While most endeavors in space have focused on travel to low-Earth orbit (LEO) — distances 100 to 200 miles above Earth’s atmosphere — for short periods of time, future plans are expected to be more ambitious. Exploration to Mars, for example, will likely involve travel to greater distances and for longer durations of time. What does this mean for astronauts and how will that translate to humans on Earth? D. Marshall Porterfield, professor of agricultural and biological engineering, has been instrumental in exploring these fundamental questions. He served as division director for NASA Space Life and Physical Sciences during the initiation and performance of NASA’s One-Year Mission, and the Twins Study with Mark and Scott Kelly, which wrapped up in April 2019.

The birth of the Twins Study

When space expeditions involve both long distances and long times, the compounding effects of both factors will need to be carefully evaluated. Within NASA’s Space Life and Physical Sciences Division, the Human Research Program (HRP) leads the research effort into such studies. It factors in many aspects of space travel, including microgravity conditions, exercise and space radiation.

Medical research on the International Space Station (ISS) is a key element of the HRP. To focus on the extended time duration aspect of the research, NASA launched the One-Year Mission that included an American astronaut, Scott Kelly, and a Russian cosmonaut, Mikhail Kornienko. Given that any planned mission to Mars might be around 30 months in duration, this project is considered to be a critical stepping stone toward future missions to Mars and beyond.

Porterfield remembers that after the One-Year Mission was announced, astronaut Scott Kelly approached the researchers and asked if his twin brother, Mark Kelly, also an astronaut, could participate. “Would it be valuable to have Mark participate as a twin?” Porterfield remembers Scott asking. The answer was yes.

“Once that recommendation was floated out there, it really fit well with the new strategy for adopting integrated omics for biomedical research,” Porterfield says. Omics is loosely defined as the study of biomolecular systems through a variety of lenses and by incorporating various biological disciplines. Omics leads to a high-resolution approach to the study of biomedicine as opposed to just a singular lens such as gene expression. The team was excited, Porterfield reports. “Now we could do this longitudinal study not only of Scott but also compare him to his twin and look at data from before and after the mission and coordinate all the biomedical experiments accordingly.”

Omics and the Twin Study

Integrated omics is a powerful window into cell behavior under a variety of conditions. “Precision or personalized medicine is predicated on genomic sequencing,” Porterfield says. “We know your genome, we know which versions of genes you have, so we can target biomedical solutions for medical problems to match your biomedical signature based on your genome.” Or at least that’s the promise. The reality, Porterfield says, is different. “There are so many variables between the genome and the actual biological activity because there are so many different ways that genes can be regulated.” This is where omics comes in. It helps drill deep down into the molecular level to make things truly personalized. The study of omics “helps capture snapshots at a systems-level, so you can decode everything that’s going on in the cell,” Porterfield says.

Such a molecular approach to personalized medicine is especially relevant in a space mission architecture as there will be limited medical resources, and little time to figure out which drug will work best on someone, Porterfield adds.

The Twin Study helps control one of the important variants of any drug research study, genetic variation among participants. NASA doesn’t have access to large numbers of participants because the crew rotates as well. “The best way to get around that is to have genetically identical individuals.” The Twins Study evaluated the brothers before and after the one-year mission to explore the effects of space: Scott traveled to space for a year and Mark remained on Earth as a control subject.

The findings from the study: Immune responses for the brothers were identical in an influenza vaccine experiment, but the team found that Scott’s immune system was compromised with respect to specific immune activities meant to protect against leukemia. “ISS is still protected from deep space cosmic radiation but if you do an interplanetary mission, you’re in a much different radiation environment,” Porterfield says. “If the immune system is compromised with regard to leukemia activation, you could have cancers associated with crew members. Now that we know that, we know where to target countermeasure research for the immune system.”

Another departure: Researchers were expecting that Scott’s telomeres (the caps on DNA that protect it from damage) would grow shorter because of wear and tear in space but surprisingly they grew longer, probably because he was exercising much more in space.

“The Twins Study is the most important biomedical research experiment that’s ever been done for space. This is also the first human research program that has adopted an integrated omics approach, which is the 21st century tool to do life sciences and biomedical research,” Porterfield says. The takeaway is that there’s still a lot more to learn. “We need to invest more in such basic research activity; there’s so much more there to unpack.” As a way toward future space habitation and long-term experiments, it’s a crucial first step.