When farmer Terry Wanzek walks out in his fields, he sometimes sees a grove of trees, which reminds him of his grandfather, who planted those trees. Or he looks out over the pond, which deer, ducks and pheasant use for water, and he knows that his grandfather made a decision to drain land and put the pond in that exact spot.
Growing more with fewer resources is becoming increasingly urgent as the Earth's population is expected to hit 9.1 billion by 2050.
"There is a connection that goes beyond running a business and making a profit," says Wanzek, a fourth-generation North Dakota farmer who raises spring wheat, corn, soybeans, barley, dry edible beans and sunflowers. "There is a connection to family, to your ancestors and there is a connection to your posterity and your kids."
Wanzek's corn and soybeans are genetically modified (GM) crops, which means that they have been altered at the DNA level to create desirable traits. This intervention, he says, allows him to start growing earlier and to produce more food per acre.
Growing more with fewer resources is becoming increasingly urgent as the Earth's population is expected to hit 9.1 billion by 2050, with nearly all of the rise coming from developing countries, according to the Food and Agriculture Organization of the United Nations. This population will be urban, which means they'll likely be eating fewer grains and other staple crops, and more vegetables, fruits, meat, dairy, and fish.
Whether those foods will be touched in some way by technology remains a high-stakes question. As for GM foods, the American public is somewhat skeptical: in a recent survey, about one-third of Americans report that they are actively avoiding GMOs or seek out non-GMO labels when shopping and purchasing foods. These consumers fear unsafe food and don't want biotechnologists to tamper with nature. This disconnect—between those who consume food and those who produce it—is only set to intensify as major agricultural companies work to develop further high-tech farming solutions to meet the needs of the growing population.
"I don't think we have a choice going forward. The world isn't getting smaller. We have to come up with a means of using less."
In the future, it may be possible to feed the world. But what if the world doesn't want the food?
A Short History
Genetically modified food is not new. The first such plant (the Flavr Savr tomato) was approved for human consumption and brought to market in 1994, but people didn't like the taste. Today, nine genetically modified food crops are commercially available in the United States (corn, soybean, squash, papaya, alfalfa, sugar beets, canola, potato and apples). Most were modified to increase resistance to disease or pests, or tolerance to a specific herbicide. Such crops have in fact been found to increase yields, with a recent study showing grain yield was up to 24.5 percent higher in genetically engineered corn.
Despite some consumer skepticism, many farmers don't have a problem with GM crops, says Jennie Schmidt, a farmer and registered dietician in Maryland. She says with a laugh that her farm is a "grocery store farm - we grow the ingredients you buy in products at the grocery store." Schmidt's father-in-law, who started the farm, watched the adoption of hybrid corn improve seeds in the 1930s and 1940s.
"It wasn't a difficult leap to see how well these hybrid corn seeds have done over the decades," she says. "So when the GMOs came out, it was a quicker adoption curve, because as farmers they had already been exposed to the first generation and this was just the next step."
Schmidt, for one, is excited about the gene-editing tool CRISPR and other ways biotechnologists can create food like apples or potatoes with a particular enzyme turned off so they don't go brown during oxidation. Other foods in the pipeline include disease-resistant citrus, low-gluten wheat, fungus-resistant bananas, and anti-browning mushrooms.
"We need to not judge our agriculture by yield per acre but nutrition per acre."
"I don't think we have a choice going forward," says Schmidt. "The world isn't getting smaller. We have to come up with a means of using less."
A Different Way Forward?
But others remain convinced that there are better ways to feed the planet. Andrew Kimball, executive director of the Center for Food Safety, a non-profit that promotes organic and sustainable agriculture, says the public has been sold a lie with biotech. "GMO technology is not proven as a food producer," he says. "It's just not being done anywhere at a large scale. Ninety-nine percent of GMOs are corn and soy, and they allow chemical companies to sell more chemicals. But that doesn't increase food or decrease hunger." Instead, Kimball advocates for a pivot from commodity agriculture to farms with crop diversity and animals.
Kimball also suggests a way to use land more appropriately: stop growing so much biofuel. Right now, in the U.S., more than 55 percent of our crop farmland is in corn and soy. About 40 percent of that goes into cars through ethanol, 40 percent is fed to animals and a good bit of the rest goes into high-fructose corn syrup. That leaves only a small amount to feed people, says Kimball. "If you want to feed the world, not just the U.S., you want to make sure to use that land to feed people," he says. "We need to not judge our agriculture by yield per acre but nutrition per acre."
Robert Streiffer, a bioethicist at the University of Wisconsin at Madison, agrees that GMOs haven't really helped alleviate hunger. Glyphosate resistance, one of the traits that is most commonly used in genetically engineered crops, doesn't improve yield or allow crops to be grown in areas where they weren't able to be grown before. "Insect resistance through the insertion of a Bt gene can improve yield, but is mostly used for cotton (which is not a food crop) and corn which goes to feed cattle, a very inefficient method of feeding the hungry, to say the least," he says. Important research is being done in crops such as cassava, which could help relieve global hunger. But in his opinion, these researchers lack the profit potential needed to motivate large private funding sources, so they require more public-sector funding.
"A substantial portion of public opposition is as much about the lack of any perceived benefits for the consumers as it is for outright fear of health or environmental dangers."
"Public opposition to biotech foods is certainly a factor, but I expect this will slowly decline as labels indicating the presence of GE (genetically engineered) ingredients become more common, and as we continue to amass reassuring data on the comparative environmental safety of GE crops," says Streiffer. "A substantial portion of public opposition is as much about the lack of any perceived benefits for the consumers as it is for outright fear of health or environmental dangers."
One sign that the public may be willing to embrace some non-natural foods is the recent interest in cultured meat, which is grown in a lab from animal cells but doesn't require raising or killing animals. A study published last year in PLOS One found that 65 percent of 673 surveyed U.S. individuals would probably or definitely try cultured meat, while only 8.5 percent said they definitely would not. In the future, lab-grown food may become another way to create more food with fewer resources.
Danielle Nierenberg, president of the Food Tank, a nonprofit organization focused on building a global community of safe and healthy food, points to an even more immediate problem: food waste. Globally, about a third of food is thrown out or goes bad before it has a chance to be eaten. She says simply fixing roads and infrastructure in developing countries would go a long way toward ensuring that food reaches the hungry. Focusing on helping small farmers (who grow 70 percent of food around the globe), especially female farmers, would go a long way, she says.
Innovation on the Farm
In addition to good roads, those farmers need fertilizer. Nitrogen-based fertilizers may get a boost in the future from technologies that release nutrients slowly over time, like slow-release medicines based on nanotechnology. In field trials on rice in Sri Lanka, one such nanotech fertilizer increased crop yields by 10 percent, even though it delivered only half the amount of urea compared with traditional fertilizer, according to a study last year.
"I'm not afraid of the food I grow. We live in the same environment, and I feel completely safe."
One startup, the San-Francisco-based Biome Makers, is profiling microbial DNA to give farmers an idea of what their soil needs to better support crops. Joyn Bio, another new startup based in Boston and West Sacramento, is looking to engineer microbes that could reduce farming's reliance on nitrogen fertilizer, which is expensive and harms the environment. (Full disclosure: Joyn Bio and this magazine are funded by the same company, Leaps by Bayer, though leapsmag is editorially independent. Also, Bayer recently acquired Monsanto, the leading producer of genetically engineered seeds and the herbicide Roundup.)
Terry Wanzek, the farmer in North Dakota, says he'd be willing to try any new technology as long as it helps his bottom line – and increases sustainability. "I'm not afraid of the food I grow," he says of his genetically modified produce. "We eat the same food, we live in the same environment, and I feel completely safe."
Only time will tell if people several decades from now feel the same way. But no matter how their food is produced, one thing is certain: those people will need to eat.
The Friday Five covers five stories in health research that you may have missed this week. There are plenty of controversies and troubling ethical issues in science – and we get into many of them in our online magazine – but this news roundup focuses on scientific creativity and progress to give you a therapeutic dose of inspiration headed into the weekend.
Listen to the Episode
Covered in this week's Friday Five:
- A new blood test for cancer
- Patches of bacteria can use your sweat to power electronic devices
- Researchers revive organs of dead pigs
- Phone apps detects cancer-causing chemicals in foods
- Stem cells generate "synthetic placentas" in mice
Plus, an honorable mention for early research involving vitamin K and Alzheimer's
The doctor will sniff you now? Well, not on his or her own, but with a device that functions like a superhuman nose. You’ll exhale into a breathalyzer, or a sensor will collect “scent data” from a quick pass over your urine or blood sample. Then, AI software combs through an olfactory database to find patterns in the volatile organic compounds (VOCs) you secreted that match those associated with thousands of VOC disease biomarkers that have been identified and cataloged.
No further biopsy, imaging test or procedures necessary for the diagnosis. According to some scientists, this is how diseases will be detected in the coming years.
All diseases alter the organic compounds found in the body and their odors. Volatolomics is an emerging branch of chemistry that uses the smell of gases emitted by breath, urine, blood, stool, tears or sweat to diagnose disease. When someone is sick, the normal biochemical process is disrupted, and this alters the makeup of the gas, including a change in odor.
“These metabolites show a snapshot of what’s going on with the body,” says Cristina Davis, a biomedical engineer and associate vice chancellor of Interdisciplinary Research and Strategic Initiatives at the University of California, Davis. This opens the door to diagnosing conditions even before symptoms are present. It’s possible to detect a sweet, fruity smell in the breath of someone with diabetes, for example.
Hippocrates may have been the first to note that people with certain diseases give off an odor but dogs provided the proof of concept. Scientists have published countless studies in which dogs or other high-performing smellers like rodents have identified people with cancer, lung disease or other conditions by smell alone. The brain region that analyzes smells is proportionally about 40 times greater in dogs than in people. The noses of rodents are even more powerful.
Take prostate cancer, which is notoriously difficult to detect accurately with standard medical testing. After sniffing a tiny urine sample, trained dogs were able to pick out prostate cancer in study subjects more than 96 percent of the time, and earlier than a physician could in some cases.
But using dogs as bio-detectors is not practical. It is labor-intensive, complicated and expensive to train dogs to bark or lie down when they smell a certain VOC, explains Bruce Kimball, a chemical ecologist at the Monell Chemical Senses Center in Philadelphia. Kimball has trained ferrets to scratch a box when they smell a specific VOC so he knows. The lab animal must be taught to distinguish the VOC from background odors and trained anew for each disease scent.
In the lab of chemical ecologist Bruce Kimball, ferrets were trained to scratch a box when they identified avian flu in mallard ducks.
Glen J. Golden
There are some human super-smellers among us. In 2019, Joy Milne of Scotland proved she could unerringly identify people with Parkinson’s disease from a musky scent emitted from their skin. Clinical testing showed that she could distinguish the odor of Parkinson’s on a worn t-shirt before clinical symptoms even appeared.
Hossam Haick, a professor at Technion-Israel Institute of Technology, maintains that volatolomics is the future of medicine. Misdiagnosis and late detection are huge problems in health care, he says. “A precise and early diagnosis is the starting point of all clinical activities.” Further, this science has the potential to eliminate costly invasive testing or imaging studies and improve outcomes through earlier treatment.
The Nose Knows a Lot
“Volatolomics is not a fringe theory. There is science behind it,” Davis stresses. Every VOC has its own fingerprint, and a method called gas chromatography-mass spectrometry (GCMS) uses highly sensitive instruments to separate the molecules of these VOCs to determine their structures. But GCMS can’t discern the telltale patterns of particular diseases, and other technologies to analyze biomarkers have been limited.
We have technology that can see, hear and sense touch but scientists don’t have a handle yet on how smell works. The ability goes beyond picking out a single scent in someone’s breath or blood sample. It’s the totality of the smell—not the smell of a single chemical— which defines a disease. The dog’s brain is able to infer something when they smell a VOC that eludes human analysis so far.
Odor is a complex ecosystem and analyzing a VOC is compounded by other scents in the environment, says Kimball. A person’s diet and use of tobacco or alcohol also will affect the breath. Even fluctuations in humidity and temperature can contaminate a sample.
If successful, a sophisticated AI network can imitate how the dog brain recognizes patterns in smells. Early versions of robot noses have already been developed.
With today’s advances in data mining, AI and machine learning, scientists are trying to create mechanical devices that can draw on algorithms based on GCMS readings and data about diseases that dogs have sniffed out. If successful, a sophisticated AI network can imitate how the dog brain recognizes patterns in smells.
In March, Nano Research published a comprehensive review of volatolomics in health care authored by Haick and seven colleagues. The intent was to bridge gaps in the field for scientists trying to connect the biomarkers and sensor technology needed to develop a robot nose. This paper serves as a reference manual for the field that lists which VOCs are associated with what disease and the biomarkers in skin, saliva, breath, and urine.
Weiwei Wu, one of the co-authors and a professor at Xidian University in China, explains that creating a robotic nose requires the expertise of chemists, computer scientists, electrical engineers, material scientists, and clinicians. These researchers use different terms and methodologies and most have not collaborated before with the other disciplines. “The electrical engineers know the device but they don’t know as much about the biomarkers they need to detect,” Wu offers as an example.
This review is significant, Wu continues, because it can facilitate progress in the field by providing experts in all the disciplines with the basic knowledge needed to create an effective robot nose for diagnostic use. The paper also includes a systematic summary of the research methodology of volatolomics.
Once scientists build a stronger database of VOCs, they can program a device to identify critical patterns of specified diseases on a reliable basis. On a machine learning model, the algorithms automatically get better at diagnosing with each use. Wu envisions further tweaks in the next few years to make the devices smaller and consume less power.
A Whiff of the Future
Early versions of robot noses have already been developed. Some of them use chemical sensors to pick up smells in the breath or other body emission molecules. That data is sent through an electrical signal to a computer network for interpretation and possible linkage to a disease.
This electronic nose, or e-nose, has been successful in small pilot studies at labs around the world. At Ben-Gurion University in Israel, researchers detected breast cancer with electronic gas sensors with 95% accuracy, a higher sensitivity than mammograms. Other robot noses, called p-noses, use photons instead of electrical signals.
The mechanical noses being developed tap different methodologies and analytic techniques which makes it hard to compare them. Plus, the devices are intended for varying uses. One team, for example, is working on an e-nose that can be waved over a plate to screen for the presence of a particular allergen when you’re dining out.
A robot nose could be used as a real-time diagnostic tool in clinical practice. Kimball is working on one such tool that can distinguish between a viral and bacterial infection. This would enable physicians to determine whether an antibiotic prescription is appropriate without waiting for a lab result.
Davis is refining a hand-held device that identifies COVID-19 through a simple breath test. She sees the tool being used at crowded airports, sports stadiums and concert venues where PCR or rapid antigen testing is impractical. Background air samples are collected from the space so that those signals can be removed from the human breath measurement. “[The sensor tool] has the same accuracy as the rapid antigen test kits but exhaled breath is easier to collect,” she notes.
The NaNose, also known as the SniffPhone, uses tiny sensors boosted by AI to distinguish Alzheimer's, Crohn's disease, the early stages of several cancers, and other diseases with 84 to 98 percent accuracy.
Haick named his team’s robot nose, “NaNose,” since it is based on nanotechnology; the prototype is called the SniffPhone. Using tiny sensors boosted by AI, it can distinguish 23 diseases in human subjects with 84 to 98 percent accuracy. This includes early stages of several cancers, Alzheimer’s, tuberculosis and Crohn’s disease. His team has been raising the accuracy level by combining biomarker signals from both breath and skin, for example. The goal is to achieve 99.9 percent accuracy consistently so no other diagnostic tests would be needed before treating the patient. Plus, it will be affordable, he says.
Kimball predicts we’ll be seeing these diagnostic tools in the next decade. “The physician would narrow down what [the diagnosis] might be and then get the correct tool,” he says. Others are envisioning one device that can screen for multiple diseases by programming the software, which would be updated regularly with new findings.
Larger volatolomics studies must be conducted before these e-noses are ready for clinical use, however. Experts also need to learn how to establish normal reference ranges for e-nose readings to support clinicians using the tool.
“Taking successful prototypes from the lab to industry is the challenge,” says Haick, ticking off issues like reproducibility, mass production and regulation. But volatolomics researchers are unanimous in believing the future of health care is so close they can smell it.