Toads, fish and nematode worms: the space station's strange menagerie

These are known as "model organisms": flies, mice, zebrafish, frogs or nematode worms are all animals used by researchers for experiments, not least because their biological organization is simpler than that of humans.

Simon Galas, University of Montpellier

An aquarium to house Medaka fish on the space station - Nasa

This is crucial for basic biology and human health studies, and it can be done on Earth but also in space. Witness the very recent NASA "Worm in space" mission, launched in December 2018, which sent 360,000 Caenorhabditis elegans roundworms into space!

Animal experimentation in space is nothing new. A survey of NASA missions from 1965 to 2011 reveals no fewer than 382 experiments carried out on various platforms: the Gemini capsule, biological experiment satellites, NASA shuttles, the NASA/MIR platform and, more recently, the International Space Station ISS, in low-Earth orbit since the 2000s.

The aim is to better understand the effects of the space environment on living systems, and on humans in particular. Astronauts undergo progressive physiological changes that become more pronounced as their stay in space progresses. These can result in an increased risk of a number of pathologies, including fractures, visual impairment, intracranial pressure, anemia, muscular atrophy, acute radiation syndrome and alteration of the immune system. The use of model organisms subjected to the same stresses as astronauts helps prevent the emergence of these problems.

Four astronauts in the space station.
NASA

Model organisms were also used very early on in space missions to define the fundamental behaviours of living organisms. One example: how can the Earth's gravitational force influence living organisms and their development from fertilization onwards? Answering this question required numerous model organisms (plants, insects, fish, amphibians, small mammals) and no fewer than fifty experiments carried out in space.

A fertile toad

As early as 1965, frog eggs and fruit fly larvae(Drosophilamelanogaster) taken on board the Gemini mission showed normal development in the absence of gravity. Embryonic development was also tested in space in a famous experiment in 1992 (frog embryology experiment, Space Shuttle Spacelab Japan mission STS47) using a toad called Xenopuslaevis, which showed that terrestrial gravity was not required for ovulation, fertilization, embryonic development or the formation of tadpoles capable of swimming.

Rat cage for space experiments.
NASA

Experiments on other models have demonstrated that the most important processes of reproduction and development are independent of the degree of gravitational force. One such experiment, carried out in 1979 during the Russian Cosmos 1129 mission, demonstrated the ability of pregnant rats to achieve normal pregnancies. However, subsequent experiments on very young rats revealed sensory-motor deficits and demonstrated reductions in motor neuron growth, indicating the existence of a period of gravitational force sensitivity in the sensory-motor system during post-embryonic development.

Very important experiments have also been carried out in the fields of microbiology and infectiology. When you consider the growing importance of our microbiome, which weighs in at around 2 kg, it's easy to feel concerned by the possible changes that could befall our microbial commensals in space!

Virulence in space

In 2006 and 2007, bacteria such as Salmonella enterica typhimurium (infectious agent of salmonellosis), Pseudomonas aeruginosa (nosocomial infections), Candida albicans (fungus responsible for candidiasis) and Streptococcus pneumoniae (responsible for pneumonia) sent into space revealed the appearance of virulence that control cultures on Earth had not developed. Analysis of these bacteria revealed that they owed the appearance of their virulence in space to a single gene (Hfq), demonstrating the immediate interest of this discovery not only in preparing astronauts for their voyage, but also in gaining a better understanding of these infectious bacterial agents, which are increasingly resistant to treatment and responsible for many deaths on Earth every year.

Salmonella. A stay in space makes it more dangerous.
Wikipedia

Another important subject is the rapid evolution of astronauts' muscles in space under the effect of microgravity. Experiments to evaluate the muscular evolution of rats in space were carried out as early as 1965 by NASA. These experiments demonstrated a rapid decrease in muscular contraction force, an increase in muscular contraction speed (velocity), a decrease in resistance with an increase in muscular fatigue and a shortening of muscle fiber length. The latter phenomenon has been associated in both rats and humans with the fetal posture adopted in space, leading to slow muscle atrophy.

The changes in muscular physiology observed in rats during spaceflight have been verified in humans, and have led to the definition of a series of exercises (walking and jogging on a treadmill) that astronauts are required to perform every day for 2.5 hours, in order to slow down the changes that affect muscles, sometimes very rapidly, at the start of a space stay.

The list below gives examples of observations made on model organisms during space missions in relation to human health:

  • Chicken, gecko, quail, mouse, rat for observations on bone physiology in space;
  • Vinegar fly (Drosophila), human cells in culture, mouse, rat for observations on immune system reactions to microgravity;
  • Bacteria, fungi, human cells in culture, yeast for observations on microbial growth and virulence;
  • Chicken, mouse, nematode, rat for observations on muscle physiology in space.
  • Cricket, fish, quail, mouse, newt, rat, toad, snail for observations on neurophysiology.

"Worm in space

Worm in space.
NASA

This month's December 2018 "Worm in space" mission sheds light on the nematode Caenorhabditis elegans. This round, non-parasitic, one-millimeter-long worm can be found on most continents and feeds on bacteria in decaying fungi, plants or fruit.

No less than three major discoveries of modern biology have already been made thanks to its meticulous observation, notably the mechanisms of apoptosis (programmed cell death), and the occurrence of cancers following anomalies in this process. Nematodes are a model of choice for studying the functioning of the apoptosis process in space, in order to prevent the risk of cancerous pathologies for astronomers. They are associated, on the one hand, with exposure to the dangerous radiation of space and, on the other, with possible modifications to the normal functioning of apoptosis, responsible for eliminating cells modified by radiation.

This is not the first time this little worm has flown into space. During mission STS-42, carried out in 1992 on the shuttle Discovery, the nematodes managed to mate and reproduce over two generations without any apparent problems. But a few years later, mission STS-76 aboard Atlantis in 1996 revealed something quite different! An abnormal rate of mutations was observed in the nematodes, indicating for the first time a direct effect of cosmic rays on living organisms.

Worms survive Columbia disaster

Following these experiments, it was proposed that nematodes could be used in space as dosimeters to inform astronauts about the risks of mutations linked to cosmic rays. Nematodes were also on board the shuttle Columbia on February1, 2003 for mission STS-107. A tragic accident during the mission resulted in an explosion that vaporized the spacecraft and killed all seven occupants. However, scientists were able to recover a 4 kg case containing the scientific expedition's nematodes from Columbia's debris in Texas. They had survived. Protected in their box, they had already reproduced over several generations.

Back to the "Worm in space" mission. On Monday December 3, the Soyuz MS-11 capsule arrived at the International Space Station with three astronauts and nearly 360,000 Caenorhabditis elegans nematodes on board. This experiment is dedicated to studying the 40% muscle loss that affects astronauts on long missions. This deficit is comparable to the muscle loss that can be observed in a man aged between 40 and 80 during a natural process known as sarcopenia.

Nematode muscles

Installed in special bags with their artificial food, the nematodes will remain there for six and a half days, after which they will be frozen and returned to Earth for analysis in 2019. Several experiments will be carried out. One involves studying a control group of normal nematodes against another group of nematodes in which genes important for the normal functioning of insulin have been modified. This hormone is known to be linked to the mechanisms of senescence and ageing via its effect on glucose utilization by tissues, particularly muscles. The use of genetically modified Caenorhabditis elegans with variations in glucose utilization will help to better define the involvement of insulin in the process of sarcopenia. This study is intended to provide a better understanding of why human muscles weaken as we age, in relation to the role of insulin.

The C. elegans model worm ([Goldstein Lab](http://labs.bio.unc.edu/Goldstein/movies.html))

Another experiment will determine whether the expression of certain genes is modified in C. Elegans by a stay in microgravity. During previous missions, it was observed that 150 nematode genes were reduced in their expression during a stay in space. This set of 150 identified genes will be studied again during this mission, in order to observe whether certain drugs can prevent or slow down muscle loss during space stays. A complementary experiment will observe the functioning of the nematode's motor neurons, which trigger the contraction of its muscles.

Other perspectives are also open. One example is the development of automatic systems for sending nematodes to other planets to study their fate over multiple generations. The general idea behind these space experiments is to better understand how humans live in space, in preparation for missions to Mars. And, on Earth, to better understand how the human body functions by observing the biological processes involved in this hostile cosmic environment.The Conversation

Simon Galas, Professor of Genetics and Molecular Biology of Aging, CNRS - Faculty of Pharmacy, University of Montpellier

This article is republished from The Conversation under a Creative Commons license. Read theoriginal article.