Businessmen are traveling longer distances to meet potential clients, launch new projects, and negotiate deals, but traveling comes with poor sleep and jet lag. Science tells us jet lag causes everything from headaches to irritability, poor decision making, and loss of concentration. Warfighters are travelers and thus suffer from travelers’ ailments including disrupted sleep cycles and limited access to safe food and water. Warfighters who have not slept well have lower alertness, weaker athletic performance, and greater disorientation. Jet lag and Sleep deprivation can thus cause mental fogginess, impaired decision-making, and decreased reaction times.
Regardless of the mission or situation, any number of stressors can reduce a Soldier’s mental or physical performance. Controlling these decrements is critical to mission effectiveness. Fatigue is the state of feeling tired, drowsy, sleepy or exhausted that results from prolonged physical or mental effort, prolonged periods without adequate sleep, or pronounced disruptions to the body’s internal clock. It is an internal physiologic state that primarily takes two forms, physical and mental, and affects different personnel to varying degrees. It has multiple causes and is worsened by forces common in an operational environment, e.g., sleep loss, circadian rhythm disturbances, stress and altitude. Physical fatigue results primarily from protracted or heavy physical exertion and will eventually degrade a person’s ability to perform both physical and mental tasks.
Mental fatigue, however, comes from a combination of poor sleep, circadian rhythm or “body clock” disruptions, or intense mental activity (e.g., short notice, prolonged planning sessions for critical missions, or tasks requiring intense concentration). Anyone can be affected by physical or mental fatigue, and either condition can lead to lapses of attention, slowed reaction times, inaccurate performance, poor judgment or teamwork, and impaired situational awareness. Effects of both physical and mental fatigue can seriously threaten morale, welfare and mission readiness.
The foremost cause of fatigue during combat operations is total or partial sleep deprivation. Sleep is a physiologic need like hunger and thirst. Inadequate sleep leads to fatigue that creates generalized decrements in performance, increased safety risks and adverse health consequences.
For the military, impaired decision-making and decreased reaction times can impact the mission. Today’s equipment requires a higher level of alertness and concentration from operators and sustainers than ever before. The demand for mental resources, coupled with the Army’s “we own the night” philosophy, increases the potential for Soldier and crew endurance-related problems.
Developments in bioelectronic technology is enabling the reality of Bioelectric implants designed to augment the body’s natural electric impulses. One of the most cutting-edge sectors of medical device research, bioelectric implants seem like the stuff of science fiction. Drawing from biology, electrical engineering, nanotechnology, medicine, biomedical engineering, and other fields, bioelectronic technology blurs the boundaries of the human/mechanical divide.
DARPA launched the ADAPTER program to develop bioelectric implants for soldiers to control their own physiology.
DARPA’s ADvanced Acclimation and Protection Tool for Environmental Readiness (ADAPTER) program
Current approaches to restoring wakefulness often lean on chemical methods that disrupt downstream sleep patterns and lead to exhaustion. For sustenance, warfighters typically rely on military-supplied food, which is logistically burdensome and may lead to warfighters having to consume local food and water that could cause otherwise preventable diseases, notably diarrhea. Data from 2003 to 2004 demonstrate that 2/5ths of diarrhea cases among warfighters in Iraq and Afghanistan required medical attention. A 2005 study, meanwhile, looked at 4,348 members of the military deployed to the same two countries and found that for 45 percent of those afflicted with diarrhea, job performance decreased for three days. Additionally, diarrhea contributed to 62 percent of subjects seeking medical care at least once. Thirty-one percent required intravenous rehydration. And for 17 percent of subjects, “diarrhea resulted in confinement to bed for a median of 2 days, causing an estimated 3.7 days of complete work loss per 100 person-months.”
Through advances in medical devices and synthetic biology, DARPA’s new ADvanced Acclimation and Protection Tool for Environmental Readiness (ADAPTER) program aims to develop a travel adapter for the human body, an implantable or ingestible bioelectronic carrier that can provide warfighters control over their own physiology. The integrated system will be designed to entrain the sleep cycle – either to a new time zone or back to a normal sleep pattern after night missions – and eliminate bacteria that cause traveler’s diarrhea after ingestion of contaminated food and water. ADAPTER will provide a transient, non-genetic means of extending and enhancing warfighter readiness.
“The goal of the ADAPTER program is to produce the therapies within the body itself. ADAPTER will manage a warfighter’s circadian rhythm, halving the time to re-establish normal sleep after a disruption such as jet lag or shift lag. It will also provide safe food and water by eliminating in vivo the top five bacterial sources of traveler’s diarrhea. Both will enhance the health and mobility of warfighters,” described Paul Sheehan, Ph.D., program manager for the DARPA ADAPTER program.
Leveraging known strategies, solutions, and molecules, performers will choose one of two application tracks: (1) in vivo compound delivery to entrain circadian rhythm/restore sleep-cycles; or (2) in vivo decontamination of food and water from bacterial causes of traveler’s diarrhea. it would likely stay in the body for up to 60 days, where it could be controlled externally by the user. This can include species E. coli, Shigella, Salmonella, Campylobacter jejuni, and Vibrio. What is important to note, too, is that these same bacteria are the ones responsible for many child deaths worldwide.The internal and signaling devices would likely communicate through live tissue by radio frequencies, ultrasound or even magnetic fields. It would be secured by highly local signal propagation as well as by encryption.
DARPA ADAPTER awards reported in May 2021
While jet lag and foodborne pathogens are inconveniences for an average traveler, they are critical challenges to operational readiness for a warfighter and can be the difference between mission success or failure. To maximize warfighter performance, the ADvanced Acclimation and Protection Tool for Environmental Readiness (ADAPTER) program will develop systems to provide warfighters control over their own physiology. This program will integrate engineered cells and biochemicals into an internal, bioelectronics carrier that the warfighter can signal, as needed, to initiate the production and timed release of therapies that either eliminate the foodborne pathogens that cause traveler’s diarrhea or regulate disrupted circadian rhythms caused by jetlag or shift-work schedules.
DARPA announced the three research teams who will tackle these challenges:
Northwestern aims to engineer a wirelessly-controlled bioelectronic implant that reduces the time needed to adapt to new time zones or drastic changes in work schedules by releasing peptide-based therapies to harmonize the warfighter’s central and peripheral circadian clocks.
The Stanford team plans to develop an implantable device that produces and releases melatonin on demand for up to 30 days.
Massachusetts Institute of Technology researchers will work on a swallowed device that deploys in the gut and then produces compounds that both kill foodborne pathogens and neutralize toxins that may have been released by the pathogens.
“The ADAPTER technology will alleviate operational limitations imposed by human physiology for two high-priority military needs – sleep and safe sustenance,” stated Dr. Paul Sheehan, ADAPTER program manager. “Generating the therapeutic system will require both accurate therapies and clear communication between the bioelectronic carrier and the external activator.”
During Phase I, performers will engineer cells to execute the desired biological function. Additionally, teams will develop a bioelectronic carrier that can house the engineered cells and deploy the therapies on-demand via secure external activation. During Phase II, performers will integrate the carrier and the engineered cells into a system that delivers physiologically relevant doses of therapy in a large animal model. The final phase will focus solely on the safety of the ADAPTER system for humans.
“ADAPTER will develop a transient, non-genetic means of extending and enhancing warfighter readiness by reducing the time to reestablish normal sleep after a disruption, such as jet lag or shift lag,” added Sheehan. “It will also provide safe food and water by eliminating the top 5 bacterial sources of traveler’s diarrhea. Both will enhance the agility and mobility of warfighters.”
Rice engineers set sights on implantable ‘living pharmacy’, reported in May 2021
Five Rice University engineering laboratories are part of a $33 million national effort to develop a wireless, fully implantable device that can control the body’s circadian clock, halving the time it takes to recover from jet lag and similar disruptions to the body’s sleep/wake cycles. Led by Northwestern University and funded by the Defense Advanced Research Projects Agency (DARPA), the project will blend bioelectronics, synthetic biology and traditional electronics to create a “living pharmacy” that produces the same peptide molecules the body naturally makes to regulate sleep cycles. The device could be a powerful tool for military personnel, who frequently travel across multiple time zones, as well as first responders and other shift workers who oscillate between overnight and daytime shifts.
Faculty in Rice’s Brown School of Engineering will lead the development of key components of the proposed technology. Omid Veiseh, assistant professor of bioengineering, will oversee the creation of engineered cells that produce the therapeutic biomolecules, and Jacob Robinson, associate professor of electrical and computer engineering, will oversee the development of the wireless bioelectronic implant that houses the engineered cells and regulates drug production.
Called NTRAIN (Normalizing Timing of Rhythms Across Internal Networks of Circadian Clocks), the project is part of DARPA’s Advanced Acclimation and Protection Tool for Environmental Readiness (ADAPTER) program to help address the challenges of travel, including jet lag, fatigue and gastrointestinal issues. “Sleep control is something we can track while we develop this implant, but the real innovation here is being able to produce drugs inside the patient,” Veiseh said.
The NTRAIN team will engineer cells to produce peptides to regulate sleep cycles. The engineered cells will respond to light, which will be delivered via bioelectronic controls that adjust timing and dose. Veiseh, who’s leading the effort, said pharmaceutical companies often make drugs using industrial scale bioengineering. “If we can bring all of that manufacturing right into the patient and produce high-quality compounds on an as-needed basis, the possibilities are infinite,” Veiseh said. For a start, the technology could be used to manage diabetes and other chronic diseases where people regularly inject themselves with drugs.
The implant’s power and communications will be delivered by a weak magnetic field generated by a wearable device. In a pioneering demonstration in 2020, Robinson and colleagues showed “magnetoelectric” technology could provide both power and communications for neural stimulators no larger than a grain of rice. Robinson said the technology will provide plenty of power while enhancing device security. “We’ll design the device so it can only communicate in the near field, meaning only over a couple of centimeters,” he said. “So you’d essentially have to be in contact with the device in order to hack it.” Veiseh and Robinson said an additional safety feature will allow a user to deactivate the device permanently by sending a signal for the engineered cells to immediately kill themselves.
The first phase of the highly interdisciplinary program will focus on developing the implant. The second phase, contingent on the first, will validate the device. If that milestone is met, then researchers will test the device in human trials as part of the third phase. The full funding corresponds to $33 million over 4 1/2 years. Rice electrical engineer Kaiyuan Yang will design an application-specific integrated circuit to handle back-end functions and integrate with the bioelectronic controls. Rice bioengineer Isaac Hilton will optimize the cells’ drug-making abilities, and Rice neuroengineer Caleb Kemere will test implants in rodents in the leadup to human trials.
Circadian clock research will be led by sleep experts at Northwestern’s Center for Sleep and Circadian Biology. Engineers from Northwestern, Carnegie Mellon University and Blackrock Microsystems will also develop bioelectronic components. “This control system allows us to deliver a peptide of interest on demand, directly into the bloodstream,” said NTRAIN principal investigator Jonathan Rivnay, an assistant professor of biomedical engineering in Northwestern’s McCormick School of Engineering. “No need to carry drugs, no need to inject therapeutics and — depending on how long we can make the device last — no need to refill the device. It’s like an implantable pharmacy on a chip that never runs out.”
Future of Cyborgs
The future may well involve the emergence of humans who are fundamentally coupled with bioelectronic devices, science fiction’s “cyborgs.” Revolutions in semiconductor devices, cognitive science, bioelectronics, nanotechnology and applied neural control technologies are facilitating breakthroughs in hybrids of humans and machines. The interactions of increased computing power, advances in prosthetic devices, artificial implants, and systems that blend electronic and biological components, are facilitating the merging of man with machines.
Used as curative devices for patients with sensory, motor or cognitive deficits, active medical implantable devices evoke little dispute, allowing those who are blind, or paralyzed, or without a limb, to surmount those conditions.
Endowing humans with night vision, X-ray vision and long-range zoom capacities, or the ability to sniff out mer cury and carbon monoxide, appreciably changes human abilities. Of even more significance, is the radical enhancement possible through approaching brain-machine interfaces. Brain machine interfaces may enhance, augment or replace those most prized of human capacities, the ability to reason and remember. These interfaces will enable humans to be constantly logged onto the internet, to cyberthink and to instantaneously retrieve encyclopedic stores of information.
Building in these interfaces, surgically implanting them in the brain, will allow for greater energy, and efficiency, and will enable humans to operate without radios, or TVs, printed newspapers, cameras, GPS units, credit cards, computer workstations, ATM machines, wireless, corded or mobile phones, and other separate devices.
Significant ethical concerns are, however, raised by the potential for using these technologies to enhance and augment human capabilities, and by the possibility that humankind, as we know it, may eventually be phased out, or become just a step in evolution.