Our team began with NASA’s call for proposals for “in-space manufacturing” along with sustainable ways to deliver medical care to astronauts. From this official document, we gleaned two vital need areas central to space exploration’s future in the 21st century and beyond: limiting upmass (material needed to be taken with astronauts from the ground) and keeping humans healthy while beyond the scope of terrestrial care. Our team members started thinking: if we could find a way to manufacture pharmaceuticals as needed, rather than taking up all the possible medications, could this help solve two issues at once? Of course, we needed to determine the specific problems facing these niche users in microgravity, determine the feasibility of our preliminary designs, and explore other avenues where our idea could help humanity as a whole.

Three questions drove our design and testing process:

Why is this healthcare avenue worth pursuing, for NASA and other key stakeholders? What are the specific problems we are up against when designing a solution for space travel? Who can we help on Earth with our novel technology, and how do we design for these need groups?

As we explored these questions and talked to experts from government, academia, and private business, the trajectory of our work this summer shifted to include the insight gained and feedback received from our various investigations into the pressing problem of healthcare in space.

Solving Problems Off-World

Designing for long-term space travel presents many niche problems and logistical considerations that engineers rarely face on Earth. To understand what specific design constraints our health solution had to operate under, we reached out to astronauts and physicians who had personal experience in designing for the extreme environment of space.

Dr. David Loftus

Dr. Loftus is a medical officer and principal investigator of the Space Biosciences Research Branch at NASA Ames Research Center. His vast experience in developing technologies for astronaut health provided us a wealth of knowledge to build our project’s foundation upon. We were able to interview him regarding the current challenges in medicating on long-term space missions, and about his patent for the Biocapsule, an implant that would treat ailments without the astronauts moving a muscle. We realized that the largest issues with medications are the initial upmass, the storage-space limitations during a mission, and the short shelf-life of many vital drugs.

After reading the extensive list of medications that are currently required to stock the ISS for astronauts, we were at a loss for which compounds to focus our attention and time upon. Dr. Loftus guided us towards some potential options, specifically teriparatide and hG-CSF, two protein-based pharmaceuticals that are given in small doses and thus perfect drug candidates for our project’s scope.

At this point in time our team started leaning towards cellular systems, in which specific strains of bacteria with drug-specific plasmids could be designed to produce these essential but small, protein-based drugs.

Dr. Yvonne Cagle

Dr. Cagle, a former astronaut, and physician with decades of experience in human health and performance related to space travel, provided invaluable insight at multiple stages during our project.

First of all, what do the astronauts want in a medical kit? They are the primary user after all, and we had one sitting right in front of us. The team learned that medications taken are only needed in small amounts and are personalized to an astronaut. So to be able to create pharmaceuticals as needed, would eliminate complexity and potential redundancy as well as provide even more of a safety-net for humans millions of miles from home, as they wouldn't have to rely on only the medication they were predetermined to require. Interestingly, we learned that for some astronauts, it has been observed that their drug tolerance increases in space, necessitating high doses than on earth; this fact led to our later calculations of the expression chamber/ microfluidic purification device sizes and tx/tl component volumes to ensure suitable amounts for use.

She described how seemingly simple tasks can become unsolvable problems under conditions of microgravity, thus exposing specifications previously unconsidered by our team. For example, we needed to make sure our synthesis system and the microfluidic device would be able to easily operate under weightless conditions and compatible with the bulky gloves of spacesuits in a low gravity environment, which are two different working environments entirely. This insight contributed to the redesign of our microfluidic device to eliminate valves and to combine the cell-free components in the expression chamber rather than as a separate step. She also stressed to us the importance of designing our device to survive the stress and vibrations of takeoff, as the experience can be quite violent for equipment, which we managed through lyophilizing materials and creating a compact, hardy microfluidic setup.

Dr. Cagle was also interested in the terrestrial applications of our idea, suggesting that we could integrate our plan with drone technology, as a way to distribute the Astropharamcy to rural areas or those operating in isolated theaters. This ignited our imaginations with the different ways we could implement our technology on Earth, and ultimately led us to focus on Insulin synthesis as a central part of our project. We were lucky to have her on Ames campus to check in and give us encouragement throughout the iGEM season!

The Astropharmacy team meets with and recieves advising from Dr. Yvonne Cagle.

Rusty Schweickart

As a team we wanted to run our preliminary designs and ideas by other astronauts, our primary users and those with the most specialized needs when it came to administering pharmaceuticals. We reached out to Rusty Schweickart, a member of NASA’s 3rd astronaut group, and flew on the Apollo 9 mission. On top of that, his extensive experience as an aeronautical and astronautical engineer in the following decades (both with NASA and in the private sector) was a great resource off-which to bounce out initial project plans.

He encouraged our team that our product had the possibility to be of great use in space and on Earth. Schweickart agreed with others we had previously communicated with that radiation is going to be one of the primary concerns for long term crewed space missions (which is why teriparatide was such an important drug for us to produce). He recounted to the team that astronauts on the Apollo missions took drugs at will (after advising Mission Control); the Astropharmacy fits into this existing standard of care quite well.

Summer Series at Ames

In order to gain insight about the larger mission of our scientific community, our team attended weekly seminar series at our home base of NASA Ames Research Center. One of the most insightful and impactful to our project was Jim Green, NASA Chief Scientist who gave a wonderful lecture on the "Future of Lunar Exploration". In relation to the newly announced Artemis Program to see humans return to the moon, he expressed the need to have better, more sustainable methods of healthcare, for the moon and beyond. The team was excited to know that the Astropharmacy was going to solving a salient problem for the administration and the future of humanity.

Jim Green gives a lecture at Ames Research Center.

Building the Astropharmacy

Once we had decided upon a dual cellular, and cell-free approach and had settled on using microfluidic devices for purification, we needed experts to help facilitate the design and fabrication of the systems. Below are the main collaborators and advisors we sought to help design and implement our ideas in line with the best current academic and industrial practices.

Dr. Kate Adamala

Using cell-free (also seen written as tx/tl in literature) systems is a cutting-edge method to quickly produce proteins, however, they can be difficult to implement for those unfamiliar with the practice. As soon as the team knew that this method was central in the preliminary plan for Astropharmacy, we reached out to an expert in the field who could help us optimize a system for our purposes. Dr. Kate Adamala is a professor of Genetics, Cell Biology, and Development at the University of Minnesota (check out her website here!). Her expertise lies with synthetic cells, cell-free protein expression, and engineering genetic pathways: exactly the knowledge the team needed.

At the beginning of the summer, Dr. Admala video conferenced the team a few times to discuss the basic procedures and theory of cell-free protein expression. After it was determined the method would be outstanding to achieve our needs of low up-mass (even no bacterial cells needed) and quick pharmaceutical production (the actual reaction can be conducted in as little as four hours), a visit to the Rothschild lab was planned. She was absolutely instrumental in providing guidance on laboratory procedures (from contamination policy to sonication specifications) once on site, helping to get our experiments up and running in order to run various iterations throughout the summer. For the rest of the iGEM season, the team has relied on her expertise to help troubleshoot problems as they arose in the cell-free process and consulted her on how best to lyophilize the procedure components for space travel.

Dr. Admala (top right) visits the lab to provide feedback and troubleshoot experiment design.

The Fordyce Lab

The fabrication of PDMS microfluidic devices requires facilities beyond the scope of Ames, thus our team reached out to Dr. Polly Fordyce at Stanford University. Her lab primarily focuses on "developing and applying new microfluidic platforms for quantitative, high-throughput biophysics and biochemistry” as stated by their wonderful website (take a look yourself!).

Dr. Fordyce and her lab not only graciously trained and allowed our microfluidic team to use the cleanroom facilities needed for our microfluidic purification devices but also provided feedback on our designs at all stages of the fabrication. Our original design involved valves, but members of the lab we spoke to suggested to remove that particular aspect of the design in order to increase ease of use and efficacy in low/zero gravity situations. This change resulted in the microfluidics team coming up with the current iteration of the purification chips, in which there are two daisy-chained together, one His-tag purification size-exclusion and the other size-exclusion chamber. This design used two filtration elements because to be of U.S. industry-standard pharmaceutical purification, which would mean it would be suitable to use on planet and off, our system needed to achieve a 98% protein purity (as learned in our meeting with Dr. Murphy from Merck). After learning the PDMS fabrication process via shadowing and sitting in on weekly lab meetings our microfluidics team was able to independently create a device. We were also able to take the information learned from this experience and make design recommendations to other teams working on microfluidic device projects.

The Astropharmacy team and advisor Patrick fabricate microfluidic chips in the Fordyce clean room.

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Seeking Broader Impact

As we solidified our cellular and cell-free system designs, we reached out to government, industry, and medical professionals to understand the process of bringing a product to market in the U.S., how the private and government space exploration spheres work together, and how to show the Astropharmacy can have a far-reaching impact for populations around the globe.

Open Insulin

While there is no intention of sending a diabetic to another planet anytime soon, 387 million people around the world currently live with diabetes. Insulin, which is a life-saving product out of reach of millions of people who desperately need it, therefore serves as a perfect proof-of-concept drug to show how our system could impact a large population of people on Earth. Lucky for us, in the Bay Area there was a team of people whose goals align with the Astropharmacy! Open Insulin is a team of biohackers based in Oakland, California working towards the goal of making insulin freely available to whoever needs the product. Our teams discussed the problems diabetes encounter with acquiring affordable and we realized the vast scope of potential social and financial benefits the Astropharmacy could have if implemented on Earth. Mutual technical obstacles were explored, such as the relative complexity of the compound and the post-translational modifications required to create insulin. We realized that we could not create the drug in an E.coli based cell-free system, and made plans to manufacture a S. cerevisiae cell lysate.

Video conference with members of Open Insulin.

Dr. Grant Murphy, Merck

As we want to use the compounds produced via our system on human patients and astronauts, our team needed to determine the current requirements for bringing pharmaceuticals to market. We reached out to Dr. Grant Murphy from Merck, currently working as Associate Principal Scientist, leading teams to develop new protein engineering technologies and design enzymes to synthesize active pharmaceutical agents. Merck is an American multinational pharmaceutical company headquartered in New Jersey, one of the largest in the world.

We realized that there was a specific threshold of drug purity levels for use in US markets, which is 98% with no other compound composing more than 0.5% of the total pharmaceutical product. This was vital in having a bar at which to judge the performance of our microfluidic purification devices. We also discussed the potential to use our system to produce orphan drugs (those that are underdeveloped due to limited financial gain potential), to which he agreed was a potential user base. Murphy turned our team on to the idea of looking into the military applications of our system, specifically for submariners who have to spend long periods of time away from commercial medical care. The conversation illuminated that the Astropharmacy has far-reaching implications for niche, underserved users on Earth, as long as we could ensure our proteins would be of adequate pharmaceutical grade.

Team members video conference with Dr. Murphy.

Oliver Morton

One of the first experts we reached out to was Oliver Morton, British writer and the current briefings editor of the Economist who was previously and editor for Nature. With a preliminary draft of our project trajectory and a collection of rough ideas about how to pursue the problem of producing medication for astronauts, we came to him to for guidance on how to present the information effectively and future areas of investigative exploration. As an expert well-steeped in the scientific community, he pointed us how best to frame our ideas to not only tell a compelling story to others but expand our notions of the applications of our product. From this point on we began looking at ways to implement our Astropharmacy in a more terrestrial manner, always thinking about how we could help humanity on and off-planet. After the conversation with Morton, we realized that keeping the “why” of our work central to our actions was essential to the eventual success and usefulness of our project to the world.

The Astropharmacy meets with Oliver Morton.

Jim Bridenstine and Steve Jurczyk

As we are seeking to send our device into space, we needed to share our vision of astronaut health with the individuals capable of helping us realize this goal. Thus we reached out to several NASA administrators to present our plan and gain valuable feedback on how the Astropharmacy fits with the agency’s plan for the future of crewed space travel.

One sunny Silicon Valley day, the Administrator of NASA, Jim Bridenstine, stopped by Ames Research Center to share his vision for the future of human space exploration, with NASA leading the way. During his tenure in Congress, he served on the Committee on Science, Space and Technology, before he was appointed to lead the future exploration into the solar system. Later in the summer, the team also met with Steve Jurczyk, NASA’s Associate Administrator, which is the highest-ranking civil servant position in the Agency. He has over 30 years of experience in NASA working as an engineer and administrator. Before becoming Associate Administrator he helmed the Space Technology Mission Directorate, which focused on partnering with industry and academia to develop new, game-changing technologies for human space exploration, which is exactly the type of novel device we believe the Astropharmacy can become. He brought with him our invaluable Center Director Dr. Eugene Tu, Associate Center Director for Research and Technology Dr. David Korsmeyer, and Ames Chief technologist Dr. Harry Partridge.

Not only were we able to share our ideas with these men, but also ask how best the Astropharmacy could solve current issues facing human space travel and assist the agency’s mission. After these meetings, the team tweaked the presentation of our ideas and the presentation of the device itself to reflect a clean aesthetic and focus on the storied history of NASA’s accomplishments, situating the Astropharmcy as part of the next giant leap for the agency.

The team meets with Jim Bridenstine.

Steve Jurczyk listens to the Astropharmacy team and tours the lab. Joining him were Ames Center Director Dr. Eugene Tu, Ames Associate Center Director for Research and Technology, Dr. David Korsmeyer, and Ames Chief Technologist, Dr. Harry Partridge.

S. Pete Worden

While we highly value the opinions from those within the NASA community we also sought advice from those working with the private sector, as the future of space travel lies with the partnership between corporate entities and government experience.

To better understand the landscape of private spaceflight innovation, we spoke to Pete Worden, Executive Director of Breakthrough Initiatives, a program to search for extraterrestrial life, and former director of Ames Research Center. After presenting our vision for the Astropharmacy, he gave us feedback on how best to market the idea to potential investors. Due to his nearly 30 years of service in the Air Force, we also naturally inquired about military and other global applications of our device, to which the potential of rural use of the Astropharmacy was discussed. The team was also treated to a presentation of Breakthrough Initiatives, and how the private sphere operates in terms of research, funding, and entrepreneurial opportunities.

The team meets with Pete Worden.

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Introduction to Integrated Human Practices