Peanut allergies affect about a million children in the U.S., and most never outgrow them. Luckily, some promising remedies are in the works.
Ever since he was a baby, Sharon Wong’s son Brandon suffered from rashes, prolonged respiratory issues and vomiting. In 2006, as a young child, he was diagnosed with a severe peanut allergy.
"My son had a history of reacting to traces of peanuts in the air or in food,” says Wong, a food allergy advocate who runs a blog focusing on nut free recipes, cooking techniques and food allergy awareness. “Any participation in school activities, social events, or travel with his peanut allergy required a lot of preparation.”
Peanut allergies affect around a million children in the U.S. Most never outgrow the condition. The problem occurs when the immune system mistakenly views the proteins in peanuts as a threat and releases chemicals to counteract it. This can lead to digestive problems, hives and shortness of breath. For some, like Wong’s son, even exposure to trace amounts of peanuts could be life threatening. They go into anaphylactic shock and need to take a shot of adrenaline as soon as possible.
Typically, people with peanut allergies try to completely avoid them and carry an adrenaline autoinjector like an EpiPen in case of emergencies. This constant vigilance is very stressful, particularly for parents with young children.
“The search for a peanut allergy ‘cure’ has been a vigorous one,” says Claudia Gray, a pediatrician and allergist at Vincent Pallotti Hospital in Cape Town, South Africa. The closest thing to a solution so far, she says, is the process of desensitization, which exposes the patient to gradually increasing doses of peanut allergen to build up a tolerance. The most common type of desensitization is oral immunotherapy, where patients ingest small quantities of peanut powder. It has been effective but there is a risk of anaphylaxis since it involves swallowing the allergen.
"By the end of the trial, my son tolerated approximately 1.5 peanuts," Sharon Wong says.
DBV Technologies, a company based in Montrouge, France has created a skin patch to address this problem. The Viaskin Patch contains a much lower amount of peanut allergen than oral immunotherapy and delivers it through the skin to slowly increase tolerance. This decreases the risk of anaphylaxis.
Wong heard about the peanut patch and wanted her son to take part in an early phase 2 trial for 4-to-11-year-olds.
“We felt that participating in DBV’s peanut patch trial would give him the best chance at desensitization or at least increase his tolerance from a speck of peanut to a peanut,” Wong says. “The daily routine was quite simple, remove the old patch and then apply a new one. By the end of the trial, he tolerated approximately 1.5 peanuts.”
How it works
For DBV Technologies, it all began when pediatric gastroenterologist Pierre-Henri Benhamou teamed up with fellow professor of gastroenterology Christopher Dupont and his brother, engineer Bertrand Dupont. Together they created a more effective skin patch to detect when babies have allergies to cow's milk. Then they realized that the patch could actually be used to treat allergies by promoting tolerance. They decided to focus on peanut allergies first as the more dangerous.
The Viaskin patch utilizes the fact that the skin can promote tolerance to external stimuli. The skin is the body’s first defense. Controlling the extent of the immune response is crucial for the skin. So it has defense mechanisms against external stimuli and can promote tolerance.
The patch consists of an adhesive foam ring with a plastic film on top. A small amount of peanut protein is placed in the center. The adhesive ring is attached to the back of the patient's body. The peanut protein sits above the skin but does not directly touch it. As the patient sweats, water droplets on the inside of the film dissolve the peanut protein, which is then absorbed into the skin.
The peanut protein is then captured by skin cells called Langerhans cells. They play an important role in getting the immune system to tolerate certain external stimuli. Langerhans cells take the peanut protein to lymph nodes which activate T regulatory cells. T regulatory cells suppress the allergic response.
A different patch is applied to the skin every day to increase tolerance. It’s both easy to use and convenient.
“The DBV approach uses much smaller amounts than oral immunotherapy and works through the skin significantly reducing the risk of allergic reactions,” says Edwin H. Kim, the division chief of Pediatric Allergy and Immunology at the University of North Carolina, U.S., and one of the principal investigators of Viaskin’s clinical trials. “By not going through the mouth, the patch also avoids the taste and texture issues. Finally, the ability to apply a patch and immediately go about your day may be very attractive to very busy patients and families.”
Brandon Wong displaying origami figures he folded at an Origami Convention in 2022
Sharon Wong
Clinical trials
Results from DBV's phase 3 trial in children ages 1 to 3 show its potential. For a positive result, patients who could not tolerate 10 milligrams or less of peanut protein had to be able to manage 300 mg or more after 12 months. Toddlers who could already tolerate more than 10 mg needed to be able to manage 1000 mg or more. In the end, 67 percent of subjects using the Viaskin patch met the target as compared to 33 percent of patients taking the placebo dose.
“The Viaskin peanut patch has been studied in several clinical trials to date with promising results,” says Suzanne M. Barshow, assistant professor of medicine in allergy and asthma research at Stanford University School of Medicine in the U.S. “The data shows that it is safe and well-tolerated. Compared to oral immunotherapy, treatment with the patch results in fewer side effects but appears to be less effective in achieving desensitization.”
The primary reason the patch is less potent is that oral immunotherapy uses a larger amount of the allergen. Additionally, absorption of the peanut protein into the skin could be erratic.
Gray also highlights that there is some tradeoff between risk and efficacy.
“The peanut patch is an exciting advance but not as effective as the oral route,” Gray says. “For those patients who are very sensitive to orally ingested peanut in oral immunotherapy or have an aversion to oral peanut, it has a use. So, essentially, the form of immunotherapy will have to be tailored to each patient.” Having different forms such as the Viaskin patch which is applied to the skin or pills that patients can swallow or dissolve under the tongue is helpful.
The hope is that the patch’s efficacy will increase over time. The team is currently running a follow-up trial, where the same patients continue using the patch.
“It is a very important study to show whether the benefit achieved after 12 months on the patch stays stable or hopefully continues to grow with longer duration,” says Kim, who is an investigator in this follow-up trial.
"My son now attends university in Massachusetts, lives on-campus, and eats dorm food. He has so much more freedom," Wong says.
The team is further ahead in the phase 3 follow-up trial for 4-to-11-year-olds. The initial phase 3 trial was not as successful as the trial for kids between one and three. The patch enabled patients to tolerate more peanuts but there was not a significant enough difference compared to the placebo group to be definitive. The follow-up trial showed greater potency. It suggests that the longer patients are on the patch, the stronger its effects.
They’re also testing if making the patch bigger, changing the shape and extending the minimum time it’s worn can improve its benefits in a trial for a new group of 4-to-11 year-olds.
The future
DBV Technologies is using the skin patch to treat cow’s milk allergies in children ages 1 to 17. They’re currently in phase 2 trials.
As for the peanut allergy trials in toddlers, the hope is to see more efficacy soon.
For Wong’s son who took part in the earlier phase 2 trial for 4-to-11-year-olds, the patch has transformed his life.
“My son continues to maintain his peanut tolerance and is not affected by peanut dust in the air or cross-contact,” Wong says. ”He attends university in Massachusetts, lives on-campus, and eats dorm food. He still carries an EpiPen but has so much more freedom than before his clinical trial. We will always be grateful.”
A worker tends to a rural farm in Hanoi, Vietnam, where technology is making it easier to harvest an ancient fern called Azolla. Some scientists and farmers view Azolla as a solution to our modern-day agricultural and environmental challenges.
This “Arctic Azolla event” had devastating impacts on marine life. To date, scientists are trying to figure out how it ended. But they documented that the extraordinary event cooled down the Arctic by at least 40 degrees Fahrenheit — effectively freezing the poles and triggering several cycles of ice ages. “This carbon dioxide sequestration changed the climate from greenhouse to white house,” says Jonathan Bujak, a paleontologist who has researched the Arctic through expeditions since 1973.
Some farmers and scientists, such as Bujak, are looking to this ancient fern, which manipulated the Earth’s climate around 49 million years ago with its insatiable appetite for carbon dioxide, as a potential solution to our modern-day agricultural and environmental challenges. “There is no other plant like Azolla in the world,” says Bujak.
Decoding the Azolla plant
Azolla lives in symbiosis with a cyanobacterium called Anabaena that made the plant’s leaf cavities its permanent home at an early stage in Earth's history. This close relationship with Anabaena enables Azolla to accomplish a feat that is impossible for most plants: directly splitting dinitrogen molecules that make up 78 percent of the Earth’s atmosphere.
A dinitrogen molecule consists of two nitrogen atoms tightly locked together in one of the strongest bonds in nature. The semi-aquatic fern’s ability to split nitrogen, called nitrogen-fixing, made it a highly revered plant in East Asia. Rice farmers used Azolla as a biofertilizer since the 11th century in Vietnam and China.
For decades, scientists have attempted to decode Azolla’s evolution. Cell biologist Francisco Carrapico, who worked at the University of Lisbon, has analyzed this distinctive symbiosis since the 1980s. To his amazement, in 1991, he found that bacteria are the third partner of the Azolla-Anabaena symbiosis.
“Azolla and Anabaena cannot survive without each other. They have co-evolved for 80 million years, continuously exchanging their genetic material with each other,” says Bujak, co-author of The Azolla Story, which he published with his daughter, Alexandra Bujak, an environmental scientist. Three different levels of nitrogen fixation take place within the plant, as Anabaena draws down as much as 2,200 pounds of atmospheric nitrogen per acre annually.
“Using Azolla to mitigate climate change might sound a bit too simple. But that is not the case,” Bujak says. “At a microscopic level, extremely complicated biochemical reactions are constantly occurring inside the plant’s cells that machines or technology cannot replicate yet.”
In 2018, researchers based in the U.S. managed to sequence Azolla’s complete genome — which is four times larger than the human genome — through a crowdfunded study, further increasing our understanding of this plant. “Azolla is a superorganism that works efficiently as a natural biotechnology system that makes it capable of doubling in size within three to five days,” says Carrapico.
Making Azolla mainstream again in agriculture
While scientific groups in the Global North have been working towards unraveling the tiny fern’s inner workings, communities in the Global South are busy devising creative ways to return to their traditional agricultural roots by tapping into Azolla’s full potential.
Pham Gia Minh, an entrepreneur living in Hanoi, Vietnam, is one such citizen scientist who believes that Azolla could be a climate savior. More than two decades after working in finance and business development, Minh is now focusing on continuing his grandfather’s legacy, an agricultural scientist who conducted Azolla research until the 1950s. “Azolla is our family’s heritage,” says Minh.
Pham Gia Minh, an entrepreneur and citizen scientist in Hanoi, Vietnam, believes that Azolla could be a climate savior
Pham Gia Minh
Since the advent of chemical fertilizers in the early 1900s, farmers in Asia abandoned Azolla to save on time and labor costs. But rice farmers in the country went back to cultivating Azolla during the Vietnam War after chemical trade embargoes made chemical fertilizers far too expensive and inaccessible.
By 1973, Azolla cultivation in rice paddy fields was established on half a million hectares in Vietnam. By injecting nitrogen into the soil, Azolla improves soil fertility and also increases rice yields by at least 27 percent compared to urea. The plants can also reduce a farm’s methane emissions by 40 percent.
“Unfortunately, after 1985, chemical fertilizers became cheap and widely available in Vietnam again. So, farmers stopped growing Azolla because of the time-consuming and labor-intensive cultivation process,” says Minh.
Minh has invested in a rural farm where he is proving that modern technology can make the process less burdensome. He uses a pump and drying equipment for harvesting Azolla in a small pond, and he deploys a drone for spraying insecticides and fertilizers on the pond at regular intervals.
As Azolla lacks phosphorus, farmers in developing countries still find it challenging to let go of chemical fertilizers completely. Still, Minh and Bujak say that farmers can use Azolla instead of chemical fertilizers after mixing it with dung.
In the last few years, the fern’s popularity has been growing in other developing countries like India, Palestine, Indonesia, the Philippines, and Bangladesh, where local governments and citizens are trying to re-introduce Azolla integrated farming by growing the ferns in small ponds.
Replacing soybeans with Azolla
In Ecuador, Mariano Montano Armijos, a former chemical engineer, has worked with Azolla for more than 20 years. Since 2008, he has shared resources and information for growing Azolla with 3,000 farmers in Ecuador. The farmers use the harvested plants as a bio-fertilizer and feed for livestock.
“The farmers do not use urea anymore,” says Armijos. “This goes against the conventional agricultural practices of using huge amounts of synthetic nitrogen on a hectare of rice or corn fields.”
He insists that Azolla’s greatest strength is that it is a rich source of proteins, making it highly nutritious for human beings as well. After growing Azolla on a small scale in ponds, Armijos and his business partner, Ivan Noboa, are now building a facility for cultivating the ferns as a superfood on an industrial scale.
According to Armijos, one hectare of Azolla in Ecuador can produce seven tons of proteins. Whereas soybeans produce only one ton of protein per hectare. “If we switch to Azolla, it could help in reducing deforestation in the Amazon. But taming Azolla and turning it into a crop is not easy,” he adds.
Henriette Schluepmann, a molecular plant biologist at Utrecht University in the Netherlands, believes that Azolla could replace soybeans and chemical fertilizers someday — only if researchers can achieve yield stability in controlled environments over long durations.
“In a country like the Netherlands that is surrounded by water with high levels of phosphates, it makes sense to grow Azolla as a substitute for soybeans,” says Schluepmann. “For that to happen, we need massive investments to understand these ferns’ reproductive system and how to replicate that within aquaculture systems on a large scale.”
Pollution control and carbon sequestration
Currently, Schluepmann and her team are growing Azolla in a plant nursery or closed system before transferring the ferns to flooded fields. So far, they have been able to continuously grow Azolla without any major setbacks for a total of 155 days. Taking care of these plants’ well-being is an uphill struggle.
Unlike most plants, Azolla does not grow from seeds because it contains female and male spores that tend to split instead of reproducing. To add to that, growing Azolla on a large scale in controlled environments makes the floating plants extremely vulnerable to insect infestations and fungi attacks.
“Even though it is easier to grow Azolla on a non-industrial scale, the long and tedious cultivation process is often in conflict with human rights,” she says. Farms in developing countries such as Indonesia sometimes use child labor for cultivating Azolla.”
History has taught us that the uncontrolled growth of Azolla plants deprives marine ecosystems of sunlight and chokes life underneath them. But researchers like Schluepmann and Bujak are optimistic that even on a much smaller scale, Azolla can put up a fight against human-driven climate change.
Schluepmann discovered an insecticide that can control Azolla blooms. But in the wild, this aquatic fern grows relentlessly in polluted rivers and lakes and has gained a notorious reputation as an invasive weed. Countries like Portugal and the UK banned Azolla after experiencing severe blooms in rivers that snuffed out local marine life.
“Azolla has been misunderstood as a nuisance. But in reality, it is highly beneficial for purifying water,” says Bujak. Through a process called phytoremediation, Azolla locks up pollutants like excess nitrogen and phosphorus and stops toxic algal blooms from occurring in rivers and lakes.
A 2018 study found that Azolla can decrease nitrogen and phosphorus levels in wastewater by 33 percent and 40.5 percent, respectively. While harmful algae like phytoplankton produce toxins and release noxious gases, Azolla automatically blocks any toxins that its cyanobacteria, Anabaena, might produce.
“In our labs, we observed that Azolla works effectively in treating wastewater,” explains Schluepmann. “Once we gain a better understanding of Azolla aquaculture, we can also use it for carbon capture and storage. But in Europe, we would have to use the entire Baltic Sea to make a difference.”
Planting massive amounts of these prehistoric ferns in any of the Northern great water bodies is out of the question. After all, history has taught us that the uncontrolled growth of Azolla plants deprives marine ecosystems of sunlight and chokes life underneath them. But researchers like Schluepmann and Bujak are optimistic that even on a much smaller scale, Azolla can put up a fight against human-driven climate change.
Traditional carbon capture and storage methods are not only expensive but also inefficient and could increase air pollution. According to Bujak’s estimates, Azolla can sequester 10 metric tonnes of carbon dioxide per hectare annually, which is 10 times the average capacity of grasslands.
“Anyone can set up their own DIY carbon capture and storage system by growing Azolla in shallow water. After harvesting and compressing the plants, carbon dioxide gets stored permanently,” says Bujak.
He envisions scaling up this process by setting up “Azolla hubs” in mega-cities where the plants are grown in shallow trays stacked on top of each other with vertical farming systems built within multi-story buildings. The compressed Azolla plants can then be converted into a biofuel, fertilizer, livestock feed, or biochar for sequestering carbon dioxide.
“Using Azolla to mitigate climate change might sound a bit too simple. But that is not the case,” Bujak adds. “At a microscopic level, extremely complicated biochemical reactions are constantly occurring inside the plant’s cells that machines or technology cannot replicate yet.”
Through Azolla, scientists hope to work with nature by tapping into four billion years of evolution.
