Here’s how you test your intracranial pressure in space. First, you collect baseline samples of your blood, saliva, and urine, and take ultrasound images of the vessels in your heart, neck, head, and eyes, lining up the scanning device on black dots tattooed on your body before you left Earth.
Then, you clamber into the Chibis, Russian for “lapwing,” a pair of hard, corrugated-rubber pants whose waist can be sealed. The pants suck: A vacuum imitates how gravity on Earth pulls blood, mucus, the water in cells, and cerebral and lymphatic fluids from our skulls to the bottom half of the body.
In space, fluids won’t drain, and astronauts develop red, puffy faces and complain of congestion or pressure in their ears. There are worse effects, too: 40 percent of the astronauts who lived on the International Space Station suffered some sort of damage to their eyes, including optic disc edema, globe flattening, and folds in the choroid, the blood-filled layer between the retina and the white sclera. NASA posits intracranial pressure is a possible explanation for what it calls “spaceflight-associated neuro-ocular syndrome,” and devised the test to measure fluid shifts to astronauts’ heads and eyes.
Wearing the lapwing is a mildly anxiety-inducing procedure. Once, a Russian cosmonaut lost consciousness when his heart rate dropped. His crewmates thought he was having a heart attack. Another time, the cosmonaut working the controls decreased the pressure too much—ratcheting up the sucking—and the astronaut felt “like I could have my intestines pulled out in the most unpleasant way possible.”
Jason Pontin
Ideas Contributor
But if nothing goes wrong, you hang out in the suit for a few hours, taking more ultrasound images. You check your blood pressure. You measure cochlear fluid with an instrument in your ear and record intraocular pressure by tapping a pressure sensor against your anesthetized eyeball. You scan your eyeball with a laser to visualize choroidal folds and optic nerve swelling.
The “Fluids Shifts” experiment was performed by astronaut Scott Kelly when he lived on the ISS from March 27, 2015, to March 1, 2016, the longest spaceflight by an American. At the same time, his twin brother Mark, also an astronaut, tested his intracranial pressure back on Earth.
Over 25 months, the brothers submitted to a parallel routine of cognitive and physical tests—including a spinal tap for Scott—in the lab before, during, and after the mission. In all, 317 samples of stool, urine, and blood from both twins were collected and analyzed for their epigenomic, metabolomic, transcriptomic, proteomic, and microbiome changes. All of this was a first for NASA, which had never conducted a complete multi-omics analysis of an astronaut, let alone of an astronaut and a monozygotic control.
The idea behind the study had a simple logic: Because the twins share the same genome, any changes that occurred to Scott and not to Mark would likely be caused by long-duration spaceflight. The results, whose findings were finally published in Science today, expand our understanding of what happens to the human body after a year in space.
“The NASA Twins Study: A Multidimensional Analysis of a Year-Long Human Spaceflight” is a triumph of cross-disciplinary science. Described as “a Herculean endeavor” by one of the article’s peer reviewers, it integrates the work of 10 different groups at universities around the country and 82 separate authors.
Francine Garrett-Bakelman, one of the article’s lead authors and a molecular biologist at the University of Virginia, said it was the “most comprehensive result possible based on the data available.” But to the essential question “Are humans fit for space?” the study provides only unsettling and incomplete answers. Long-term exposure to spaceflight is dangerous; based on what we know now, a journey to Mars is still too risky to contemplate.
More than 500 people have flown in space, and some of the bodily changes they experienced during missions lasting less than a month or as long as six months are well understood. Fluids shift to astronauts’ heads; the left side of their hearts grow. Unless they exercise vigorously, they lose muscle and bone.
But only four individuals have lived in space for a year or more, and the physiological effects of long-duration spaceflight are unknown. A human mission to Mars could last as long as three years, and in the laconic tones of the twins study, “genetic, immune system, and metabolic functions are of particular concern given exposure to space radiations, restricted diets … disrupted circadian rhythms, and weightlessness.”
The US government has proposed Americans return to the Moon by 2024. Mars is next, during a “low-energy launch window“ in 2033, when the Red Planet’s eccentric orbit brings it closest to Earth. If we hope to embark on what NASA calls “exploration-class missions,” we must know more.
Surprisingly, then, the origins of the twins study were not within NASA Human Research. Scott Kelly suggested the idea himself. “I was being briefed for a media event when the crew members were announced” for ISS missions 43 to 36. “They wanted Misha”—Mikhail Kornienko, Scott’s cosmonaut counterpart—“and me to know the science program so we could answer questions about it. At that meeting I said, ‘Hey, if somebody asks a question about my brother Mark, do you guys have any intention of doing genetic studies on us?’ And they said no. But a couple of weeks later, I had another meeting with these same guys, and they had reached out to some university researchers who thought there was some value in the idea.”
Scott and Mark Kelly were born in Orange, New Jersey, in 1964. They are the only twin astronauts in NASA’s history, and are remarkable by any measure. No one observing their boyhoods would have marked them as future astronauts—except, perhaps, a pediatric psychologist specializing in stimulus-seeking siblings. In Scott’s autobiography, Endurance, he recounts the “crazy risks” he and Mark took as boys and their inevitable consequences in broken bones. During summers vacations, the family bought “crappy boats” with no navigation equipment or working radio, and sailed them out beyond the horizon of the Jersey shore in all weathers.
Their parents were hard-drinking cops, the father a violent alcoholic. Scott writes, “Sometimes I think if my father hadn’t been a police officer, he would have been a criminal.” And it’s easy to think something similar of the two brothers: If their parents hadn’t been cops, they might have been delinquents in juvenile detention.
Both did badly in school, and Scott struggled more than Mark. Both were quickly bored. But both conceived an implausible desire to become astronauts, Scott because he fell in love with Tom Wolfe’s vivid prose. “I wanted to be a naval aviator. I was still a directionless, undereducated 18-year-old with terrible grades who knew nothing about airplanes. But The Right Stuff had given me the outline of a life plan.”
They found a backdoor into naval aviation through ROTC at the Merchant Marine Academy (Mark) and the State University of New York Maritime College (Scott). At college, they discovered they were highly intelligent engineers—perfect scores in calculus came easily now that they had a goal—and in the Navy they landed jets on carriers and became test pilots. Mark flew in combat during the Gulf War.
They were both selected as astronauts in the class of 1996. During their NASA careers, Mark was the pilot or commander of four Space Shuttle missions; Scott piloted and commanded two Shuttles and spent six months on the ISS before his year in space. After Mark’s wife, Arizona Representative Gabby Giffords, was shot in 2011, he flew his last mission and retired from the space agency. Scott is unfailingly generous about what the twins study demanded of his brother: “You have to give him a lot of credit. He wasn't getting any of the glory about being the person in space. He did it completely for the sake of the science.”
But the physical demands of the research weren’t glorious for Scott, either. “There were times—maybe once a week—where I had what seemed like a whole day of collecting samples. You wake up in the morning and collect blood and centrifuge it and put it in the freezer. Then, you do your first urine collection and you keep collecting urine throughout the day: 24-hour urine collecting, which is annoying because you can't use the toilet designed for space. It’s messy. And once you’ve peed in this bag, you’ve got to remove the test tubes from the bag of urine and then you’ve got to bar code them, scan them, and put them in the freezer. Even the lab freezer is a little complicated. Every time you open the door you can't leave it open too long: it’s –80° Celsius, and you might get a little get a little cold burn on you. That same day, you might do skin samples, feces.”
For the subject of the study, the ISS was unlike any terrestrial lab or clinic. In conversation and in his book, Scott Kelly artfully evokes the sensorial assault of his home in space. The International Space Station is deafeningly noisy: fans whirr and electronics hum. It smells bad, too: of the off-gassing of plastics, garbage, and body odor. (Space itself smells, Scott tells us—or, rather, objects exposed to the vacuum of space possess a unique odor: “a strong burned metal smell, like the smell of sparklers on the Fourth of July, [or] the smell of welding.”)
Weightlessness posed particular challenges for a human research program, especially for an astronaut who was often tired, cold, and crabby from breathing too much CO2. Collection devices and samples could never be put down, but had to be attached to walls; experiments had to progress in prearranged sequences.
Once the samples were collected aboard the ISS and on Earth, the work had barely begun. Scott’s samples had to be returned to Earth aboard Soyuz capsules (Mark used the US Post Office), and the twins’ blood separated into plasma and different kinds of cells, including the cells that govern the immune system. All the samples had to be assayed, and the data shared and analyzed among the 10 working groups. No wonder the whole project took more than four years to complete.
What was learned? Chris Mason, the principal investigator of the Gene Expression Group and a professor of physiology and biophysics at Weill Cornell Medicine, described the effect of space travel on Scott’s genes as “not just a sparkler—it was like fireworks in the sky.” More than 10,000 genes were activated by spaceflight. “To give you some context,” Mason explains, “there are about 58,000 known genes in the human genome, so we were seeing a lot of the body’s ability to respond activating.”
That makes sense, given the punitive stresses of lift-off, a year-long mission, and reentry. Even so, the twins study groups were stunned by the extensive changes that occurred everywhere in Scott’s body, including the length of his telomeres, the caps at the end of chromosomes that protect the integrity of DNA; gene regulation, measured by both interaction with the environment and the orchestration of gene activity; the microbiome or bacteria in his gut; the dimensions of his carotid artery; and the health of his eyes.
Scott’s immune system was generally turbulent during his year in space: Many of his immune-related cellular pathways were disrupted, including the adaptive immune system, innate immune response, and the natural killer-cells that protect the body from cancers like leukemia and viruses. (The result confirms a shocking study published in January that compared the immune systems of eight astronauts who completed spaceflights longer than six months with healthy adults on Earth: Just 90 days into their flights, the astronauts’ natural-killer cells were 50 percent less capable of fighting leukemia cells.) Scott’s cognitive function was also whacked: He got dumber on the ISS.
The human body is wonderfully adaptive, and almost all of these changes were transient: Scott returned to normal within six months of returning to Earth. He became his old self, except for the ordinary depredations of age. But some of the effects of spaceflight left their mark. Scott got dumber on the ISS, but he stayed dumber, too. The decline in the speed and accuracy of his mental functions persisted six months after his mission.
Most surprising of all were Scott’s accordioning telomeres. While he was on the ISS, his telomeres weirdly lengthened, perhaps because of how much he exercised and how little he ate. But within 48 hours of returning to Earth, his telomeres rapidly shortened in reaction to the stresses of landing. Although most of Scott’s telomeres eventually shifted back to baseline levels, six months after his mission he had substantially fewer telomeres overall and increased numbers of critically short telomeres. That finding was alarming: Telomere loss might increase astronauts’ risk of developing cancer and other diseases of old age.
The authors of the NASA twins study helpfully distinguish between the potentially low-risk, mid-level or unknown risks, and high-risk effects of a year-long spaceflight: Scott’s telomere loss was an “unknown risk.” An example of a “highly dynamic association with potentially low risk” were the changes to Scott’s microbiome. A few well-known high-risk changes were confirmed by the study, including spaceflight-associated neuro-ocular syndrome. However, some high-risk changes were newly discovered, and long-duration space travel will require their solution. By far the most serious changes were to gene expression and DNA.
Fully 91.3 percent of Scott’s genes whose expression changed during spaceflight returned to normal ranges within six months. But a distinct subset of genes never did: 811 genes across different cell types, almost all of them related to immune function and DNA repair. That’s bad news for the future of humans in space, because these are precisely the genes that must protect astronauts from space radiation.
Earth’s magnetic fields and atmosphere shelter us from most of the ionizing radiation that streams through space. A typical Earthling absorbs about three Sieverts (mSv) every year. During a Space Shuttle mission lasting a week, an astronaut might have received 5.59 mSv. The crew of Apollo 14 were exposed to 11.4 mSv. Scott Kelly received 146.34 mSv during his year in space. When he closed his eyes to sleep in his cramped quarters at night, Scott would see “cosmic flashes … light up his field of vision,” the result of radiation striking his retinas.
Scott's DNA was strangely twisted. Sections of his chromosomes were translocated and inverted. Much of the genomic instability and rearrangement recorded by the twins study was probably the result of space radiation. And that DNA damage may be contributing to dysregulated gene expression. In an especially worrying detail, the number of differentially expressed genes were six-fold higher in the last six months of Scott’s mission.
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Neither Chris Mason nor anyone else knows whether this dysregulated gene expression would have plateaued or continued to scale had Scott lived another six months or longer on the ISS. “We know that it is not the direction we want,” Mason says. “We see a flurry of gene networks activating to respond to the DNA damage and the body adapting, but it may not be enough of a response to overcome radiation damage.”
This matters because the highly charged energies of space radiation kill cells and make them malfunction, or break strands in DNA and knock out base pairs. Dead or poorly functioning cells cause heart disease or cognitive decline; if cells cannot repair DNA damage, mutations accumulate that cause cancer and heritable diseases.
The ISS is only 250 miles above Earth, still beneath the Van Allen radiation belt’s clement umbrella. During a Mars mission, an astronaut might absorb as much as 1,200 mSv. “The overall risk of cancer for astronauts is still relatively low, but almost everyone has flown close to the Earth,” Mason says. “We don’t yet know, but I would say radiation is the big problem.”
The NASA twins study has obvious limitations. Its n=1: “With a single test subject in the spaceflight environment for this particular set of measures, it is impossible to attribute causality to spaceflight versus a coincidental event.” (A senior MIT biochemical engineer was more dismissive: “What a stunt,” he sneered. “A real control would be to compare the NASA twins with a second set, where one brother lived in an American suburb while the other was put in a loud, frightening Iraqi prison for a year.”)
Bill Paloski, director of NASA’s human research program and the study’s ultimate progenitor, understands this line of criticism. “We would like to continue to experiment with our flight crews. But I came away impressed by how adaptive humans are. We found no showstoppers,” he says.
Paloski believes that the study should be considered a hypothesis generator. Chris Mason, who first proposed monitoring the genomes and epigenomes of astronauts before, during, and after spaceflight in 2010, is happy to comply. His group has seven more papers under review, including articles on somatic mutations and single cell dynamics. There are five or six upcoming papers from other groups.
Mason has even grander ambitions. He has proposed a “500-year plan” for space colonization, whose most radical suggestion is adding, deleting, or modifying genes to create permanent, heritable changes in a new species of spacefaring hominins. “The twins study is the most comprehensive molecular map of the human body ever made from spaceflight. It is the first big step on a 500-year stairwell, representing a biomedical roadmap of response and risks for long-duration spaceflight, which will help astronauts survive the trip to, and thrive on, Mars.”
Mark Kelly once said, “Going to Mars is not about rocket science. It’s about political science.” That’s surely true: A NASA Mars mission would be a political decision, with political costs and benefits, that would only be approved if it had widespread political support. In comparison, the problems of building a sufficiently robust spacecraft, choosing its optimal trajectory, and provisioning its crew seem relatively straightforward. But going to Mars would also be a dumbfounding life sciences problem.
Today, we simply don’t know what years of exposure to the radiation astronauts would encounter beyond Earth’s magnetosphere would do to the human body. Nor what interventions would prevent or cure the diseases that could result. What’s next is for NASA Human Research to work with the same sorts of academic scientists who produced the twins study to complement its data with future studies of more astronauts.
But for Mark and Scott, their scientific contributions to the problems of long-duration human spaceflight are in their pasts. Scott Kelly retired from NASA and married his long-time partner. Mark is running for the US Senate.
Asked if he feels any different, Scott says, “Something I feel directly from the flight, I can't really say that much. I have those changes to my vision. I have the radiation that affected my DNA. I don't feel any of that, but I know it's there. I don’t really worry about it. I certainly will feel things in 20 years, no doubt.”
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