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Scott Kelly’s genes and NASA’s twin study on him, explained

The astronaut’s DNA didn’t change in space. Here’s what might have. 

Expedition 46 Landing
Scott Kelly, just minutes after he landed back on Earth in 2016. He was still genetically human.
Bill Ingalls/NASA via Getty Images
Brian Resnick is Vox’s science and health editor, and is the co-creator of Unexplainable, Vox's podcast about unanswered questions in science. Previously, Brian was a reporter at Vox and at National Journal.

Scott Kelly did not mutate into a genetic freak during his year living aboard the International Space Station.

You might have gotten that impression last week, though, when several news outlets wrongly reported that 7 percent of the astronaut’s genes had changed after his year on the International Space Station. Kelly added to the confusion by cheekily tweeting:

This, as many have pointed out, was complete hogwash. Kelly’s genetic code — the thousands of base pairs that form his DNA — didn’t change. Instead, NASA, in its long-term study of Kelly, was sharing some (confusingly worded) preliminary evidence of changes in the ways his genes were used during his time in space, and upon returning.

The episode was a complete communications misfire, stemming from a misinterpreted press release from NASA. But it revealed there’s a lot of confusion about this story, from why NASA was interested in Kelly’s genes in the first place to how DNA gene expression works. So let’s clear things up.

Scott Kelly spent a year in space. NASA is curious what that does to the human body.

Scott Kelly and Russian cosmonaut Mikhail Kornienko spent 340 days aboard the space station in 2015-’16. This was the longest single spaceflight on the ISS.

But Kelly and Kornienko were not just trying to get their names into the record book. The length of the mission provided a vital test for future long-duration missions to Mars and beyond. A trip to Mars would take several months to a year, and NASA is curious to see what toll that amount of time in space takes on the human body.

NASA and its international partners commonly keep astronauts aboard the space station for six-month missions. But even half a year in space takes a toll.

Astronauts commonly report diminished eyesight that doesn’t return to normal upon their return home. Bones can become more brittle in microgravity. Muscles atrophy. It’s harder to get to sleep in space. And scientists are worried that prolonged missions could have wide-ranging impacts on human biology, from altering the levels of beneficial bacteria in the gut to diminishing the power of the immune system.

NASA will be comparing the changes in Kelly’s body to those of astronauts who have spent shorter times in space. The basic question is: Does added time in space cause even more disruptions?

As a test subject, Scott Kelly is a bit special. Perhaps you’ve heard of his identical twin brother, Mark Kelly. Mark was also an astronaut, and he now advocates for gun control alongside his wife, former Rep. Gabrielle Giffords.

The Kellys went to NASA and pointed out that since they have the same DNA, Mark Kelly might make for an interesting control for the tests. NASA liked the idea and put out a call for outside researchers to submit proposals to study differences in the Kelly twins.

In all, there are 10 research projects in what NASA is calling the “Twin Study,” ranging from testing the cognitive abilities of the Kelly twins to assessing changes to how their genes are expressed to looking for signs of change in their metabolisms.

It’s not a perfect control (more on that below), but because the researchers have data from multiple points in time for each twin, they can compare. If Scott’s levels on any of these tests vary wildly from Mark’s over that course of time, then perhaps those changes can be attributed to the time Scott spent in space.

How the NASA press release got misinterpreted

Here’s where things went haywire. In a press release dated January 31, NASA reported:

Researchers now know that 93 percent of Scott’s genes returned to normal after landing. However, the remaining 7 percent point to possible longer-term changes in genes related to his immune system, DNA repair, bone-formation networks, hypoxia, and hypercapnia.

When the press release went out in January, it drew modest attention. NASA wasn’t reporting the results of the final study (which is expected out later this year). It was more of a reminder: Hey, we’re still working on this.

In mid-March, a few outlets picked up on the press release, “for reasons that remain unclear,” as the Atlantic explains.

Newsweek, for one, ran the headline “Scott Kelly: NASA Twins Study Confirms Astronaut’s DNA Actually Changed In Space.” Live Science ran a similar article but later admirably admitted to the goof: “We Were Totally Wrong About That Scott Kelly Space Genes Story.”

This is what got wildly misreported, in part because NASA didn’t explain what “changes in genes” means. Scott Kelly’s DNA didn’t change. If 7 percent of your DNA changed, you’d no longer be a human being. Human and chimpanzees share 98.8 percent of their genetic code. If 7 percent of your genes changed, who knows what you’d be. (NASA also confusingly referred to the genetic changes as occurring in a “space gene,” which is not a thing. By that, NASA just meant genes that could conceivably be influenced during space travel.)

Scott Kelly is still a human. And he’s still Mark Kelly’s twin, with identical DNA. So what changed?

Gene expression, explained briefly

Humans have about 20,000 genes that are contained within 23 chromosomes of DNA. You have each of these genes in every single cell of your body. Still, our cells are different — a neuron looks nothing like the cells that line your stomach. And they have vastly different functions. One transmits electrical and chemical signals throughout the nervous system; the other oozes acid to help digest food.

The differences are not due to differences in DNA, but rather how they are expressed. Complex chemical pathways and feedback loops lead to certain genes being turned on and certain genes being turned off. Each gene codes for a protein (a building block of the body), and depending on which genes are on, different structures get built and different things happen.

Subtle changes in gene expression won’t turn your neurons into blood cells, but they can alter how they function. Changes in gene expression can lead cells to become cancerous, or start a chain of events that increases a person’s chances of heart disease.

There are different ways to identify changes in gene expression. One is by looking at levels of RNA, the messenger molecule that helps execute and create the protein a gene codes for. Another is to look for methylation, which is when a DNA molecule is essentially tagged with a chemical. This chemical can keep that section of the gene from turning on, as Nature explains.

NASA reported changes in expression for genes “related to [Scott Kelly’s] immune system, DNA repair, bone formation networks, hypoxia, and hypercapnia [excess carbon dioxide in the bloodstream.” That’s not much to go with, so we’ll have to wait for the final paper to better evaluate these claims. In an update to its press release, NASA clarified that the 7 percent change in the expression of Kelly’s genes was “very minimal” and likely “within the range for humans under stress, such as mountain climbing or SCUBA diving.”

Another arm of the twin study is looking into changes in Kelly’s telomeres, which are regions of DNA that act like caps on strands of chromosomes. Changes in the length of telomeres are a rough measure of cellular health (they tend to grow shorter as we age). Oddly, NASA reported that Kelly’s telomeres grew while he was in space. This is another claim we’ll have to assess more carefully when the final paper comes out.

It’s still too early to tell how a year in space might affect Kelly’s long-term health

Overall, it’s hard to draw concrete conclusions about what aspects of spaceflight led to these changes (provided they are real).

Here’s why: Genes turn on and off all the time, and these cycles are influenced by “basically everything,” Ran Blekhman, a genetics researcher at the University of Minnesota, says. Stress, diet, exposure to pathogens, physical activity, and even loneliness could potentially tweak the way genes are turned on and off. Many genes also run on a circadian rhythm, meaning they cycle on and off regularly on a 24-hour cycle. Heck, there was even a study that found meditation altered gene expression.

All this noise makes the work that goes into identifying meaningful changes in gene expression (like the ones the make the difference between a cancerous cell and a healthy cell) and what exactly caused those changes very difficult, painstaking work.

And if there are changes, it will be hard to attribute them to any one aspect of spaceflight. They could be due to living in microgravity, a lack of exercise or disturbed sleep, or a diet of freeze-dried foods. They could also just be the result of random chance.

So what can we learn from this twins study?

Andy Feinberg is a molecular biologist at Johns Hopkins University involved in the Kelly twins study, studying the methylation of the Kellys’ genes. (The press release wasn’t referring to his results but to the results of another lab.)

The plan, he says, is for all the researchers involved in the twin study to draft an academic paper, have it peer-reviewed, and then, hopefully, accepted to an academic journal.

Feinberg cautions that the genetic tests in the twin studies are not designed to yield definitive conclusions about the impact spaceflight has on our genetics. You could never do that with just one subject and one control. “You could form a hypothesis from that, but you couldn’t prove anything,” he says.

And overall, the researchers aren’t just looking at genetics. They’re looking at measures of cognitive function, immune function, metabolism, and vital signs. Across all these studies, the data may hint at a comprehensive story about how space impacts health, a hypothesis to test in future missions.

What’s underappreciated but perhaps more important, Feinberg says, is that this twins study is a way for scientists to refine their methods for conducting biological tests on astronauts. For instance, he says he and his colleagues spent some time in the “vomit comet” — NASA’s airplane that mimics the effects of zero gravity — so that they could develop rigorous blood drawing procedures for the astronauts to collect samples.

“Just figuring out how to do these things is a big deal,” he says. Even if the results only yield a hypothesis to test in the future, that’s okay. The work of getting human beings ready for interplanetary travel is “intergenerational,” he says. This study is just one small step.

So scientists may not learn a huge amount about how space impacts the way our genes work from Scott and Mark Kelly. But they’ll have a better idea of how to answer that question in the future.

Correction: This article originally stated that Scott Kelly and Mikhail Kornienko broke the record for longest single spaceflight. That distinction goes to Valeri Polyakov, who spent 437 days aboard the Russian space station Mir in the mid 90s. (Kelly has the American record, and he and Kornienko both spent a record amount of time aboard the ISS in a single mission.)

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