One small cell for a man
If you asked the 6-year-old me who she wants to be when she grows up, with no little sense of conviction she would reply she is becoming an astronaut. I can only hope being a biologist was somewhere close to the top of the list, as she could otherwise be a little bit disappointed, she ended up working in a lab and not on orbit. Perhaps she would argue that feeling violently nauseous after a spin on a playground carousel is not enough evidence she would be a terrible astronaut.
Despite the deep-rooted conviction that we are a generation born too late to explore the world, and too early to explore the galaxy, space research is a blooming area of science. Apart from studying rocket propulsion, black holes, and other things we traditionally associate with venturing into outer space, researchers also examine how our bodies react to spaceflight. Bioastronautics, as it is sometimes called, is an area of research concerned with biological effects of microgravity and cosmic radiation on living organisms.
And so it was shown, for example, that astronauts who feel fine on rollercoasters on Earth could get space sickness whilst living on a space station, while on the other hand, there is no certainty that people who normally suffer from motion sickness will experience it in zero-gravity. Fellow space enthusiasts with innate fear of playground carousels – rejoice! Not all hope is lost! That is, of course, if you are not too concerned about the deterioration of your musculoskeletal system, balance disorders, onset of anaemia, shifts of body fluids, disruption of sleep cycle, and more, that come with working in outer space.
Researchers in laboratories both on Earth and on orbit work tirelessly to elucidate the causes behind these spaceflight-associated conditions. The myriad of investigations is imperative for ensuring the safety of future space exploration. More importantly for now, their applications can be remarkably beneficial also on Earth. Examinations of retinal lesions, common in astronauts, might help people struggling with glaucoma or age-related vision issues. Similarly, the phenomenon of bone decalcification during spaceflight has many parallels with osteoporosis in terrestrial patients.
The microgravity environment also allows us to design new disease models, that are otherwise impossible to recreate on Earth. For instance, endothelial cells cultured in space are being tested as models for verifying the effectiveness of vascular drugs, as preliminary data suggests they share more features with human blood vessels than their lab counterparts grown in normal gravity1. If testing drugs in outer space does not sound futuristic enough for you, astronauts are now participating in the development of new drugs as well.
The latter has been made possible by a novel method of crystallising proteins in space, which is now estimated to be the single most common type of experiment performed on the International Space Station (ISS). Proteins are the molecular players and communicators of the natural world, and the human body alone needs a mind-boggling range of 100 000 different ones to ensure its proper functioning. When we fall ill, proteins become the targets of medical intervention; a drug which binds to a specific protein can alter its function and bring us back to health.
But how is specificity achieved? How can we ensure a drug knows which one of these 100 000 proteins it should stick to? This dilemma has always constituted as one of the biggest challenges in drug development, as creating highly-specific molecules results in greater efficacy of treatment and fewer side effects. However, to ensure a snug fit we first need to properly understand the structure of the protein we are trying to target.
Here come the protein crystals. One of the best ways to study the structure of a given protein is to grow it in crystalline form, which comprises of producing millions of copies of the protein of interest and arranging them in a three-dimensional shape. Intriguingly, it was found that when it comes to protein crystallisation, space environment of microgravity surpasses conditions found on Earth. With no convection, that is, no movement of warmer and cooler masses of air, the crystals can grow slower and achieve much higher quality.
This is how the orbiting ISS became a mobile laboratory for growing crystals (sounds oddly familiar to all “Breaking Bad” fans), which can then be transported back to Earth for X-ray structural analysis. This rather exotic approach has allowed researchers to find a new way to inhibit hematopoietic prostaglandin D synthase, a protein involved in the degradation of muscles in Duchenne muscular dystrophy (DMD) patients. A compound they have designed is now in phase 3 of clinical trials, with a potential to double the lifespan of people suffering from DMD2,3. These studies have also resulted in the creation of artificial albumin, which is the most abundant protein in blood4.
Protein crystallisation is just one of many exciting avenues of biomedical research that is carried out on orbit. The equipment available on the ISS allows for performing an impressive range of molecular biology methods, including routine DNA sequencing, or even CRISPR, the current golden standard of gene editing. Astronauts have studied muscle loss in mice5, chromosomal abnormalities in fruit flies6, or the formation of amyloid fibres during Alzheimer’s disease7, all aboard a satellite that makes 16 orbits around Earth in a day. One of the most captivating space investigations was that of NASA Twins Study, which examined cell behaviour and gene expression in identical twin astronauts, one working on the ISS, and one remaining on Earth8. For instance, it showed that telomeres, the protective ends of our chromosomes which shorten during aging, actually lengthened during spaceflight.
One thing is for sure – the field of bioastronautics is swiftly growing in importance, and will only continue to do so, as our human nature pushes us to explore the worlds beyond Earth’s orbit. Although nowadays intergalactic travel and zero-gravity laboratories sound more like work of science fiction, achievements of space research have an exquisite effect of taking away the “fiction”, and emphasising the “science”.
References
- Cazzaniga, A., Moscheni, C., Maier, J. A. M. & Castiglioni, S. Culture of human cells in experimental units for spaceflight impacts on their behavior. https://doi.org/10.1177/1535370216684039 242, 1072–1078 (2016).
- Taiho Pharmaceutical Co. Ltd. A Phase 3 Study of TAS-205 in Patients With Duchenne Muscular Dystrophy（REACH-DMD). ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT04587908 (2020).
- Komaki, H. et al. Early phase 2 trial of TAS-205 in patients with Duchenne muscular dystrophy. Ann Clin Transl Neurol 7, 181–190 (2020).
- Haruki, R. et al. Safety Evaluation of Hemoglobin-Albumin Cluster ‘HemoAct’ as a Red Blood Cell Substitute. Sci Rep 5, (2015).
- Lee, S. J. et al. Targeting myostatin/activin A protects against skeletal muscle and bone loss during spaceflight. Proc Natl Acad Sci U S A 117, 23942–23951 (2020).
- Ogneva, I. V., Belyakin, S. N. & Sarantseva, S. V. The Development Of Drosophila Melanogaster under Different Duration Space Flight and Subsequent Adaptation to Earth Gravity. PLoS One 11, e0166885 (2016).
- McMackin, P., Adam, J., Griffin, S. & Hirsa, A. Amyloidogenesis via interfacial shear in a containerless biochemical reactor aboard the International Space Station. npj Microgravity 2022 8:1 8, 1–8 (2022).
- Garrett-Bakelman, F. E. et al. The NASA Twins Study: A multidimensional analysis of a year-long human spaceflight. Science 364, (2019).
Having completed her undergraduate degree in Biomedical Sciences at the University of Manchester, Aleksandra Pluta is now pursuing a PhD in Molecular Biology at the University of Oxford. Currently in her third year, she is trying to elucidate the role of CDK1 in transcription in cancer cells, working under the supervision of Prof Shona Murphy and Prof Chris Norbury. She loves art – for the ability to create things that did not exist before, dance – for the joy and energy it gives her, and scuba diving – for its sense of weightlessness and wonder of discovery.