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#SpaceWatchGL Summer Reading: The Wonders of Micro-G Medicine 1

by Christophe Bosquillon

The Boiling Experiment Facility, operated in the Microgravity Science Glovebox on the International Space Station. Credit: NASA

Part 1: 50 years of quest

A cat’s whisker

Back in the 70’s, the Japanese space agency JAXA ran an experiment called the Japanese Cat’s Whisker Experiment. It took place aboard Skylab between May 1973 and February 1974, the same year Pink Floyd released The Dark Side of the Moon. Contrary to what you might think, it did not involve cats.

A cat’s whisker can be dipped into a protein solution and drawn through it: the whisker will leave protein crystals in its trail, a technique called “micro-seeding“. Japan dedicated its first on-orbit experiment to something somehow unorthodox. The experiment’s goal was to disperse fine crystals of silicon carbide in molten silver. Japanese researchers were curious about growing metal alloys in microgravity, that is, as per NASA’s definition, “the condition in which people or objects appear to be weightless. The effects of microgravity can be seen when astronauts and objects float in space”. They wanted to understand if low gravity conditions could influence how semiconductor materials grow, maybe resulting in larger size crystals of higher and more uniform quality, in particular more uniform electrical characteristics that were linked to improving overall performance.

Micro-G preparations are highly homogeneous and quite suitable as a drug delivery system.

Metal alloys such as gold and germanium produced under Earth’s gravity will always exhibit a rather rough pattern of dispersal and separation. However, the JAXA team thought that low gravity could help to grow a more uniformed, and thus higher, metal quality. The experiment, deemed successful, was noted by the global semiconductor industry. But for lack of orbital factories, it remained just that, an experiment. Yet, a Cat’s Whisker had just opened a door to a large avenue of discoveries that would go on for a half-century to this day.

Indeed, these properties of metal growth can be applied to liquid and gaseous components as well, and they affect the physical and (bio-)chemical behaviour of materials coming into play. Innovators and early adopters contemplated the commercial prospects of more effective solutions to specific problems, from semiconductor and industrial components supplies, to drug manufacturing and delivery systems, and vaccines. But also, specific life science issues, such as human body parts replacement. But what is the science behind micro-gravity (micro-G)? What is the relevance of a microgravity environment? What are the technologies involved? How to deal with industrial and logistics constraints in orbit? Is the business case credible and is it financially sustainable? What does it mean for the pharmaceutical markets intersecting with the space business ecosystem? How will that be affected by the transition from the ISS to commercial space stations by 2030? Perhaps more questions than answers. But let’s try to answer some of them, starting from the beginning.

The scientific foundation of micro-G research

Micro-G primarily boils down to four characteristics of the laws of physics. First, in micro-G liquids don’t need a container, because, with no gravity to force liquids to the bottom of a container, they cling to its surfaces instead. It’s quite convenient to be able to study liquid molecules that do not need a container to remain in place, and won’t be contaminated by this container material when being produced. It’s called “container-less float” and you can find some examples of it here (Canadian Space Agency: Wringing out Water on the ISS) and here (Tiangong Class: Taikonauts show kids effervescent tablet experiment in zero-gravity setting, using a water ball).

Second, in a micro-G liquid bubble the liquid at the bottom isn’t being compressed by the liquid at the top, for the liquid at the top is weightless: that’s rather convenient too and is called “absence of hydrostatic pressure“.

There is a need to do more to take advantage of these micro-G essential qualities, such as controlling sedimentation, temperature, and diffusion of particles.

Third, when you heat some liquid or gaseous material on Earth, it will become lesser in density, which means the weight it measures within a reference volume will become lighter, something called “convection“. But in micro-G, there is no weight, therefore no “convection“.

And fourth, the most evident and crucial aspect, in micro-G there is no such thing as “buoyancy”. You won’t see the heaviest particles race to the bottom to deposit themselves in a process called “sedimentation“, while lighter particles will keep floating, or will fall too, but much more slowly. In micro-G, bubbles of heavy glycerine or mercury would disperse as evenly as bubbles of water and even of much lighter oil.

First Experiments

It didn’t escape the intuition and attention of pioneering scientists that micro-G material manufacturing could directly affect the study, understanding, design, synthesis, and potential production of any natural or synthetic structure, whether solid, liquid, or gas. This explains why micro-G scientific research dates back to the start of the Space Age itself, with closer-to-Earth micro-G experiments in the 1950s and 1960s, using free-fall facilities, planes, small rockets, and free-flyers. But during the half-century that has elapsed since the early 1970s, micro-G took off thanks to the Space Shuttles missions. As a matter of fact, the Space Shuttle program conducted micro-G experiments way before the International Space Station (ISS) became operational in 2000.

The Shuttle Columbia’s STS-9 mission, which launched in November 1983, was the first to conduct experiments under micro-G in a reusable laboratory and ISS precursor called Spacelab. Spacelab, managed by NASA Marshall, was built by ESA in exchange for flying experiments and European astronauts in space, as well as Japanese and German space agency-supported research missions. STS-9 astronauts cultivated the first protein crystals ever grown in space. In a fashion that mirrored what had been observed a decade earlier on Skylab with the Japanese Cat’s Whisker Experiment, it was also found that protein crystals grown in space are larger, more neatly ordered, and easier to subject to X-ray structural analysis than those grown on Earth. This enhanced prospects to understand how certain proteins work, leading to better-targeted life science applications such as drugs or bio-components and human body parts.

Micro-G experiments continued during the lifespan of the Space Shuttle program and got embarked on the ISS at inception in 2000. STS-107, the Shuttle Columbia mission that met a tragic fate in February 2003, was carrying a micro-G micro-encapsulation experiment that survived the shuttle break-up on re-entry, burning, and crash. But for all these early innovators’ breakthroughs, and astronauts’ sacrifices over 3 decades from the early 70s to the early 00s, terrestrial market applications of micro-G were still being met with scepticism from the industrial and pharmaceutical establishment.

Micro-G pharmaceutical and life science breakthroughs in the 2020s

Fast forward twenty years, and there is recognition of the relevance of micro-G for pharmaceutical and life science use cases. Getting buy-in and traction from pharmaceutical majors does matter: as highlighted lately during the Financial Times Investing in Space Summit (on which SWGL reported here), an American major such as Merck Research Labs has emerged as a leader in the pharmaceutical industry’s use of space. As detailed by Paul Reichert, Associate Principal Scientist at Merck Research Labs, a promising research goal is the synthesis of new “crystalline suspension” using micro-G. The market it addresses is drug delivery systems at the doctor’s office, a new system that competes with IVs. The idea of a crystalline-suspension-based drug delivery system in itself isn’t at all new: it’s an engineering problem linked to the manufacturing of drugs. When an industrial drug is poorly soluble, it’s not going to disseminate itself in optimal ways through a human organism: this is what is called an issue of “bioavailability”.

Does it make industrial, logistical, and financial sense to send something to be researched and potentially produced on an orbital space station?

It turns out that “nanocrystalization” for nano-crystalline suspension of drugs is an emerging technology that enhances bioavailability. There is a large array of manufacturing technologies to produce nano-crystalline suspensions that have been studied and compared under terrestrial gravity, for their properties and stabilization mechanisms. Yet, according to Merck and others, this is where terrestrial nano-crystalline suspension specifications fall short, compared with similar experiments under micro-G. They fall short because different physical conditions between a micro-G and a terrestrial environment conduce to different physical properties: comparable terrestrial experiments produced crystals with heterogeneous repartition, and that is unsuitable for use in a patient organism, whereas micro-G preparations are highly homogeneous and quite suitable as a drug delivery system.

Could production in space under micro-G be viable?

As Paul Reichert observed, there is a need to do more to take advantage of these micro-G essential qualities, such as controlling sedimentation, temperature, and diffusion of particles. The above use case is one example of potential applications of micro-G to medicine, as one of the steps across the design and manufacturing process of a therapeutic solution. There are others, such as the development of a modified bioreactor to enhance organ models, or “Organ-on-Chip” (OOC) technology, or protein and body parts manufacturing, or again bone density loss linked to aging. And while the above use case appears to make scientific and marketing sense, does it make industrial, logistical, and financial sense to send something to be researched and potentially produced on an orbital space station?

As soon as you start producing something in Earth orbit that serves terrestrial markets, you’ll have some back-and-forth space transportation that comes at a cost. That includes not only that substance, crystal, or component involved, but also its conditioning device, plus the hardware and humans to make it happen. When the cost of space transportation is several thousand times what it costs on Earth, economic constraints kick in: you can’t afford to send your lab equipment in space, so you need to miniaturize the experiment down to, say, a large shoe box. You can’t afford to send humans either, so you need to make the experimental device automatic and autonomous, requiring minimum supervision from the space station residents. Finally, your material, product, or the content of your experiment, whether it’s for an electronic application, creating a special alloy, or any pharmaceutical or medical use case, must weigh significantly below the kilogram range.

It’s all about the relationship between the cost and the value of involving space in a step of your process. Tons of vaccines or critical infrastructure material in space: no. A small and light component that provides rather high value to an end-product: yes. And in the pharmaceutical field, you have several applications involving nanograms to grams of material that fit this profile and that you can send back to Earth via ISS routine transportation: crystals for drugs, protein manufacturing, organ-on-chips, but also oncology (cancer), and Medicine 2.0 in micro-G. But to be able to continue to do so, considering the ISS will be decommissioned in 2030, you need such experiments to make commercial and economic sense as part of a deal with new private space stations owners and operators, something we review in Part 2.

Christophe Bosquillon. Credit of the author themselves.

Christophe Bosquillon has a diverse professional background, having operated globally with a focus on the Indo-Pacific region. His experiences in Japan, the Koreas, Taiwan, China, ASEAN, India, Russia, and Australia have given him a deep understanding of the multipolar realpolitik of our world under the Pax Americana. With a background in engineering, trade, and foreign direct investment in industries relevant to Space Resource Utilization (SRU), such as mining, transportation, energy, manufacturing, agrifood, environment, and digitalization, Chris is committed to developing SRU value chains that benefit the Earth. As an executive, owner, writer, and founder of Autonomous Space Futures Ltd, Chris has extensive experience in collaborative policy crafting and works to develop space business and governance models relevant to society. He is a member of NGOs that provide input to the United Nations Committee on the Peaceful Uses of Outer Space (UNCOPUOS) legal subcommittee Working Group on Space Resources. Chris contributes to regulatory clarity on appropriation, priority, sustainability, and sharing in a way that balances national interests with civil society inclusion, provided a transparent due process is followed. When advocating for access to technology and space for the Global South, Chris believes that emerging space powers’ participation in space markets must be commensurate with their interest and involvement in international space politics. He believes that their ability to develop sovereign domestic capabilities with spillover potential is also essential. Chris is keen on ‘Peace Through Strength’ diplomacy and deterrence-based security as enablers of secure space access. He supports sovereign cislunar space situational awareness as mandatory for freedom of circulation in the space domain and deconflicted cooperation on the Moon.

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