Biomedical engineer Kevin Zhao has a sensor in his arm and his chest that monitors his oxygen level in those tissues in real time.
Last month, at a conference celebrating DARPA, the research arm of the Defense Department, FBI Special Agent Edward You declared, "The 21st century will be the revolution of the life sciences."
Biomedical engineer Kevin Zhao has a sensor in his arm and chest that monitors his oxygen level in real time.
Indeed, four years ago, the agency dedicated a new office solely to advancing biotechnology. Its primary goal is to combat bioterrorism, protect U.S. forces, and promote warfighter readiness. But its research could also carry over to improve health care for the general public.
With an annual budget of about $3 billion, DARPA's employees oversee about 250 research and development programs, working with contractors from corporations, universities, and government labs to bring new technologies to life.
Check out these three current programs:
1) IMPLANTABLE SENSORS TO MEASURE OXYGEN, LACTATE, AND GLUCOSE LEVELS IN REAL TIME
Biomedical engineer Kevin Zhao has a sensor in his arm and his chest that monitors his oxygen level in those tissues in real time. With funding from DARPA for the program "In Vivo Nanoplatforms," he developed soft, flexible hydrogels that are injected just beneath the skin to perform the monitoring and that sync to a smartphone app to give the user immediate health insights.
A first-in-man trial for the glucose sensor is now underway in Europe for monitoring diabetics, according to Zhao. Volunteers eat sugary food to spike their glucose levels and prompt the monitor to register the changes.
"If this pans out, with approval from FDA, then consumers could get the sensors implanted in their core to measure their levels of glucose, oxygen, and lactate," Zhao said.
Lactate, especially, interests DARPA because it's a first responder molecule to the onset of trauma, sepsis, and potentially infection.
"The sensor could potentially detect rise of these [body chemistry numbers] and alert the user to prevent onset of dangerous illness."
2) NEAR INSTANTANEOUS VACCINE PROTECTION DURING A PANDEMIC
Traditional vaccines can take months or years to develop, then weeks to become effective once you get it. But when an unknown virus emerges, there's no time to waste.
This program, called P3, envisions a much more ambitious approach to stop a pandemic in its tracks.
"We want to confer near instantaneous protection by doing it a different way – enlist the body as a bioreactor to produce therapeutics," said Col. Matthew Hepburn, the program manager.
So how would it work?
To fight a pandemic, we will need 20,000 doses of a vaccine in 60 days.
If you have antibodies against a certain infection, you'll be protected against that infection. This idea is to discover the genetic code for the antibody to a specific pathogen, manufacture those pieces of DNA and RNA, and then inject the code into a person's arm so the muscle cells will begin producing the required antibodies.
"The amazing thing is that it actually works, at least in animal models," said Hepburn. "The mouse muscles made enough protective antibodies so that the mice were protected."
The next step is to test the approach in humans, which the program will do over the next two years.
But the hard part is actually not discovering the genetic code for highly potent antibodies, according to Hepburn. In fact, researchers already have been able to do so in two to four weeks' time.
"The hard part is once I have an antibody, a large pharma company will say in 2 years, I can make 100-200 doses. Give us 4 years to get to 20,000 doses. That's not good enough," Hepburn said.
To fight a pandemic, we will need 20,000 doses of a vaccine in 60 days.
"We have to fundamentally change the idea that it takes a billion dollars and ten years to make a drug," he concluded. "We're going to do something radically different."
3) RAPID DIAGNOSING OF PATHOGEN EXPOSURE THROUGH EPIGENETICS
Imagine that you come down with a mysterious illness. It could be caused by a virus, bacteria, or in the most extreme catastrophe, a biological agent from a weapon of mass destruction.
What if a portable device existed that could identify--within 30 minutes—which pathogen you have been exposed to and when? It would be pretty remarkable for soldiers in the field, but also for civilians seeking medical treatment.
This is the lofty ambition of a DARPA program called Epigenetic Characterization and Observation, or ECHO.
Its success depends on a biological phenomenon known as the epigenome. While your DNA is relatively immutable, your environment can modify how your DNA is expressed, leaving marks of exposure that register within seconds to minutes; these marks can persist for decades. It's thanks to the epigenome that identical twins – who share identical DNA – can differ in health, temperament, and appearance.
These three mice are genetically identical. Epigenetic differences, however, result in vastly different observed characteristics.
Reading your epigenetic marks could theoretically reveal a time-stamped history of your body's environmental exposures.
Researchers in the ECHO program plan to create a database of signatures for exposure events, so that their envisioned device will be able to quickly scan someone's epigenome and refer to the database to sort out a diagnosis.
"One difficult part is to put a timestamp on this result, in addition to the sign of which exposure it was -- to tell us when this exposure happened," says Thomas Thomou, a contract scientist who is providing technical assistance to the ECHO program manager.
Other questions that remain up in the air for now: Do all humans have the same epigenetic response to the same exposure events? Is it possible to distinguish viral from bacterial exposures? Does dose and duration of exposure affect the signature of epigenome modification?
The program will kick off in January 2019 and is planned to last four years, as long as certain milestones of development are reached along the way. The desired prototype would be a simple device that any untrained person could operate by taking a swab or a fingerprick.
"In an outbreak," says Dr. Thomou, "it will help everyone on the ground immediately to have a rapidly deployable machine that will give you very quick answers to issues that could have far-reaching ramifications for public health safety."
NASA astronaut Frank Rubio floats by the International Space Station’s “window to the world.” Yesterday, he returned from the longest single spaceflight by a U.S. astronaut on record - over one year. Exploring deep space will require even longer missions.
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.
Swiss researchers have found a type of brain cell that appears to be a hybrid of the two other main types — and it could lead to new treatments for brain disorders.
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.
