“This study is the first to scientifically document use of ghost pipe in North America, along with the growing influence of social media and the internet on how and why people are turning to ghost pipe as a medicinal plant,” said team leader and senior author on the study Eric Burkhart, teaching professor in the College of Agricultural Sciences. “As a wild harvested species, little has been documented about its use throughout the U.S. and any growing conservation needs. This study helps to inform future research and education efforts so that consumer safety and wild conservation efforts can both be appropriately targeted and aligned.”

In findings recently published in Economic Botany, the researchers reported the results of a digital survey they conducted within the United States asking participants whether they have foraged, consumed or prescribed ghost pipe. The results showed that social media and the internet were the primary source of information and learning for respondents. Notably, respondents overwhelmingly reported consuming ghost pipe in tincture form and for pain management. Both findings appear to be recent developments, Burkhart said, as there is limited indication from the historical record that ghost pipe was prepared and used in these ways.

The survey received responses from 489 individuals. Most respondents — 96% — identified as a consumer of ghost pipe, and 87% identified as a forager or both. While pain management was the most commonly reported reason for consuming ghost pipe, survey respondents reported that they ingested ghost pipe for a myriad of reasons, including as a sedative to help them sleep, enhance relaxation, deal with depression or grief, ease anxiety or trauma, lessen eye irritation and reduce symptoms of alcohol or opiate withdrawal.

These results suggest that the internet has emerged as an important platform not only for learning and sharing ghost pipe ethnobotany, the study of the relationship between people and plants, but also for developing new traditions and practices, according to study first author Savannah Anez, a doctoral degree candidate in plant biology. The survey results highlight the contemporary need to understand ghost pipe ethnobotany in the context of an increasingly influential digital world, she suggested.

“We use the term ‘digital ethnobotany’ to refer to ethnobotany within a virtual environment, leveraging new technology to study the relationship between people and plants, while also exploring the development of traditional knowledge and practices within the digital spaces themselves,” Anez said.

Ghost pipe is a parasite to mycorrhizal fungi in forest soils — meaning that it draws nutrients from those fungi, while those fungi in turn are connected to trees in the forest in a symbiotic relationship, Anez explained. She pointed out that ghost pipe is one of thousands of traditional medicinal plants around the world with a documented ethnobotanical use that has not had its specific biochemistry studied. Traditional medicinal plants have historically been excellent sources for drug discovery, she said, so this is a massive biochemical frontier just waiting to be explored.

Anez explained that she is trying to fill that knowledge gap through her dissertation work characterizing the specific chemistry and bioactivity of ghost pipe. Her goal is to identify the specific pain-relieving compounds in the plant. One research project currently underway is a study of ghost pipe’s pain-relieving effects in mice, which she said has produced promising preliminary results. She was recently awarded a F31 Predoctoral Fellowship through the National Institutes of Health that will fund her investigation of ghost pipe as a potential pain reliever through 2027.

“We need to determine whether or not it has potential as a novel therapeutic or medicine,” she said. “We have acquired a lot of the chemistry data already but given that plant extracts are a complex mix of thousands of compounds, we need more medicinal activity data to be able to identify the specific compound(s) responsible for pain relief — finding the actual ‘smoking gun’ is the challenge. Because ghost pipe siphons nutrients from an underground fungal network it shares with trees, the question of its bioactivity and biochemistry is also more complex than a typical medicinal plant.”

Joshua Kellogg, assistant professor in veterinary and biomedical sciences, contributed to the study.

The research was funded by the U.S. Department of Agriculture and the Pennsylvania Department of Conservation and Natural Resources Wild Resource Conservation Program.

Nearly all these inserted elements have been silenced by our cells’ defense mechanisms over time, but a few, nicknamed “jumping genes,” can still move around the human genome like viruses. Just one, called long interspersed nuclear element 1 (LINE-1), can still move by itself.

As an element type that behaves like the retrovirus HIV, the LINE-1 “retrotransposon” is first copied into a molecule of RNA, the genetic material that partners with DNA, and then the RNA LINE-1 copy is converted back into DNA in a new place in the genome. In this way, retrotransposons add code to the human genome every time they move, which explains why 500,000 LINE-1 repeats now represent a “staggering” 20 percent of the human genome. These repeats drive genome evolution, but can also cause neurological diseases, cancer, and aging when LINE-1 randomly jumps into essential genes, or triggers an immune response like a virus to cause inflammation.

To copy itself, however, LINE-1 must enter each cell’s nucleus, the inner barrier that houses DNA. Now a new study, published online May 2 in the journal Science Advances, reveals that LINE-1 binds to cellular DNA during the brief periods when nuclei break open as cells continually divide in two, creating replacements to keep tissues viable as we age. The research team found that LINE-1 RNA takes advantage of these moments, assembling into clusters with one of the two proteins it encodes, ORF1p, to hold tightly to DNA until the nucleus reforms after cell division.

Led by researchers at NYU Langone Health and the Munich Gene Center at Ludwig-Maximilians-Universität (LMU) München in Germany, the work revealed specifically that LINE-1 can only bind to DNA when ORF1p — which can bind to RNA, DNA, and itself in linked copies called multimers — accumulates into clusters of hundreds of molecules called condensates. As more ORF1p molecules build up, they eventually envelop the LINE-1 RNA, which makes more binding sites available for the entire cluster to attach to DNA.

“Our study provides crucial insight into how a genetic element that has come to make up a large part of human DNA can successfully invade the nucleus to copy itself, said Liam J. Holt, PhD., associate professor in the Department of Biochemistry and Molecular Pharmacology, and the Institute for Systems Genetics, at NYU Grossman School of Medicine.”These findings on the precise mechanisms behind LINE-1 insertion lay the foundations for the design of future therapies to prevent LINE-1 replication.”

The work also suggests that the LINE-1 condensate acts as a delivery vehicle to bring its RNA into proximity of the right sequences (rich in the DNA bases adenine and thymine) on DNA where the retrotransposon tends to insert, say the study authors. Packaged in its condensates, LINE-1 is thought to evade mechanisms that exclude large particles from the nucleus during mitosis as a cellular defense against viruses.

“LINE-1 condensates have a remarkable feature in that their DNA binding ability emerges only when the ratio of ORF1p copies to RNA is high enough in the condensates,” added Dr. Holt. “Moving forward we will be looking to see if other condensates undergo functional changes as the ratios between their components change.”

Along with Dr. Holt, the first study authors were graduate student Farida Ettefa at NYU Grossman School of Medicine and its Institutes for Systems Genetics; and Sarah Zernia of Gene Center Munich at Ludwig-Maximilians-Universität (LMU) München in Germany. Also study authors were Cas Koeman, Joëlle Deplazes-Lauber, Marvin Freitag, and co-senior author Johannes Stigler from Ludwig-Maximilians-Universität München. The study was supported by the LMU-NYU Research Cooperation Program.

“Despite many advances in understanding the genomic drivers and other factors causing cancer, with few exceptions, stage IV colorectal cancer remains a largely incurable disease,” said Emil Lou, MD, PhD, a gastrointestinal oncologist with the University of Minnesota Medical School, Masonic Cancer Center and M Health Fairview, and clinical principal investigator for the trial. “This trial brings a new approach from our research labs into the clinic and shows potential for improving outcomes in patients with late-stage disease.”

In the study, researchers used CRISPR/Cas9 gene-editing to modify a type of immune cell called tumor-infiltrating lymphocytes (TILs). By deactivating a gene called CISH, the researchers found that modified TILs were better able to recognize and attack cancer cells.

The treatment was tested in 12 highly metastatic, end-stage patients and found to be generally safe, with no serious side effects from the gene editing. Several patients in the trial saw the growth of their cancer halt, and one patient had a complete response, meaning that in this patient, the metastatic tumors disappeared over the course of several months and have not returned in over two years.

“We believe that CISH is a key factor preventing T cells from recognizing and eliminating tumors,” said Branden Moriarity, PhD, associate professor at the University of Minnesota Medical School, Masonic Cancer Center researcher and co-director of the Center for Genome Engineering. “Because it acts inside the cell, it couldn’t be blocked using traditional methods, so we turned to CRISPR-based genetic engineering.”

Unlike other cancer therapies that require ongoing doses, this gene edit is permanent and built into the T cells from the start.

“With our gene-editing approach, the checkpoint inhibition is accomplished in one step and is permanently hardwired into the T cells,” said Beau Webber, PhD, associate professor at the University of Minnesota Medical School and Masonic Cancer Center researcher.

The research team delivered more than 10 billion engineered TIL without adverse side effects, demonstrating the feasibility of genetically engineering TIL without sacrificing the ability to grow them to large numbers in the lab in a clinically compliant environment, which has never been done before.

While the results are promising, the process remains costly and complex. Efforts are underway to streamline production and better understand why the therapy worked so effectively in the patient with a complete response in order to improve the approach in future trials.

This research was funded by Intima Bioscience.

“The Haenyeo are amazing, and their incredible ability is written in their genes,” says geneticist Melissa Ilardo of the University of Utah. “The fact that women are diving through their pregnancy, which is a really tough thing to do, has actually influenced an entire island’s people.”

The Haenyeo, or “women of the sea,” dive year-round in social collectives to harvest food for their communities. They begin training at around age ten and continue for their whole lives. Inspired by the Haenyeo’s remarkable diving abilities, the researchers wanted to know whether they have distinguishable physiological traits that help them cope with the strain of diving, and if so, whether these traits are due to genetic adaptation or training.

To find out, the team compared the physiological traits and genomes of 30 Haenyeo divers to 30 non-Haenyeo people from Jeju, as well as 31 people from mainland Korea. To match the age of the divers, the average age of all participants was 65. The researchers compared the participants’ heart rate and blood pressure at rest and during “simulated dives” where the participants held their breath while submerging their faces in cold water.

“If you hold your breath and put your face in a bowl full of cold water, your body responds as if you’re diving,” says Ilardo. “A lot of the same processes happen in your body that would happen if you were to jump in the ocean, but it’s done in a way that’s safe for people with no diving experience.”

The team’s genomic analysis showed that Jeju residents — both Haenyeo and non-Haenyeo — were distinct from individuals from mainland Korea, suggesting that all Jeju residents are descended from the same ancestral population.

“We can essentially think of everyone from Jeju as either ‘diving Haenyeo’ or ‘non-diving Haenyeo,’ because their genetics are the same,” says Ilardo.

The genomic analysis also revealed two gene variants in the Haenyeo that may help them cope with the pressures of diving, making the Haenyeo the second known population of traditional breath-hold divers that has evolved for diving. One gene is associated with cold tolerance, which could make the divers less vulnerable to hypothermia. The other gene is associated with decreased diastolic blood pressure (i.e., blood pressure in between heart contractions). The variant was found in 33% of participants from Jeju but only 7% of mainland participants.

“This association may reflect natural selection to mitigate the complications of diastolic hypertension experienced by female divers while diving through pregnancy,” says Ilardo. “Since Bajau women also dive while they’re pregnant, we wonder whether pregnancy is actually driving a lot of the genetic changes in these diving populations.”

During the simulated dives, all of the participants showed decreased heart rates, but the Haenyeo’s heart rates dropped significantly more than those of either control group. On average, the divers’ heart rates decreased by 18.8 beats per minute (bpm) compared to a decrease of 12.6 bpm in the Jeju non-divers. A lowered heart rate during diving is beneficial because it saves energy and conserves oxygen. Since their genomic analysis indicated that Haenyeo and non-diving Jeju are genetically members of the same population, the researchers concluded that this feature is likely due to the divers’ training.

“Because the Haenyeo have been diving for a very long time, their heart rate has been trained to drop more,” says Ilardo. “This was something we could actually visually see — we had one diver whose heart rate dropped by over 40 beats per minute in less than 15 seconds.”

The researchers say that these findings highlight the potential of studying traditional diving populations to better understand human genetic and physiological adaptation.

“We’re really excited to learn more about how these genetic changes may be affecting the health of the broader population of Jeju,” says Ilardo. “If we can more deeply characterize how those changes affect physiology, it could inspire the development of therapeutics to treat different conditions, such as hypertensive disorders of pregnancy and stroke.”

This research was supported by the Office of Naval Research, the National Institutes of Health, and the National Science Foundation.

How we make antivenom has not changed much over the past century. Typically, it involves immunizing horses or sheep with venom from single snake species and collecting the antibodies produced. While effective, this process could result in adverse reactions to the non-human antibodies, and treatments tend to be species and region-specific.

While exploring ways to improve this process, scientists stumbled upon someone hyper-immune to the effects of snake neurotoxins. “The donor, for a period of nearly 18 years, had undertaken hundreds of bites and self-immunizations with escalating doses from 16 species of very lethal snakes that would normally a kill a horse,” says first author Jacob Glanville, CEO of Centivax, Inc.

After the donor, Tim Friede, agreed to participate in the study, researchers found that by exposing himself to the venom of various snakes over several years, he had generated antibodies that were effective against several snake neurotoxins at once.

“What was exciting about the donor was his once-in-a-lifetime unique immune history,” says Glanville. “Not only did he potentially create these broadly neutralizing antibodies, in this case, it could give rise to a broad-spectrum or universal antivenom.”

To build the antivenom, the team first created a testing panel with 19 of the World Health Organization’s category 1 and 2 deadliest snakes across the elapid family, a group which contains roughly half of all venomous species, including coral snakes, mambas, cobras, taipans, and kraits. Next, researchers isolated target antibodies from the donor’s blood that reacted with neurotoxins found within the snake species tested. One by one, the antibodies were tested in mice envenomated from each species included in the panel. In this way, scientists could systematically build a cocktail comprising a minimum but sufficient number of components to render all the venoms ineffective.

The team formulated a mixture comprising three major components: two antibodies isolated from the donor and a small molecule. The first donor antibody, called LNX-D09, protected mice from a lethal dose of whole venom from six of the snake species present in the panel. To strengthen the antiserum further, the team added the small molecule varespladib, a known toxin inhibitor, which granted protection against an additional three species. Finally, they added a second antibody isolated from the donor, called SNX-B03, which extended protection across the full panel.

“By the time we reached 3 components, we had a dramatically unparalleled breadth of full protection for 13 of the 19 species and then partial protection for the remaining that we looked at,” says Glanville. “We were looking down at our list and thought, ‘what’s that fourth agent’? And if we could neutralize that, do we get further protection?” Even without a fourth agent, their results suggest that the three-part cocktail could be effective against many other, if not most, elapid snakes not tested in this study.

With the antivenom cocktail proving effective in mouse models, the team now looks to test its efficacy out in the field, beginning by providing the antivenom to dogs brought into veterinary clinics for snake bites in Australia. Further, they wish to develop an antivenom targeting the other major snake family, the vipers.

“We’re turning the crank now, setting up reagents to go through this iterative process of saying what’s the minimum sufficient cocktail to provide broad protection against venom from the viperids,” says lead author Peter Kwong, Richard J. Stock professor of medical sciences at Columbia University Vagelos College of Physicians and Surgeons and formerly of the National Institutes of Health. “The final contemplated product would be a single, pan-antivenom cocktail or we potentially would make two: one that is for the elapids and another that is for the viperids because some areas of the world only have one or the other.”

The other major goal is to approach philanthropic foundations, governments, and pharmaceutical companies to support the manufacturing and clinical development of the broad-spectrum antivenom. “This is critical, because although there are millions of snake envenomations per year, the majority of those are in the developing world, disproportionately affecting rural communities,” Glanville says.

This work was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health, the National Institutes of Health Small Business Innovation Research program, and the US Department of Energy.