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The One Year Mission Learning Continues Past the Crew’s Landing

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With the return of the One Year Mission crew, many people will be asking, “What did you learn?” The answer: we are still learning, and will be for quite some time.

NASA astronaut Scott Kelly’s and Russian cosmonaut Mikhail Kornienko’s yearlong mission in space has ended, but the landing is just one milestone in a much larger picture of science. Baseline data collection started a year before the pair left the Earth in 2015, continued throughout their time in space, and will be collected for one or more years now that they have returned. From there, analysis, writing papers and seeing those papers through to publication will take even more time. In the case of the One Year Mission, the science is far from complete.

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Collecting data before, during and after the mission in space

We are already aware of risks to astronauts during spaceflight, and adverse effects caused by long-term living in microgravity. Extending that knowledge base to longer missions is one piece of the focus of studies for the One Year Mission, but another piece that is even more important is watching the astronauts’ recovery once they return home, and that will take time.

One example of the time it takes to understand astronaut recovery from life in microgravity is the Subregional Bone study, with Adrian LeBlanc, Ph.D. in a time when crew members were still losing a lot of bone, before the ARED was introduced on the space station. LeBlanc studied what was happening inside crew members’ bones as they rebuilt over time once astronauts returned to Earth. He learned that it took three years before the bones returned to their pre-flight bone mass density, and even when the bones reached that point, they still hadn’t completely recovered the same structure they had as before the astronauts’ flight. The bone was larger and more porous on the inside; it didn’t rebuild back to the original bone structure. Although our new exercise regimes are significantly reducing or eliminating the loss of bone mass density, studying the structural recovery is still a key part of the puzzle for reducing the risks of broken bones while astronauts operate on the surface of Mars someday.

Data collection for the One Year Mission began a year before Scott Kelly and Mikhail Kornienko left Earth, intensified during their 340 days in space, and will continue for a year - or longer - now that they are home. Click to enlarge this infographic to see a breakdown of the data collections for every #YearInSpace investigation. Credits: NASA

Data collection for the One Year Mission began a year before Scott Kelly and Mikhail Kornienko left Earth, intensified during their 340 days in space, and will continue for a year – or longer – now that they are home. Click to enlarge this infographic to see a breakdown of the data collections for every #YearInSpace investigation. Credits: NASA

This is an example of why it’s not just about the study you do in space. You also have to watch the recovery period after the crew members return to Earth. That period might be a year for sensory motor effects, but post-flight data collection could take three years for studies dealing with bone. Investigators will look at Kelly’s return to ground normal after being in space, so those studies – by their nature – will have years between when the spaceflight was completed, and when papers will be published.

Additionally, even now that Kelly’s boots are on the ground, most of the samples collected from him will actually still be orbiting the Earth aboard the space station, waiting to be returned on a cargo flight at a later date. We also have to collect all his post-flight baseline data that will start from the moment he gets back to Earth through as many as three years.

Once all collections are complete, scientists will analyze the data, which can take three to six months or longer. After the data has been analyzed, papers will be written and submitted to journals for publication. Depending on the publication, it could take a few weeks or months to get a response, and when that response does come, it could include a request for additional data analysis, revisions and reviews. When the journal does accept the paper, the scientists will work with the publication to make sure formatting and proofing is completed correctly. At that point, some journals will publish a pre-print version of the article online, while others could take up to a year to release the printed publication. So what that really means is that, while we could expect some published results within a year of his return to Earth, there are a number of studies that would not be expected to publish until three years, or more, later.

A first in genetics data collection

Retired astronaut Mark Kelly (L) and his identical twin brother Scott (R) are participating in a series of genetics studies as part of the One Year Mission.

Retired astronaut Mark Kelly (L) and his identical twin brother Scott (R) are participating in a series of genetics studies as part of the One Year Mission. Credits: TIME

Another special thing about Scott’s mission is that it marks the first time that flying astronauts have ever contributed genetic data to a study. This genetic data is covered under the Genetic Information Non-Discrimination Act (GINA). GINA protects employees from being discriminated against based on their genetic information. When Scott and Mark Kelly first asked NASA to include the fact that they were twins as a research tool, NASA developed an interim policy on the medical ethics of asking a crew member to give genetic information to support the Twins Study. We were able to collect this data, because Scott and his twin brother, retired astronaut Mark Kelly, were the ones who said they were open to participate as studies that compared them as genetically identical twins, rather than NASA going to Scott to ask for genetic information in order for him to be an astronaut.

However, Scott and Mark still have the right to restrict use of their data. If something were to come out of these studies that they felt would be a personal compromise to their medical privacy, or the privacy of their families, they could decide to disallow any use of that data. In that case, it would be unethical for the scientists complete the studies or publish the results. Since Scott and Mark are the only participants in the Twins Study, they have almost no privacy when the data gets published. When a person participates in a study with a thousand other subjects, they don’t give up as many rights to privacy, so the ethical issues are not the same.

If Scott or Mark ask to restrict the data, scientists will not be able to talk about the data or share the data; it has to be as though the studies never happened. It is the job of our institutional review board to make sure all the studies that use astronauts as human subjects are carried out ethically and appropriately.

What these studies mean for a mission to Mars

The reason behind these studies is to enable crew members to go to Mars. We have to understand not only the effects of microgravity on the body during long-duration missions, but we also have to understand how the measures we’re using to prevent some of those effects are working to prevent them. For example, we need to understand bone loss in crew members, and if or how the exercise and nutrition measures we’ve put in place are working.

Journey to Mars

We also have to understand how crew members recover one they are home, because it’s all about risk over time. When an astronaut goes to Mars someday, we’ll be concerned about vision issues. It may be that their vision could be compromised on the way to Mars, but if – when they are spending a year on the surface of the planet – everything corrects itself, and then they fly again, the long-term risk might not be too high. On the other hand, if their vision doesn’t recover while they are on the surface of Mars, then it could be a much higher risk as they are returning, so we have to understand the process of recovery as well as the process of impacts. If crew members can recover, and effects are only short-lived, the risks may not be as concerning. All this data collection and analysis – by nature of the recovery time needed to return to “ground normal” – will take time, which means our learning is far from complete.

NASA’s International Space Station Chief Scientist Julie Robinson, Ph.D. (NASA)

NASA’s International Space Station Chief Scientist Julie Robinson, Ph.D. (NASA)

Twins Double the Data for Space Station Research – Part One

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In today’s A Lab Aloft, Graham Scott, Ph.D., kicks off a two-part series looking at the National Space Biomedical Research Institute’s (NSBRI’s) and NASA’s Twins Study that is conducting biomedical research on a pair of identical twin brothers, who are both astronauts.

Medical care and biomedical research are rapidly becoming personal—as underscored by President Obama’s recently announced Precision Medicine Initiative that considers patient’s individual variations in genes, environment and lifestyle as inputs to disease prevention and treatment. The President’s Precision Medicine Initiative has the goal of generating the scientific evidence needed to propel precision medicine into clinical practice. Individualized healthcare unleashes powerful 21st century molecular diagnostics that offer exciting new treatment options for patients and their families. Molecular diagnostics analyze biological markers such as genes, proteins and metabolites present in a person’s tissues, cells and biofluids (such as blood or urine), by applying techniques developed by molecular biologists to medical testing.

In an effort to address the age-old question of “nature versus nurture,” the NASA and the National Space Biomedical Research Institute (NSBRI) funded Twins Study is conducting biomedical research on the Kelly brothers—identical twin astronauts. This first of its kind integrated “astro-omics” study will lay the foundations for the eventual development of precision medicine-based countermeasures for astronauts that may contribute to future missions to Mars. Spaceflight challenges humans in new, unexpected and extreme ways, and people on and off the ground will undoubtedly benefit from the knowledge obtained as a result of this unique investigation.

The origins of this research are also personal. The twins themselves, Mark and Scott Kelly, raised the idea that they be studied before, during, and after Scott’s current one year mission aboard the International Space Station. Scott is one of two selected crew members who will spend a full 12 months on orbit, rather than the usual six months. Meanwhile his brother Mark, a retired astronaut, remains firmly on the ground.

During a news conference on Jan. 19, 2015 at Johnson Space Center in Houston Texas, Expedition 45/46 Commander, astronaut Scott Kelly—along with his brother, former astronaut Mark Kelly—spoke about Scott Kelly's impending one-year mission aboard the International Space Station (ISS). (NASA/Robert Markowitz)

During a news conference on Jan. 19, 2015 at Johnson Space Center in Houston Texas, Expedition 45/46 Commander, astronaut Scott Kelly—along with his brother, former astronaut Mark Kelly—spoke about Scott Kelly’s impending one-year mission aboard the International Space Station (ISS). (NASA/Robert Markowitz)

The Twins Study dovetails seamlessly with the one-year mission, creating an opportunity to take a detailed look at Scott’s DNA, his complement of proteins, the ensemble of bacteria living in his gut, and the milieu of metabolites found in his bloodstream. We call this type of research—where we simultaneously look at many different biomolecular levels—an integrated omics study.

The term “omics” is relatively new. In 2003 the first “finished” human genome, which detailed the genetic make-up or blueprint of a person, became broadly available to the scientific community. This led to an observation of how genes are copied or “transcribed” ahead of ultimately being synthesized into proteins, which we refer to as the transcriptome. This work was quickly followed by efforts to study the proteome, cataloging the thousands of proteins that are circulating at any given time in our blood or performing signaling within our cells. More recently we have characterized the microbiome, which refers to the community of microorganisms living within our gut and on our skin. We also are studying the epigenome, which involves investigating reversible chemical changes that occur dynamically within our DNA and the histone proteins that “package” our DNA as a result of environmental stressors. The number of “omes” that we can examine seems to continually increase and the term “omics” is an umbrella term to cover these areas of molecular research as a newly emerged category of biomedical study.

The opportunity to observe Scott (in space) and Mark (on the ground) at a fundamental biomolecular level is unique because they are identical twin brother astronauts. Around the turn of the 21st century we would have stated that they were genetically the same. Actually, it turns out that identical twins are not 100 percent identical. To a first order of approximation their DNA sequence is matched, but there are actually some small underlying genetic differences. Moreover, the biomolecules that are generated or “expressed” at the RNA, protein, and metabolite levels are quite different. This is due to the responses of each twin to the environment that they encounter at any given moment, as well as the experiences that have accumulated throughout their lifetimes.

We plan to look at both Mark and Scott’s molecular profiles at a fine, granular-level to see what is occurring with their genomes, transcriptomes, proteomes, metabolomes, etc. in space, relative to on the ground. Mark provides about as ideal of a control subject as one could imagine, because he is so close genetically to Scott. Starting in late 2014 we have been collecting biofluids and obtaining baseline measurements from Scott and Mark for the study. We will continue to collect samples from both twins following Scott’s return to Earth in early 2016.

An image of NASA astronaut Scott Kelly after arriving aboard the ISS to begin his year-long stay in space. (NASA)

An image of NASA astronaut Scott Kelly after arriving aboard the ISS to begin his year-long stay in space. (NASA)

What we may see with Scott, based on experiments previously performed using animal research models, are different RNA expression levels for certain genes, relative to what we typically observe on the ground. We can also perform a comparison of Scott’s RNA expression profile to that of his brother, Mark. For instance, during his mission Scott will experience approximately 20 times higher levels of radiation than Mark. This is because the combined effect of our planet’s protective atmosphere and strong magnetic field protects Earth-bound humans.

The impact that space radiation has on a person’s DNA is one of the things we’re interested in learning more about. We will study how rapidly the ends of the chromosomes or “telomeres” shorten in response to the effects of radiation and other stressors that are inherent to the space environment. This research on telomeres will provide follow-up data to the chromosomal damage published in 2008 by Dr. Francis Cucinotta and colleagues in Radiation Research.

A better understanding of the impact of space radiation at the molecular level may ultimately benefit cancer patients who undergo proton radiation as part of their treatment regimen. Up until the 21st century, cancer patients received radiation treatments that were quite different from what astronauts are bombarded with in space. Now many leading cancer hospitals are using proton therapy and some are even beginning to employ carbon ions to fight cancer. This “particle therapy” is similar to the heavy particle component of space radiation, though with varied rates and doses.

This higher radiation exposure Scott will experience in space may reveal biomolecular impacts in ways that could lead to new findings. The twins close genetics make them ideal study subjects for attempting to tease out the role of environmental effects in disease development, versus the inherent genetic makeup of a person.

We factored into the studies that Mark was an astronaut up until 2012, meaning he also spent a significant amount of time in space. Mark has spent 54 days in space, while Scott will accumulate 540 days on orbit by the end of his one-year mission—ten times as many days as his brother. Both of the brothers’ biomolecular profiles have almost certainly been impacted by their previous experience in space. Scott will of course encounter a new set of stressors, now that he is once again aboard the ISS.

Astronaut Mark Kelly, STS-124 commander, looking through the Earth observation window in the Japanese Experiment Module of the ISS during his 2008 mission. (NASA)

Astronaut Mark Kelly, STS-124 commander, looking through the Earth observation window in the Japanese Experiment Module of the ISS during his 2008 mission. (NASA)

As with many scientific projects, the Twins Study is likely to raise more questions than answers. That said, we hope to have many tantalizing leads and interesting pieces of data to follow up on with more integrated omics research on larger numbers of astronauts.

To baseline the biomolecular profiles of both Scott and Mark, we obtained and safely stored blood, urine, saliva, and other biofluid samples. We also are performing a longitudinal study on Scott, by collecting samples while he was on Earth prior to launch, then following him throughout his space mission and again periodically for many months after his return. The same goes for Mark; we will perform a similar longitudinal study on him. For both twin astronaut brothers we will track them over time, specifically for several years. In fact we will be looking at Scott’s telomeres, as far out as 720 days after his landing in March 2016.

The results of this study won’t just impact the twins, but actually will have a lot to do with the rest of us living here on Earth. One of the things you may have noticed if you saw the President’s State of the Union speech was that Scott Kelly was in the First Lady‘s boxed seating area. During his speech President Obama specifically mentioned the one year mission and cited the importance of the area of personalized or precision medicine that is rapidly emerging as a powerful new set of techniques within biomedical research and clinical practice.

NASA astronaut Scott Kelly stands as he is recognized by President Barack Obama, while First Lady Michelle Obama (lower left corner) and other guests applaud. The President recognized Kelly during the State of the Union address on Capitol Hill in Washington D.C. on Jan. 20, 2015. (NASA/Bill Ingalls)

NASA astronaut Scott Kelly stands as he is recognized by President Barack Obama, while First Lady Michelle Obama (lower left corner) and other guests applaud. The President recognized Kelly during the State of the Union address on Capitol Hill in Washington D.C. on Jan. 20, 2015. (NASA/Bill Ingalls)

In part two of this blog posting, I will share with you the ethics and impacts of personalized medicine in space and on the ground.

Graham B.I. Scott, Ph.D. (NSBRI)

Graham B.I. Scott, Ph.D. (NSBRI)

Graham Scott, Ph.D., is the Chief Scientist and Institute Associate Director at the National Space Biomedical Research Institute (NSBRI), NASA’s biomedical research institute that was established in 1997 to work in partnership with the agency’s Human Research Program. A New Zealander by birth, Scott served as a Royal New Zealand Air Force pilot before obtaining a Ph.D. in astrochemistry. He came to the U.S. in 1997 where he worked for Nobel Laureate Robert F. Curl, Jr, Ph.D., at Rice University. Scott then went on to work on the Human Genome Project at Baylor College of Medicine, followed by a decade of leading R&D and marketing teams in corporate America, before being recruited back to Baylor to undertake his current leadership role with NSBRI.