Research in Space: The Next Frontier for Brigham Investigators
Space exploration has made its way into the labs and research of clinicians and scientists at the Brigham. Researchers are exploring ways to study cancer cells in space, understand the sleep cycle of astronauts and simulate medical emergencies in space on Earth.
Launching 3-D Bioprinted Cancer Cells into Space
On Aug. 25 2018, three hours south of Albuquerque, N.M., a small rocket launched from the world’s first commercial spaceport—Spaceport America. It remained in flight for a few minutes before landing at the same place from which it launched. Conjuring more than just local excitement for its first test flight, the success of the rocket was celebrated 2,000 miles away in the lab of Yu Shrike Zhang, PhD, in Cambridge, Mass.
Zhang, an associate bioengineer at the Brigham, had something riding on the rocket—quite literally. Zhang’s team was interested in seeing how 3-D bioprinted breast cancer cells would respond to the acceleration of the rocket and the space environment. Bio-printed tissue models had not been launched into space before, so the team had no idea how they were going to hold up during the launch process.
Zhang has developed 3-D bioprinting techniques to conduct research on breast cancer cells. Zhang uses sacrificial bioprinting, a technique in which a fugitive bioink—a biomaterial that disappears quickly—is embedded in a hydrogel and then removed, leaving behind a mold that can be used to create hollow structures populated by cells. Using this technology, Zhang can create breast cancer models that include bioprinted mammary duct-like channels. Breast cancer cells can be populated into the bioprinted mammary ducts, and allowed to proliferate over time, enabling them to spread to the surrounding matrix simulating the metastasis process.
During his research, Zhang began engaging in conversations with friends and colleagues at the Mayo Clinic, including Michelle Freeman, MD, William Freeman, MD, and Alfredo Quiñones-Hinojosa, MD, who were developing imaging technology for astronauts. In one of these conversations, the scientists at the Mayo Clinic mentioned their relationship with EXOS Aerospace Systems & Technology, a company focused on providing service to science-based experiences in sub-altitude conditions.
A few months later, accompanying the technology developed by the Mayo Clinic, Zhang’s breast cancer models were launched into space on the SARGE, a reusable launch vehicle made by EXOS. The data were jointly presented at the Mayo Clinic Neuroscience and Oncology Innovation Summit 2018, October at Key Biscayne, Fla.
The launch in August served as an initial test. As soon as it became clear that the bioprinted cells returned to Earth intact, Zhang began planning for a second launch.
“The second launch, hopefully, will be more sophisticated, as casing devices will be used to hold the samples for their longer-term viability,” said Zhang. “It will include more specimens to see how the biology of the cells changes in the space condition, compared to how cancer cells typically progress on Earth.”
Understanding the Sleep Cycles of Astronauts
On Earth, we experience a 24-hour day with one sunrise and one sunset, leaving us with extended periods of lightness and darkness. On the International Space Station (ISS), astronauts may experience approximately 16 90-minute cycles within a 24-hour day; this contributes (along with their work schedule, noise and other environmental factors) to astronaut problems obtaining a good night’s sleep without sleeping pills or aids.
Just like people on Earth, when astronauts fail to sleep well, they experience a multitude of health-related issues, including general fatigue. Fatigue and tiredness can increase the risk of accidents occurring, a major concern for the overseers of space programs at NASA.
Researchers in the Brigham’s Division of Sleep and Circadian Disorders, including Steven Lockley, PhD, Charles Czeisler, PhD, MD, Laura Barger PhD, and Elizabeth Klerman, MD, PhD, have been investigating new lighting systems that would allow astronauts to sleep peacefully, undisturbed by the frequent changes between lightness and darkness.
At the Brigham, Lockley, Czeisler, Barger and Klerman were part of a team (NASA International Space Station Flexible Lighting Team) that developed a new LED lighting system that would allow users to change the color pattern depending on the time of day. This team won the 2014 NASA JSC Director’s Innovation Award.
Photoreceptors in the human eye send signals about light exposure to the brain, allowing the brain to shift its internal clock. Blue light, at the shorter of the visible light spectrum, helps us to be more alert and attentive. Red light, which has a longer wavelength, does not. Adding or subtracting each of these wavelengths from white light allows researchers to influence sleep or wakefulness, depending on the time of day.
Understanding the effect of wavelength on sleep cycles has enabled researchers to test different light patterns in simulated space experiences, including a recent study in NASA’s Human Exploration Research Analog (HERA) facility at Johnston Space Center. Lockley, with Division of Sleep colleagues Shadab Rahman, PhD, MPH, and Melissa St Hilaire, PhD, examined the benefits of dynamic lighting in response to chronic sleep deprivation. Four teams of four ‘crew’ lived in the mocked-up space habitat for 45 days without leaving and were given five hours of sleep for five nights a week and eight hours of sleep for two nights a week. Half were exposed to typical light, while the other half experienced a dynamic lighting schedule similar to that on the ISS.
The results of studies and simulations like this one could drive the changes implemented by NASA on space missions in the future.
The urgency of understanding sleep cycles in space is increasing, as NASA looks to have tools, mechanisms and resources ready for long-duration missions to Mars.
“As we move toward long-duration missions to asteroids, Mars and beyond, astronauts will not be able to push through sleep deprivation in the same ways that they have in the shorter missions of the past,” said Lockley. “There needs to be a long-term solution. Installing new lighting to ensure better sleep and better alignment of circadian rhythms is vital to the success of these missions.”
Simulating Space Emergencies at STRATUS
In addition to sleep deprivation, medical emergencies are bound to arise on the space shuttle. However, astronauts often lack the extensive medical training necessary to confront an emergency without assistance from NASA.
At the Brigham’s Neil and Elise Wallace STRATUS Center for Medical Simulation, Steven Yule, PhD, and Roger Dias, MD, MBA, PhD, are looking to change that. Using a grant from the National Space Biomedical Research Institute (NSBRI), a NASA-funded consortium, their team simulated a series of medical emergencies in a spacecraft simulator, which mimics the alarms, lights, smoke and vibrations that might be experienced in a spacecraft’s medical bay, looking for the best ways to optimize team performance among astronauts.
Armed with a new grant for 2019, they are looking to incorporate more novel technology, such as wearable devices and sensors, to measure heart rate, brain activity, motions and movements of participants in these simulations.
With this research, Yule and Dias hope to collaborate with NASA to implement standard training programs for astronauts that would develop skills essential to an effective response if an emergency were to arise.
“Our research program focuses on team behavior,” said Yule. “We want to see how astronaut crew respond to different medical events and the specific non-technical skills that improve performance and outcomes. The incorporation of wearable devices and new sensor technology will help us understand this better than before.”
The two scientists believe that the incorporation of technology into these simulations will help NASA standardize their behavioral evaluations, leaving them less subject to human error.
“Without the incorporation of these devices, it’s difficult to measure and correct behaviors in real time,” said Dias.
The prospect of long-duration missions also makes effective emergency response programs all the more important, and Yule and Dias hope to play a role in designing programs that address issues of team performance and management under these circumstances.
“When an astronaut is on the moon, it takes 1.3 seconds for radio waves to reach Earth,” said Dias. “From Mars, it would take up to 22 minutes. It makes an independent, effective response that much more important.”
Even though Yule, Dias, Klerman, Lockley and Zhang are stationed at the Brigham, their research and work could have far-reaching implications. As they explore how journeys into space can affect cellular biology, human physiology and emergency responses, their work may lead to new insights and discoveries that could help everyone from patients on Earth to Mars-bound space explorers.