Congenital disorders
The Study of Smell Loss Still Struggles for Support
Sep
Growing up, Julian Meeks knew what a life without a sense of smell could look like. He’d watched this grandfather navigate the condition, known as anosmia, observing that he didn’t perceive flavor and only enjoyed eating very salty or meaty foods.
The experience influenced him, in part, to study chemosensation, which involves both smell and taste. Meeks, now a professor of neuroscience at the University of Rochester, told Undark that neither gets much attention compared to other senses: “Often, they’re thought of as second or third in order of importance.”
The pandemic changed that, at least somewhat, after it left millions of people without a sense of smell, albeit some temporarily. In particular, more researchers started looking at a specific type of condition called acquired anosmia. Common causes include traumatic brain injury, or TBI, neurodegenerative diseases like Parkinson’s or Alzheimer’s, or following a viral infection like Covid-19. Due to the pandemic, “many people found it scientifically interesting to focus their research on smell,” said Valentina Parma, the assistant director of the Monell Chemical Senses Center, a nonprofit research institute in Philadelphia. By one account, NIH funding of anosmia research nearly doubled between 2019 and 2021.
But many of the research findings do not apply to those who have lacked the ability to smell since birth: congenital anosmics. And, despite the increased attention to smell loss more broadly, some researchers still face challenges in funding studies. In March 2023, for instance, Meeks received a peer review for a small grant, of less than $275,000, from the National Institutes of Health, with which he had planned to look into anosmia in the context of TBI.
For Meeks, the response was frustrating. One expert reviewer in particular “didn’t really understand why there would be any need to establish a preclinical model of anosmia with TBI,” he said, noting that the reviewer also wrote that because anosmia is not a major health problem, the value of the research was low. The comment, Meeks added, was “quite discouraging.”
In response to a request for comment on that decision, Shirley Simson, a spokesperson for NIH’s National Institute on Deafness and Other Communication Disorders, or NIDCD, which funds smell and taste research, replied that “NIH does not discuss the peer review process for individual grant applications.” She noted in a separate email that “all NIH grant applications, including those submitted by investigators to NIDCD, undergo the same review process.”
The sense of smell is complicated, and not fully understood. Jay Piccirillo, an otolaryngologist at Washington University School of Medicine in St. Louis, likens its complexity, with its many neuronal connections, to Times Square. Compared to the nose, the eye looks relatively simple, he told Undark.
There are a few basic steps, however, on which researchers do agree. Humans smell by detecting molecules, or odorants, in the environment around them. These odorants latch on to one of 400 receptors in the nose, called olfactory receptor neurons, which then send a signal the brain. The result: a dizzying array of odors.
“We can smell and discriminate tens of thousands or maybe billions or trillions of smells,” said Hiroaki Matsunami, an olfaction researcher at Duke University who, along with colleagues, recently published a study on how one of these receptors works.
Both congenital and acquired smell loss can either entail complete loss (anosmia) or minimal loss (hyposmia). Some people also have a distorted sense of smell, a condition known as parosmia, or perceive odors that aren’t there, known as phantosmia. And because of the connection between smell and taste, sometimes smell loss is accompanied by the inability to taste, or ageusia, as it did for many Covid patients.
For all of Undark’s coverage of the global Covid-19 pandemic, please visit our extensive coronavirus archive.
Any form of anosmia can have a broad effect on daily function. For one, it can be a safety hazard, since affected people may not be able to detect a fire, gas leak, or spoiled food. Smell loss is also associated with depression, and because of the close link between smell and taste, the condition can affect appetite and, by extension, nutritional health.
The cause of anosmia isn’t entirely known. For congenital anosmia, researchers suspect a genetic link or developmental abnormalities. As for acquired anosmia, an injury or illness appears to disrupt the transmission of an odorant to the brain, but the exact spot of that break isn’t clear — and it may vary, depending on the cause. When it comes to Covid, for instance, some researchers initially suspected that the virus was killing the cells that transmit the odorant signal to the brain. More recent research suggests that, instead, it could be because of inflammation or damaged supporting cells.
It’s also not entirely clear how many people have anosmia. In 2012, research analyzing the U.S. National Health and Nutrition Examination Survey estimated that 23 percent of Americans over the age of 40 report some alteration to their sense of smell. A 2016 paper that examined results from a later version of same survey estimated that more than 12 percent of American adults had some sort of olfactory dysfunction. And Fifth Sense, a charity for smell and taste disorders, estimates that 1 in 10,000 people have congenital anosmia.
The numbers are uncertain in part because, compared to other sensory dysfunctions like vision or hearing loss, experts say there are fewer resources or people involved in smell research. And prior to the pandemic, anosmia research was typically relegated to smell and taste research centers or otolaryngologists (also known as ear, nose, and throat doctors). “It was like a niche,” said Thomas Hummel, a smell and taste disorder researcher at the University of Dresden in Germany. Studying smell loss, he added, wasn’t “in the foreground of research.”
When anosmia was reported as a symptom of Covid-19, there was a switch. Smell and taste researchers were suddenly inundated with requests. For Hummel, who works in a clinic, the phone didn’t stop ringing from patients. Others were similarly in demand. “We were flooded with emails, with calls by patients and reporters,” said Parma. “It was the time I gave the most interviews in my entire career.”
While NIH did not provide Undark with statistics detailing exactly how much the field of smell loss research grew, a search for the word “anosmia” on their online database turned up 35 distinct projects, totaling more than $14.6 million in funding for the 2019 fiscal year. In the 2021 fiscal year, that number grew to $28.5 million in funding for 63 projects.
As a result, experts say, the anosmia research community began collaborating more, wanting to use their knowledge and skills to help in whatever way they could. Many researchers, including Parma, developed smell tests that could gauge a user’s sense of smell and, by extension, to see whether they had a Covid-19 infection at a time when PCR and antigen tests were limited. Some conducted longitudinal surveys where they could track reported progression of smell loss and quality of life among Covid-19 patients. Others started exploring potential treatments of Covid-19-linked anosmia, such as olfactory training and topical steroids.
“We were flooded with emails, with calls by patients and reporters. It was the time I gave the most interviews in my entire career.”
While the effectiveness of such treatments is still unclear, more than three years later, interest in such scientific collaborations is still going strong. “Even if that’s not your primary area of research, many people are at least considering the question or reaching out to other investigators that are experts on taste and smell disorders to ask ‘What is a question I can add in my research?’ or ‘Can we collaborate?” said Paule Joseph, a researcher at NIH’s Division of Intramural Clinical and Biological Research within the National Institute on Alcohol Abuse and Alcoholism.
Despite the interest, some scientists, like Meeks, are still running into the same problems they had before the pandemic: It’s difficult to capture funding and attention related to smell and smell loss. When Meeks took to X, the platform formerly known as Twitter, to lament the discouraging peer feedback on his grant proposal for traumatic brain injury and anosmia, he said, the responses were telling.
“There were several people who responded that they had received similar critiques on their own research grants or their scientific research by whoever was evaluating the research or the grant proposal,” he told Undark. “Although it was nice to know we weren’t singled out, it was a moment where I became a little bit more conscious of the need for greater communication with the broader public and with other scientists.”
Parma thinks some may be dubious to invest in research given the lack of sufficient treatments. “The biggest counterargument is: We don’t know how to treat this, so therefore it’s okay for us not to care about it,” she said. And when there are successes in the field, it’s difficult to implement them on a larger scale. Although Parma’s group has received NIH funding for their smell test, for instance, smell tests are often not covered by insurance.
But research, many scientists in the field say, is not just about developing tests or finding a cure. It’s also about informing and understanding the anosmia experience. This is especially important because not all anosmia affects the olfactory system in the same way — and it is not always treatable. A recent survey found that within a sample of nearly 30,000 Americans who were infected with Covid-19, for instance, 60 percent lost some sense of smell and taste. Among those, a quarter didn’t fully recover.
In one longitudinal survey to assess people who contracted the virus and lost their sense of smell, researchers from Virginia Commonwealth University found that among 267 people, more than half reported partial recovery and 7.5 percent reported none over a two-year period. And out of 946 people who had lost their sense of smell for at least three months, more than half reported partial recovery, and more than 10 percent reported no improvement at all.
“It depends on how severe the damage is,” said Richard Costanzo, director of research at the Smell and Taste Disorders Center at VCU and an author of the study, noting that if there is damage in certain regenerative cells in the nose, there is a lower likelihood of recovery.
While recent studies that focus on Covid-19 anosmia can be applied to other forms of acquired smell loss, one group has largely been left out of research: congenital anosmia. The condition is a different, and understudied, form of anosmia.
“It’s like the community of woodworking but the whole world only knows about wooden bowls,” said Sam Lenarczak, a Seattle-based 23-year-old with the condition. And congenital anosmics, like Lenarczak, want to be understood.
“Every time I look to see if I can get involved in research, they’re recruiting very specific people,” said Charlotte Atkins, who also has congenital anosmia and lives in the U.K. Those studies, she added, are nearly always about acquired smell loss, so she’s unable to participate.
Atkins acknowledges that acquired anosmia can be treated. The culprit, especially in the case of Covid-19, can be known. But she is concerned about what treatment for those conditions could mean for congenital anosmics like her –– or really anyone who hasn’t had a successful recovery. “I worry that with a cure comes no more help with living,” she said, “which is what a lot more people need.”
Some smell loss scientists are still running into the same problems they had before the pandemic: It’s difficult to capture funding and attention.
Joseph, the NIH researcher, agreed that much of anosmia research focuses on smell loss –– and she sees qualitative studies of other anosmics as a next step. By understanding the lived experience, she said, researchers can develop interventions that could help people with smell loss navigate day-today life: “We need evidence to be able to develop policies, to develop guidelines, to just have a way to inform patients of what is the latest thing that could be helpful to them. We need the science.”
Still, there are some Covid-era innovations that may be repurposed. Parma is among a group of researchers pushing to implement testing more universally so that the inability to smell can be gauged earlier on, as many congenital anosmics don’t realize their condition until they start school — or even much later. In Europe, Hummel has received funding for research in olfactory dysfunction more generally, not just reserved to Covid-19 patients.
Meeks is also looking to the future, and determined to push back against the idea that smell is just a luxury and its loss pales in comparison to the loss of any other sense or bodily function. To him, it’s a “dated and narrow-minded view” that needs to be broken if the field wants to keep making progress. And despite the initial pushback from the grant reviewers, Meeks is determined to continue his research. In July, he submitted a new grant application on the topic.
“We’re not going to stop,” he said. “We’re going to keep going as long as we can.”
Hannah Docter-Loeb is a freelance writer based in Washington D.C. Her writing has appeared in the Washington Post, National Geographic, Scientific American, and more.
