by Aparna Nathan
Graphics by Nicholas Lue

Space: It has been the final frontier ever since Captain Kirk and Starfleet shot into space at warp speed in the 1960s.

But are humans really made for space? We did not evolve for the environment of space and we don’t know how space travels affects our biology. Now, NASA has a powerful new tool to tease out the changes a human body sustains in space: identical twins.

NASA’s Twins Study is a new investigation into how a year in zero-gravity—without the protections of the Earth’s atmosphere—affects an astronaut’s biology, with his land-bound twin as a point of comparison. It’s one of NASA’s boldest forays yet into the field of “space medicine,” and it gives scientists the opportunity to understand what might happen if humans one day move into space.  

To boldly go where no twins have gone before

NASA launched the Twins Study three years ago. Along with a network of investigators across the country, they are using one of biology’s unique phenomena — twins — to understand the exact biological changes that humans undergo in space.

Former astronauts Mark and Scott Kelly are identical twins who volunteered to participate in the NASA Twins Study. In this experiment, Scott was sent into space to live at the International Space Station for just under one year. Starting before the mission and continuing after the mission ended, Mark and Scott periodically underwent a slew of medical tests: saliva swabs, blood draws, urine collections, and stool samples (all frozen aboard the Space Station until the astronauts’ return to Earth), along with cognitive exams and body imaging. From these samples and tests, scientists could observe modifications to the twins’ DNA, molecules circulating in their blood, physical and cognitive abilities, and the collection of microscopic bacteria that live inside and outside the body called the microbiome (Figure 1).

Figure 1. Aspects of biology monitored in the Twins Study. NASA’s Twins Study set out to take a wide range of biological measurements of their identical twin subjects. This will allowed them to look at human biology in space through many different lenses.

The driving force behind this slew of medical tests was NASA’s interest in the effects of altered gravity and radiation on the body. For example, when a shuttle launches into space at 18,000 miles per hour, astronauts feel the g-force, or the increased force of gravity, as they accelerate. Since the human heart was designed to pump blood throughout the body within the constraints of Earth’s gravity, with high g-force it becomes harder for blood to reach the head, leading to fainting. Furthermore, once astronauts are in space, they experience the opposite feeling: zero-gravity. And at zero-G, the heart doesn’t have gravity’s help to pull blood back down to the extremities, so fluids pool in the upper body and head (Figure 2).

In addition to dealing with the effects of gravity, astronauts are also at the mercy of the elements. A space suit helps, but your body is still vulnerable to the radiation that permeates throughout space and damages our cells (Figure 2). At the most basic level, radiation is just energy, and space is full of it.  On Earth, we’re protected from this radiation by the planet’s magnetic field—but once we exit the atmosphere, all bets are off. According to Mars rover Curiosity, an astronaut on a round trip between Earth and Mars would experience over 200 times more radiation than what we experience on Earth, which can increase the chance of developing cancer, immunodeficiency, and cognitive impairment.

When Scott was launched into space, his body was put through this battery of challenges, while Mark’s body remained in the comparably comfortable environment of Earth. By taking measurements of everything from DNA to urine to cognitive ability and comparing the twins, NASA scientists hoped to be able to see just how the human body changes in the zero-gravity, radiation-filled space outside the Earth’s atmosphere.

Figure 2: The effects of space on the human body. Space disrupts the careful balance that the human body achieves on Earth, and astronauts’ bodies can undergo many changes.

Space genes on Earth

When Scott returned to Earth in March 2016, researchers observed the cumulative effects of spaceflight on his biology. Some of the results weren’t particularly informative, such as changes in the bacteria that compose Scott’s microbiome. The microbiome composition can change quickly in response to factors like diet or medications, and because Scott’s diet of dehydrated space food was undoubtedly different from Mark’s diet back on earth, the altered microbiome could not be attributed to being in space.  This microbial shift also reverted back to normal upon Scott’s return to Earth.

Other results, though, were more unexpected, like changes to Scott’s DNA. Importantly, these changes were not in the actual genetic sequence: Scott’s genes were still identical to Mark’s. Instead, the activity of Scott’s genes was altered (Figure 3). Genes are sections of DNA that contain the instructions for how to make  proteins, which are molecules that carry out most biological functions inside of our cells. When a gene is more active, it produces more of its respective protein product, thereby changing the biological activity within our bodies.

So how is a gene’s activity changed without changing the gene’s sequence? The answer lies in small modifications to the DNA termed epigenetic marks. These marks can take many forms, such attaching molecules (like groups of carbon and hydrogen) to the DNA itself. If we imagine that a gene is like a word in this article, like the word “space,” an epigenetic mark is the equivalent of making the font bold. The word “spacestill says the same thing, but now it says it in a different way. Bold font may also garner readers’ attention, increasing the number of times the word “space” is read. Similarly, epigenetic marks change the way that genes look without actually altering their sequence. In so doing, these marks impact how many times the genes is “read” and how much protein is  produced.

In Scott’s case, scientists noticed that some of his epigenetic marks changed, causing some of his genes to produce more or less protein compared to his Earth-bound twin. Interestingly, even after returning to Earth, about 7% of Scott’s altered genes were still as active as they were in space, and Earth’s gravity didn’t bring them back to normal (Figure 3). While some of the epigenetic changes observed between Scott and his twin weren’t big enough to be notable, this study illustrated there is still a lot we don’t know about the effects of space on our genes.

Figure 3: Genetic changes in space. Some genes (like the green ones) became more or less active when Scott was in space, and stayed that way even when he returned to Earth.

Of space-mice and space-men

The Twins Study revealed just how broadly space can affect the human body: everything from bacteria to gene activity. But it was hard for scientists to discern which changes were because of Scott’s year in microgravity, and what was just because he was eating different food and living a different daily lifestyle compared to Mark. To get around this obstacle, NASA needed to be able to study subjects whose lifestyles they could fully control: like mice, for example.

As part of the next steps of the twin study, the SpaceX Dragon capsule launched on June 29, 2018 carried twenty space-bound mice, while leaving another twenty mice on Earth. By using mice, the scientists have more control over the subjects’ environments, diets, and activity, so the mice on Earth can serve as better points of comparison for their twin siblings. Scientists will be studying these mice to see whether their microbiomes also change as a result of space travel. Ultimately, NASA hopes that studying these mice will teach us more about how the body changes in space and that this knowledge, combined with what we learned from Scott and Mark, will enable us to expand our exploration of space, maybe even to Mars.

It’s not yet clear what these missions will uncover, but as the last human twin study showed, the effects of space flight on humans are numerous and complex. But just like our astronauts, science will boldly go and find the answers.

Aparna Nathan is a second year Ph.D. student in the Bioinformatics and Integrative Genomics program at Harvard University.Follow her on Twitter at @aparnanathan.

Nicholas Lue is a graduate student in the Chemical Biology PhD program at Harvard University. Follow him on Twitter at @nicklue8.

For more information:

  • To learn more about what it was like for Mark and Scott Kelly to participate in the Twins Study, check out this short video
  • A lot of news outlets got the results of the Twins Study wrong. Read more about their misinterpretation here
  • Learn more about how twin studies are used outside of space medicine in this Atlantic article
  • Epigenetic changes don’t just happen in space — the Dutch famine was an example of extreme conditions on Earth driving epigenetic changes in humans; learn more in this New York Times article

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