also make the final product better for the planet.

The team has invented a simple “one pot” process to break down mixtures of petroleum-based and bio-based plastics using naturally derived salt solutions paired with specialized microbes. In a single vat, the salts act as a catalyst to break the materials down from polymers, large structures of repeating molecules bonded together, into the individual molecules called monomers, which the microbes then ferment into a new type of biodegradable polymer that can be made into fresh commodity products. The process is described in a One Earth paper published November 17.

“It’s sort of ironic because the purpose of using bio-based plastics is to be more sustainable, but it’s causing problems,” said first author Chang Dou, a senior scientific engineering associate at the Advanced Biofuels and Bioproducts Process Development Unit (ABPDU) at Berkeley Lab. Dou was recently named as one of the American Institute of Chemical Engineer’s 35 Under 35. “Our project is trying to get around the separation issue and make it so you don’t have to worry about whether you mix your recycling bin. You can put all the plastic in one bucket.”

In addition to streamlining recycling, the team’s approach could enable bio-based manufacturing of other valuable products using the same bacteria that are happily munching on plastic monomers. Imagine a world where biofuels or even medicines could be made from plastic waste — of which there is about 8.3 billion tons sitting around in landfills.

“There is an open discussion on whether we can use waste plastics as a carbon source for biomanufacturing. It is a very advanced idea. But we proved that using waste plastics, we can feed microbes. With more genetic engineering tools, microbes might be able to grow on multiple types of plastics at the same time. We foresee the potential to continue this study where we can replace the sugars, traditional carbon sources for microbes, with the processed hard-to-recycle mixed plastics that can be converted to valuable products through fermentation,” said Zilong Wang, a UC Berkeley postdoctoral researcher working at JBEI.

The Berkeley Lab scientists’ next step is to experiment with other organic salt catalysts to try to find one that is both highly effective at breaking polymers down and can be reused in multiple batches to lower costs. They are also modeling how the process would work at the large scales of real-world recycling facilities.

In their recent paper, the scientists demonstrated the potential of their approach in laboratory bench-scale experiments with mixtures of polyethylene terephthalate (PET) — the most common petroleum-based plastic, used in things like water bottles and spun into polyester fibers — and PLA, the most common bio-based plastic.

They used an amino-acid-based salt catalyst previously developed by colleagues at JBEI and a strain of Pseudomonas putida engineered by scientists at Oak Ridge National Laboratory. This combination successfully broke down 95% of the PET/PLA mixture and converted the molecules into a type of polyhydroxyalkanoate (PHA) polymer. PHAs are a new class of biodegradable plastic substitutes designed to efficiently break down in a variety of natural environments, unlike petroleum-based plastics.

Team member Hemant Choudhary noted that although their chemical recycling process is currently only proven for PET plastics contaminated with biodegradable PLA, it would still be beneficial for the diverse plastic streams encountered in real recycling facilities. “It can be completely integrated with existing plastic sources,” said Choudhary, a Sandia National Laboratories staff scientist working at JBEI. Most commercial products are not just one kind of plastic, but a handful of different kinds combined, he explained. For example, a fleece jacket is made with PET-based polyesters alongside polyolefins or polyamides. “We can throw it in our one-pot process and easily process the polyester component from that mixture and convert it into a bioplastic. These monomers are soluble in water, but the leftover parts, the polyolefins or polyamides, are not.” The leftovers can be easily removed by simple filtration and then sent off for a traditional mechanical recycling process where the material is shredded and melted, said Choudhary.

“Chemical recycling has been a hot topic, but it’s difficult to make it happen at the commercial scale because all the separation steps are so expensive,” said Ning Sun, a staff scientist at the ABPDU, lead author, and principal investigator of this project. “But by using a biocompatible catalyst in water, the microbes can directly convert the depolymerized plastics without extra separation steps. These results are very exciting, although we acknowledge that a number of improvements are still needed to realize the economic viability of the developed process.”

Co-authors Nawa R. Baral and Corinne Scown, experts in technoeconomic analysis in JBEI and Berkeley Lab’s Biosciences Area, also demonstrated that once optimized with a reusable salt solution, the process could reduce the cost and carbon footprint of PHAs by 62% and 29%, respectively, compared with today’s commercial PHA production.

JBEI is a Department of Energy (DOE) Bioenergy Research Center managed by Berkeley Lab. The ABPDU is a collaboration facility supported by the DOE BioEnergy Technologies Office.

The capsule, which is about the size of a multivitamin, uses an accelerometer to measure the patient’s breathing rate and heart rate. In addition to diagnosing sleep apnea, the device could also be useful for detecting opioid overdoses in people at high risk, the researchers say.

“It’s an exciting intervention to help people be diagnosed and then receive the appropriate treatment if they suffer from obstructive sleep apnea,” says Giovanni Traverso, an associate professor of mechanical engineering at MIT and a gastroenterologist at Brigham and Women’s Hospital. “The device also has the potential for early detection of changes in respiratory status, whether it’s a result of opiates or other conditions that could be monitored, like asthma or chronic obstructive pulmonary disease (COPD).”

In a study of 10 human volunteers, the researchers showed that the capsule can be used to monitor vital signs and to detect sleep apnea episodes, which occur when the patient repeatedly stops and starts breathing during sleep. The patients did not show any adverse effects from the capsule, which passed harmlessly through the digestive tract.

Traverso is one of the senior authors of the study, along with Robert Langer, an MIT Institute Professor and member of MIT’s Koch Institute for Integrative Cancer Research; Victor Finomore, director of the Human Performance and Applied Neuroscience Research Center at the West Virginia University School of Medicine; and Ali Rezai, director of the Rockefeller Neuroscience Institute at the West Virginia University School of Medicine. The paper appears today in the journal Device.

Vital sign measurements

Over the past decade, Traverso and Langer have developed a range of ingestible sensors that could be used to monitor vital signs and diagnose disorders of the GI tract, such as gastrointestinal slowdown and inflammatory bowel diseases.

This new study focused on measuring vital signs, using a capsule developed by Celero Systems that includes an accelerometer that detects slight movements generated by the beating of the heart and the expansion of the lungs. The capsule also contains two small batteries and a wireless antenna that transmits data to an external device such as a laptop.

In tests in an animal model, the researchers found that this capsule could accurately measure breathing rate and heart rate. In one experiment, they showed that the sensor could detect the depression of breathing rate that resulted from a large dose of fentanyl, an opioid drug.

Building on those results, the researchers decided to further test the capsule in a clinical trial at the West Virginia University Rockefeller Neuroscience Institute. Ten patients who enrolled in the study were monitored using the ingestible capsule, and these patients were also connected to the sensors typically used to monitor sleep, so the researchers could compare measurements from both types of sensors.

The researchers found that their ingestible sensor was able to accurately measure both breathing rate and heart rate, and it also detected a sleep apnea episode that one of the patients experienced.

“What we were able to show is that using the capsule, we could capture data that matched what the traditional transdermal sensors would capture,” Traverso says. “We also observed that the capsule could detect apnea, and that was confirmed with standard monitoring systems that are available in the sleep lab.”

In this study, the researchers monitored signals emitted by the capsule while it was in the stomach, but in a previous study, they showed that vital signs can also be measured from other parts of the GI tract.

“The stomach generally offers some of the best signals, mainly because it’s close to the heart and the lungs, but we know that we can also sense them elsewhere,” Traverso says.

None of the patients reported any discomfort or harm from the capsule. Radiographic imaging performed 14 days after the capsules were ingested revealed that all of them had passed through the patients’ bodies. The research team’s previous work has shown that objects of similar size usually move through the digestive tract in a little more than a day.

Close monitoring

The researchers envision that this kind of sensor could be used to diagnose sleep apnea in a less intrusive way than the skin-based sensors that are now used. It could also be used to monitor patients when they begin treatment for apnea, to make sure that the treatments are effective.

Celero Systems, a company founded by Traverso, Langer, Jeremy Ruskin, a professor of medicine at Harvard Medical School, and Benjamin Pless, now CEO of the company, is now working on sensors that could be used to detect sleep apnea or opioid overdose.

“We know that people who have had an overdose are at higher risk of recurrence, so those individuals could be monitored more closely so that in the event of another overdose, someone could help them,” Traverso says.

In future work, the researchers hope to incorporate an overdose reversal agent such as nalmefene into the device, so that drug release would be triggered when the person’s breathing rate slowed or stopped. They are also working on strategies to lengthen the amount of time that the capsules could remain in the stomach.

The research was funded by the Karl van Tassel Career Professorship, MIT’s Department of Mechanical Engineering, and Celero Systems.

Authors of the paper also include Pless, James Mahoney, Justin Kupec, Robert Stansbury, Daniel Bacher, Shannon Schuetz, and Alison Hayward.