User login
Scientists Create First Map of a Human Ovary: What to Know
For years, scientists have sought to create a human artificial ovary, restoring fertility in patients without other options. The first cellular map of a human ovary, recently developed at the University of Michigan, Ann Arbor, represents a big leap forward in that quest.
“You cannot build something if you don’t have the blueprint,” said biomedical engineer Ariella Shikanov, PhD, associate professor at University of Michigan, who helped create what she and colleagues call an atlas of the ovary. “By creating a map or an atlas, we can now follow what nature created and engineer the building blocks of an ovary — and build a nature-like structure.”
So far, the concept of an artificial ovary has been successful only in mice, with the development of a 3D-printed prosthetic ovary that enabled sterilized mice to have pups. Researchers hope that artificial human ovary technology could someday help women left infertile after cancer treatment, as well as patients who don›t respond to fertility treatments and those with premature ovarian failure.
But Dr. Shikanov believes this research will go even further, providing a valuable resource to scientists studying diseases and other conditions related to the ovary.
“Whenever people think about the ovary, if they think about it at all, they usually think about fertility,” said Dr. Shikanov. The ovary is so much more.
Besides producing and carrying a woman’s unfertilized eggs during her lifetime, the ovary is also responsible for endocrine function — the production of estrogen and progesterone, which in addition to supporting reproductive health, help maintain a woman’s cardiovascular, bone, and mental health.
“We don’t really understand everything that is happening in the ovary yet,” Dr. Shikanov said. “But we know it is an important organ.”
Mapping the Ovary
Because people don’t typically donate their ovaries, there are not many available for research, especially from younger reproductive age women, said Dr. Shikanov. So, the scientists set out to build a resource. They described their work in Science Advances.
To create their atlas, the researchers studied two premenopausal donor ovaries, profiling 18,000 genes in 257 regions. From three additional donor ovaries, they also generated single-cell RNA sequencing data for 21,198 cells.
“We identified four major cell types and four immune cell subtypes in the ovary,” said Dr. Shikanov. Taking samples from different areas of the ovary revealed distinct gene activities for oocytes, theca cells, and granulosa cells — expanding scientists’ understanding of the molecular programs driving ovarian follicle development.
What’s unique about their work is the focus on both single cell and spatial analysis, said study coauthor Jun Z. Li, PhD, associate chair of the University of Michigan’s department of computational medicine and bioinformatics. Specifically, they used a relatively new method called spatial transcriptomics, which allows them to see which genes are being activated and where.
“We are constructing the spatial arrangement of the cells in the ovary,” said Dr. Li. “This spatial analysis is like saying, ‘Let me look at where you are and who your neighbor is.’ ”
Their findings are built on other genetic and cellular research in the field, Dr. Li noted. Biomedical engineers in other areas of medicine are applying similar technologies to other organs including the heart, the breast, and bone — part of a larger project called the Human Cell Atlas.
Advancing Women’s Health Research
Historically, women’s health research has been underfunded and underrepresented, but the authors believe their atlas of the ovary is a significant step forward.
“There are a lot of biological questions that we don’t know the answers to about the ovary,” said Dr. Shikanov.
One of the biggest mysteries is why so many eggs never become fertilizable. Each human female is born with about one to two million ovarian follicles. Each follicle carries one immature egg. Around puberty, two thirds of these follicles die off. And most that are left never develop into fertilizable eggs.
“The majority of these follicles either just grow and secrete hormones or undergo atresia,” Dr. Shikanov said. “One question that we wanted to understand is, what determines an egg that can grow, ovulate, and become a fertilizable egg and potentially develop into a new human being from one that does not?”
Another big question researchers have is, what’s happening with other types of cells in the ovary — the supporting cells that produce endocrine hormones? Where are they located and what proteins and RNA are they making? Their research begins to unravel some of these questions and lays a foundation for future studies.
“We wanted to analyze the transcriptional signatures from specific regions and then do bioinformatical analysis and really combine structure, function, and transcriptional signatures,” Dr. Shikanov said.
Knowing the transcriptional signatures can help researchers understand disease mechanisms and then go on to develop treatments for these diseases.
Winifred Mak, MD, PhD, a reproductive endocrinologist and infertility specialist at Dell Medical School, University of Texas, Austin, studies cancer fertility preservation. “For me, it is interesting to see that there are so many different clusters of cells in the ovary that have been identified by this study that we were not necessarily aware of before,” said Dr. Mak, who is not involved in the new research. “Also, the identification of new genes not previously studied in the human ovary.”
What’s Next
Dozens of scientists who study reproductive health are already reaching out to the researchers about their work, Dr. Shikanov said.
“We get contacted almost every day from researchers all around the world asking for data sets or asking for details from this paper,” she said, “from people who study ovarian cancer, for example.”
Dr. Mak said having a map of a normal ovary could also help researchers who study premature ovarian insufficiency — why the ovary sometimes goes into premature menopause — and polycystic ovarian syndrome.
Another big area of research interest is ovarian aging. “Women live so much longer now, but we still reach menopause at the age of 50,” Dr. Shikanov said. “So, there are efforts going toward understanding ovarian aging and maybe preventing it to extend ovarian longevity.”
Dr. Mak said it will enable scientists to “look at different age women and see what genes change across the reproductive lifespan.”
The atlas may also eventually lead to treatments that help restore fertility in individuals who had and were treated for cancer as children, people who undergo sex transitions, and those whose reproductive organs have been impacted by trauma in conflict settings or accidents, Dr. Li said.
The applications are numerous and exciting, Dr. Shikanov said. “Our atlas is like a benchmark. Now researchers can collect ovaries from individuals with these diseases and conditions and try to compare what’s different.”
A version of this article appeared on Medscape.com.
For years, scientists have sought to create a human artificial ovary, restoring fertility in patients without other options. The first cellular map of a human ovary, recently developed at the University of Michigan, Ann Arbor, represents a big leap forward in that quest.
“You cannot build something if you don’t have the blueprint,” said biomedical engineer Ariella Shikanov, PhD, associate professor at University of Michigan, who helped create what she and colleagues call an atlas of the ovary. “By creating a map or an atlas, we can now follow what nature created and engineer the building blocks of an ovary — and build a nature-like structure.”
So far, the concept of an artificial ovary has been successful only in mice, with the development of a 3D-printed prosthetic ovary that enabled sterilized mice to have pups. Researchers hope that artificial human ovary technology could someday help women left infertile after cancer treatment, as well as patients who don›t respond to fertility treatments and those with premature ovarian failure.
But Dr. Shikanov believes this research will go even further, providing a valuable resource to scientists studying diseases and other conditions related to the ovary.
“Whenever people think about the ovary, if they think about it at all, they usually think about fertility,” said Dr. Shikanov. The ovary is so much more.
Besides producing and carrying a woman’s unfertilized eggs during her lifetime, the ovary is also responsible for endocrine function — the production of estrogen and progesterone, which in addition to supporting reproductive health, help maintain a woman’s cardiovascular, bone, and mental health.
“We don’t really understand everything that is happening in the ovary yet,” Dr. Shikanov said. “But we know it is an important organ.”
Mapping the Ovary
Because people don’t typically donate their ovaries, there are not many available for research, especially from younger reproductive age women, said Dr. Shikanov. So, the scientists set out to build a resource. They described their work in Science Advances.
To create their atlas, the researchers studied two premenopausal donor ovaries, profiling 18,000 genes in 257 regions. From three additional donor ovaries, they also generated single-cell RNA sequencing data for 21,198 cells.
“We identified four major cell types and four immune cell subtypes in the ovary,” said Dr. Shikanov. Taking samples from different areas of the ovary revealed distinct gene activities for oocytes, theca cells, and granulosa cells — expanding scientists’ understanding of the molecular programs driving ovarian follicle development.
What’s unique about their work is the focus on both single cell and spatial analysis, said study coauthor Jun Z. Li, PhD, associate chair of the University of Michigan’s department of computational medicine and bioinformatics. Specifically, they used a relatively new method called spatial transcriptomics, which allows them to see which genes are being activated and where.
“We are constructing the spatial arrangement of the cells in the ovary,” said Dr. Li. “This spatial analysis is like saying, ‘Let me look at where you are and who your neighbor is.’ ”
Their findings are built on other genetic and cellular research in the field, Dr. Li noted. Biomedical engineers in other areas of medicine are applying similar technologies to other organs including the heart, the breast, and bone — part of a larger project called the Human Cell Atlas.
Advancing Women’s Health Research
Historically, women’s health research has been underfunded and underrepresented, but the authors believe their atlas of the ovary is a significant step forward.
“There are a lot of biological questions that we don’t know the answers to about the ovary,” said Dr. Shikanov.
One of the biggest mysteries is why so many eggs never become fertilizable. Each human female is born with about one to two million ovarian follicles. Each follicle carries one immature egg. Around puberty, two thirds of these follicles die off. And most that are left never develop into fertilizable eggs.
“The majority of these follicles either just grow and secrete hormones or undergo atresia,” Dr. Shikanov said. “One question that we wanted to understand is, what determines an egg that can grow, ovulate, and become a fertilizable egg and potentially develop into a new human being from one that does not?”
Another big question researchers have is, what’s happening with other types of cells in the ovary — the supporting cells that produce endocrine hormones? Where are they located and what proteins and RNA are they making? Their research begins to unravel some of these questions and lays a foundation for future studies.
“We wanted to analyze the transcriptional signatures from specific regions and then do bioinformatical analysis and really combine structure, function, and transcriptional signatures,” Dr. Shikanov said.
Knowing the transcriptional signatures can help researchers understand disease mechanisms and then go on to develop treatments for these diseases.
Winifred Mak, MD, PhD, a reproductive endocrinologist and infertility specialist at Dell Medical School, University of Texas, Austin, studies cancer fertility preservation. “For me, it is interesting to see that there are so many different clusters of cells in the ovary that have been identified by this study that we were not necessarily aware of before,” said Dr. Mak, who is not involved in the new research. “Also, the identification of new genes not previously studied in the human ovary.”
What’s Next
Dozens of scientists who study reproductive health are already reaching out to the researchers about their work, Dr. Shikanov said.
“We get contacted almost every day from researchers all around the world asking for data sets or asking for details from this paper,” she said, “from people who study ovarian cancer, for example.”
Dr. Mak said having a map of a normal ovary could also help researchers who study premature ovarian insufficiency — why the ovary sometimes goes into premature menopause — and polycystic ovarian syndrome.
Another big area of research interest is ovarian aging. “Women live so much longer now, but we still reach menopause at the age of 50,” Dr. Shikanov said. “So, there are efforts going toward understanding ovarian aging and maybe preventing it to extend ovarian longevity.”
Dr. Mak said it will enable scientists to “look at different age women and see what genes change across the reproductive lifespan.”
The atlas may also eventually lead to treatments that help restore fertility in individuals who had and were treated for cancer as children, people who undergo sex transitions, and those whose reproductive organs have been impacted by trauma in conflict settings or accidents, Dr. Li said.
The applications are numerous and exciting, Dr. Shikanov said. “Our atlas is like a benchmark. Now researchers can collect ovaries from individuals with these diseases and conditions and try to compare what’s different.”
A version of this article appeared on Medscape.com.
For years, scientists have sought to create a human artificial ovary, restoring fertility in patients without other options. The first cellular map of a human ovary, recently developed at the University of Michigan, Ann Arbor, represents a big leap forward in that quest.
“You cannot build something if you don’t have the blueprint,” said biomedical engineer Ariella Shikanov, PhD, associate professor at University of Michigan, who helped create what she and colleagues call an atlas of the ovary. “By creating a map or an atlas, we can now follow what nature created and engineer the building blocks of an ovary — and build a nature-like structure.”
So far, the concept of an artificial ovary has been successful only in mice, with the development of a 3D-printed prosthetic ovary that enabled sterilized mice to have pups. Researchers hope that artificial human ovary technology could someday help women left infertile after cancer treatment, as well as patients who don›t respond to fertility treatments and those with premature ovarian failure.
But Dr. Shikanov believes this research will go even further, providing a valuable resource to scientists studying diseases and other conditions related to the ovary.
“Whenever people think about the ovary, if they think about it at all, they usually think about fertility,” said Dr. Shikanov. The ovary is so much more.
Besides producing and carrying a woman’s unfertilized eggs during her lifetime, the ovary is also responsible for endocrine function — the production of estrogen and progesterone, which in addition to supporting reproductive health, help maintain a woman’s cardiovascular, bone, and mental health.
“We don’t really understand everything that is happening in the ovary yet,” Dr. Shikanov said. “But we know it is an important organ.”
Mapping the Ovary
Because people don’t typically donate their ovaries, there are not many available for research, especially from younger reproductive age women, said Dr. Shikanov. So, the scientists set out to build a resource. They described their work in Science Advances.
To create their atlas, the researchers studied two premenopausal donor ovaries, profiling 18,000 genes in 257 regions. From three additional donor ovaries, they also generated single-cell RNA sequencing data for 21,198 cells.
“We identified four major cell types and four immune cell subtypes in the ovary,” said Dr. Shikanov. Taking samples from different areas of the ovary revealed distinct gene activities for oocytes, theca cells, and granulosa cells — expanding scientists’ understanding of the molecular programs driving ovarian follicle development.
What’s unique about their work is the focus on both single cell and spatial analysis, said study coauthor Jun Z. Li, PhD, associate chair of the University of Michigan’s department of computational medicine and bioinformatics. Specifically, they used a relatively new method called spatial transcriptomics, which allows them to see which genes are being activated and where.
“We are constructing the spatial arrangement of the cells in the ovary,” said Dr. Li. “This spatial analysis is like saying, ‘Let me look at where you are and who your neighbor is.’ ”
Their findings are built on other genetic and cellular research in the field, Dr. Li noted. Biomedical engineers in other areas of medicine are applying similar technologies to other organs including the heart, the breast, and bone — part of a larger project called the Human Cell Atlas.
Advancing Women’s Health Research
Historically, women’s health research has been underfunded and underrepresented, but the authors believe their atlas of the ovary is a significant step forward.
“There are a lot of biological questions that we don’t know the answers to about the ovary,” said Dr. Shikanov.
One of the biggest mysteries is why so many eggs never become fertilizable. Each human female is born with about one to two million ovarian follicles. Each follicle carries one immature egg. Around puberty, two thirds of these follicles die off. And most that are left never develop into fertilizable eggs.
“The majority of these follicles either just grow and secrete hormones or undergo atresia,” Dr. Shikanov said. “One question that we wanted to understand is, what determines an egg that can grow, ovulate, and become a fertilizable egg and potentially develop into a new human being from one that does not?”
Another big question researchers have is, what’s happening with other types of cells in the ovary — the supporting cells that produce endocrine hormones? Where are they located and what proteins and RNA are they making? Their research begins to unravel some of these questions and lays a foundation for future studies.
“We wanted to analyze the transcriptional signatures from specific regions and then do bioinformatical analysis and really combine structure, function, and transcriptional signatures,” Dr. Shikanov said.
Knowing the transcriptional signatures can help researchers understand disease mechanisms and then go on to develop treatments for these diseases.
Winifred Mak, MD, PhD, a reproductive endocrinologist and infertility specialist at Dell Medical School, University of Texas, Austin, studies cancer fertility preservation. “For me, it is interesting to see that there are so many different clusters of cells in the ovary that have been identified by this study that we were not necessarily aware of before,” said Dr. Mak, who is not involved in the new research. “Also, the identification of new genes not previously studied in the human ovary.”
What’s Next
Dozens of scientists who study reproductive health are already reaching out to the researchers about their work, Dr. Shikanov said.
“We get contacted almost every day from researchers all around the world asking for data sets or asking for details from this paper,” she said, “from people who study ovarian cancer, for example.”
Dr. Mak said having a map of a normal ovary could also help researchers who study premature ovarian insufficiency — why the ovary sometimes goes into premature menopause — and polycystic ovarian syndrome.
Another big area of research interest is ovarian aging. “Women live so much longer now, but we still reach menopause at the age of 50,” Dr. Shikanov said. “So, there are efforts going toward understanding ovarian aging and maybe preventing it to extend ovarian longevity.”
Dr. Mak said it will enable scientists to “look at different age women and see what genes change across the reproductive lifespan.”
The atlas may also eventually lead to treatments that help restore fertility in individuals who had and were treated for cancer as children, people who undergo sex transitions, and those whose reproductive organs have been impacted by trauma in conflict settings or accidents, Dr. Li said.
The applications are numerous and exciting, Dr. Shikanov said. “Our atlas is like a benchmark. Now researchers can collect ovaries from individuals with these diseases and conditions and try to compare what’s different.”
A version of this article appeared on Medscape.com.
Poop Doesn’t Lie: What Fecal ‘Forensics’ Tells Us About Diet
A lightbulb moment hit as Lawrence David was chatting one day with an ecologist who studies the microbiomes and diets of large herbivores in the African savanna. David was envious. He’d been studying the human microbiome, and this ecologist had tons of animal statistics that were way more specific than what David had obtained from people.
“How on earth do you get all these dietary data?” David recalled asking. “Obviously, he didn’t ask the animals what they ate.”
All those specific statistics came from DNA sequencing of animal scat scooped up from the savanna.
Indeed.
Depending on when you read this, you may have the DNA of more than a dozen plant species, plus another three or four animal species, gurgling through your gut. That’s the straight poop taken straight from, well, poop.
Diet, DNA, and Feces
Everything we eat (except vitamins, minerals, and salt) came from something that was living, and all living things have genomes.
“A decent fraction of that DNA” goes undigested and is then excreted, said David, a PhD and associate professor of molecular genetics and microbiology at Duke University, Durham, North Carolina.
“We are using DNA sequencing to reconstruct what people eat,” David said. “We try to see if there are patterns in what people eat and how we can measure them by DNA, or kind of genetic forensics.” Then they connect that data to health outcomes like obesity.
A typical person’s excrement probably contains the DNA of 10-20 plant species and three or four types of animal DNA. “And that’s the average person. Some people may have more like 40 types at any given time,” David said.
Studying DNA in human feces has potential applications in research and in clinical settings. For instance, it could help design personalized nutrition strategies for patients, something that’s already being tested. He hopes that DNA information will help “connect patterns in what people eat to their microbiomes.”
One big advantage: Feces don’t lie. In reconstructing someone’s diet, people either forget what they ate, fudge the truth, or can’t be bothered to keep track.
“Patients report the fruit they ate yesterday but not the M&Ms,” said Neil Stollman, MD, chief of the division of gastroenterology at Alta Bates Summit Medical Center in Oakland, California.
Some people can’t write it all down because they’re too old or too young — the very people at highest risk of nutrition-associated disease, said David.
Fetching and Figuring Out Feces
It’s a lot of work to collect and analyze fecal matter, for ethical, legal, and logistical reasons. “And then there’s sort of an ick factor to this kind of work,” David said.
To get samples, people place a plastic collection cup under the toilet seat to catch the stool. The person then swabs or scoops some of that into a tube, seals the top, and either brings it in or mails it to the lab.
In the lab, David said, “if the DNA is still inside the plant cells, we crack the cells open using a variety of methods. We use what’s called ‘a stomacher,’ which is like two big paddles, and we load the poop [which is in a plastic bag] into it and then squash it — mash it up. We also sometimes load small particles of what is basically glass into it and then shake really hard — it is another way you can physically break open the plant cells. This can also be done with chemicals. It’s like a chemistry lab,” he said, noting that this process takes about half a day to do.
There is much more bacterial DNA in stool than there is food DNA, and even a little human DNA and sometimes fungi, said David. “The concentration of bacteria in stool is amongst the highest concentrations of bacteria on the planet,” he said, but his lab focuses on the plant DNA they find.
They use a molecular process called polymerase chain reaction (PCR) that amplifies and selectively copies DNA from plants. (The scientists who invented this “ingenious” process won a Nobel Prize, David noted.) Like a COVID PCR test, the process only matches up for certain kinds of DNA and can be designed to be more specific or less specific. In David’s lab, they shoot for a middle ground of specificity, where the PCR process is targeting chloroplasts in plants.
Once they’ve detected all the different sequences of food species, they need to find the DNA code, a time-consuming step. His colleague Briana Petrone compiled a reference database of specific sequences of DNA that correspond to different species of plants. This work took more than a year, said David, noting that only a handful of other labs around the country are sequencing DNA in feces, most of them looking at it in animals, not humans.
There are 200,000 to 300,000 species of edible plants estimated to be on the planet, he said. “I think historically, humans have eaten about 7000 of them. We’re kind of like a walking repository of all this genetic material.”
What Scientists Learn from Fecal DNA
Tracking DNA in digested food can provide valuable data to researchers — information that could have a major impact on nutritional guidance for people with obesity and digestive diseases and other gastrointestinal and nutrition-related issues.
David and Petrone’s 2023 study analyzing DNA in stool samples, published in the Proceedings of the National Academy of Sciences (PNAS), showed what — and roughly how much — people ate.
They noticed that kids with obesity had a higher diversity of plants in them than kids without obesity. Sounds backward — wouldn’t a child who eats more plants be a healthier weight? “The more I dug into it, it turns out that foods that are more processed often tend to have more ingredients. So, a Big Mac and fries and a coffee have 19 different plant species,” said David.
Going forward, he said, researchers may have to be “more specific about how we think about dietary diversity. Maybe not all plant species count toward health in the same way.”
David’s work provides an innovative way to conduct nutrition research, said Jotham Suez, PhD, an assistant professor in the department of molecular microbiology and immunology at Johns Hopkins Bloomberg School of Public Health.
“We need to have some means of tracking what people actually ate during a study, whether it’s an intervention where we provide them with the food or an observational study where we let people eat their habitual diet and track it themselves,” said Suez, who studies the gut microbiome.
“Recall bias” makes food questionnaires and apps unreliable. And research suggests that some participants may underreport food intake, possibly because they don’t want to be judged or they misestimate how much they actually consumed.
“There’s huge promise” with a tool like the one described in the PNAS study for making connections between diet and disease, Suez said. But access may be an issue for many researchers. He expects techniques to improve and costs to go down, but there will be challenges. “This method is also almost exclusively looking at plant DNA material, Suez added, “and our diets contain multiple components that are not plants.”
And even if a person just eats an apple or a single cucumber, that food may be degraded somewhere else in the gut, and it may be digested differently in different people’s guts. “Metabolism, of course, can be different between people,” Suez said, so the amounts of data will vary. “In their study, the qualitative data is convincing. The quantitative is TBD [to be determined].”
But he said it might be “a perfect tool” for scientists who want to study indigestible fiber, which is an important area of science, too.
“I totally buy it as a potentially better way to do dietary analytics for disease associations,” said Stollman, an expert in fecal transplant and diverticulitis and a trustee of the American College of Gastroenterology. Stollman sees many patients with diverticular disease who could benefit.
“One of the core questions in the diverticular world is, what causes diverticular disease, so we can ideally prevent it? For decades, the theory has been that a low fiber diet contributes to it,” said Stollman, but testing DNA in patients’ stools could help researchers explore the question in a new and potentially more nuanced and accurate way. Findings might allow scientists to learn, “Do people who eat X get polyps? Is this diet a risk factor for X, Y, or Z disease?” said Stollman.
Future Clinical Applications
Brenda Davy, PhD, is a registered dietitian and professor in the Department of Human Nutrition, Foods, and Exercise at Virginia Tech. She conducts research investigating the role of diet in the prevention and treatment of obesity and related conditions such as type 2 diabetes. She also develops dietary assessment methods. More than a decade ago, she developed one of the first rapid assessment tools for quantifying beverage intake — the Beverage Intake Questionnaire — an assessment that is still used today.
“Dietary assessment is necessary in both research and clinical settings,” Davy said. “If a physician diagnoses a patient with a certain condition, information about the patient’s usual dietary habits can help him or her prescribe dietary changes that may help treat that condition.”
Biospecimens, like fecal and urine samples, can be a safe, accurate way to collect that data, she said. Samples can be obtained easily and noninvasively “in a wide variety of populations such as children or older adults” and in clinical settings.
Davy and her team use David’s technology in their work — in particular, a tool called FoodSeq that applies DNA metabarcoding to human stool to collect information about food taxa consumed. Their two labs are now collaborating on a project investigating how ultraprocessed foods might impact type 2 diabetes risk and cardiovascular health.
There are many directions David’s lab would like to take their research, possibly partnering with epidemiologists on global studies that would help them expand their DNA database and better understand how, for example, climate change may be affecting diet diversity and to learn more about diet across different populations.
A version of this article appeared on Medscape.com.
A lightbulb moment hit as Lawrence David was chatting one day with an ecologist who studies the microbiomes and diets of large herbivores in the African savanna. David was envious. He’d been studying the human microbiome, and this ecologist had tons of animal statistics that were way more specific than what David had obtained from people.
“How on earth do you get all these dietary data?” David recalled asking. “Obviously, he didn’t ask the animals what they ate.”
All those specific statistics came from DNA sequencing of animal scat scooped up from the savanna.
Indeed.
Depending on when you read this, you may have the DNA of more than a dozen plant species, plus another three or four animal species, gurgling through your gut. That’s the straight poop taken straight from, well, poop.
Diet, DNA, and Feces
Everything we eat (except vitamins, minerals, and salt) came from something that was living, and all living things have genomes.
“A decent fraction of that DNA” goes undigested and is then excreted, said David, a PhD and associate professor of molecular genetics and microbiology at Duke University, Durham, North Carolina.
“We are using DNA sequencing to reconstruct what people eat,” David said. “We try to see if there are patterns in what people eat and how we can measure them by DNA, or kind of genetic forensics.” Then they connect that data to health outcomes like obesity.
A typical person’s excrement probably contains the DNA of 10-20 plant species and three or four types of animal DNA. “And that’s the average person. Some people may have more like 40 types at any given time,” David said.
Studying DNA in human feces has potential applications in research and in clinical settings. For instance, it could help design personalized nutrition strategies for patients, something that’s already being tested. He hopes that DNA information will help “connect patterns in what people eat to their microbiomes.”
One big advantage: Feces don’t lie. In reconstructing someone’s diet, people either forget what they ate, fudge the truth, or can’t be bothered to keep track.
“Patients report the fruit they ate yesterday but not the M&Ms,” said Neil Stollman, MD, chief of the division of gastroenterology at Alta Bates Summit Medical Center in Oakland, California.
Some people can’t write it all down because they’re too old or too young — the very people at highest risk of nutrition-associated disease, said David.
Fetching and Figuring Out Feces
It’s a lot of work to collect and analyze fecal matter, for ethical, legal, and logistical reasons. “And then there’s sort of an ick factor to this kind of work,” David said.
To get samples, people place a plastic collection cup under the toilet seat to catch the stool. The person then swabs or scoops some of that into a tube, seals the top, and either brings it in or mails it to the lab.
In the lab, David said, “if the DNA is still inside the plant cells, we crack the cells open using a variety of methods. We use what’s called ‘a stomacher,’ which is like two big paddles, and we load the poop [which is in a plastic bag] into it and then squash it — mash it up. We also sometimes load small particles of what is basically glass into it and then shake really hard — it is another way you can physically break open the plant cells. This can also be done with chemicals. It’s like a chemistry lab,” he said, noting that this process takes about half a day to do.
There is much more bacterial DNA in stool than there is food DNA, and even a little human DNA and sometimes fungi, said David. “The concentration of bacteria in stool is amongst the highest concentrations of bacteria on the planet,” he said, but his lab focuses on the plant DNA they find.
They use a molecular process called polymerase chain reaction (PCR) that amplifies and selectively copies DNA from plants. (The scientists who invented this “ingenious” process won a Nobel Prize, David noted.) Like a COVID PCR test, the process only matches up for certain kinds of DNA and can be designed to be more specific or less specific. In David’s lab, they shoot for a middle ground of specificity, where the PCR process is targeting chloroplasts in plants.
Once they’ve detected all the different sequences of food species, they need to find the DNA code, a time-consuming step. His colleague Briana Petrone compiled a reference database of specific sequences of DNA that correspond to different species of plants. This work took more than a year, said David, noting that only a handful of other labs around the country are sequencing DNA in feces, most of them looking at it in animals, not humans.
There are 200,000 to 300,000 species of edible plants estimated to be on the planet, he said. “I think historically, humans have eaten about 7000 of them. We’re kind of like a walking repository of all this genetic material.”
What Scientists Learn from Fecal DNA
Tracking DNA in digested food can provide valuable data to researchers — information that could have a major impact on nutritional guidance for people with obesity and digestive diseases and other gastrointestinal and nutrition-related issues.
David and Petrone’s 2023 study analyzing DNA in stool samples, published in the Proceedings of the National Academy of Sciences (PNAS), showed what — and roughly how much — people ate.
They noticed that kids with obesity had a higher diversity of plants in them than kids without obesity. Sounds backward — wouldn’t a child who eats more plants be a healthier weight? “The more I dug into it, it turns out that foods that are more processed often tend to have more ingredients. So, a Big Mac and fries and a coffee have 19 different plant species,” said David.
Going forward, he said, researchers may have to be “more specific about how we think about dietary diversity. Maybe not all plant species count toward health in the same way.”
David’s work provides an innovative way to conduct nutrition research, said Jotham Suez, PhD, an assistant professor in the department of molecular microbiology and immunology at Johns Hopkins Bloomberg School of Public Health.
“We need to have some means of tracking what people actually ate during a study, whether it’s an intervention where we provide them with the food or an observational study where we let people eat their habitual diet and track it themselves,” said Suez, who studies the gut microbiome.
“Recall bias” makes food questionnaires and apps unreliable. And research suggests that some participants may underreport food intake, possibly because they don’t want to be judged or they misestimate how much they actually consumed.
“There’s huge promise” with a tool like the one described in the PNAS study for making connections between diet and disease, Suez said. But access may be an issue for many researchers. He expects techniques to improve and costs to go down, but there will be challenges. “This method is also almost exclusively looking at plant DNA material, Suez added, “and our diets contain multiple components that are not plants.”
And even if a person just eats an apple or a single cucumber, that food may be degraded somewhere else in the gut, and it may be digested differently in different people’s guts. “Metabolism, of course, can be different between people,” Suez said, so the amounts of data will vary. “In their study, the qualitative data is convincing. The quantitative is TBD [to be determined].”
But he said it might be “a perfect tool” for scientists who want to study indigestible fiber, which is an important area of science, too.
“I totally buy it as a potentially better way to do dietary analytics for disease associations,” said Stollman, an expert in fecal transplant and diverticulitis and a trustee of the American College of Gastroenterology. Stollman sees many patients with diverticular disease who could benefit.
“One of the core questions in the diverticular world is, what causes diverticular disease, so we can ideally prevent it? For decades, the theory has been that a low fiber diet contributes to it,” said Stollman, but testing DNA in patients’ stools could help researchers explore the question in a new and potentially more nuanced and accurate way. Findings might allow scientists to learn, “Do people who eat X get polyps? Is this diet a risk factor for X, Y, or Z disease?” said Stollman.
Future Clinical Applications
Brenda Davy, PhD, is a registered dietitian and professor in the Department of Human Nutrition, Foods, and Exercise at Virginia Tech. She conducts research investigating the role of diet in the prevention and treatment of obesity and related conditions such as type 2 diabetes. She also develops dietary assessment methods. More than a decade ago, she developed one of the first rapid assessment tools for quantifying beverage intake — the Beverage Intake Questionnaire — an assessment that is still used today.
“Dietary assessment is necessary in both research and clinical settings,” Davy said. “If a physician diagnoses a patient with a certain condition, information about the patient’s usual dietary habits can help him or her prescribe dietary changes that may help treat that condition.”
Biospecimens, like fecal and urine samples, can be a safe, accurate way to collect that data, she said. Samples can be obtained easily and noninvasively “in a wide variety of populations such as children or older adults” and in clinical settings.
Davy and her team use David’s technology in their work — in particular, a tool called FoodSeq that applies DNA metabarcoding to human stool to collect information about food taxa consumed. Their two labs are now collaborating on a project investigating how ultraprocessed foods might impact type 2 diabetes risk and cardiovascular health.
There are many directions David’s lab would like to take their research, possibly partnering with epidemiologists on global studies that would help them expand their DNA database and better understand how, for example, climate change may be affecting diet diversity and to learn more about diet across different populations.
A version of this article appeared on Medscape.com.
A lightbulb moment hit as Lawrence David was chatting one day with an ecologist who studies the microbiomes and diets of large herbivores in the African savanna. David was envious. He’d been studying the human microbiome, and this ecologist had tons of animal statistics that were way more specific than what David had obtained from people.
“How on earth do you get all these dietary data?” David recalled asking. “Obviously, he didn’t ask the animals what they ate.”
All those specific statistics came from DNA sequencing of animal scat scooped up from the savanna.
Indeed.
Depending on when you read this, you may have the DNA of more than a dozen plant species, plus another three or four animal species, gurgling through your gut. That’s the straight poop taken straight from, well, poop.
Diet, DNA, and Feces
Everything we eat (except vitamins, minerals, and salt) came from something that was living, and all living things have genomes.
“A decent fraction of that DNA” goes undigested and is then excreted, said David, a PhD and associate professor of molecular genetics and microbiology at Duke University, Durham, North Carolina.
“We are using DNA sequencing to reconstruct what people eat,” David said. “We try to see if there are patterns in what people eat and how we can measure them by DNA, or kind of genetic forensics.” Then they connect that data to health outcomes like obesity.
A typical person’s excrement probably contains the DNA of 10-20 plant species and three or four types of animal DNA. “And that’s the average person. Some people may have more like 40 types at any given time,” David said.
Studying DNA in human feces has potential applications in research and in clinical settings. For instance, it could help design personalized nutrition strategies for patients, something that’s already being tested. He hopes that DNA information will help “connect patterns in what people eat to their microbiomes.”
One big advantage: Feces don’t lie. In reconstructing someone’s diet, people either forget what they ate, fudge the truth, or can’t be bothered to keep track.
“Patients report the fruit they ate yesterday but not the M&Ms,” said Neil Stollman, MD, chief of the division of gastroenterology at Alta Bates Summit Medical Center in Oakland, California.
Some people can’t write it all down because they’re too old or too young — the very people at highest risk of nutrition-associated disease, said David.
Fetching and Figuring Out Feces
It’s a lot of work to collect and analyze fecal matter, for ethical, legal, and logistical reasons. “And then there’s sort of an ick factor to this kind of work,” David said.
To get samples, people place a plastic collection cup under the toilet seat to catch the stool. The person then swabs or scoops some of that into a tube, seals the top, and either brings it in or mails it to the lab.
In the lab, David said, “if the DNA is still inside the plant cells, we crack the cells open using a variety of methods. We use what’s called ‘a stomacher,’ which is like two big paddles, and we load the poop [which is in a plastic bag] into it and then squash it — mash it up. We also sometimes load small particles of what is basically glass into it and then shake really hard — it is another way you can physically break open the plant cells. This can also be done with chemicals. It’s like a chemistry lab,” he said, noting that this process takes about half a day to do.
There is much more bacterial DNA in stool than there is food DNA, and even a little human DNA and sometimes fungi, said David. “The concentration of bacteria in stool is amongst the highest concentrations of bacteria on the planet,” he said, but his lab focuses on the plant DNA they find.
They use a molecular process called polymerase chain reaction (PCR) that amplifies and selectively copies DNA from plants. (The scientists who invented this “ingenious” process won a Nobel Prize, David noted.) Like a COVID PCR test, the process only matches up for certain kinds of DNA and can be designed to be more specific or less specific. In David’s lab, they shoot for a middle ground of specificity, where the PCR process is targeting chloroplasts in plants.
Once they’ve detected all the different sequences of food species, they need to find the DNA code, a time-consuming step. His colleague Briana Petrone compiled a reference database of specific sequences of DNA that correspond to different species of plants. This work took more than a year, said David, noting that only a handful of other labs around the country are sequencing DNA in feces, most of them looking at it in animals, not humans.
There are 200,000 to 300,000 species of edible plants estimated to be on the planet, he said. “I think historically, humans have eaten about 7000 of them. We’re kind of like a walking repository of all this genetic material.”
What Scientists Learn from Fecal DNA
Tracking DNA in digested food can provide valuable data to researchers — information that could have a major impact on nutritional guidance for people with obesity and digestive diseases and other gastrointestinal and nutrition-related issues.
David and Petrone’s 2023 study analyzing DNA in stool samples, published in the Proceedings of the National Academy of Sciences (PNAS), showed what — and roughly how much — people ate.
They noticed that kids with obesity had a higher diversity of plants in them than kids without obesity. Sounds backward — wouldn’t a child who eats more plants be a healthier weight? “The more I dug into it, it turns out that foods that are more processed often tend to have more ingredients. So, a Big Mac and fries and a coffee have 19 different plant species,” said David.
Going forward, he said, researchers may have to be “more specific about how we think about dietary diversity. Maybe not all plant species count toward health in the same way.”
David’s work provides an innovative way to conduct nutrition research, said Jotham Suez, PhD, an assistant professor in the department of molecular microbiology and immunology at Johns Hopkins Bloomberg School of Public Health.
“We need to have some means of tracking what people actually ate during a study, whether it’s an intervention where we provide them with the food or an observational study where we let people eat their habitual diet and track it themselves,” said Suez, who studies the gut microbiome.
“Recall bias” makes food questionnaires and apps unreliable. And research suggests that some participants may underreport food intake, possibly because they don’t want to be judged or they misestimate how much they actually consumed.
“There’s huge promise” with a tool like the one described in the PNAS study for making connections between diet and disease, Suez said. But access may be an issue for many researchers. He expects techniques to improve and costs to go down, but there will be challenges. “This method is also almost exclusively looking at plant DNA material, Suez added, “and our diets contain multiple components that are not plants.”
And even if a person just eats an apple or a single cucumber, that food may be degraded somewhere else in the gut, and it may be digested differently in different people’s guts. “Metabolism, of course, can be different between people,” Suez said, so the amounts of data will vary. “In their study, the qualitative data is convincing. The quantitative is TBD [to be determined].”
But he said it might be “a perfect tool” for scientists who want to study indigestible fiber, which is an important area of science, too.
“I totally buy it as a potentially better way to do dietary analytics for disease associations,” said Stollman, an expert in fecal transplant and diverticulitis and a trustee of the American College of Gastroenterology. Stollman sees many patients with diverticular disease who could benefit.
“One of the core questions in the diverticular world is, what causes diverticular disease, so we can ideally prevent it? For decades, the theory has been that a low fiber diet contributes to it,” said Stollman, but testing DNA in patients’ stools could help researchers explore the question in a new and potentially more nuanced and accurate way. Findings might allow scientists to learn, “Do people who eat X get polyps? Is this diet a risk factor for X, Y, or Z disease?” said Stollman.
Future Clinical Applications
Brenda Davy, PhD, is a registered dietitian and professor in the Department of Human Nutrition, Foods, and Exercise at Virginia Tech. She conducts research investigating the role of diet in the prevention and treatment of obesity and related conditions such as type 2 diabetes. She also develops dietary assessment methods. More than a decade ago, she developed one of the first rapid assessment tools for quantifying beverage intake — the Beverage Intake Questionnaire — an assessment that is still used today.
“Dietary assessment is necessary in both research and clinical settings,” Davy said. “If a physician diagnoses a patient with a certain condition, information about the patient’s usual dietary habits can help him or her prescribe dietary changes that may help treat that condition.”
Biospecimens, like fecal and urine samples, can be a safe, accurate way to collect that data, she said. Samples can be obtained easily and noninvasively “in a wide variety of populations such as children or older adults” and in clinical settings.
Davy and her team use David’s technology in their work — in particular, a tool called FoodSeq that applies DNA metabarcoding to human stool to collect information about food taxa consumed. Their two labs are now collaborating on a project investigating how ultraprocessed foods might impact type 2 diabetes risk and cardiovascular health.
There are many directions David’s lab would like to take their research, possibly partnering with epidemiologists on global studies that would help them expand their DNA database and better understand how, for example, climate change may be affecting diet diversity and to learn more about diet across different populations.
A version of this article appeared on Medscape.com.
Are ants the future of cancer detection?
Cancer diagnosis is frightening, invasive, time-consuming, and expensive. And more than 1.6 million people get that cancer diagnosis every year in the United States. That’s a lot of biopsies and a lot of looking at cells under highly sensitive microscopes.
But imagine if detecting cancer in those samples was as simple as taking a whiff.
We know some animals – like dogs and mice – have very sensitive noses that can sniff out disease. Inspired by those studies, French scientists decided to explore whether ants – known for their olfactory prowess – could do the same.
“Using olfaction to detect diseases is not a novel idea,” says Baptiste Piqueret, PhD, a researcher at Sorbonne Paris Nord University and lead author of the study. “Knowing how well ants can learn and how they use olfaction, we tested the abilities of ants to learn and detect diseases.”
While this is still far away from real-life clinical use, it could one day lead to a cheaper, more accessible (if not a little weird) alternative for detecting cancer. What would this new diagnostic method look like?
Pavlov’s ant
Cancer cell metabolism produces volatile organic compounds (VOCs) – organic chemicals that smell and can serve as biomarkers for diagnosis.
To train the ants to target VOCs, the researchers placed breast cancer cells and healthy cells in a petri dish – but the cancer cells included a sugary treat. “We associated a reward to the smell of cancer,” Dr. Piqueret says.
It’s a technique scientists call classical, or Pavlovian, conditioning. A neutral stimulus (cancer smell) is associated with a second stimulus (food) that elicits a behavior. After doing this a few times, the ant learns that the first stimulus predicts the second, and it will seek out the odor hoping to find that food.
Once the training was complete, the researchers presented the ant with the learned odor and a novel one – this time without a reward. Sure enough, the ants spent more time investigating the learned odor than the novel one.
“If you are hungry and you smell the odor of fresh bread, you will enter the closest bakery,” says Dr. Piqueret. “This is the same mechanism the ants are using, as you learned that fresh bread odor equals food.”
Dogs can detect VOCs via the same technique but take months and hundreds of trials to condition, the researchers note. F. fusca ants learn fast, requiring only three training trials.
Why ants?
Ants communicate primarily through olfaction or scent, and this sophisticated “language” makes them very sensitive to odors.
“Since ants are already well-attuned to detecting different chemicals, this makes them ideal for scent recognition,” says Corrie Moreau, PhD, an evolutionary biologist and entomologist at Cornell University, Ithaca, N.Y.
In their tiny ant worlds, the little creatures use chemicals, called pheromones, to convey information to other members of their nest.
“There are alarm pheromones to signal an intruder, trail pheromones so an ant knows which way to walk to a food source, and colony-level odors that signal another ant is a member of the same colony,” Dr. Moreau says.
But on closer inspection, you won’t see a nose on an ant. They “smell” with their antennas.
“These specialized structures are covered with highly sensitive receptors to be able to discern even small chemical differences,” Dr. Moreau says.
There are over 14,000 species of ants and as far as scientists like Dr. Moreau know, all of them use chemical communication, though some are better than others at detecting compounds, such as those scientists are interested in using to detect disease.
Diagnostic ants: Realistic or a curiosity?
Whether or not the new research findings could lead to a real tool for diagnosing cancer is difficult to say, says Dr. Moreau. The study only focused on pure cancer cells in a lab and not those growing inside a human body.
Anna Wanda Komorowski, MD, a medical oncologist-hematologist at Northwell Health in New York, found the study interesting and was impressed with how the researchers trained the ants. But she notes more research would be needed to parse out things like how long the ants would remember their training, and how long they could be kept in a lab for testing.
One of the attractive aspects of the research is that if it worked it might be a cheaper alternative to normal lab practices for detecting cancer cells, and possibly useful in some low-income settings where labs do not have access to cell stain technologies used to detect cancer cells.
Another glitch with the study, notes Dr. Komorowski: “The cells we’d expose them to probably would not be the same cells as those used in the study. They exposed the ants to live cell cultures. Usually, we collect material from biopsy and drop it into formaldehyde, which has such a strong odor. So the lab protocol for cancer detection would have to be different. It could be kind of tricky.”
And while ants are cheaper than stains and dyes and formaldehyde, you’d have to hire someone to train the ants – there’d still be a human factor and related costs.
“It would take much more research to figure out cost, and how applicable and reproducible it would be,” Dr. Komorowski says.
And then there’s the question of whether the ants would do their cancer-detecting work in the lab only, or if direct patient interaction might lead to a diagnosis more swiftly.
Ant expert Dr. Moreau adds, “The human body emits many other odors, so the question is whether the ants would be able to ignore all the other scents and focus only on the target scent.”
“But these results are promising,” she continues. “I guess the question is whether a patient would be willing to have trained ants crawl all over their body looking for potential cancer cells.”
A version of this article first appeared on WebMD.com.
Cancer diagnosis is frightening, invasive, time-consuming, and expensive. And more than 1.6 million people get that cancer diagnosis every year in the United States. That’s a lot of biopsies and a lot of looking at cells under highly sensitive microscopes.
But imagine if detecting cancer in those samples was as simple as taking a whiff.
We know some animals – like dogs and mice – have very sensitive noses that can sniff out disease. Inspired by those studies, French scientists decided to explore whether ants – known for their olfactory prowess – could do the same.
“Using olfaction to detect diseases is not a novel idea,” says Baptiste Piqueret, PhD, a researcher at Sorbonne Paris Nord University and lead author of the study. “Knowing how well ants can learn and how they use olfaction, we tested the abilities of ants to learn and detect diseases.”
While this is still far away from real-life clinical use, it could one day lead to a cheaper, more accessible (if not a little weird) alternative for detecting cancer. What would this new diagnostic method look like?
Pavlov’s ant
Cancer cell metabolism produces volatile organic compounds (VOCs) – organic chemicals that smell and can serve as biomarkers for diagnosis.
To train the ants to target VOCs, the researchers placed breast cancer cells and healthy cells in a petri dish – but the cancer cells included a sugary treat. “We associated a reward to the smell of cancer,” Dr. Piqueret says.
It’s a technique scientists call classical, or Pavlovian, conditioning. A neutral stimulus (cancer smell) is associated with a second stimulus (food) that elicits a behavior. After doing this a few times, the ant learns that the first stimulus predicts the second, and it will seek out the odor hoping to find that food.
Once the training was complete, the researchers presented the ant with the learned odor and a novel one – this time without a reward. Sure enough, the ants spent more time investigating the learned odor than the novel one.
“If you are hungry and you smell the odor of fresh bread, you will enter the closest bakery,” says Dr. Piqueret. “This is the same mechanism the ants are using, as you learned that fresh bread odor equals food.”
Dogs can detect VOCs via the same technique but take months and hundreds of trials to condition, the researchers note. F. fusca ants learn fast, requiring only three training trials.
Why ants?
Ants communicate primarily through olfaction or scent, and this sophisticated “language” makes them very sensitive to odors.
“Since ants are already well-attuned to detecting different chemicals, this makes them ideal for scent recognition,” says Corrie Moreau, PhD, an evolutionary biologist and entomologist at Cornell University, Ithaca, N.Y.
In their tiny ant worlds, the little creatures use chemicals, called pheromones, to convey information to other members of their nest.
“There are alarm pheromones to signal an intruder, trail pheromones so an ant knows which way to walk to a food source, and colony-level odors that signal another ant is a member of the same colony,” Dr. Moreau says.
But on closer inspection, you won’t see a nose on an ant. They “smell” with their antennas.
“These specialized structures are covered with highly sensitive receptors to be able to discern even small chemical differences,” Dr. Moreau says.
There are over 14,000 species of ants and as far as scientists like Dr. Moreau know, all of them use chemical communication, though some are better than others at detecting compounds, such as those scientists are interested in using to detect disease.
Diagnostic ants: Realistic or a curiosity?
Whether or not the new research findings could lead to a real tool for diagnosing cancer is difficult to say, says Dr. Moreau. The study only focused on pure cancer cells in a lab and not those growing inside a human body.
Anna Wanda Komorowski, MD, a medical oncologist-hematologist at Northwell Health in New York, found the study interesting and was impressed with how the researchers trained the ants. But she notes more research would be needed to parse out things like how long the ants would remember their training, and how long they could be kept in a lab for testing.
One of the attractive aspects of the research is that if it worked it might be a cheaper alternative to normal lab practices for detecting cancer cells, and possibly useful in some low-income settings where labs do not have access to cell stain technologies used to detect cancer cells.
Another glitch with the study, notes Dr. Komorowski: “The cells we’d expose them to probably would not be the same cells as those used in the study. They exposed the ants to live cell cultures. Usually, we collect material from biopsy and drop it into formaldehyde, which has such a strong odor. So the lab protocol for cancer detection would have to be different. It could be kind of tricky.”
And while ants are cheaper than stains and dyes and formaldehyde, you’d have to hire someone to train the ants – there’d still be a human factor and related costs.
“It would take much more research to figure out cost, and how applicable and reproducible it would be,” Dr. Komorowski says.
And then there’s the question of whether the ants would do their cancer-detecting work in the lab only, or if direct patient interaction might lead to a diagnosis more swiftly.
Ant expert Dr. Moreau adds, “The human body emits many other odors, so the question is whether the ants would be able to ignore all the other scents and focus only on the target scent.”
“But these results are promising,” she continues. “I guess the question is whether a patient would be willing to have trained ants crawl all over their body looking for potential cancer cells.”
A version of this article first appeared on WebMD.com.
Cancer diagnosis is frightening, invasive, time-consuming, and expensive. And more than 1.6 million people get that cancer diagnosis every year in the United States. That’s a lot of biopsies and a lot of looking at cells under highly sensitive microscopes.
But imagine if detecting cancer in those samples was as simple as taking a whiff.
We know some animals – like dogs and mice – have very sensitive noses that can sniff out disease. Inspired by those studies, French scientists decided to explore whether ants – known for their olfactory prowess – could do the same.
“Using olfaction to detect diseases is not a novel idea,” says Baptiste Piqueret, PhD, a researcher at Sorbonne Paris Nord University and lead author of the study. “Knowing how well ants can learn and how they use olfaction, we tested the abilities of ants to learn and detect diseases.”
While this is still far away from real-life clinical use, it could one day lead to a cheaper, more accessible (if not a little weird) alternative for detecting cancer. What would this new diagnostic method look like?
Pavlov’s ant
Cancer cell metabolism produces volatile organic compounds (VOCs) – organic chemicals that smell and can serve as biomarkers for diagnosis.
To train the ants to target VOCs, the researchers placed breast cancer cells and healthy cells in a petri dish – but the cancer cells included a sugary treat. “We associated a reward to the smell of cancer,” Dr. Piqueret says.
It’s a technique scientists call classical, or Pavlovian, conditioning. A neutral stimulus (cancer smell) is associated with a second stimulus (food) that elicits a behavior. After doing this a few times, the ant learns that the first stimulus predicts the second, and it will seek out the odor hoping to find that food.
Once the training was complete, the researchers presented the ant with the learned odor and a novel one – this time without a reward. Sure enough, the ants spent more time investigating the learned odor than the novel one.
“If you are hungry and you smell the odor of fresh bread, you will enter the closest bakery,” says Dr. Piqueret. “This is the same mechanism the ants are using, as you learned that fresh bread odor equals food.”
Dogs can detect VOCs via the same technique but take months and hundreds of trials to condition, the researchers note. F. fusca ants learn fast, requiring only three training trials.
Why ants?
Ants communicate primarily through olfaction or scent, and this sophisticated “language” makes them very sensitive to odors.
“Since ants are already well-attuned to detecting different chemicals, this makes them ideal for scent recognition,” says Corrie Moreau, PhD, an evolutionary biologist and entomologist at Cornell University, Ithaca, N.Y.
In their tiny ant worlds, the little creatures use chemicals, called pheromones, to convey information to other members of their nest.
“There are alarm pheromones to signal an intruder, trail pheromones so an ant knows which way to walk to a food source, and colony-level odors that signal another ant is a member of the same colony,” Dr. Moreau says.
But on closer inspection, you won’t see a nose on an ant. They “smell” with their antennas.
“These specialized structures are covered with highly sensitive receptors to be able to discern even small chemical differences,” Dr. Moreau says.
There are over 14,000 species of ants and as far as scientists like Dr. Moreau know, all of them use chemical communication, though some are better than others at detecting compounds, such as those scientists are interested in using to detect disease.
Diagnostic ants: Realistic or a curiosity?
Whether or not the new research findings could lead to a real tool for diagnosing cancer is difficult to say, says Dr. Moreau. The study only focused on pure cancer cells in a lab and not those growing inside a human body.
Anna Wanda Komorowski, MD, a medical oncologist-hematologist at Northwell Health in New York, found the study interesting and was impressed with how the researchers trained the ants. But she notes more research would be needed to parse out things like how long the ants would remember their training, and how long they could be kept in a lab for testing.
One of the attractive aspects of the research is that if it worked it might be a cheaper alternative to normal lab practices for detecting cancer cells, and possibly useful in some low-income settings where labs do not have access to cell stain technologies used to detect cancer cells.
Another glitch with the study, notes Dr. Komorowski: “The cells we’d expose them to probably would not be the same cells as those used in the study. They exposed the ants to live cell cultures. Usually, we collect material from biopsy and drop it into formaldehyde, which has such a strong odor. So the lab protocol for cancer detection would have to be different. It could be kind of tricky.”
And while ants are cheaper than stains and dyes and formaldehyde, you’d have to hire someone to train the ants – there’d still be a human factor and related costs.
“It would take much more research to figure out cost, and how applicable and reproducible it would be,” Dr. Komorowski says.
And then there’s the question of whether the ants would do their cancer-detecting work in the lab only, or if direct patient interaction might lead to a diagnosis more swiftly.
Ant expert Dr. Moreau adds, “The human body emits many other odors, so the question is whether the ants would be able to ignore all the other scents and focus only on the target scent.”
“But these results are promising,” she continues. “I guess the question is whether a patient would be willing to have trained ants crawl all over their body looking for potential cancer cells.”
A version of this article first appeared on WebMD.com.