Food Poisoning Outbreaks Are Still A Problem. Powerful Tech Is Fighting Back.
With the pandemic at the forefront of everyone's minds, many people have wondered if food could be a source of coronavirus transmission. Luckily, that "seems unlikely," according to the CDC, but foodborne illnesses do still sicken a whopping 48 million people per year.
Whole genome sequencing is like "going from an eight-bit image—maybe like what you would see in Minecraft—to a high definition image."
In normal times, when there isn't a historic global health crisis infecting millions and affecting the lives of billions, foodborne outbreaks are real and frightening, potentially deadly, and can cause widespread fear of particular foods. Think of Romaine lettuce spreading E. coli last year— an outbreak that infected more than 500 people and killed eight—or peanut butter spreading salmonella in 2008, which infected 167 people.
The technologies available to detect and prevent the next foodborne disease outbreak have improved greatly over the past 30-plus years, particularly during the past decade, and better, more nimble technologies are being developed, according to experts in government, academia, and private industry. The key to advancing detection of harmful foodborne pathogens, they say, is increasing speed and portability of detection, and the precision of that detection.
Getting to Rapid Results
Researchers at Purdue University have recently developed a lateral flow assay that, with the help of a laser, can detect toxins and pathogenic E. coli. Lateral flow assays are cheap and easy to use; a good example is a home pregnancy test. You place a liquid or liquefied sample on a piece of paper designed to detect a single substance and soon after you get the results in the form of a colored line: yes or no.
"They're a great portable tool for us for food contaminant detection," says Carmen Gondhalekar, a fifth-year biomedical engineering graduate student at Purdue. "But one of the areas where paper-based lateral flow assays could use improvement is in multiplexing capability and their sensitivity."
J. Paul Robinson, a professor in Purdue's Colleges of Veterinary Medicine and Engineering, and Gondhalekar's advisor, agrees. "One of the fundamental problems that we have in detection is that it is hard to identify pathogens in complex samples," he says.
When it comes to foodborne disease outbreaks, you don't always know what substance you're looking for, so an assay made to detect only a single substance isn't always effective. The goal of the project at Purdue is to make assays that can detect multiple substances at once.
These assays would be more complex than a pregnancy test. As detailed in Gondhalekar's recent paper, a laser pulse helps create a spectral signal from the sample on the assay paper, and the spectral signal is then used to determine if any unique wavelengths associated with one of several toxins or pathogens are present in the sample. Though the handheld technology has yet to be built, the idea is that the results would be given on the spot. So someone in the field trying to track the source of a Salmonella infection could, for instance, put a suspected lettuce sample on the assay and see if it has the pathogen on it.
"What our technology is designed to do is to give you a rapid assessment of the sample," says Robinson. "The goal here is speed."
Seeing the Pathogen in "High-Def"
"One in six Americans will get a foodborne illness every year," according to Dr. Heather Carleton, a microbiologist at the Centers for Disease Control and Prevention's Enteric Diseases Laboratory Branch. But not every foodborne outbreak makes the news. In 2017 alone, the CDC monitored between 18 and 37 foodborne poison clusters per week and investigated 200 multi-state clusters. Hardboiled eggs, ground beef, chopped salad kits, raw oysters, frozen tuna, and pre-cut melon are just a taste of the foods that were investigated last year for different strains of listeria, salmonella, and E. coli.
At the heart of the CDC investigations is PulseNet, a national network of laboratories that uses DNA fingerprinting to detect outbreaks at local and regional levels. This is how it works: When a patient gets sick—with symptoms like vomiting and fever, for instance—they will go to a hospital or clinic for treatment. Since we're talking about foodborne illnesses, a clinician will likely take a stool sample from the patient and send it off to a laboratory to see if there is a foodborne pathogen, like salmonella, E. Coli, or another one. If it does contain a potentially harmful pathogen, then a bacterial isolate of that identified sample is sent to a regional public health lab so that whole genome sequencing can be performed.
Whole genome sequencing can differentiate "virtually all" strains of foodborne pathogens, no matter the species, according to the FDA.
Whole genome sequencing is a method for reading the entire genome of a bacterial isolate (or from any organism, for that matter). Instead of working with a couple dozen data points, now you're working with millions of base pairs. Carleton likes to describe it as "going from an eight-bit image—maybe like what you would see in Minecraft—to a high definition image," she says. "It's really an evolution of how we detect foodborne illnesses and identify outbreaks."
If the bacterial isolate matches another in the CDC's database, this means there could be a potential outbreak and an investigation may be started, with the goal of tracking the pathogen to its source.
Whole genome sequencing has been a relatively recent shift in foodborne disease detection. For more than 20 years, the standard technique for analyzing pathogens in foodborne disease outbreaks was pulsed-field gel electrophoresis. This method creates a DNA fingerprint for each sample in the form of a pattern of about 15-30 "bands," with each band representing a piece of DNA. Researchers like Carleton can use this fingerprint to see if two samples are from the same bacteria. The problem is that 15-30 bands are not enough to differentiate all isolates. Some isolates whose bands look very similar may actually come from different sources and some whose bands look different may be from the same source. But if you can see the entire DNA fingerprint, then you don't have that issue. That's where whole genome sequencing comes in.
Although the PulseNet team had piloted whole genome sequencing as early as 2013, it wasn't until July of last year that the transition to using whole genome sequencing for all pathogens was complete. Though whole genome sequencing requires far more computing power to generate, analyze, and compare those millions of data points, the payoff is huge.
Stopping Outbreaks Sooner
The U.S. Food and Drug Administration (FDA) acquired their first whole genome sequencers in 2008, according to Dr. Eric Brown, the Director of the Division of Microbiology in the FDA's Office of Regulatory Science. Since then, through their GenomeTrakr program, a network of more than 60 domestic and international labs, the FDA has sequenced and publicly shared more than 400,000 isolates. "The impact of what whole genome sequencing could do to resolve a foodborne outbreak event was no less impactful than when NASA turned on the Hubble Telescope for the first time," says Brown.
Whole genome sequencing has helped identify strains of Salmonella that prior methods were unable to differentiate. In fact, whole genome sequencing can differentiate "virtually all" strains of foodborne pathogens, no matter the species, according to the FDA. This means it takes fewer clinical cases—fewer sick people—to detect and end an outbreak.
And perhaps the largest benefit of whole genome sequencing is that these detailed sequences—the millions of base pairs—can imply geographic location. The genomic information of bacterial strains can be different depending on the area of the country, helping these public health agencies eventually track the source of outbreaks—a restaurant, a farm, a food-processing center.
Coming Soon: "Lab in a Backpack"
Now that whole genome sequencing has become the go-to technology of choice for analyzing foodborne pathogens, the next step is making the process nimbler and more portable. Putting "the lab in a backpack," as Brown says.
The CDC's Carleton agrees. "Right now, the sequencer we use is a fairly big box that weighs about 60 pounds," she says. "We can't take it into the field."
A company called Oxford Nanopore Technologies is developing handheld sequencers. Their devices are meant to "enable the sequencing of anything by anyone anywhere," according to Dan Turner, the VP of Applications at Oxford Nanopore.
"The sooner that we can see linkages…the sooner the FDA gets in action to mitigate the problem and put in some kind of preventative control."
"Right now, sequencing is very much something that is done by people in white coats in laboratories that are set up for that purpose," says Turner. Oxford Nanopore would like to create a new, democratized paradigm.
The FDA is currently testing these types of portable sequencers. "We're very excited about it. We've done some pilots, to be able to do that sequencing in the field. To actually do it at a pond, at a river, at a canal. To do it on site right there," says Brown. "This, of course, is huge because it means we can have real-time sequencing capability to stay in step with an actual laboratory investigation in the field."
"The timeliness of this information is critical," says Marc Allard, a senior biomedical research officer and Brown's colleague at the FDA. "The sooner that we can see linkages…the sooner the FDA gets in action to mitigate the problem and put in some kind of preventative control."
At the moment, the world is rightly focused on COVID-19. But as the danger of one virus subsides, it's only a matter of time before another pathogen strikes. Hopefully, with new and advancing technology like whole genome sequencing, we can stop the next deadly outbreak before it really gets going.
After spaceflight record, NASA looks to protect astronauts on even longer trips
At T-minus six seconds, the main engines of the Atlantis Space Shuttle ignited, rattling its capsule “like a skyscraper in an earthquake,” according to astronaut Tom Jones, describing the 1988 launch. As the rocket lifted off and accelerated to three times the force of Earth's gravity, “It felt as if two of my friends were standing on my chest and wouldn’t get off.” But when Atlantis reached orbit, the main engines cut off, and the astronauts were suddenly weightless.
Since 1961, NASA has sent hundreds of astronauts into space while working to making their voyages safer and smoother. Yet, challenges remain. Weightlessness may look amusing when watched from Earth, but it has myriad effects on cognition, movement and other functions. When missions to space stretch to six months or longer, microgravity can impact astronauts’ health and performance, making it more difficult to operate their spacecraft.
Yesterday, NASA astronaut Frank Rubio returned to Earth after over one year, the longest single spaceflight for a U.S. astronaut. But this is just the start; longer and more complex missions into deep space loom ahead, from returning to the moon in 2025 to eventually sending humans to Mars. To ensure that these missions succeed, NASA is increasing efforts to study the biological effects and prevent harm.
The dangers of microgravity are real
A NASA report published in 2016 details a long list of incidents and near-misses caused – at least partly – by space-induced changes in astronauts’ vision and coordination. These issues make it harder to move with precision and to judge distance and velocity.
According to the report, in 1997, a resupply ship collided with the Mir space station, possibly because a crew member bumped into the commander during the final docking maneuver. This mishap caused significant damage to the space station.
Returns to Earth suffered from problems, too. The same report notes that touchdown speeds during the first 100 space shuttle landings were “outside acceptable limits. The fastest landing on record – 224 knots (258 miles) per hour – was linked to the commander’s momentary spatial disorientation.” Earlier, each of the six Apollo crews that landed on the moon had difficulty recognizing moon landmarks and estimating distances. For example, Apollo 15 landed in an unplanned area, ultimately straddling the rim of a five-foot deep crater on the moon, harming one of its engines.
Spaceflight causes unique stresses on astronauts’ brains and central nervous systems. NASA is working to reduce these harmful effects.
NASA
Space messes up your brain
In space, astronauts face the challenges of microgravity, ionizing radiation, social isolation, high workloads, altered circadian rhythms, monotony, confined living quarters and a high-risk environment. Among these issues, microgravity is one of the most consequential in terms of physiological changes. It changes the brain’s structure and its functioning, which can hurt astronauts’ performance.
The brain shifts upwards within the skull, displacing the cerebrospinal fluid, which reduces the brain’s cushioning. Essentially, the brain becomes crowded inside the skull like a pair of too-tight shoes.
That’s partly because of how being in space alters blood flow. On Earth, gravity pulls our blood and other internal fluids toward our feet, but our circulatory valves ensure that the fluids are evenly distributed throughout the body. In space, there’s not enough gravity to pull the fluids down, and they shift up, says Rachael D. Seidler, a physiologist specializing in spaceflight at the University of Florida and principal investigator on many space-related studies. The head swells and legs appear thinner, causing what astronauts call “puffy face chicken legs.”
“The brain changes at the structural and functional level,” says Steven Jillings, equilibrium and aerospace researcher at the University of Antwerp in Belgium. “The brain shifts upwards within the skull,” displacing the cerebrospinal fluid, which reduces the brain’s cushioning. Essentially, the brain becomes crowded inside the skull like a pair of too-tight shoes. Some of the displaced cerebrospinal fluid goes into cavities within the brain, called ventricles, enlarging them. “The remaining fluids pool near the chest and heart,” explains Jillings. After 12 consecutive months in space, one astronaut had a ventricle that was 25 percent larger than before the mission.
Some changes reverse themselves while others persist for a while. An example of a longer-lasting problem is spaceflight-induced neuro-ocular syndrome, which results in near-sightedness and pressure inside the skull. A study of approximately 300 astronauts shows near-sightedness affects about 60 percent of astronauts after long missions on the International Space Station (ISS) and more than 25 percent after spaceflights of only a few weeks.
Another long-term change could be the decreased ability of cerebrospinal fluid to clear waste products from the brain, Seidler says. That’s because compressing the brain also compresses its waste-removing glymphatic pathways, resulting in inflammation, vulnerability to injuries and worsening its overall health.
The effects of long space missions were best demonstrated on astronaut twins Scott and Mark Kelly. This NASA Twins Study showed multiple, perhaps permanent, changes in Scott after his 340-day mission aboard the ISS, compared to Mark, who remained on Earth. The differences included declines in Scott’s speed, accuracy and cognitive abilities that persisted longer than six months after returning to Earth in March 2016.
By the end of 2020, Scott’s cognitive abilities improved, but structural and physiological changes to his eyes still remained, he said in a BBC interview.
“It seems clear that the upward shift of the brain and compression of the surrounding tissues with ventricular expansion might not be a good thing,” Seidler says. “But, at this point, the long-term consequences to brain health and human performance are not really known.”
NASA astronaut Kate Rubins conducts a session for the Neuromapping investigation.
NASA
Staying sharp in space
To investigate how prolonged space travel affects the brain, NASA launched a new initiative called the Complement of Integrated Protocols for Human Exploration Research (CIPHER). “CIPHER investigates how long-duration spaceflight affects both brain structure and function,” says neurobehavioral scientist Mathias Basner at the University of Pennsylvania, a principal investigator for several NASA studies. “Through it, we can find out how the brain adapts to the spaceflight environment and how certain brain regions (behave) differently after – relative to before – the mission.”
To do this, he says, “Astronauts will perform NASA’s cognition test battery before, during and after six- to 12-month missions, and will also perform the same test battery in an MRI scanner before and after the mission. We have to make sure we better understand the functional consequences of spaceflight on the human brain before we can send humans safely to the moon and, especially, to Mars.”
As we go deeper into space, astronauts cognitive and physical functions will be even more important. “A trip to Mars will take about one year…and will introduce long communication delays,” Seidler says. “If you are on that mission and have a problem, it may take eight to 10 minutes for your message to reach mission control, and another eight to 10 minutes for the response to get back to you.” In an emergency situation, that may be too late for the response to matter.
“On a mission to Mars, astronauts will be exposed to stressors for unprecedented amounts of time,” Basner says. To counter them, NASA is considering the continuous use of artificial gravity during the journey, and Seidler is studying whether artificial gravity can reduce the harmful effects of microgravity. Some scientists are looking at precision brain stimulation as a way to improve memory and reduce anxiety due to prolonged exposure to radiation in space.
Other scientists are exploring how to protect neural stem cells (which create brain cells) from radiation damage, developing drugs to repair damaged brain cells and protect cells from radiation.
To boldly go where no astronauts have gone before, they must have optimal reflexes, vision and decision-making. In the era of deep space exploration, the brain—without a doubt—is the final frontier.
Additionally, NASA is scrutinizing each aspect of the mission, including astronaut exercise, nutrition and intellectual engagement. “We need to give astronauts meaningful work. We need to stimulate their sensory, cognitive and other systems appropriately,” Basner says, especially given their extreme confinement and isolation. The scientific experiments performed on the ISS – like studying how microgravity affects the ability of tissue to regenerate is a good example.
“We need to keep them engaged socially, too,” he continues. The ISS crew, for example, regularly broadcasts from space and answers prerecorded questions from students on Earth, and can engage with social media in real time. And, despite tight quarters, NASA is ensuring the crew capsule and living quarters on the moon or Mars include private space, which is critical for good mental health.
Exploring deep space builds on a foundation that began when astronauts first left the planet. With each mission, scientists learn more about spaceflight effects on astronauts’ bodies. NASA will be using these lessons to succeed with its plans to build science stations on the moon and, eventually, Mars.
“Through internally and externally led research, investigations implemented in space and in spaceflight simulations on Earth, we are striving to reduce the likelihood and potential impacts of neurostructural changes in future, extended spaceflight,” summarizes NASA scientist Alexandra Whitmire. To boldly go where no astronauts have gone before, they must have optimal reflexes, vision and decision-making. In the era of deep space exploration, the brain—without a doubt—is the final frontier.
A newly discovered brain cell may lead to better treatments for cognitive disorders
Swiss researchers have discovered a third type of brain cell that appears to be a hybrid of the two other primary types — and it could lead to new treatments for many brain disorders.
The challenge: Most of the cells in the brain are either neurons or glial cells. While neurons use electrical and chemical signals to send messages to one another across small gaps called synapses, glial cells exist to support and protect neurons.
Astrocytes are a type of glial cell found near synapses. This close proximity to the place where brain signals are sent and received has led researchers to suspect that astrocytes might play an active role in the transmission of information inside the brain — a.k.a. “neurotransmission” — but no one has been able to prove the theory.
A new brain cell: Researchers at the Wyss Center for Bio and Neuroengineering and the University of Lausanne believe they’ve definitively proven that some astrocytes do actively participate in neurotransmission, making them a sort of hybrid of neurons and glial cells.
According to the researchers, this third type of brain cell, which they call a “glutamatergic astrocyte,” could offer a way to treat Alzheimer’s, Parkinson’s, and other disorders of the nervous system.
“Its discovery opens up immense research prospects,” said study co-director Andrea Volterra.
The study: Neurotransmission starts with a neuron releasing a chemical called a neurotransmitter, so the first thing the researchers did in their study was look at whether astrocytes can release the main neurotransmitter used by neurons: glutamate.
By analyzing astrocytes taken from the brains of mice, they discovered that certain astrocytes in the brain’s hippocampus did include the “molecular machinery” needed to excrete glutamate. They found evidence of the same machinery when they looked at datasets of human glial cells.
Finally, to demonstrate that these hybrid cells are actually playing a role in brain signaling, the researchers suppressed their ability to secrete glutamate in the brains of mice. This caused the rodents to experience memory problems.
“Our next studies will explore the potential protective role of this type of cell against memory impairment in Alzheimer’s disease, as well as its role in other regions and pathologies than those explored here,” said Andrea Volterra, University of Lausanne.
But why? The researchers aren’t sure why the brain needs glutamatergic astrocytes when it already has neurons, but Volterra suspects the hybrid brain cells may help with the distribution of signals — a single astrocyte can be in contact with thousands of synapses.
“Often, we have neuronal information that needs to spread to larger ensembles, and neurons are not very good for the coordination of this,” researcher Ludovic Telley told New Scientist.
Looking ahead: More research is needed to see how the new brain cell functions in people, but the discovery that it plays a role in memory in mice suggests it might be a worthwhile target for Alzheimer’s disease treatments.
The researchers also found evidence during their study that the cell might play a role in brain circuits linked to seizures and voluntary movements, meaning it’s also a new lead in the hunt for better epilepsy and Parkinson’s treatments.
“Our next studies will explore the potential protective role of this type of cell against memory impairment in Alzheimer’s disease, as well as its role in other regions and pathologies than those explored here,” said Volterra.