Health Risks of Space Flight Probed with Targeted Sequencing

Space travel has intrigued humanity for more than a century, and now that it’s happening quite frequently, scientists are taking a hard look at the potential health issues astronauts may face. Even in a pressurized, sealed, environmentally-controlled canister, astronauts encounter zero gravity, cosmic rays, and other unique hazards. NASA wanted to know what is happening to astronaut bodies over time.

To understand these risks and develop better biomarkers to track their health, NASA conducted the Twins Study. Identical twins Mark and Scott Kelly were astronauts for more than two decades. Scott spent more than 500 days in space, including a year on the International Space Station (ISS). Mark spent more than 50 days above the atmosphere.

Mark and Scott’s unique relationship amongst the astronaut population was a golden opportunity to study how space flight affects the human body. For several years, including when Scott worked on the ISS and Mark was on Earth, researchers took blood samples and conducted numerous tests. Having two subjects with virtually identical genetics gave NASA an ideal opportunity to study spaceflight’s health impacts.

One of the many papers to come out of the Twins research was recently published in the journal Cell Reports. In the study, researchers focused on a process called clonal hematopoiesis (CH), in which a group of blood cells develops one or more mutations causing them to propagate more rapidly than neighboring cells.

Twist Bioscience played a major role in the study, providing custom, next-generation sequencing panels to analyze the Kelly’s blood, compare it to similarly-aged control subjects and patients who had undergone radiation therapy, and determine whether space flight increases CH risk.

Looking for Cancer and Cardiovascular Disease Biomarkers

CH is found mostly in older adults and people who have smoked or been exposed to ionizing radiation. Though not a disease itself, CH is inflammatory and dramatically increases the risk of developing blood cancer or heart disease. As a result, identifying CH biomarkers in the Kellys’ blood could give NASA physicians new tools to track astronauts’ health.

The Twist panels were used for target enrichment, allowing researchers to focus more heavily on certain genes of interest rather than sifting through the entire genome. This specificity gives scientists better opportunities to separate signals from noise and provide more specific results.

In the study, researchers looked for evidence of CH biomarkers in the Kelly brothers’ blood over a four-year period. The results were sobering. Compared to controls, the two astronauts exhibited evidence of CH decades before it would normally show up.

In one astronaut, the study found a variant for the TET2 gene, which has been linked to blood cancers and heart disease. While the astronaut was 50 when the mutation was discovered, the median age for these types of mutations is 68. In fact, TET2 variations are generally found in only 1% of people under 55.

The researchers also found two distinct mutations in DNMT3A genes, which may increase the risk for heart disease and acute myeloid leukemia. The risk of having one DNMT3A mutation for people under 55 is around 5%. The risk of having two such variations is significantly lower. DNMT3A mutations usually show up in people around age 65.

Though the study does not specifically identify which space flight-associated factors may have triggered CH in these astronauts, the authors believe reduced gravity, weight loss, and increased exposure to radiation are likely to play a role.

Though further study is required to unwind the risks associated with these, and possibly other mutations, it’s clear the astronauts were exposed to factors that increased their overall risks for cardiovascular disease and cancer. These results offer new opportunities to monitor astronauts throughout their careers to manage their health better and perhaps develop prophylactic measures to decrease these risks.