Diagnosed by App: Medical Testing in the Palm of Your Hand
Urinary tract infections aren't life-threatening, but they can be excruciatingly painful and debilitating.
"Overnight, I'd be gripped by this searing pain and I can barely walk," says Ling Koh, a Los Angeles-based bioengineer. But short of going to the ER or urgent care, she'd have to suffer for a few days until she could get in to see her family doctor for an antibiotic prescription.
Smartphones are now able to do on-the-spot diagnostic tests that were previously only able to be performed in a lab.
No longer. Koh, who works for Scanwell Health, was instrumental in the development of the company's smartphone app that is FDA-cleared for urinary tract infection screening. It allows someone to test urine at home using a paper test strip — the same one used by doctors in ERs and labs. The phone app reads a scan card from the test kit that can analyze what's on the strip and then connect the patient to a physician who can make a virtual diagnosis.
Test strips cost $15 for a three-pack and consultation with a doc is about the same as an average co-pay -- $25, and the app matches the quality of clinical laboratory tests, according to the company. Right now, you can get a referral to a telehealth visit with a doctor in California and get a prescription. A national rollout is in the works within the next couple of months.
"It's so easy to use them at home and eliminate the inefficiencies in the process," says Koh. "A telemedicine doctor can look at the test results and prescribe directly to the pharmacy instead of women waiting at home, miserable, and crying in the bathtub."
Scanwell is now involved in an ongoing National Institutes of Health- sponsored study of chronic kidney disease to test a version of the app to identify patients who have the disease, which affects more than 30 million Americans. "Because kidney disease has virtually no symptoms, by the time people realize they're sick, their illness is advanced and they're ready for dialysis," says Koh. "If we can catch it sooner, early intervention can help them avoid kidney failure."
Smartphones have changed society — and now they may change medical care, too. Thanks to the incredible processing capabilities of our smartphones, which come equipped with a camera, access to the internet and are thousands of times faster than the 1960s era NASA computers that ran the Apollo Moon Mission, these pocket-sized powerhouses have become an invaluable tool for managing our health and are even able to do on-the-spot diagnostic tests that were previously only able to be performed in a lab.
This shift to in-home testing is the wave of the future, promising to ease some of the medical care bottlenecks in which patients can have two- to three-week waits to see their family doctors and lift some of the burdens on overworked physicians.
"This is really the democratization of medicine because a lot of the things we used to rely on doctors, hospitals, or labs to do we'll be able to do ourselves," says Dr. Eric Topol, an eminent cardiologist and digital health pioneer at the Scripps Clinic and Research Institute in La Jolla.
But troubling questions remain. Aside from the obvious convenience, are these tests truly as accurate as ones in a doctor's office? And with all this medical information stored and collected by smartphones, will privacy be sacrificed? Will friends, family members, and employers suddenly have access to personal medical information we'd rather keep to ourselves?
The range of what these DIY health care apps can do is mind-boggling, and even more complex tests are on the way.
"I'm really worried about that because we've let our guard down," says Topol. "Data stored on servers is a target for cyber thieves — and data is being breached, hacked, brokered, and sold, and we're complacent."
Still, the apps have come a long way since 2011 when Topol whipped out an experimental smartphone electro-cardiogram that he had been testing on his patients when a fellow passenger on a flight from Washington D.C. was seized with severe chest pains. At 35,000 feet in the air, the app, which uses fingertip sensors to detect heart rate, showed the man was having a heart attack. After an emergency landing, the passenger was rushed to the closest hospital and survived. These days, even the Apple Watch has an FDA-approved app that can monitor your electro-cardiogram readings.
The range of what these DIY health care apps can do is mind-boggling, and even more complex tests are on the way. Phone apps can now monitor sleep quality to detect sleep apnea, blood pressure, weight and temperature. In the future, rapid diagnostic tests for infectious diseases, like flu, Dengue or Zika, and urinalysis will become common.
"There is virtually no limit to the kinds of testing that can be done using a smartphone," says Dr. John Halamka, Executive Director of the Health Technology Exploration Center at Beth Israel Lahey Health. "No one wants to drive to a clinician's office or lab if that same quality testing can be achieved at a lower cost without leaving home."
SkinVision's skin cancer screening tool, for instance, can tell if a suspicious mole is cancerous. Users take three photos, which are then run through the app's algorithm that compares their lesions with more than three million pictures, evaluating such elements as asymmetry, color, and shape, and spits out an assessment within thirty seconds. A team of in-house experts provide a review regardless of whether the mole is high or low risk, and the app encourages users to see their doctors. The Dutch-based company's app has been used by more than a million people globally in the EU, and in New Zealand and Australia, where skin cancer is rampant and early detection can save lives. The company has plans to enter the U.S. market, according to a spokesperson.
Apps like Instant Heart Rate analyze blood flow, which can indicate whether your heart is functioning normally, while uChek examines urine samples for up to 10 markers for conditions like diabetes and urinary tract infections. Some behavioral apps even have sensors that can spot suicide risks if users are less active, indicating they may be suffering from a bout of the blues.
Even more complex tests are in the research pipeline. Apps like ResAppDX could eventually replace x-rays, CT scans, and blood tests in diagnosing severe respiratory infections in kids, while an EU-funded project called i-Prognosis can track a variety of clues — voice changes, facial expressions, hand steadiness — that indicate the onset of Parkinson's disease.
These hand-held testing devices can be especially helpful in developing countries, and there are pilot programs to use smartphone technology to diagnose malaria and HIV infections in remote outposts in Africa.
"In a lot of these places, there's no infrastructure but everyone has a smartphone," says Scanwell's Koh. "We need to leverage the smartphone in a clinically relevant way."
However, patient privacy is an ongoing concern. A 2019 review in the Journal of the American Medical Association conducted by Australian and American researchers looked at three dozen behavioral health apps, mainly for depression and smoking cessation. They found that about 70 percent shared data with third parties, like Facebook and Google, but only one third of them disclosed this in a privacy policy.
"Patients just blindly accept the end user agreements without understanding the implications."
Users need to be vigilant, too. "Patients just blindly accept the end user agreements without understanding the implications," says Hamalka, who is also the Chief Information Officer and Dean for Technology at Harvard Medical School.
And quality control is an issue. Right now, the diagnostic tools currently available have been vetted by the FDA, and overseas companies like Skin Vision have been scrutinized by the U.K.'s National Health Service and the EU. But the danger is that a lot of apps are going to be popping up soon that haven't been properly tested, due to loopholes in the regulations.
"All we want," says Topol, "are rigorous studies to make sure what consumers are using is validated."
[Correction, August 19th, 2019: An earlier version of this story misstated the specifics of SkinVision's service. A team of in-house experts reviews users' submissions, not in-house dermatologists, and the service is not free.]
Scientists aim to preserve donkeys, one frozen embryo at a time
Every day for a week in 2022, Andres Gambini, a veterinarian and senior lecturer in animal science at the University of Queensland in Australia, walked into his lab—and headed straight to the video camera. Trained on an array of about 50 donkey embryos, all created by Gambini’s manual in vitro fertilization, or IVF, the camera kept an eye on their developmental progress. To eventually create a viable embryo that could be implanted into a female donkey, the embryos’ cells had to keep dividing, first in two, then in four and so on.
But the embryos weren’t cooperating. Some would start splitting up only to stop a day or two later, and others wouldn’t start at all. Every day he came in, Gambini saw fewer and fewer dividing embryos, so he was losing faith in the effort. “You see many failed attempts and get disappointed,” he says.
Gambini and his team, a group of Argentinian and Spanish researchers, were working to create these embryos because many donkey populations around the world are declining. It may sound counterintuitive that domesticated animals may need preservation, but out of 28 European donkey breeds, 20 are endangered and seven are in critical status. It is partly because of the inbreeding that happened over the course of many years and partly because in today’s Western world donkeys aren’t really used anymore.
“That's the reason why some breeds begin to disappear because humans were not really interested in having that specific breed anymore,” Gambini says. Nonetheless, in Africa, India and Latin America millions of rural families still rely on these hardy creatures for agriculture and transportation. And the only two wild donkey species—Equus africanus in Africa and Equus hemionus in Asia—are also dwindling, due to losing their habitats to human activities, diseases and slow reproduction rates. Gambini’s team wanted to create a way to preserve the animals for the future. “Donkeys are more endangered than people realize,” he says.
There’s much more to donkeys' trouble though. For the past 20 or so years, they have been facing a huge existential threat due to their hide gelatin, a compound derived from their skins by soaking and stewing. In Chinese traditional medicine, the compound, called ejiao, is believed to have a medicinal value, so it’s used in skin creams, added to food and taken in capsules. Centuries ago, ejiao was a very expensive luxury product available only for the emperor and his household. That changed in the 1990s when the Chinese economy boomed, and many people were suddenly able to afford it. “It went from a very elite product to a very popular product,” says Janneke Merkx, a campaign manager at The Donkey Sanctuary, a United Kingdom-based nonprofit organization that keeps tabs on the animals’ welfare worldwide. “It is a status symbol for gift giving.”
Having evolved in the harsh and arid mountainous terrains where food and water were scarce, donkeys are extremely adaptable and hardy. But the Donkey Sanctuary documented cases in which an entire village had their animals disappear overnight, finding them killed and skinned outside their settlement.
The Chinese donkey population was quickly decimated. Unlike many other farm animals, donkeys are finicky breeders. When stressed and unhappy, they don’t procreate, so growing them in large industrial settings isn’t possible. “Donkeys are notoriously slow breeders and really very difficult to farm,” says Merkx. “They are not the same as other livestock like sheep and pigs and cattle.” Within years the, the donkey numbers in China dropped precipitously. “China used to have the largest donkey population in the world in the 1990s. They had 11 million donkeys, and it's now down to less than 3 million, and they just can't keep up with the demand.”
To keep the ejiao conveyor going, some producers turned to the illegal wildlife trade. Poachers began to steal and slaughter donkeys from rural villages in Africa. The Donkey Sanctuary documented cases in which an entire village had their animals disappear overnight, finding them killed and skinned outside their settlement. Exactly how many creatures were lost to the skin trade to-date isn’t possible to calculate, says Faith Burden, the Donkey Sanctuary’s director of equine operations. Traditionally a poor people’s beast of burden, donkey counts are hard to keep track of. “When an animal doesn't produce meat, milk or eggs or whatever edible product, they're often less likely to be acknowledged in a government population census,” Burden says. “So reliable statistics are hard to come by.” The nonprofit estimates that about 4.8 million are slaughtered annually.
During their six to seven thousand years of domestication, donkeys rarely got the full appreciation for their services. They are often compared to horses, which doesn’t do them justice. They’re entirely different animals, Burden says. Built for speed, horses respond to predators and other dangers by running as fast as they can. Donkeys, which originate from the rocky, mountainous regions of Africa where running is dangerous, react to threats by freezing and assessing the situation for the best response. “Those so-called stubborn donkeys that won’t move as you want, they are actually thinking ‘what’s the best approach,’” Burden says. They may even choose to fight the predators rather than flee, she adds. “In some parts of the world, people use them as guard animals against things like coyotes and wolves.”
Scientists believe that domestic donkeys take their origin from Equus africanus or African wild ass, originally roaming where Kenya, Ethiopia and Eritrea are today. Having evolved in the harsh and arid mountainous terrains where food and water were scarce, they are extremely adaptable and hardy. Research finds that they can go without water for 72 hours and then drink their fill without any negative consequences. Their big jaws let them chew tough desert shrubs, which horses can’t exist on. Their large ears help dissipate heat. Their little upright hooves are a perfect fit for the uneven rocky or other dangerous grounds. Accustomed to the mountain desert climate with hot days and cold nights, they don’t mind temperature flux.
“The donkey is the most supremely adapted animal to deal with hostile conditions,” Burden says. “They can survive on much lower nutritional quality food than a cow, sheep or horse. That’s why communities living in some of the most inhospitable places will often have donkeys with them.” And that’s why losing a donkey to an illegal skin trade can devastate a family in places like Eritrea. Suddenly everything from water to firewood to produce must be carried by family members—and often women.
Workers unloading donkeys at the Shinyanga slaughterhouse in Tanzania. Fearing a future in which donkeys go extinct, scientists have found ways to cryopreserve a donkey embryo in liquid nitrogen.
TAHUCHA
One can imagine a time when worldwide donkey populations may dwindle to the point that they would need to be restored. That includes their genetic variability too. That’s where the frozen embryos may come in handy. We may be able to use them to increase the genetic variability of donkeys, which will be especially important if they get closer to extinction, Gambini says. His team had already created frozen embryos for horses and zebras, an idea similar to a seed bank. “We call this concept the Frozen Zoo.”
Creating donkey embryos proved much harder than those of zebras and horses. To improve chances of fertilization, Gambini used the intracytoplasmic sperm injection or ICSI, in which he employed a tiny needle called a micropipette to inject a donkey sperm into an egg. That was a step above the traditional IVF method, in which the egg and a sperm are left floating in a test tube together. The injection took, but during the incubating week, one after the other, the embryos stopped dividing. Finally, on day seven, Gambini finally spotted the exact sight he was hoping to see. One of the embryos developed into a burgeoning ball of cells.
“That stage is called a blastocyst,” Gambini says. The clump of cells had a lot of fluids mixed within them, which indicated that they were finally developing into a viable embryo. “When we see a blastocyst, we know we can transfer that into a female.” He was so excited he immediately called all his collaborators to tell them the good news, which they later published in the journal of Theriogenology.
The one and only embryo to reach that stage, the blastocyst was cryopreserved in liquid nitrogen. The team is waiting for the next breeding season to see if a female donkey may carry it to term and give birth to a healthy foal. Gambini’s team is hoping to polish the process and create more embryos. “It’s our weapon in the conservation ass-enal,” he says.
Lina Zeldovich has written about science, medicine and technology for Popular Science, Smithsonian, National Geographic, Scientific American, Reader’s Digest, the New York Times and other major national and international publications. A Columbia J-School alumna, she has won several awards for her stories, including the ASJA Crisis Coverage Award for Covid reporting, and has been a contributing editor at Nautilus Magazine. In 2021, Zeldovich released her first book, The Other Dark Matter, published by the University of Chicago Press, about the science and business of turning waste into wealth and health. You can find her on http://linazeldovich.com/ and @linazeldovich.
Too much of this ingredient leads to autoimmune diseases, new research shows. Here's how to cut back.
For more than a century, doctors have warned that too much salt in your diet can lead to high blood pressure, heart disease and stroke - and many of the reasons for these effects are well known. But recently scientists have been looking deeper, into the cellular level, and they are finding additional reasons to minimize sodium intake; it is bad for immune cells, creating patterns of gene expression and activity seen in a variety of autoimmune diseases such as multiple sclerosis, lupus, rheumatoid arthritis, and type-1 diabetes.
Salt is a major part of the ocean from which life evolved on this planet. We carry that legacy in our blood, which tastes salty. It is an important element for conducting electrical signals along nerves and balancing water and metabolites transported throughout our bodies. We need to consume about 500 milligrams of salt each day to maintain these functions, more with exercise and heavy sweating as that is a major way the body loses salt. The problem is that most Americans eating a modern western diet consume about 3400 milligrams, 1.5 teaspoons per day.
Evidence has been accumulating over the last few years that elevated levels of sodium can be harmful to at least some types of immune cells. The first signal came in monocytes, which are immune cells that travel to various tissues in the body, where some of them turn into macrophages, a subset of white blood cells that can directly kill microorganisms and make chemical signals that bring other types of immune cells into play.
Two years ago, Dominik N. Müller from the Max-Delbrueck-Center in Berlin, Germany and Markus Kleinewietfeld, an immunologist at Hasselt University in Belgium, ran a study where they fed people pizza and then measured their immune cell function. “We saw that in any monocytes, metabolic function was down, even after a single salty meal,” Kleinewietfeld says. It seemed to be the cellular equivalent of the sluggish feeling we get after eating too much. The cells were able to recover but more research is needed to answer questions about what dose of sodium causes impairment, how long the damage lasts, and whether there is a cumulative effect of salt toxicity.
Kleinewietfeld and his colleagues have hypothesized that too much salt could be a significant factor in the increased number of autoimmune diseases and allergies over the last few generations.
The latest series of experiments focused on a type of T cell called T regulatory cells, or Tregs. Most T cells release inflammatory mediators to fight pathogens and, once that job is done, Tregs come along to calm down their hyperactive brethren. Failure to do so can result in continued inflammation and possibly autoimmune diseases.
In the lab, Kleinewietfeld and his large team of international collaborators saw that high levels of sodium had a huge effect on Tregs, upregulating 1250 genes and downregulating an additional 1380 genes so that they looked similar to patterns of gene expression seen in autoimmune diseases.
Digging deeper, they found that sodium affected mitochondria, the tiny organelles inside of cells that produce much of its energy. The sodium was interfering with how the mitochondria use oxygen, which resulted in increased levels of an unstable form of oxygen that can damage cell function. The researchers injected those damaged Tregs into mice and found that they impaired the animals' immune function, allowing the inflammation to continue rather than shutting it down.
That finding dovetailed nicely with a 2019 paper in Nature from Navdeep Chandel's lab at Northwestern University, which showed in mice that inhibiting the mitochondrial use of oxygen reduced the ability of Tregs to regulate other T cells. “Mitochondria were controlling directly the immunosuppressive program, they were this master regulator tuning the right amount of genes to give you proper immunosuppression,” Chandel said. “And if you lose that function, then you get autoimmunity.”
Kleinewietfeld's team studied the Treg cells of humans and found that sodium can similarly decrease mitochondrial use of oxygen and immunosuppressive activity. “I would have never predicted that myself,” Chandel says, but now researchers can look at the mitochondria of patients with autoimmune disease and see if their gene expression also changes under high salt conditions. He sees the link between the patterns of gene expression in Tregs generated by high salt exposure and those patterns seen in autoimmune diseases, but he is cautious about claiming a causal effect.
Kleinewietfeld and his colleagues have hypothesized that too much salt could be a significant factor in the increased number of autoimmune diseases and allergies over the last few generations. He says a high salt diet could also have an indirect effect on immune function through the way it affects the gut microbiome and the molecules made by microbes when they break down food. But the research results are too preliminary to say that for sure, much less parse out the role of salt compared with other possible factors. “It is still an exciting journey to try to understand this field,” he says.
Additionally, it is difficult to say precisely how this research in animals and human cell cultures will translate into a whole human body. Individual differences in genetics can affect how the body absorbs, transports, and gets rid of sodium, such that some people are more sensitive to salt than are others.
So how should people apply these research findings to daily life?
Salt is obvious when we sprinkle it on at the table or eat tasty things like potato chips, but we may be unaware of sodium hidden in packaged foods. That's because salt is an easy and cheap way to boost the flavor of foods. And if we do read the labeled salt content on a package, we focus on the number for a single serving, but then eat more than that.
Last September, the U.S. Food and Drug Administration (FDA) began a process to update labels on the content of food, including what is meant by the word “healthy” and how food manufacturers can use the term. Many in the food industry are resisting those proposed changes.
Chandel cautions against trying to counter the effects of salt by reaching for foods or supplements full of antioxidants, which, in theory, could reduce the harmful effects on mitochondria caused by a heavy hand with the salt shaker.
Until labels are updated, it would be prudent to try to reduce sodium intake by cutting down on packaged foods while making your own food at home, where you know just how much salt has been added. The Mayo Clinic offers guidance on how to become more aware of the sodium in your diet and eat less of it.
Chandel thinks many people will struggle with minimizing salt in their diets. It’s similar to the challenge of eating less sugar, in that the body craves both, and it is difficult to fight that. He cautions against trying to counter the effects of salt by reaching for foods or supplements full of antioxidants, which, in theory, could reduce the harmful effects on mitochondria caused by a heavy hand with the salt shaker. “Dietary antioxidants have failed in just about every clinical trial, yet the public continues to take them,” Chandel says. But he is optimistic that research will lead us to a better understanding of how Tregs function, and uncover new targets for treating autoimmune diseases.