In today’s A Lab Aloft, guest blogger Liz Warren, Ph.D., looks at the differences between male and female astronaut physiology on long duration space missions.
I hate to break it to you, but men are not actually from Mars and women are not really from Venus. This silly saying illustrates a question that researchers, however, are serious about studying. With International Women’s Day around the corner, I thought it the ideal time to address the question: Is there a difference between the sexes as the human body adapts to microgravity?
In the fall of 2015, Sarah Brightman will be the 60th woman to fly in space. As we approach longer durations in human spaceflight, such as the one-year mission and the journey to Mars, it is important to tease out all aspects of how humans handle life in microgravity to ensure crew safety. The answers may also hold insights for human health even if you never leave the ground.
Our current crew aboard the space station includes ESA (European Space Agency) astronaut of Italian nationality, Samantha Cristoforetti, and a Roscosmos cosmonaut of Russian nationality, Yelena Serova. While serving aboard the orbiting laboratory for about six months, they each perform experiments in disciplines that range from technology development, physical sciences, human research, biology and biotechnology to Earth observations. This research helps in benefitting our lives here on Earth and enables future space exploration. They also engage students through educational activities in addition to operational tasks such as equipment maintenance and visiting vehicle tasks.
It’s important to acknowledge the contributions women in space make to both exploration and research. For instance, on Feb. 3, a prestigious tribute went to another woman space explorer, Japan Aerospace Exploration Agency (JAXA) astronaut Chiaki Mukai. She was conferred the National Order of the Legion of Honour, Chevalier. Mukai flew aboard space shuttle missions STS-65 and STS-95, and is currently the director of the JAXA Center for Applied Space Medicine and Human Research (J-CASMHR). The work these trailblazers accomplish also includes their role as research subjects themselves.
Female space explorers are skilled professionals, representing the best humanity has to offer, executing complex tasks in an unforgiving environment. Their sex differentiates them only so far as biology determines—which is exactly the topic covered in a recent compendium titled “Impact of Sex and Gender on Adaptation to Space.” The results were published in the November 2014 issue of the Journal of Women’s Health.
Space exploration is inherently dangerous, and as we look to longer duration spaceflights to Mars and beyond, NASA wants to make sure we are addressing the right questions to minimize risk to our astronaut crews. Based on a recommendation by the National Academy of Sciences, NASA and the National Space Biomedical Research Institute (NSBRI) assembled six scientific working groups to compile and summarize the current body of knowledge about the different ways that spaceflight affects the bodies of men and women. The groups focused on cardiovascular, immunological, sensorimotor, musculoskeletal, reproductive and behavioral implications on spaceflight adaptation for men and women. NASA and NSBRI created a diagram summarizing differences between men and women in cardiovascular, immunologic, sensorimotor, musculoskeletal, and behavioral adaptations to human spaceflight.
Thus far, the differences between the male and female adaptation to spaceflight are not significant. In other words, mission managers planning a trip to Mars, for example, can do so without consideration of the sex of the crew members. However, many questions remain unanswered and require further studies and more women subjects in the human-health investigations. There is an imbalance in data available for men and women, primarily due to fewer women having flown in space.
As a physiologist, I am intrigued by several of the differences described in the journal. An area that interests me in particular is cardiovascular physiology. According to the Centers for Disease Control and Prevention, cardiovascular disease—including heart disease, stroke and high blood pressure—is the number one killer of men and women across America. Many studies have shown that healthy habits including good nutrition and exercise are important for maintaining a healthy heart here on Earth. Those habits are even more important for astronauts on the space station.
Of the findings described in the journal, one is that women astronauts tend to suffer more orthostatic intolerance upon standing after return to Earth. Related to this finding, women also appear to lose more blood plasma during spaceflight. Possibly connected to the inherent differences in the cardiovascular system between men and women, male astronauts appear to suffer more vision impairment issues in space than women, although the difference is not statistically significant due to the small number of subjects—meaning more research needs to be done.
Another difference between men and women in spaceflight is worth noting, and that is the radiation standard. While the level of risk allowed for both men and women in space is the same, women have a lower threshold for space radiation exposure than men, according to our models.
This is an exciting time in human space exploration. We are addressing questions today that will lead to safer journeys off our planet. This month, NASA astronaut Scott Kelly and Russian cosmonaut Mikhail Kornienko will embark on the first joint U.S.-Russian one-year mission to the space station. Most stays on station are six months in duration, but planners anticipate a journey to Mars to be closer to 1,000 days. This first one-year mission is a stepping stone in our travels beyond low-Earth orbit. NASA anticipates to continue one-year long missions, and women will be part of these crew selections.
In the meantime, what we learn about our bodies off the Earth has benefits for the Earth. In part one of this guest blog, I stated that, “in space exploration and in science, we stand on the shoulders of those who came before us.” I am thrilled to think of what we are about to learn from the one-year mission, as well as the continued research on and by both men and women in orbit. What an exciting time for humanity!
Liz Warren, Ph.D., is a physiologist with Barrios Technology, a NASA contractor supporting the International Space Station Program Science Office. Warren has a doctorate in molecular, cellular, and integrative physiology from the University of California at Davis, completed post-doctoral fellowships in molecular and cell biology and neuroscience, and has authored publications ranging from artificial gravity protocols to neuroscience to energy balance and metabolism.
In today’s A Lab Aloft NASA research scientist Sara Zwart, Ph.D., shares the compelling results of studying nutrition with the crew of the International Space Station.
What you eat can affect your performance and health, in both the short term, and over the course of your life. Eating a balanced diet is important to be sure you get all required nutrients to avoid deficiencies, but at the same time to avoid getting too much. The reason is that nutritional status in general, and the status of particular individual nutrients, often follows a bell-shaped curve. The top of the bell, representing the most favorable amount of a nutrient, is between two unfavorable amounts, not enough and too much. Iron is one of those nutrients.
Most people are familiar with iron deficiency, and now there is a growing awareness of health problems associated with having too much iron in the body. It can be difficult for the body to get too much iron, as it absorbs only a small fraction of the amount consumed in the diet. Once iron is absorbed, however, the body doesn’t have a routine way to get rid of any excess. One way to reduce the amount of iron in the body is to donate blood. In population studies, people who donated blood more often had a lower risk of cardiovascular disease than those who did not donate blood or donated it less often. This is just one example of the relationship between iron excess and disease.
Iron status is one of the areas covered by our lab’s ongoing Biochemical Profile study, for which blood samples are collected before, during, and after crew members’ flights to and from the International Space Station. These samples allow us to monitor changes in nutrition and other physiological systems during missions aboard the orbiting lab. As a side note—the amount of blood we collect at each blood draw is relatively small, less than 10 percent of a typical blood donation.
When the body has an excess of iron, it uses specific molecules to transport and store the iron. We see an increase in body iron stores in astronauts early during spaceflight, and iron stores return to preflight levels in most crew members by the end of the flight. There are several potential causes for this increase astronauts experience when they begin their time in orbit.
First – the food system contains more iron than desired, on average about three times the recommended dietary allowance. Many food items on the space station are commercially available, and common items found on grocery store shelves (like bread and cereal) are fortified with iron.
Second – iron stores increase in response to a decrease in red blood cell mass. That decrease is a normal physiological change of spaceflight. We believe that because it is easier for the heart to pump blood to the body in microgravity, less blood is required, and the body reduces the volume of blood in the circulation. This reduction happens in the first two weeks of spaceflight, and the iron from the blood cells is put into storage—because, as noted earlier, the body doesn’t have a way to get rid of it.
In looking closely at the pattern of changes in iron status, we found that the increase in iron stores during spaceflight was related to both oxidative damage and bone loss. Think of oxidative stress in the body as similar to rust on a car. There are molecules in the body that react when exposed to certain factors such as oxygen, radiation, and even excess iron. The crew members who had the biggest increase in iron stores had the most bone loss. Those who had taken the longest time for iron stores to return toward preflight levels also had more bone loss. The next step will be to study the mechanism for how the oxidative damage is associated with bone loss, which is currently being studied on Earth as well.
Among the unique aspects of spaceflight research are the generally very healthy condition of astronauts, and the nature of the changes observes in the spaceflight environment. We observed these changes in a matter of months, whereas similar research on Earth would take years. The findings emphasize that excess iron can have negative consequences on many systems in the body in space or on Earth.
Further spaceflight research is needed to better understand how iron metabolism changes in astronauts on long-duration missions, and how these changes are related to other health concerns of space travel, including immune dysfunction and radiation-induced cancer risk. On exploration-class missions to other planets or celestial bodies, changes in iron metabolism on either side of the bell-shaped curve could cause or contribute to significant health issues. Our Biochemical Profile study, for which we are tracking nutrition status along with markers of bone metabolism and general chemistry, will allow us to continue to monitor iron status of astronauts and determine what other body systems are affected.
On either side of the iron bell curve, humans face health challenges and we hope to find data to help advance answers for the medical community. In the broader context, research on the far-reaching effects of increased iron stores suggests that studies aboard the space station have implications well beyond NASA for the general medical and scientific communities. Better recommendations for optimizing iron status for people on Earth may come in the future, thanks in part to the answers discovered for space explorers, but that found their way back home.
Sara R. Zwart is a research scientist with NASA’s Nutritional Biochemistry Laboratory at the Johnson Space Center in Houston. She obtained her doctorate in Nutritional Sciences from the University of Florida in 2003, and B.S. in Biology from The University of Notre Dame. She is a co-author on a recent book, Human Adaptation to Spaceflight: The Role of Nutrition.
In today’s A Lab Aloft International Space Station Chief Scientist Julie Robinson, Ph.D., looks back on 2014 to highlight some of the year’s milestones and research achievements.
As I take a moment to reflect on the accomplishments of the past 12 months, I can’t help but think of how they relate to where we’re going next with the International Space Station. From the crew capabilities to research goals, from NASA’s plans for continued exploration to the benefits for humanity from station studies, there are some key areas that stand out from 2014.
During the last year there has been so much demand for research on the space station—including investigations that require crew time—planners really have had to push the schedule. We deferred some preventative maintenance, scaling back on some filter changes, for instance, to adjust operations for increased crew time for research. That’s allowed us to get as much as 47 hours a week averaged in a six-month period. This number is the total for the three U.S. astronauts, rather than the original standard of 35 hours for science. When you think about it, that’s almost half again as much research as the designed schedule.
This is a great performance of balancing time aboard station, though we won’t always be able to hold to that. This is why we still need to go to seven crew members. The crew dedicating time to tend to investigations helps us to optimize the research coming out of space station, as well. Currently we house six crew members in orbit aboard the space station, and some of you may know that this is one person short of the craft’s design to sleep seven. This is because our Soyuz “lifeboat” can only return six crew members in an emergency. The advent of commercial crew will allow us to expand by that extra crew member, as the new vehicles can ferry four. This is a future goal that we all look forward to: a full house.
The crew was particularly busy during the latter part of 2014 with a huge new capability for biological research using model animals. This also was driven by user demand to launch rodents—meaning mice and rats, though so far we’re starting with mice on the space station. We now have a system that can launch rodents aboard the SpaceX Dragon vehicle. The animals can live aboard station for a long period of time in special habitats, and then either be processed on orbit or eventually returned live. This system was important to get online this year, because we had a large number of users in medical research and pharmaceuticals interested in using space station as a test bed for their studies.
There are many discoveries that have affected human health that were dependent on the use of animals as what we call “model organisms,” from the discovery of insulin to the that of tamoxifen to treat breast cancer to kidney transplants. This doesn’t mean these organisms are going to grace the cover of a magazine, but rather that they provide a model for humans to help us understand disease processes. By watching how they respond to research, we can in turn learn how to fight those diseases.
Having the ability to fly mice to space for long-duration studies is a huge advance. Fulfilling this capability was our response to the Decadal Survey recommendations of the National Academy of Sciences. We have years of research already lined up hoping to get access to these mice. To optimize the potential for discovery, we combine as many experiments together on this precious resource as possible.
This is an exciting area of study, as just a handful of mice have flown in the past—both on space station assembly flights and one flight in a system called mice drawer system. Even so, those findings account for a significant number of our highest profile publications from space station research. With access twice per year, we now have this type of study as a routine capability. This means we can expect to see a huge ramp-up in high-impact research in biomedical areas.
Another big change this year has been the space station maturing as a platform for Earth science. My colleagues in Earth sciences at NASA have called this the year of the Earth, because they’ve had five related instruments go into space this year. That’s a record, and two of these are on the space station, a first!
Moving forward we’re going to see a couple instruments a year go up until the space station’s current external sites are primarily full, likely in 2017. We now need to study whether to grow our capabilities to support more Earth sciences instruments, as well as astrophysics and heliophysics studies.
It’s really thrilling to see these initial instruments come to station and begin operations right off the bat. The first of these, ISS-RapidScat, was bringing hurricane data home within three hours—this was less than a week after installation. The instrument measured the sea-surface winds and was used to look at Typhoon Vongfong in Japan. How quickly scientists can use these data and incorporate findings into use for us on the ground can provide real benefits. The results can give valuable information that people need to know to protect their lives and property, making it an important advance to have available aboard station.
Next is the Cloud-Aerosol Transport System (CATS), an imager that looks at clouds and aerosols for climate research. CATS will be followed by a number of instruments that are either brand new to science or that fill a gap from similar satellites to provide cross calibration. Our understanding of the Earth is going to improve thanks to the research from all of these instruments.
One of the areas that congress has encouraged us to pursue is the development of commercial applications and commercial research on the space station. To this end, they declared the space station U.S. segment a national laboratory in 2005. In 2011 we selected CASIS, the Center for Advancement of Science in Space, to manage that national lab side for use by researchers that are not funded by NASA. These scientists may be funded by other government agencies or the private sector or nonprofit organizations.
I recently spoke with Brian Talbot, marketing and communications director with CASIS, and he shared his thoughts with me on the accomplishments of the organization for the past year. “The continued growth of CASIS as an organization in 2014 speaks to the limitless opportunities commercial and academic researchers see aboard the space station. Through funded solicitations in proven areas of space-based research to innovative and non-traditional commercial users, CASIS is moving ever closer towards its goal of fully utilizing of the national lab for Earth-benefit inquiry.”
When I talked about crew time, you may have noticed that it was broken down by U.S. and Russian segments and crew members. While this division is useful for tracking purposes, it’s important to mention how we are blurring those boundaries. This international laboratory brings collaborations together through research that transcend relations on the ground. The space station exemplifies a global partnership at its best.
One thing that has driven us to continue advancing our partnership is the announcement of the joint one-year expedition. Since the 2013 announcement, we have made advances in finalizing our research goals in preparation for the 2015 launch. This extended expedition will have an astronaut and a cosmonaut both stay aboard the space station for 12 months, instead of the current six-month standard. It’s been decades since astronauts were in space that long. With the leaps in our medical technology, the one-year stay will help us to better understand what happens to the human body on long-duration flights. These studies also may help answer related concerns for health here on Earth.
I’m really excited about how that international collaboration across all of our partners has evolved. We’re combining more investigations, we’re releasing open data for the entire global scientific community to work with and we’re joining crew member resources to optimize all of these activities. Whether it’s microbial sampling, taking care of plants or making specific observations of the human body, our crew members are working together on what is truly an international station in space.
Early this year, John Holdren, the director of the Office of Science and Technology Policy for the Obama administration, announced their support of extending the space station to 2024. We have worked through the impacts that this has for space station research and this extension gives us 90 percent more external research and close to 50 percent more pressurized research—those studies taking place in the cabin. 2024 is very important to what we can achieve with this global microgravity resource of the space station.
When we have scientists already in line wanting to do investigations, having more time to get those studies done and even to do follow-on research opens up the discovery potential. This also provides more time for research markets to develop independently. Just like on the ground, when someone wants to study a certain area, they contract a lab to do the experiments. Someday, when space station is gone, we want scientists to have continued access through this emerging market of microgravity research in space. This longer duration for station to remain as a platform helps to open up those opportunities for researchers around the world. This is the world’s chance to continue the mission of discovery off the Earth for the Earth.
Julie A. Robinson, Ph.D., is NASA’s International Space Station Chief Scientist, representing all space station research and scientific disciplines. Robinson provides recommendations regarding research on the space station to NASA Headquarters. Her background is interdisciplinary in the physical and biological sciences. Robinson’s professional experience includes research activities in a variety of fields, such as virology, analytical chemistry, genetics, statistics, field biology, and remote sensing. She has authored more than 50 scientific publications and earned a Bachelor of Science in Chemistry and a Bachelor of Science in Biology from Utah State University, as well as a Doctor of Philosophy in Ecology, Evolution and Conservation Biology from the University of Nevada Reno.
In today’s A Lab Aloft we hear from William Wells Jr., aSTEAM Village SSEP Kansas City program director, as he shares the difference made in the lives of students when schools work together to support education opportunities. These students literally reach for the stars with the Student Spaceflight Experiments Program when they send their studies to the International Space Station.
Many U.S. students lack foundational skills and knowledge in science, technology, engineering, and mathematics (STEM, or with art added STEAM) as a result of the absence of authentic learning activities in STEM subjects. They have little to no exposure to highly competent role models in STEM fields and limited opportunities to think critically, solve problems, research, publish and hypothesize.
Through the Student Spaceflight Experiment Program (SSEP), which is led by the National Center for Earth and Space Science Education (NCESSE), Benjamin Banneker Charter Academy of Technology in Kansas City, Missouri, engaged with other public and private school districts through aSTEAM Village, and I am honored to serve as the SSEP Kansas City program director. I work to fulfill the aSTEAM Village mission of helping to level the playing field for students in the Kansas City area. Our goal is to ensure all students are exposed to 21st-century knowledge through an expanded learning strategy in before/after-school and regular classroom environments using STEAM curriculum.
Through this in-depth program, our community’s students are presented an opportunity to be immersed in a high-profile community science competition. The objective is for students to submit an experiment that they hope will be selected to ferry to the International Space Station. Aboard the orbiting laboratory astronauts will perform the student experiment in microgravity. Meanwhile, the students conduct the ground truth of the study here on Earth. This is a real space program and not a simulation!
I was speaking recently with Marian Brown, Ed.D., superintendent for Benjamin Banneker Charter Academy of Technology, who shared with me the difference she has noticed in students attending aSTEAM Village partner schools through their participation with SSEP.
“We are so pleased that teachers and mentors have embraced the struggle to immerse and engage students in every facet of real science to ensure all students are provided the chance to explore the scientific method, as well as experience science firsthand. More importantly, we have observed an increase in our students’ capacity for hard work, perseverance and resilience. In addition, this program and partnership will help alter the path of children’s lives by fostering creative thinking, real-world problem-solving and true innovation for urban revitalization.”
I was not surprised that Dr. Brown’s thoughts were echoed in a conversation I recently had with Kristen Marriott, a middle school STEM teacher who has been involved with SSEP in three missions at two different aSTEAM Village partner schools: Della Lamb and Crossroads Academy. Marriott believes that the best thing about the program is watching the students problem solve and work collaboratively.
“They start the project as individuals but end up as a group, working through difficulties and limitations together. I have been amazed with the variety of experiments the students have proposed. We truly have a generation of STEM leaders making their way through school at this time.”
I think it’s safe to say there is plenty of evidence to support Marriott’s assertion. Two teams from another aSTEAM Village community partner, St. Peter’s School, had two flights selected, Mission 5 and Mission 6, which Robert J. Jacobsen, the school’s science teacher and SSEP coordinator said, “provided not only St. Peter’s, but the Kansas City community, a sense of achievement and pride.”
It has been fun watching the students reap the rewards of their diligent work and effort, from brainstorming and proposing ideas to presenting their projects at the NCESSE 2014 National SSEP Conference in Washington. The student researchers, grades 5-8, discovered the need to be flexible yet manage their time and energy. They learned to value review boards, both at the local and national level, and the important input that they had to offer. The student teams also mastered answering questions from the media (and what a wonderful job they have done). We have seen the enthusiasm of the student teams involved with both Missions 5 and 6 act as a motivating force for the Mission 7 teams who have just completed their proposals to be evaluated by the local review board.
Through mostly local funding, SSEP also provided the opportunity for the Mission 5 finalists and first-time SSEP participants from the Kansas City area to get a life-altering VIP tour of NASA’s Wallops Flight Facility in Virginia. The aSTEAM Village students, from six different public, charter and private schools, had the opportunity to learn, explore and enjoy an experience of a lifetime in the Chincoteague, Va., and Washington, D.C., areas.
For several of the students, it was the first time they had ever left the immediate Kansas City area. The highlight of our trip was the visit to the flight facility center where the flight project manager made it his point to host the tour. He spent several hours with the students, teachers and chaperones. What came forth was the utmost and genuine enthusiasm and passion for science and engineering that the individuals and teams of the flight facilities displayed. This experience was so important and it definitely left an unforgettable impression upon both the students and us adults in the Kansas City delegation.
I have been truly amazed to see the realization of the vision of NCESSE director, Jeff Goldstein, Ph.D., and his message to educators, students and parents that, “the world is a classroom.” It is an honor to serve as SSEP Kansas City program director as this program not only has all of us mentors, students and parents looking to the skies and beyond, but it also without question, has inspired the next generation of scientists, technologists and engineers. More importantly, it is infusing the confidence in the student researchers that indeed they can become whatever they want to become, because at a very early age of their life they can truthfully say that participation in SSEP has made them a part of America’s space program.
Seeing these kids take to STEM, NASA can rest assured that SSEP will produce their next wave of talented explorers and leaders. They’ll be ready for hire when NASA ushers our nation deep into the galaxy and beyond over the next century. I know from my experience with these bright and enthusiastic student scientists that they’ll take us great places!
SSEP and its passionate team are a wonderful gift to the younger generation. We need people to challenge the young minds. They indeed are the future. Go, SSEP!
William Wells, Jr., is a seasoned tech professional and entrepreneur who leverages his knowledge and expertise to inspire the next generation of STEAM professionals as the aSTEAM Village SSEP Kansas City program director. He has successfully formed collaborations among a diverse coalition of schools to bring unique STEAM-related programming to hundreds of K-8 students through the aSTEAM Village. Wells currently serves as the lead robotics and computer science instructor at Benjamin Banneker Charter Academy of Technology. He has been named the National and Local Black Engineer of the Year and attended the Tuck School of Business at Dartmouth College and Kansas City Kansas Community College.
The Student Spaceflight Experiments Program (SSEP) is a program of the National Center for Earth and Space Science Education (NCESSE) in the U.S., and the Arthur C. Clarke Institute for Space Education internationally. It is enabled through a strategic partnership with NanoRacks LLC, working with NASA under a Space Act Agreement as part of the utilization of the International Space Station as a National Laboratory. SSEP is the first pre-college STEM education program that is both a U.S. national initiative and implemented as an on-orbit commercial space venture.
In today’s A Lab Aloft International Space Station Assistant Program Scientist Kirt Costello, Ph.D., lays out what’s new in rodent research in orbit. The updated facility and planned studies will advance capabilities for microgravity life science and biology research.
In this blog we often talk about the “why” reasons for the research that we are doing on the International Space Station, but sometimes it’s also important to talk about “where” NASA gets the ideas. Specifically, where do the concepts and research announcements come from? How does NASA know that the science being selected fits the needs of the country in its quest to get the most beneficial use of the space station’s national laboratory?
Today’s discussion is on the new space station Rodent Research Facility and the objectives that NASA is trying to meet by making this system available to both researchers seeking safe exploration of space and those seeking improvements in health here on Earth. Many of these investigations directed specifically at improving life on Earth come through the Center for the Advancement of Science in Space (CASIS) as the manager of the space station’s national laboratory resources.
NASA has been conducting rodent research in space for many years. The majority of those investigations focus on clinical questions about how we keep our astronauts healthy in space for longer periods. They also address very basic life science questions about how animal physiology changes in a weightless environment. Prior to and during the time of station assembly, the Space Shuttle Program hosted the Animal Enclosure Module (AEM) studies. The AEM flew 28 missions conducting research, such as the Commercial Biomedical Testing Module or CBTM investigations. The AEM system was well suited to the Space Transportation System (STS), allowing researchers important access to their rodent subjects both before flight and during post flight recovery.
With the end of the shuttle program, it was clear that the use of newly designed transportation vehicles would necessitate redesign efforts for AEM use aboard station. Conducting such investigations not on the vehicle, but aboard the station would enable longer-duration studies. The change from a few weeks to a few months in microgravity increases the potential research returns, but also requires some changes in the design of the hardware.
The importance of continuing rodent research aboard the space station is laid out by the National Research Council (NRC) in their 2010 Decadal Study Report, “Recapturing a Future for Space Exploration Life and Physical Sciences Research for a new Era.” In that study’s section on animal and human biology a third of the recommendations specifically called out the use of mouse or animal model organisms as the mechanism to proceed with research on the orbiting laboratory. These recommendations focus on muscle and bone loss, the testing of drugs for osteoporosis, changes to the animal immune system, the effects of aerosol exposures to the lungs and multi-generational and developmental studies.
To accomplish the wide array of research that the NRC proposed, some improvements were made to the AEM system to update the workhorse that had served well during the shuttle years. Improvements include features such as upgraded longer lasting filters, changeable food trays and support systems within the microgravity science glovebox (MSG) facility. These changes allow for studies to focus on the effects of microgravity exposure over much longer time frames. While the AEM of the shuttle era only housed rodents for up to 17 days, the new facility on space station can maintain an investigation for months.
Part of what makes rodents ideal test subjects is the fact that they reach maturity and age much quicker than humans. The typical rodent lifetime is about 2.5 years versus about 72 years for the comparable human. The capability to support rodents for up to 180 day stays is in development for the space station. During stays that long, researchers can begin to investigate questions that deal with developmental biology and extended exposure to microgravity. A half a year stay for a rodent might be the equivalent of a 14 year exposure to a human.
Updates to the old system also add both white light and infrared cameras for observing rodent conditions and behaviors. This capability allows researchers on the ground to closely monitor their studies. It also requires less crew time, as the observations can be done remotely, which in turn frees up that crew time to get more science done aboard the space station.
The first flight of the new Rodent Research Facility is on the upcoming SpaceX-4 mission to the space station. During this flight, designers will validate all of the initial performance goals for the rodent research hardware. The facility also will get a head start on some of the NRC decadal recommended goals with the CASIS sponsored portion of the Rodent Research-1 investigation. This study will include 10 of the 20 mice flying in the two habitats, and is in partnership with the commercial pharmaceutical company, Novartis.
The test subjects will live aboard the space station for about 21 days. The CASIS mice will include five wild type—or typical—and five transgenic MuRF-1 knockout mice. Researchers will compare results from these two groups and the ground control counterparts to determine whether this genetic knockout impacts muscle atrophy and muscle sparing—where tissue is conserved—in those mice.
While the inaugural flight of the new rodent habitat system is right around the bend, the rodent research project team at NASA’s Ames Research Center is already hard at work. They are planning more complex investigations and improving the system to accommodate longer durations and more experimental aims for researchers. Rodent research will become a routine part of space station for the decade to come.
For me, personally, it’s been a great experience working with these teams to get this facility ready for flight. I’m excited by all the possibilities for the new research avenues that this opens for NASA and CASIS researchers. I’m humbled by the effort that has gone into this capability, and I hope you all will tune in during the mission to follow along with the accomplishments of the team.
Kirt Costello completed a Ph.D. in Space Physics and Astronomy at Rice University in 1998. Kirt is the Assistant International Space Station Program Scientist for National Research. In this position he works with the International Space Station Chief Scientist, NASA research organizations and CASIS to advise on the objectives and priorities of science being prepared to fly to the space station.
In today’s A Lab Aloft our guest blogger is Trent Martin, the NASA project manager for the Alpha Magnetic Spectrometer instrument. Martin shares the challenges and excitement of seeking to unravel the mysteries of the universe.
Can a single data point make a difference? When speaking of the collected billions of data points since the inception of the Alpha Magnetic Spectrometer-02 (AMS-02) to the International Space Station (ISS), the answer is yes. Every data point leads us closer to unveiling the answers to the questions of the universe.
A handful of those unique data points were the topic of the keynote speech delivered by AMS principal investigator Professor Samuel Ting at this year’s ISS Research and Development Conference in Chicago. Approximately 90 percent of the universe is not visible and is called dark matter. Collisions of “ordinary” cosmic rays produce positrons. Collisions of dark matter will produce additional positrons. This excess of positrons has been seen in the AMS data. While more data is needed, this specific handful of points tells us something we didn’t know before about our universe. It adds to our current knowledge and guides us on our path to answers in the areas of dark matter and more.
In May, 2011 as the space shuttle Endeavor sat on the pad ready to launch the AMS-02 to the space station, it carried the hopes and dreams of 600 physicists, engineers and technicians from 60 institutes in 16 countries who had worked for nearly 1.5 decades to build the most sophisticated magnetic spectrometer ever to be put into space. Led by Ting, a Nobel Laureate from the Massachusetts Institute of Technology, the detector is designed to cull through galactic cosmic rays searching for the origins of the universe, evidence of dark matter, evidence of naturally occurring anti-matter and other cosmic phenomena.
In the words of Ting, “the most exciting objective of AMS is to probe the unknown; to search for phenomena which exist in nature that we have not yet imagined nor had the tools to discover.” AMS-02 provides that set of tools.
It is exciting to have the chance to continue to collect data to close the gap on these types of questions. The AMS-02 will run aboard station for the next decade—a timeline granted by the station extension to 2024, but also thanks to a design change just prior to the launch to the space station. This was at the time of an earlier station extension to 2020, at which point the original cryogenic magnet was swapped for a permanent magnet. Had we kept the original magnet, the AMS-02’s life expectancy for operations on orbit would already be at a close—and we’d be left with questions unanswered. Instead, the final selection of a permanent magnet enabled our continued quest towards discovery today.
Let’s take a closer look at how AMS-02 works to help us seek those answers. If you asked a high-energy experimental physicist to provide a wish list of every instrument they would like to see on some theoretical detector, they would likely provide a list that is identical to the six instruments that make up the AMS-02. Since the detectors are so complex and include over 300,000 data channels, providing for easily replaceable systems in space was nearly impossible. Instead, the systems were designed and built with a significant amount of redundancy. Multiple detectors measure charge, momentum, and energy of a passing particle. Although each detector measures in a different way, it provides us redundant and confirming measurements. The electronics for the detectors are also redundant. In most cases, the electronic systems have four-fold redundancy. This makes for a reasonably secure fail-safe, most would agree.
Operations on the station began within hours of the AMS-02 installation on the S3 truss. Since May 2011, there has been very little time when AMS-02 was not collecting data. The amount of information has been somewhat unexpected. AMS-02 has measured more than 52,000,000,000 particles. In fact, we measure at a rate of 16,000,000,000 particles per year. We were expecting more like 11 billion particles per year. This improved rate of return means more data points in each communication for ground teams to analyze.
In addition to the external instrument, which is the largest payload aboard station, the AMS-02 employs a laptop that is dedicated to the instrument’s operations from the interior of the orbiting laboratory. This internal system acts as a crew interface to AMS-02 and provides a backup system in the event of a long-term loss of data from the space station to the ground. This is an important capability for our search for antimatter because it only takes one of the billions of events to see an antimatter particle.
The search for anti-matter is actually quite challenging. I think of it like this, during the spring in Houston, there are many rain showers. If we assume it is a very rainy day in the large city of Houston, it would be like someone asking you to look at all of those clear rain drops and find one drop that is colored red! As we look at the billions of data points, we are seeking a drop in a rainstorm of information.
The AMS-02 science data points are stored on NASA computers as soon as the information reaches the ground at the Marshall Space Flight Center in Huntsville, Alabama. It is stored again as soon as it reaches Geneva. Teams of scientists work daily to analyze the data coming from the AMS-02. Typically these teams are broken into two groups to ensure that the analysis is independently analyzed. The teams meet about once per month to go through their results, work on papers, and identify new areas of interest. AMS-02 publications can be found here.
Thanks to the extremely high data rate and the precision of the AMS-02 detectors, the data is providing significantly improved tolerance bands on the measured data when compared to other detectors. In the past hundred years, measurements of charged cosmic rays by balloons and satellites have typically contained approximately 30 percent uncertainty. AMS-02 will provide cosmic ray information with closer to one percent uncertainty.
There is a lot of excitement that surrounds the findings from this instrument. The first paper published by AMS-02 was published in Physical Review Letters. The paper was highlighted in a Viewpoint appearing in the April 2013 issue of Physics. Being chosen for Viewpoint is a very selective process. According to the editor in chief of American Physical Society, “The APS published a total of about 18,000 articles last year, but only around 100 Viewpoints will appear each year. This places your paper in an elite subset of our very best papers.”
Based on the data coming from AMS-02, the space station has become a unique platform for precision physics research. During this orbiting laboratory’s lifetime, we expect to obtain 300 billion events. It is my hope and belief that somewhere buried in those 300 billion events we will find a better understanding of the origins of the universe.
Trent Martin is currently the associate director of engineering for advanced development at NASA’s Johnson Space Center in Houston, in addition to serving as the AMS NASA project manager. Martin has a bachelor’s degree in Aerospace Engineering from the University of Texas and an MBA from the University of Houston at Clear Lake. He has worked at Johnson since 1995.
In today’s A Lab Aloft, International Space Station Payload Operations Director Stephanie Buskirk Dudley shares a behind-the-scenes look at work on the ground leading up to and supporting research in orbit.
Right now, at this very minute, there are hundreds of investigations going on above your head. This research ranges from growing plants to burning different kinds of materials. Twenty-four hours a day, seven days a week, astronauts aboard the International Space Station are living and working in the most sophisticated laboratory ever built. And it’s my job to keep track of all that research and ensure that the orbital lab runs like a well-tuned orchestra.
I am one of 23 payload operations directors (PODs) in the Payloads Operations Integration Center (POIC) at NASA’s Marshall Space Flight Center in Huntsville, Alabama. Together, we are responsible for planning the crew’s work schedules down to 5-minute increments, ensuring research stays on track and liaising between the astronauts performing experiments and the investigators conducting the research. It is a lot like conducting a symphony. At any given time we could have 10, 20 or 50 different things happening in orbit, in the POIC and in the five similar control rooms around the world. It’s a thrilling, high-intensity job that leaves me exhausted at the end of the day. There are times I don’t get a chance to eat or even run to the bathroom; but I love it. I really do have the coolest job, and when my shift is over, I look back and say, “Wow. Look what we accomplished!”
We have three shifts working around the clock every day of year—including holidays and weekends—supporting space station research. We have research that requires astronauts’ participation, but we also have studies that we control from the ground. This ground-controlled research frees up the astronauts’ time to do other research or maintenance on the station. It also allows us to do research while the crew is asleep. Since we have research going on all day and night, our schedules vary between the day, afternoon and midnight shifts.
Our work begins long before we show up for our shift. In fact, we start planning any given day on the space station about 12 months in advance. We need to consider a number of logistics when planning for the crew to run an experiment. For example, we need to factor the amount of power needed, the thermal output and gaseous exhaust produced, limitations of specific systems, spatial conflicts and bandwidth for video and data, as well as the set number of video channels needed to observe and record the experiment. And that’s just naming a few things we worry about. Sometimes, a year just doesn’t seem enough.
Even with all that planning, we still have to deal with the unforeseen and be prepared to adapt. Just like in our homes on Earth, things need to be repaired aboard the station. If the toilet breaks, for instance, that becomes the highest priority for the crew, and research gets pushed to the backburner until the facilities are fixed. My fellow PODs and I understand. The exercise equipment also is a high priority in orbit since the crew members must work out for two hours a day to keep their bones and muscles healthy.
So, how do we balance all these constraints, logistics and demands? With lots of preparation and a well-trained team. I actually begin reviewing plans about a week prior. I will check to see if the investigations have been conducted in the past and ask myself how did we do them before and what’s different this time. I will refresh my training on the old and new studies, payload regulations, flight rules and any planning constraints that may impact the day’s activities for both the crew and the ground teams.
This research helps me be prepared for anything. Let’s say I’m working the day shift–my favorite shift because the crew is still awake. They have been working all morning, and I need to be up-to-speed on what they’re doing even before I get to work. If I get to the POIC and find the crew is ahead of schedule, I can adjust the timeline accordingly. Likewise, if they are behind schedule or an investigation hasn’t gone according to plan that morning, I need to be prepared for that as well. The research I’ve done the previous week helps greatly.
I am also briefed when I arrive at work. The day shift begins at 7 a.m., but I’m usually there about a half hour before to review the stack of papers the midnight shift has left me. After reading the daily logs and familiarizing myself with what went on overnight, I scan the handover sheet. This document details what’s going on with the crew, provides information related to specific payloads and lists items the previous shift was unable to complete. The outgoing PODs work hard to ensure that incoming PODs have everything they need, and the previous POD will always include notes that will help the incoming POD.
Armed with the latest information, I have a conference call with the morning flight director in Mission Control at the Johnson Space Center in Houston as well as my counterparts from NASA’s International Space Station partners. In that call, I get more information about what happened before I arrived and how the day is scheduled to go. I also provide a report to the morning flight director on what our shift will look like. This includes issues my team and I are tracking, crew and research statuses and anything else that might be out of the ordinary. Once everyone has spoken and the flight director is confident we’re all on the same page, we officially transfer from the midnight shift to the day shift.
Once the shift transfers, I literally take the outgoing POD’s seat and lead my team for the day. From this point until the day shift hands over the reins to the afternoon shift, I am responsible for all the research on the space station NASA is conducting. When you think about it, that’s a pretty incredible thing! If things go well, I have an awesome sense of accomplishment. If, on the other hand, things don’t go so well, I am the person the flight director calls for answers.
Fortunately, I have a solid team working with me in the POIC, and we’re all focused on making sure the space station is producing the best research possible. Depending on the shift, the team ranges from five to 10 people, as well as two to four addition folks who are responsible for managing the POIC facility. They ensure we have power to run the computers that crunch the data coming down from the station day and night.
Like a band where each member has a specific instrument, everyone on the team has a specific responsibility. The PAYCOMs, what we call the payload communications managers, are vital to ensuring the research gets done properly. If the crew has a question about the study they are working on, the PAYCOMs have the answers. They are the voice of the POIC. It’s not an easy job either; the PAYCOM must be able to understand the research well enough to explain the investigator’s hypothesis to the crew and describe the actions the astronaut is to perform. Although it’s a demanding job, it also has its perks. The PAYCOMs get to speak regularly with the crew. Some might find this intimidating, but our PAYCOMs really enjoy it.
The operations controllers (OC) are responsible for helping all of us stay on track. Without the OCs, the timelines could fall apart, and the past 12 plus months of planning would have been in vain. The OCs try to stay ahead of the astronauts and anticipate what tools or resources might be needed. This way, everything will be on hand when it’s needed, and we won’t have to slow down to find the right information. The operations controllers are also responsible for any safety issues that might arise. Safety is our number one priority, and the PODs rely heavily on the OCs to make sure we stay safe.
Another member of the team is the payload rack officer (PRO). This position definitely has the best acronym, and it’s apropos because the men and women who are PROs really are pros! The PROs are responsible for sending the commands to the space station that enable the research. They ensure there is enough power to run the experiment, thermal controls are set properly, adequate venting is provided, communications links are established and other logistics needed to allow the research to be conducted. They also manage the command link, which allows investigators all over the world to operate their studies on the station. Thanks to computers and the Internet, it probably surprises no one that these days scientists conducting investigations aboard the space station could be located anywhere in the world. Researchers from countries such as Belgium, Canada, France, Italy, Norway, Spain and Switzerland operate and command research everyday with the help of our PROs.
It’s no small task to get the scientific data to these researchers in far off countries. The data management coordinators (DMC) are responsible for providing the data, including video when available, to the scientists on the ground. They route the information from the various science facilities on the station to the POIC, and our ground systems teams get the data to the researchers. The DMCs must negotiate limited bandwidth and manage our up- and downlink capabilities. For instance, if the Alpha Magnetic Spectrometer (AMS)—an investigation looking into dark matter and one of our biggest data users—started to get behind on downlinking data, a DMC would adjust demands to free up bandwidth for AMS from other studies that are perhaps ahead of schedule or of a lower priority.
One of the greatest challenges for most of us is remembering where we left things. Imagine how much harder it is to keep track of objects when they can float away instead of just dropping to the floor if you let go. The responsibility of remembering where everything is falls to the stowage engineer. Personally, I think they have the greatest challenges of everyone on the team, especially when new hardware arrives at the station. Stowage information is only as good as the information the crew gives us. We tell the crew where to find tools and materials and where to return them; however, if the crew doesn’t secure the objects properly, they could float away. It’s the stowage engineers who are tasked with finding the missing objects. This is a pretty stressful task from 250 miles away, but our stowage engineers are experts at finding missing objects and knowing where to store things. They keep the station a tight ship.
Each shift has an increment scientist representative (LIS rep) who helps us make priority calls on operations. They are the science experts in attendance and can make a call on how to adjust an investigation if things aren’t running as smoothly as planned. If the LIS reps don’t know the answers, they get in touch with the principal investigators or payload developers immediately. If things are not going right or running longer than the schedule allows, the LIS reps help determine the best course of action.
If it becomes necessary to adjust the schedule, the timeline change officer (TCO) helps make those changes. We don’t always change the timeline because of problems. Sometimes unexpectedresults occur, and the investigator wants to spend a little more time to understand what’s happening. When it becomes necessary to extend or shorten the schedule for one reason or another, it is the TCOs who process the paperwork to get the timeline changed and manage all the residual effects of the change.
So much is going on all day, every day that it can seem like a cacophony of investigations, data transmissions and research questions. It is my job as a POD to manage the various aspects of the day and bring harmony to the clamor of science in the POIC. I love what I do. I love being the conductor of this amazing orchestra of research.
Stephanie Buskirk Dudley is an International Space Station payload operations director at NASA’s Marshall Space Flight Center in Huntsville, Alabama. She has a Bachelor of Science in engineering science, a Master of Science in biomedical engineering and a Master of Engineering in industrial and systems engineering from the University of Florida. She previously worked at NASA’s Kennedy Space Center in Florida as an analytical engineer on the space shuttle solid rocket boosters.
In today’s A Lab Aloft, guest blogger Tara Ruttley, Ph.D., NASA International Space Station associate program scientist, shares her experience from the 2014 World Science Festival.
I think I’m finally recovering from the amazing whirlwind that was the World Science Festival. From May 28 to 31, NASA had the exciting opportunity to participate in the event held in New York City. The festival, created by physicist Brian Greene, is an annual city-wide series of events that include smaller panels, interactives, demonstrations and presentations, all with the goal of sharing fascinating and cutting-edge science with the public.
My role was to coordinate and present the science happening on the International Space Station (ISS) with attendees in a World Science Festival style. This means “Go Big!” The kinds of exchanges that happen in environments like this have dual benefits for the agency. The public gets informed about the work that NASA does—and we really hope they get inspired and motivated—and NASA gets to learn just what the public thinks about us, for better or worse.
When given the challenge last fall to prepare for NASA’s participation in the festival, the first thing I did was identify some of the most passionate, excited space station scientists. I then invited them to showcase their work among the many World Science Festival activities sprinkled throughout the week in June. Of course our very own International Space Station Program Science Office was ready to share our investigations with the masses. There were so many great researchers and experiments that came to mind that I wanted to share with the visitors to the event.
Considering the array of schedule constraints and correct alignment of the cosmos, I was finally able to put a team together to represent space station research at the event. I recruited space station fluid physicist Mark Weislogel from Portland State University, who talked with audiences about his wild findings on fluid behavior in microgravity. I also asked aerospace engineer Nancy Hall, who brought her drop tower out for public interaction from NASA’s Glenn Research Center in Ohio. Then I also recruited Alvar Saenz-Otero and his award-winning MIT SPHERES team, who had demonstration units used for the Zero Robotics: ISS Programing Challenge for the public to try out.
From NASA’s Human Research Program, Andrea Dunn attended and demonstrated the space station’s new Force Shoes investigation. Team members from NASA’s Human Research Program based at the agency’s Johnson Space Center in Houston showed visitors how liquid recycling happens in space. They explained the importance of hydration for astronauts and those of us here on Earth.
This was quite a unique series of events with an assortment of participants representing the research we have done, continue to do and plan to do for the next decade aboard the space station. As we scientists were celebrated for our love of discovery—BONUS!—we got to share that enthusiasm with a massive crowd. For self-proclaimed science geeks like me, it was utopia!
For months leading up to the big week, our space station teams were hard at work to deck out the NASA mobile exhibit to look like the inside of the space station. We also included displays of some of the most stunning science footage ever taken aboard the station. We really wanted the public to experience what the astronauts feel in orbit—Ok, I admit the addition of a microgravity component itself would have been really cool, if we could create such a thing. I believe we achieved our goal of conveying the importance of the types of science we do on station to advance both human exploration of space and to improve our lives on Earth.
All of these questions can be answered along the same theme: we’re learning about new behaviors, relationships and processes we’ve never even discovered before on Earth. In so doing, we apply that knowledge to existing systems on Earth and in space to constantly improve our very existence. During the week of the World Science Festival, we must have answered hundreds of questions as we interacted with upwards of 150,000 people interested in space station science!
And, inevitably, yes, we did get the common question we’ve come to expect: how do you go to the bathroom in space? The NASA exhibit even came prepared with a demonstration unit of the Waste Management Center (WMC)—that is, a space potty! For display purposes only, of course.
Potty talk aside, the public cares about the science we conduct on the space station. They ask many of the common questions surrounding science in space, and they also ask new questions, which leads us all to think about “what if…” ideas that we may just try out in space one day. One thing’s for certain, when we support science outreach events like these, the people we meet usually have as big an impact on us as we do on them. And for that, many thanks for your inspiration!
Tara Ruttley, Ph.D., is associate program scientist for the International Space Station at NASA’s Johnson Space Center in Houston. Ruttley previously served as the lead flight hardware engineer for the ISS Health Maintenance System and later for the ISS Human Research Facility. She has a Bachelor of Science in biology and a Master of Science in mechanical engineering from Colorado State University and a doctorate in neuroscience from the University of Texas Medical Branch. Ruttley has authored publications ranging from hardware design to neurological science and holds a U.S. utility patent.
In today’s A Lab Aloft, Joshua S. Alwood, Ph.D., shares his postdoctoral research into the impact of microgravity and ionizing radiation exposure on bone health – work that led to his receiving the 2012 Presidential Early Career Award for Scientists and Engineers.
The big question motivating our studies is, how does spaceflight cause bone loss in astronauts? While weightless, astronauts lose about one percent bone mineral density per month. To put this into context, this is about 10 times faster than osteoporosis typically progresses on Earth. The longer the mission, particularly outside Earth’s protective magnetic fields, the greater the doses of ionizing radiation astronauts will accumulate, which may also negatively impact the skeleton.
In our ground-based research, we asked the following questions: how do the conditions of simulated weightlessness and ionizing radiation exposure affect the skeleton, and are the results any different when these conditions are combined? Our results suggest that each condition causes bone loss on its own, though at differing rates and severity. Together, weightlessness and radiation exposure cause bone loss to worsen beyond either treatment alone. These results have to do with the behavior of different types of bone cells. Combined, the balance of bone formation and bone resorption—breaking down—define a normal process called bone remodeling, which the body uses to maintain a healthy skeletal structure throughout life.
Following radiation exposure, there is a rapid stimulation of bone resorption—this can lead to a net loss of skeletal tissue caused by a specific cell called an osteoclast. We quantify this by measuring the number of osteoclast cells on the surface on the bone and their level of activity through specific proteins secreted into circulation. At the tissue level, we use X-ray imaging and computed tomography to build and quantify three-dimensional models of the skeleton. This rapid resorption is concentrated, yet it appears to be short-lived. At the doses we’ve investigated, it doesn’t get worse after the initial burst.
In contrast, structural changes caused by simulated weightlessness gradually appear. Simulated weightlessness activates bone resorption by the osteoclasts and additionally reduces bone formation by inhibiting a second cell type called an osteoblast.
Exposure to space radiation affects osteoblasts as well. Our research shows that at the estimated doses potentially accumulated over a three-year Mars mission, long-lasting effects to the osteoblast-lineage cells occur. This may result in abnormal bone remodeling in the long-term. To this end, we determined that spongy bone—found on the inside of some bones—recovered less efficiently following radiation exposure vs. recovery from simulated microgravity.
The second component of the PECASE acknowledges my work with the Biospecimen Sharing Program for shuttle flight STS-131. Along with Almeida, the project investigator, I used a new application of a high-resolution (30 nanometer) X-ray transmission microscope at the SLAC National Accelerator Laboratory to analyze bone health following 15 days of spaceflight.
We scanned the bones and processed the images for three-dimensional tomographic analyses. As a result, we were able to quantify changes in the bone’s osteocyte cells. In a unique mechanism of bone loss, osteocytes actively remodel and enlarge their living spaces, known as lacunae, in response to spaceflight. This is an additional mode of bone resorption that occurs during spaceflight at the bone’s surface.
My research employs a basic biology approach with the overriding motivation to enable human exploration of space. In other words, the goal is to expand the envelope of mission durations, the distance from Earth that missions can access, and to mitigate the skeletal consequences following radiation exposure for astronauts. My colleagues and I use a basic approach to uncover the cellular and molecular mechanisms that underlie skeletal changes in the space environment. Eventually we can use this knowledge to develop countermeasures to better manage astronaut skeletal health.
On Earth, this research has applications towards improving our knowledge of bone diseases such as osteoporosis. It may also help people living sedentary lifestyles, providing positive impacts to their health. The sedentary environment is somewhat similar to weightlessness. The take-home message: use your skeleton or lose it. The ability to work on advancing an area of biology that may help humans both in space and on the ground is truly its own reward.
I was inspired to enter this area of research from childhood experiences. I grew up in Florida and witnessed space shuttle launches in my front yard. This really captivated my attention towards space. As I got older, I learned about the skeleton and how it is a living structure that adapts to its mechanical environment. For example, joggers experience forces equivalent to about three times their body weight. Those two factors overlapped in my extracurricular readings on astronauts and the changes in their bodies during weightlessness. That connection propelled me to focus on science and engineering in my education, and further to study the skeleton. I am driven to continually learn new things, which prompted me to enter graduate school and become an independent researcher.
Although I do not have an immediate investigation going to the space station, I am applying for opportunities through NASA’s Space Biology Project. It’s an exciting time to be part of NASA’s research program. In the meantime, I continue to develop hypotheses worth studying aboard the space station and generating preliminary evidence while working in my lab on the ground. My goal is to eventually take my science into orbit or beyond.
The work cited in this PECASE Award was made possible by key funding organizations, including NASA Space Biology; grants to Globus from the National Space Biomedicine Research Institute; the U.S. Department of Energy and the NASA Space Radiation Project Element; and grants to Almeida from the NASA Bion-M1 Biospecimen Sharing Program and the National Institutes of Health / National Institute of Biomedical Imaging and Bioengineering.
Joshua S. Alwood, Ph.D., is a senior scientist with CSS-Dynamac working at the Bone and Signaling Lab at NASA’s Ames Research Center in Moffett Field, Calif. Alwood earned his Ph.D. in Aeronautics and Astronautics from Stanford University, as well B.S. degrees in Physics and Astronomy from the University of Florida.
In today’s A Lab Aloft, Dr. Larry DeLucas, a primary investigator for International Space Station studies on protein crystal growth in microgravity, explains the importance of such investigations and how they can lead to human health benefits.
We have many proteins in our body, but nobody knows just how many. Consider that the human genome project is more than 20,000 protein-coding genes, and many of these genes or portions of those genes combine with others to create new proteins. The human body could have anywhere from a half million to as many as two million proteins—we’re not sure. What we do know, is that these proteins control aspects of human health and understanding them is an important beginning step in developing and improving treatments for diseases and much more.
A protein crystal is a specific protein repeated over and over a hundred thousand times or more in a perfect lattice. Like a row of bricks on a wall, but in three dimensions. The more perfectly aligned that row of bricks or the protein in the crystal, the more we can learn of its nature. Today there are more than 50,000 proteins that have been crystallized and the structures of the three-dimensional proteins comprising these crystals have been determined. Unfortunately many important proteins that we would like to know the three-dimensional structures for have either resisted crystallization or have yielded crystals of such inferior quality that their structures cannot be determined.
Once we have a usable protein crystal—one that is large and perfect enough to examine—the primary technique we use to determine the protein molecular structures is x-ray crystallography. When we expose protein crystals to an x-ray beam, we get what’s called constructive interference. This is where the diffracted x-rays coming from the electrons around each atom and each protein come together, providing a more intense diffraction spot. We collect hundreds of thousands, sometimes millions of diffraction spots for a protein. The more perfectly ordered the individual protein molecules are within the crystals, the more intense these spots. The higher signal to noise ratio in these strong spots creates an improved resolution of the structure, allowing us to map the crystal in detail.
Using computers, we take those diffraction spots and mathematically determine the structure of where every atom is in the protein. For example, in most protein structures we can’t even see the hydrogen atoms. We guess where they are because we know the length of a hydrogen bond. So if we see a nitrogen atom from an amino acid that we know has a hydrogen linked to it, and then at a hydrogen-bonding distance away we see an oxygen atom, then we can make an educated guess that the hydrogen is pointed towards that oxygen atom, so we position it there.
While we can grow high-resolution crystals both in space and on the ground, those grown in space are often more perfectly formed. That’s the main advantage and reason we’ve gone to space for these studies. In many cases where we could not see hydrogen crystals on the ground, we then flew that protein crystal in space and let them grow in microgravity. Because of the resulting improved order of the molecules laying down in the crystal lattice, we were able to actually see the hydrogen atoms. Usually to see the hydrogen atoms, you are talking about getting down to a resolution of one angstrom, which is not easy to do—it would take 10 million angstroms to equal one millimeter!
We also can look at bacteria and virus protein structures to identify how to target those proteins with drugs. Having this information is very important to pharmaceutical companies and universities. That structure provides a road map that is critical for the understanding of the life cycle of the bacteria or virus.
We’ve only done a fraction of the more important complex protein structures–I’m referring to membrane proteins and protein-protein complexes. Protein complexes are often composed of two, three or more proteins that interact together to form new macromolecular complexes that are often important in terms of disease and drug development. Membrane proteins are the targets for about 55 percent of the drugs on the market today. Scientists have determined the three-dimensional structures for less than 300 membrane protein structures thus far. However, there remain thousands more for which the structures would help scientists understand their important roles in chronic and infectious diseases.
When we see a specific region in a protein and we know exactly where every atom is, chemists can design drugs that will interact in those regions. We can take some of the drugs they design that work, but maybe not as well as we would like. We then grow new crystals of the protein with the drug attached to the protein to see exactly how it’s bound to the protein. That lets other scientists—modelers—determine very clearly how the drug interacts with the protein, information that enables them to design new, more effective compounds. This whole process is called structure-based drug design.
The International Space Station provides a unique environment where we can improve the quality of protein crystals. During the days of protein crystallization studies on the space shuttle, one of the most frustrating aspects of the microgravity experiments was the length of time it took to produce a usable crystal. This is actually part of why space-developed crystals are better—they grow much more slowly. On the shuttle you only had 10-12 days for a study, but aboard the space station you have as long as you need.
As an astronaut and scientist, I personally flew a record 14-day flight in 1992 where we studied 31 proteins. I was looking at results and planning to set up new experiments, changing the chemical conditions to optimize the crystallization. The rule for my sample selection was that the proteins had to nucleate—that means to begin to grow a crystal—and grow to full size in three days. Once I got up there, however, by the third day nothing had nucleated. I was worried, but then on the fourth day I could see little sparkles where crystals had started to grow in about half of the proteins. By mission end I was really only able to optimize the crystal growth for six of the proteins. How much longer it takes a crystal to nucleate and grow to full size was a dramatic discovery.
With constant access to a microgravity lab, such as the space station, I am confident that we can improve the quality of any crystal. With protein crystals it is important to note that just because we get a better structure with higher resolution, it doesn’t at all mean it’s going to lead to a drug.
The ability to grow good crystals typically involves a great deal of preparation on the ground where we first express and purify and grow the initial crystals. But if space can give you higher resolution, there’s no drug discovery program that’s going to take a lower resolution option. From the time you determine that structure and chemists work with it, the typical time frame to develop a drug is 15 to 20 years and the cost is around a billion dollars. Identifying the structure of the protein crystal is only the first step. Many times even with the structure a project goes nowhere because the drugs they develop end up being unusable. There are so many aspects to drug discovery beyond the opening act of structure mapping.
If crystals and the structure of a target protein are available, pharmaceutical and biotech companies certainly prefer to use that structure to help guide the drug discovery. After the first 18 months they’ve developed the drug candidates, they may not need to use the crystal structure again for say 10 years. During that time they are doing clinical trials and pharmacology. The majority of the money it takes to get a drug approved by the FDA is after the initial phase. If you break down what they say is about a billion dollars to develop a drug, the portion needed to get the structure up front will range from half to two million dollars—a small fraction of the whole process.
For the upcoming Comprehensive Evaluation of Microgravity Protein Crystallization investigation we focused on two things. First, we selected proteins that are of high value based on their biology. Having this information of their structure can lead to new information about structural biology—how proteins work in our body. The other major requirement for the candidates for selection was that the proteins had to have already been crystallized on Earth, but the Earth-grown crystals were not of good quality.
We are flying 100 proteins to the space station on SpaceX-3, currently scheduled for March 2014. Twenty-two of these are membrane proteins, 12 are protein complexes, and the rest are aqueous proteins important for the biology we will learn from their structures. The associated disease was the last thing we considered, as we were looking at the bigger picture of the biology. That being said, for the upcoming proteins flying you can almost name a disease: cystic fibrosis, diabetes; several types of cancer, including colon and prostate; many antibacterial proteins; antifungals; etc. There are even some involved with understanding how cells produce energy, which I suspect could lead to a better understanding of molecular energy.
Not long ago a Nobel Prize was awarded for the mapping of the ribosomes complex protein structure. This key cellular structure will also fly for study aboard the space station, because the resolution was not all that great using the ground-grown crystals. We now have the chance to learn more about how the ribosomes actually makes proteins and clarify the whole process. This is just one of the exciting projects flying in relation to protein crystal growth.
This space station experimentation is a double blind study. This means that all the experiment chambers are bar coded for anonymity. We also will have exact controls done with the exact same batch of proteins prepared at the same time. The crystals will grow for the same length of time, as they are activated simultaneously in space and on the ground. When the samples come down, we will perform the entire analysis not knowing which are samples grown in space versus Earth. Only one engineer will have the key to the bar codes. When we’re completely done with the analysis, then he will let us know which were from space or ground. This will allow our study to provide definitive data on the value of space crystallization.
We also wanted to ensure that our analysis looked at a sufficient number of samples, statistically speaking, to provide conclusive data. How many data sets we collect per crystal sample will depend on the quality of that crystal. Statistically the study will be relevant in terms of how many proteins we fly, as well as how many crystals we evaluate from space and ground to make the comparison.
The microgravity environment is so beneficial because it allows the crystals to grow freely. Without the gravitational force obscuring the crystal molecules, as seen on Earth, the crystals can reveal their full form. We are giving all of these protein crystals the chance to grow to their full size in a quiescent environment. This is a very important investigation, not only because of the high number of proteins we are flying, but the statistical way we will evaluate them. Based on the results of the study, we will know if PCG in space is worth continuing.
Once the crystals come back to Earth, it will take at least one year to complete the full analysis. However, we will likely know that we’ve got some exciting results within the first three months. To publish something, it will be at least a year to complete the analysis, as we will have about 1,400 data sets to analyze. These results will determine the future of microgravity protein crystallization.
Larry DeLucas, O.D., Ph.D. is Director for the Center of Structural Biology and a professor at the University of Alabama at Birmingham. Dr. DeLucas flew as a payload specialist on the United States Microgravity Laboratory-1 flight, Mission STS-50, in June1992. His work is currently funded through NASA and the National Institutes of Health.