Claire Guest, co-founder of Medical Detection Dogs, with Daisy, whom she credits with saving her life.
Daisy wouldn't leave Claire Guest alone. Instead of joining Guest's other dogs for a run in the park, the golden retriever with the soulful eyes kept nudging Guest's chest, and stared at her intently, somehow hoping she'd get the message.
"I was incredibly lucky to be told by Daisy."
When Guest got home, she detected a tiny lump in one of her breasts. She dismissed it, but her sister, who is a family doctor, insisted she get it checked out.
That saved her life. A series of tests, including a biopsy and a mammogram, revealed the cyst was benign. But doctors discovered a tumor hidden deep inside her chest wall, an insidious malignancy that normally isn't detected until the cancer has rampaged out of control throughout the body. "My prognosis would have been very poor," says Guest, who is an animal behavioralist. "I was incredibly lucky to be told by Daisy."
Ironically, at the time, Guest was training hearing dogs for the deaf—alerting them to doorbells or phones--for a charitable foundation. But she had been working on a side project to harness dogs' exquisitely sensitive sense of smell to spot cancer at its earliest and most treatable stages. When Guest was diagnosed with cancer two decades ago, however, the use of dogs to detect diseases was in its infancy and scientific evidence was largely anecdotal.
In the years since, Guest and the British charitable foundation she co-founded with Dr. John Church in 2008, Medical Detection Dogs (MDD), has shown that dogs can be trained to detect odors that predict a looming medical crisis hours in advance, in the case of diabetes or epilepsy, as well as the presence of cancers.
In a proof of principle study published in the BMJ in 2004, they showed dogs had better than a 40 percent success rate in identifying bladder cancer, which was significantly better than random chance (14 percent). Subsequent research indicated dogs can detect odors down to parts per trillion, which is the equivalent of sniffing out a teaspoon of sugar in two Olympic size swimming pools (a million gallons).
American scientists are devising artificial noses that mimic dogs' sense of smell, so these potentially life-saving diagnostic tools are widely available.
But the problem is "dogs can't be scaled up"—it costs upwards of $25,000 to train them—"and you can't keep a trained dog in every oncology practice," says Guest.
The good news is that the pivotal 2004 BMJ paper caught the attention of two American scientists—Andreas Mershin, a physicist at MIT, and Wen-Yee Yee, a chemistry professor at The University of Texas at El Paso. They have joined Guest's quest to leverage canines' highly attuned olfactory systems and devise artificial noses that mimic dogs' sense of smell, so these potentially life-saving diagnostic tools are widely available.
"What we do know is that this is real," says Guest. "Anything that can improve diagnosis of cancer is something we ought to know about."
Dogs have routinely been used for centuries as trackers for hunting and more recently, for ferreting out bombs and bodies. Dogs like Daisy, who went on to become a star performer in Guest's pack of highly trained cancer detecting canines before her death in 2018, have shared a special bond with their human companions for thousands of years. But their vastly superior olfaction is the result of simple anatomy.
Humans possess about six million olfactory receptors—the antenna-like structures inside cell membranes in our nose that latch on to the molecules in the air when we inhale. In contrast, dogs have about 300 million of them and the brain region that analyzes smells is, proportionally, about 40 times greater than ours.
Research indicates that cancerous cells interfere with normal metabolic processes, prompting them to produce volatile organic compounds (VOCs), which enter the blood stream and are either exhaled in our breath or excreted in urine. Dogs can identify these VOCs in urine samples at the tiniest concentrations, 0.001 parts per million, and can be trained to identify the specific "odor fingerprint" of different cancers, although teaching them how to distinguish these signals from background odors is far more complicated than training them to detect drugs or explosives.
For the past fifteen years, Andreas Mershin of MIT has been grappling with this complexity in his quest to devise an artificial nose, which he calls the Nano-Nose, first as a military tool to spot land mines and IEDS, and more recently as a cancer detection tool that can be used in doctors' offices. The ultimate goal is to create an easy-to-use olfaction system powered by artificial intelligence that can fit inside of smartphones and can replicate dogs' ability to sniff out early signs of prostate cancer, which could eliminate a lot of painful and costly biopsies.
Trained canines have a better than 90 percent accuracy in spotting prostate cancer, which is normally difficult to detect. The current diagnostic, the prostate specific antigen test, which measures levels of certain immune system cells associated with prostate cancer, has about as much accuracy "as a coin toss," according to the scientist who discovered PSA. These false positives can lead to unnecessary and horrifically invasive biopsies to retrieve tissue samples.
So far, Mershin's prototype device has the same sensitivity as the dogs—and can detect odors at parts per trillion—but it still can't distinguish that cancer smell in individual human patients the way a dog can. "What we're trying to understand from the dogs is how they look at the data they are collecting so we can copy it," says Mershin. "We still have to make it intelligent enough to know what it is looking at—what we are lacking is artificial dog intelligence."
The intricate parts of the artificial nose are designed to fit inside a smartphone.
At UT El Paso, Wen-Yee Lee and her research team has used the canine olfactory system as a model for a new screening test for prostate cancer, which has a 92 percent accuracy in tests of urine samples and could be eventually developed as a kit similar to the home pregnancy test. "If dogs can do it, we can do it better," says Lee, whose husband was diagnosed with prostate cancer in 2005.
The UT scientists used samples from about 150 patients, and looked at about 9,000 compounds before they were able to zero in on the key VOCs that are released by prostate cancers—"it was like finding a needle in the haystack," says Lee. But a more reliable test that can also distinguish which cancers are more aggressive could help patients decide their best treatment options and avoid invasive procedures that can render them incontinent and impotent.
"This is much more accurate than the PSA—we were able to see a very distinct difference between people with prostate cancer and those without cancer," says Lee, who has been sharing her research with Guest and hopes to have the test on the market within the next few years.
In the meantime, Guest's foundation has drawn the approving attention of royal animal lovers: Camilla, the Duchess of Cornwall, is a patron, which opened up the charitable floodgates and helped legitimize MDD in the scientific community. Even Camilla's mother-in-law, Queen Elizabeth, has had a demonstration of these canny canines' unique abilities.
Claire Guest, and two of MDDs medical detection dogs, Jodie and Nimbus, meet with queen Elizabeth.
"She actually held one of my [artificial] noses in her hand and asked really good questions, including things we hadn't thought of, like the range of how far away a dog can pick up the scent or if this can be used to screen for malaria," says Mershin. "I was floored by this curious 93-year-old lady. Half of humanity's deaths are from chronic diseases and what the dogs are showing is a whole new way of understanding holistic diseases of the system."
Katalin Karikó, pictured, and Drew Weissman won the Nobel Prize for advances in mRNA research that led to the first Covid vaccines.
The work for which they garnered the illustrious award and its accompanying $1,000,000 cash windfall was completed about two decades ago, wrought through long hours in the lab over many arduous years. But humanity collectively benefited from its life-saving outcome three years ago, when both Moderna and Pfizer/BioNTech’s mRNA vaccines against COVID were found to be safe and highly effective at preventing severe disease. Billions of doses have since been given out to protect humans from the upstart viral scourge.
“I thought of going somewhere else, or doing something else,” said Katalin Karikó. “I also thought maybe I’m not good enough, not smart enough. I tried to imagine: Everything is here, and I just have to do better experiments.”
Unlocking the power of mRNA
Weissman and Karikó unlocked mRNA vaccines for the world back in the early 2000s when they made a key breakthrough. Messenger RNA molecules are essentially instructions for cells’ ribosomes to make specific proteins, so in the 1980s and 1990s, researchers started wondering if sneaking mRNA into the body could trigger cells to manufacture antibodies, enzymes, or growth agents for protecting against infection, treating disease, or repairing tissues. But there was a big problem: injecting this synthetic mRNA triggered a dangerous, inflammatory immune response resulting in the mRNA’s destruction.
While most other researchers chose not to tackle this perplexing problem to instead pursue more lucrative and publishable exploits, Karikó stuck with it. The choice sent her academic career into depressing doldrums. Nobody would fund her work, publications dried up, and after six years as an assistant professor at the University of Pennsylvania, Karikó got demoted. She was going backward.
“I thought of going somewhere else, or doing something else,” Karikó told Stat in 2020. “I also thought maybe I’m not good enough, not smart enough. I tried to imagine: Everything is here, and I just have to do better experiments.”
A tale of tenacity
Collaborating with Drew Weissman, a new professor at the University of Pennsylvania, in the late 1990s helped provide Karikó with the tenacity to continue. Weissman nurtured a goal of developing a vaccine against HIV-1, and saw mRNA as a potential way to do it.
“For the 20 years that we’ve worked together before anybody knew what RNA is, or cared, it was the two of us literally side by side at a bench working together,” Weissman said in an interview with Adam Smith of the Nobel Foundation.
In 2005, the duo made their 2023 Nobel Prize-winning breakthrough, detailing it in a relatively small journal, Immunity. (Their paper was rejected by larger journals, including Science and Nature.) They figured out that chemically modifying the nucleoside bases that make up mRNA allowed the molecule to slip past the body’s immune defenses. Karikó and Weissman followed up that finding by creating mRNA that’s more efficiently translated within cells, greatly boosting protein production. In 2020, scientists at Moderna and BioNTech (where Karikó worked from 2013 to 2022) rushed to craft vaccines against COVID, putting their methods to life-saving use.
The future of vaccines
Buoyed by the resounding success of mRNA vaccines, scientists are now hurriedly researching ways to use mRNA medicine against other infectious diseases, cancer, and genetic disorders. The now ubiquitous efforts stand in stark contrast to Karikó and Weissman’s previously unheralded struggles years ago as they doggedly worked to realize a shared dream that so many others shied away from. Katalin Karikó and Drew Weissman were brave enough to walk a scientific path that very well could have ended in a dead end, and for that, they absolutely deserve their 2023 Nobel Prize.
This article originally appeared on Big Think, home of the brightest minds and biggest ideas of all time.
With conventional fuel cells as their model, researchers learned to use similar chemical reactions to make a fuel from microbes in pee.
Plus, urine contains water, phosphorus, potassium and nitrogen, the key ingredients plants need to grow and survive. Human urine could replace about 25 percent of current nitrogen and phosphorous fertilizers worldwide and could save water for gardens and crops. The average U.S. resident flushes a toilet bowl containing only pee and paper about six to seven times a day, which adds up to about 3,500 gallons of water down per year. Plus cows in the U.S. produce 231 gallons of the stuff each year.
Pee power
A conventional fuel cell uses chemical reactions to produce energy, as electrons move from one electrode to another to power a lightbulb or phone. Ioannis Ieropoulos, a professor and chair of Environmental Engineering at the University of Southampton in England, realized the same type of reaction could be used to make a fuel from microbes in pee.
Bacterial species like Shewanella oneidensis and Pseudomonas aeruginosa can consume carbon and other nutrients in urine and pop out electrons as a result of their digestion. In a microbial fuel cell, one electrode is covered in microbes, immersed in urine and kept away from oxygen. Another electrode is in contact with oxygen. When the microbes feed on nutrients, they produce the electrons that flow through the circuit from one electrod to another to combine with oxygen on the other side. As long as the microbes have fresh pee to chomp on, electrons keep flowing. And after the microbes are done with the pee, it can be used as fertilizer.
These microbes are easily found in wastewater treatment plants, ponds, lakes, rivers or soil. Keeping them alive is the easy part, says Ieropoulos. Once the cells start producing stable power, his group sequences the microbes and keeps using them.
Like many promising technologies, scaling these devices for mass consumption won’t be easy, says Kevin Orner, a civil engineering professor at West Virginia University. But it’s moving in the right direction. Ieropoulos’s device has shrunk from the size of about three packs of cards to a large glue stick. It looks and works much like a AAA battery and produce about the same power. By itself, the device can barely power a light bulb, but when stacked together, they can do much more—just like photovoltaic cells in solar panels. His lab has produced 1760 fuel cells stacked together, and with manufacturing support, there’s no theoretical ceiling, he says.
Although pure urine produces the most power, Ieropoulos’s devices also work with the mixed liquids of the wastewater treatment plants, so they can be retrofit into urban wastewater utilities.
This image shows how the pee-powered system works. Pee feeds bacteria in the stack of fuel cells (1), which give off electrons (2) stored in parallel cylindrical cells (3). These cells are connected to a voltage regulator (4), which smooths out the electrical signal to ensure consistent power to the LED strips lighting the toilet.
Courtesy Ioannis Ieropoulos
Key to the long-term success of any urine reclamation effort, says Orner, is avoiding what he calls “parachute engineering”—when well-meaning scientists solve a problem with novel tech and then abandon it. “The way around that is to have either the need come from the community or to have an organization in a community that is committed to seeing a project operate and maintained,” he says.
Success with urine reclamation also depends on the economy. “If energy prices are low, it may not make sense to recover energy,” says Orner. “But right now, fertilizer prices worldwide are generally pretty high, so it may make sense to recover fertilizer and nutrients.” There are obstacles, too, such as few incentives for builders to incorporate urine recycling into new construction. And any hiccups like leaks or waste seepage will cost builders money and reputation. Right now, Orner says, the risks are just too high.
Despite the challenges, Ieropoulos envisions a future in which urine is passed through microbial fuel cells at wastewater treatment plants, retrofitted septic tanks, and building basements, and is then delivered to businesses to use as agricultural fertilizers. Although pure urine produces the most power, Ieropoulos’s devices also work with the mixed liquids of the wastewater treatment plants, so they can be retrofitted into urban wastewater utilities where they can make electricity from the effluent. And unlike solar cells, which are a common target of theft in some areas, nobody wants to steal a bunch of pee.
When Ieropoulos’s team returned to wrap up their pilot project 18 months later, the school’s director begged them to leave the fuel cells in place—because they made a major difference in students’ lives. “We replaced it with a substantial photovoltaic panel,” says Ieropoulos, They couldn’t leave the units forever, he explained, because of intellectual property reasons—their funders worried about theft of both the technology and the idea. But the photovoltaic replacement could be stolen, too, leaving the girls in the dark.
The story repeated itself at another school, in Nairobi, Kenya, as well as in an informal settlement in Durban, South Africa. Each time, Ieropoulos vowed to return. Though the pandemic has delayed his promise, he is resolute about continuing his work—it is a moral and legal obligation. “We've made a commitment to ourselves and to the pupils,” he says. “That's why we need to go back.”
Urine as fertilizer
Modern day industrial systems perpetuate the broken cycle of nutrients. When plants grow, they use up nutrients the soil. We eat the plans and excrete some of the nutrients we pass them into rivers and oceans. As a result, farmers must keep fertilizing the fields while our waste keeps fertilizing the waterways, where the algae, overfertilized with nitrogen, phosphorous and other nutrients grows out of control, sucking up oxygen that other marine species need to live. Few global communities remain untouched by the related challenges this broken chain create: insufficient clean water, food, and energy, and too much human and animal waste.
The Rich Earth Institute in Vermont runs a community-wide urine nutrient recovery program, which collects urine from homes and businesses, transports it for processing, and then supplies it as fertilizer to local farms.
One solution to this broken cycle is reclaiming urine and returning it back to the land. The Rich Earth Institute in Vermont is one of several organizations around the world working to divert and save urine for agricultural use. “The urine produced by an adult in one day contains enough fertilizer to grow all the wheat in one loaf of bread,” states their website.
Notably, while urine is not entirely sterile, it tends to harbor fewer pathogens than feces. That’s largely because urine has less organic matter and therefore less food for pathogens to feed on, but also because the urinary tract and the bladder have built-in antimicrobial defenses that kill many germs. In fact, the Rich Earth Institute says it’s safe to put your own urine onto crops grown for home consumption. Nonetheless, you’ll want to dilute it first because pee usually has too much nitrogen and can cause “fertilizer burn” if applied straight without dilution. Other projects to turn urine into fertilizer are in progress in Niger, South Africa, Kenya, Ethiopia, Sweden, Switzerland, The Netherlands, Australia, and France.
Eleven years ago, the Institute started a program that collects urine from homes and businesses, transports it for processing, and then supplies it as fertilizer to local farms. By 2021, the program included 180 donors producing over 12,000 gallons of urine each year. This urine is helping to fertilize hay fields at four partnering farms. Orner, the West Virginia professor, sees it as a success story. “They've shown how you can do this right--implementing it at a community level scale."