ExoBi: Preparing the Human Body for Space Exploration

Human biology changes in space, and usually not for the better

Let’s take a trip back a few years to when you were still in kindergarten, and ask 5-year-old you a question many of us can’t even answer in undergrad:

What do you want to do when you grow up?

  • *Famous*
  • a Doctor
  • a Police officer
  • a Firefighter
  • a Teacher
  • an Astronaut!

Lots of kids dream about being astronauts, and it makes sense given how we celebrate and honor their work.

But… what if you told 5-year-old you about the problems that would hit you while you’re in space? What if you were told that your bones would weaken every month, that your genes become unstable, that your eyes and heart could physically change their form?

You may get second thoughts about boarding the next ship to Mars…

Being an astronaut comes with enough risks as it is, chronic health problems should not be another thing to worry about. Unfortunately, this is a very real aspect of an astronaut’s life, but what if it doesn’t have to be?

We didn’t choose the Mars life, the Mars life chose us. (PC: Wikipedia)

ExoBi: Our Fundamentals

Elon Musk’s SpaceX wants to land human beings on Mars by 2024. This would take people on a ~7-month journey to the Red Planet, settle them down for a period of time, and then assumably transport them back to Earth on another ~7-month journey.

That’s around 14 months (approx 426 days) in the depths of space, with more realistic time frames for Mars missions putting the estimate at 500+ days.

A few of us came together and realized that this isn’t the smartest way to get people out to the stars; we need to understand and mitigate radical health changes in our bodies when in the depths of space.

That is why we founded ExoBi, an exobiology (space-biology) company that aims to maintain astronaut health through long space exploration missions!

And like any good problem solver, ExoBi came up with an actionable plan.

The planned-out quest

NASA has been compiling research and data for decades on physiological and some cognitive effects on astronauts in the microgravity environment. Specifically muscle, bone, and ocular effects were the main areas of their focus, having the most researched data as of 2019.

With there being the most data in bone loss and its effects, ExoBi’s first “quest” or actionable step is to mitigate the effects of bone mass loss (Space Osteopenia) in astronaut bodies.

We would then follow up with bodily changes that follow Osteopenia in the amount of quality data and research on their functions, with Neuro-Ocular diseases and Cardiovascular reshaping being very likely future targets.

But let’s back things up, what actually happens to our bodies in space? Our widest-ranging answers got published just about a month ago, thanks to the NASA Twins study.

Mark and Scott Kelly

Our calling: NASA Twins Study

The reality check for human space exploration goals right now is that we are only just starting to learn about what happens to our bodies during prolonged space travel.

Lucky for us, we’ve got astronauts like Mark and Scott Kelly who are willing to be test subjects to help us understand our bodies better in space.

The experiment and its results

In 2014 NASA set out on observing the effects of long-duration spaceflight on the bodies of astronauts. They picked a pair of astronaut identical twins - Mark and Scott, to be the test subjects of their study.

Throughout the study, the NASA experiment observed these aspects of the twins’ bodies for changes:

  • Epigenetics
  • Gut Microbiome
  • Metabolomics
  • Cognitive Ability
  • Telomeres
  • Immune System
  • Gene Expression
  • Proteomics
  • Physiology

Stage 1 (2014–2015): The identical Kelly twins started off with relatively similar health, both of whom were still living their lives on Earth.

Stage 2 (2015–2016): Scott Kelly begins his 340-day mission on the ISS, while Mark stays on the ground as a comparative measure to compare to his twin brother’s health. Samples indicating the status of the twins “multi-omic” health were collected throughout Stage 2.

During this time the most profound changes occurred in Scott’s: global Gene Expression levels, telomere length, increased genome instability with more inversions & translocations, bone health, and ocular structure.

Stage 3 (2016–2017): Scott returns to Earth, and his health is monitored over a year to observe it adjust back to Earth conditions.

While aspects like bone health gene expression began normalizing, the profound changes like genome instability and ocular structure deformation remained. Even Scott’s telomere health was effected long term: having reverted back to normal lengths after growing in space, only to then shorten further than preflight-levels.

Takeaways from the study

Arguably the most interesting aspect was Scott Kelly’s gene expression and genome stability changing a great deal from the prolonged experience in space, which indicates a large range of potential side-effects.

So we learned that the genes your cells express change, as well as how effective your chromosomes are maintaining itself from serious errors and mistakes. We also got more confirmation of your bones weakening, as well as how your eye and heart structure change.

Ultimately all this spells a rocky road for humans who want to be a part of space-exploration missions, but who also don’t want their vision being jeopardized, their heart altering its shape, their chromosomes swapping parts, and their gene expression going up the wall.

This is where ExoBi spies with its little eye, an opportunity to make space travel healthy!

Additional health effects that have been recorded in astronauts. (PC: NASA/NSBRI)

ExoBi’s first step: Spaceflight osteopenia

Our bones are actually complex organs that are way smarter than we think. Rather than just being a solid mix of collagen that gives us structure, bones are actually intricate networks of cells, proteins, calcium, and intention.

It just so happens that our bones don’t act in our best interest while in space. An astronaut in space will lose an average of 1%-2% if their bone mass monthly, which is how much osteoporosis patients lose every year.

This means for a 6-month mission, you would lose about 10% of your bone mass and would need about 3–4 years to recover. Now imagine how long it’ll take to recover your bones from a 500+ day mission?…

The rotten cherry on top of all this? Lost calcium from your bones often accumulates calcium deposits elsewhere in astronaut’s bodies- kidney stones.

Bone remodeling is everything

Bones are being replaced all the time whether we’re on Earth or in the depths of space, in a process called bone remodeling. The bone remodeling process occurs primarily at the hands of three types of cells:

  1. Osteoclasts (Demolition): These specialized cells kickstart the bone remodeling process by causing bone degradation via acids and proteins.
  2. Osteoblasts (Building): Cells that like to work together in groups, repairing the cavities caused by osteoclasts with layers of new bone.
  3. Osteocytes (Manager): Small cells which direct the bone remodeling process by controlling the levels of osteoblasts and osteoclasts. Osteocytes also network together to sense mechanical loads on the bone structure.

In the bone remodeling process, osteoclasts first arrive at a location of bone to be eroded. They engulf themselves in an acidic matrix which begins corroding the bone surface and then recruit proteins to chip away at the deeper levels of the bone tissue.

Then come the osteoblasts which work in groups to replenish the area of bone that the osteoclasts got rid of, replacing the bone cavities with fresh bone cells.

All of this is directed by our osteocytes, which given they make the right calls, leads to an equilibrium between the osteoclasts and osteoblasts. This equilibrium of the demolition and rebuilding of bone is what healthy bone remodeling looks like.

Technical dive into bone remodeling, the third stage indicates cell differentiation. (PC: Researchgate)

In the space microgravity environment, your osteocytes’ mechanosensory abilities get altered. They feel less work being done by gravity and they start calling the different shots, recruiting fewer osteoblasts to the bone and keeping around the same amount of osteoclasts.

The result? A net loss in bone tissue ofdue to fewer osteoblasts being around to repair osteoclast demolition.

The current way to mitigate the loss of bone is by heavy lifting and applying mechanical loads to the astronaut’s body with exercise. This works well in mitigating the damage but falls short with injured astronauts and with fully mitigating the osteopenia effects.

We wanted to find the root cause as to how osteocytes act up when gravity changes, as well as the mechanism behind it. What ultimately happens in the osteocyte that allows it to detect gravity acting upon it and react?

ExoBi’s plan for osteocytes in space

It turns out that there’s a special liquid that’s excreted by a complex system of entrenched osteocytes called the Lacuno-Canalicular network. This system consists of individual osteocyte cells which are embedded in little holes called lacunae, who branch out to other osteocytes in their own lacunae holes.

This branching network of entrenched osteocytes is subject to the flowing of a liquid called canalicular fluid. This fluid forces the cells to physically move around in their lacunae differently. In their lacunae, Osteocytes and protruding chemicals triggers on their cell surface are subject to the drag caused by the flowing of this canalicular fluid.

All in all, this flow causes chain reactions within osteocytes that change how they behave and also change how they direct bone remodeling.

You can imagine like being in a calm bath versus being in a very violent jacuzzi. Your behavior and focus would quickly change if your calm bath suddenly felt like white-water rafting!

Entrenched osteocytes connect to each other in intricate networks within your bones.

With the osteocytes being dragged around by the canalicular fluid, their behavior alters via gene expression and cell signaling changes. This may be a key function that leads osteocytes to lower osteoblast activity in those with osteopenia.

With the current knowledge available, we created a plan to go about researching a way to possibly prevent space osteopenia.

  • We can compare the properties (ie: volume) of canalicular fluid in the bodies of mid-flight astronauts to subjects on Earth, seeing how differing levels of it affect osteocyte function and signaling.
  • We would then need to obtain more data on what genes does the canalicular fluid alter gene expression levels for. This will allow us to paint a holistic picture of the role of canalicular fluid in the osteocyte environment.

At this point, we would have what levels of canalicular fluid are normal and which cause abnormal behavior, as well as have confirmed or disproven canalicular fluid’s influence on osteoblast recruitment. Bisphosphates would also likely be an area of interest alongside our canalicular fluid research.

If everything checks out as we theorize, the testing and implementation launches:

  • We would either extract or inject canalicular fluid into/from astronauts in space, depending on what levels of the fluid constitute healthy bone remodeling or osteopenia. This process would be done in order to maintain an equilibrium in the osteocyte environment.
  • This balanced osteocyte environment would ideally behave normally in space as it does in Earth: recruiting the appropriate numbers of osteoblasts to complement the osteoclasts for a healthy bone remodeling process.

With that, we have a potential path to go about preventing spaceflight osteopenia. What’s left from there is implementing everything that’s laid out.

Other promising opportunities for ExoBi to help include osteopenia-mitigating drugs known as Bisphosphonates, however, these are also still undergoing experiments.

Key takeaways and final thoughts

ExoBi is taking humanity’s dream of interplanetary space travel, and making it into a viable and healthy reality. Without answering the key questions about what happens to our bodies out in space, our extraterrestrial dreams will just stay as dreams.

Here’s what we at ExoBi want you to remember about us:

  • ExoBi is a space biology company dedicated to maintaining astronaut health by mitigating known health risks in space.
  • We are starting out by pursuing health issues that are the most well-researched, beginning with Spaceflight osteopenia.
  • After getting significant progress in osteopenia, we would then be moving onto researching and/or mitigating neuro-ocular disease and cardiovascular effects in space.
  • Without addressing the biological changes and effects that space inflicts on our bodies, human space colonization cannot be sustained.

Humanity is taking to the stars in the next decade, and we have the privilege to see it all happen in front of us. The less our Mars-bound astronauts worry about chronic health problems, the more they can focus on building up humanity’s legacy outside Earth.

Our idea at ExoBi is simple, our vision is grand, our path is hard:

We are getting rid of the seemingly inhibitory health challenges that are holding our species back from exploring and settling worlds beyond our own.

At the end of the day… we want the Mars-destined kindergartners of the world to follow through on their dreams, without having their adult selves worry about breaking down.

Want to hear more about this project and other work I do? Subscribe to my monthly newsletter: https://mailchi.mp/9703090cb6dd/michaeltnewsform

Undergraduate builder & researcher @UofT in the crossroads of computer science, immunology, and genetic engineering.