Space & Health News – Bioengineering for Space Resilience

Data collected from spaceflight missions over the past five decades have taught us that gravity, cosmic radiation and confinement can have tremendous impacts on astronauts’ health. Living in microgravity leads to bone loss, muscle deconditioning, dangerous build-up of fluid pressure in the head, high-blood pressure and temporary or persistent eye problems. Prolonged exposure to cosmic radiation can cause sickness and fatigue and lead to cancer and damage of the nervous system. Life in isolation, in a confined environment, without exposure to the natural cycle of night and day triggers sleep disorders, behavioral issues, and even depression, and it weakens the immune system’s ability to fend off microbes.

Still, as much knowledge as we have accumulated so far, we are only at the beginning of a long journey of discovery. New studies carried out with more accurate measurements and instrumentation can still hold surprises for researchers and astronauts alike.

Just recently, a study of 11 astronauts stationed onboard the International Space Station has revealed a health risk hitherto unknown. The study found that of the 11 healthy astronauts, during the course of the space mission one had developed a blood clot, another astronaut had a potential partial blood clot, and six of the astronauts had stagnant or reverse blood flow in their left jugular vein. As Karina Marshall-Goebel, the author of the study and a senior scientist at NASA, stated in her findings – the blood was “sloshing back and forth a bit, but there was no net-forward movement”.  

Blood stagnating or moving in reverse, from the heart to the head, is an abnormal event which impacts the ability of the brain to drain cerebral spinal fluid away from the head. Stagnant blood flow can over time lead to the formation of blood clots (thrombosis), which in turn can increase the risk of a pulmonary embolism.

Is this a show-stopper, one might ask, for the much-hailed future journeys to Mars? After all, the astronauts in this study who experienced blood clots were treated with blood-thinning medication and, upon return to Earth, reported no further side effects. Nevertheless, added to the plethora of other space health hazards previously discovered, this new risk casts a shadow on the prospect of long-term, interplanetary spaceflight. The time may be ripe to consider the possibility that Chibis pants, vitamins and exercise are not enough to carry astronauts through to Mars, and that the first humans to step on the Red Planet will have to be specifically bioengineered for space resilience.


WELCOME TO SPACE & HEALTH NEWS, our monthly briefing on opportunities and advances in deep space medicine and space healthcare. In this issue, we take a closer look at cutting-edge research and exponential technologies aimed at turning humans into space farers.


RESEARCH

The “Mighty Mice” Experiment: Researchers from the Jackson Laboratory for Genomic Medicine (JAX-GM), UConn Health, and Connecticut Children’s have sent genetically-engineered mice to the International Space Station to study the effect of microgravity on muscle and bone loss. These special mice, raised by JAX’s custom breeding team in Bar Harbor, Maine, are genetically engineered to lack myostatin and as a result display approximately twice the average muscle mass.

The “mighty mice”, as their designer – researcher Se-Jin Lee, M.D., Ph.D., professor at JAX-GM – calls them, traveled to the International Space Station aboard the SpaceX’s Dragon spacecraft launched on December 5th, 2019. Researchers often turn to animal models to understand the complex molecular mechanisms of the human body, and the mouse has long been used to gain insights into gene function, disease, and drug development given the many genetic features shared by humans and mice. The bio-engineered mice’ 30-day space sejour will help scientists understand how to limit muscle and bone loss in humans while they’re in space.

What does this mean for future astronauts? Therapies targeting the myostatin and activity signaling to prevent muscle and bone loss may at some point become part of the mandatory pre-mission physical conditioning required for all space crew.

ISS National Lab Mission Overview, SpaceX CRS-19

Mason Lab’s Mars Colonization Project: The Mason Laboratory, established by Christopher E. Mason, Associate Professor and Director of the WorldQuant Initiative for Quantitative Prediction Physiology and Biophysics, Weill Cornell Medicine, is the home of an ambitious project aimed at ensuring the survival of the human species on Earth and in space.

Researchers at the Mason Lab are developing and deploying new biochemical and computational methods to investigate the genetic basis of human disease and human physiology, and to carry out experiments to identify those elements of the genome which cannot be changed, as well as those that are most tolerant of mutations.

The Mason Lab’s goal, laid out in a 10-stage, 500-year plan, is to improve the ability of humans and other species to survive in spaced-based environments or on other planets through safe genetic engineering, thus enabling human settlement throughout and even outside of our solar system.

Discovering and designing genomes for Earth, Mars, and beyond – TEDMed Talk by geneticist and urban metagenome researcher Chris Mason of Weill Cornell Medicine

The idea of tinkering with human genes is highly controversial, but, Mason argues, genetically engineering humans could be ethical if it makes people more capable of inhabiting Mars or other planets safely – without interfering with their ability to live on Earth. To this end, Dr. Mason has put forth the radical idea of gene-hacking humans with the DNA from tardigrades – hardy micro-organisms capable of surviving extremely harsh conditions, up to and including exposure to outer space.

Building on research done by scientists at the University of Tokyo which show that the tardigrade’s resilience can be transferred to cultures of human cells thus helping them withstand radiation, Dr. Mason envisions combining tardigrade DNA with human cells through epigenetic engineering. This would allow the expression of tardigrade-derived genes to be turned on or off, allowing astronauts to be better protected while in outer space, but not interfering with their biology while on Earth.

Audacious? Sure! Crazy? Possibly. Yet, having led one of the 10 teams of researchers NASA chose to study twin astronauts Mark and Scott Kelly, Dr. Mason is one of the most respected biologists today in favor of leveraging the advances made in genome sequencing and gene therapy to make astronauts more resilient to space health hazards. “Pharmacology can only take you so far,” says Mason. “To some degree, we need our biology to fundamentally be adapted to space.”

Harvard Medical School’s Consortium for Space Genetics:  Co-founded by George Church, a Harvard geneticist and leading synthetic biologist, along with other prominent biologists like the anti-aging researcher David Sinclair, the Consortium for Space Genetics focuses on the study of  human health in space and the development of technology for reading and writing genomes with increased resistance to space hazards.

Dr. Church vision is that astronauts would undergo “virus-delivered gene therapies, or microbiome or epigenome therapies” to transform and harden their biologies. “Quite a bit is already known about resistance to radiation, osteoporosis, cancer, and senescence in mice,” he says, adding that many of these genes are already targeted by pharmaceutical companies, with drugs in clinical trials. His website at Harvard University lists 40-some genes that might be advantageous for long-term spaceflight – including CTNNBI, for  radiation resistance; LRP5, for strong bones; ESPA1 (common in Tibetans), which allows people to live with less oxygen; PCSK9, to reduce the risk of coronary disease; and a host of other genes that can turn humans into smarter, more performant and less anxious versions of themselves.

His vision is to design and build long strands of human DNA, not solely by cutting and pasting small fixes using a technology like Crispr, but by rewriting critical sequences of chromosomes that can then be stitched together with a naturally occurring genome. “What we’re planning to do is far beyond Crispr,” Church says. “It’s the difference between editing a book and writing one.”

Pioneering gene-editing I George Church & Chris Smith

Where Next?

Jamie Meztl, technology futurist and geopolitics expert, points out the obvious in his book Hacking Darwin when he states, “it is almost impossible to believe that our species will forego chasing advances in technologies that have the potential to eradicate terrible diseases, improve our health, and increase our life spans.”

For those who (rightfully) believe bioengineering experiments should be tempered by caution and humility, Meztl  offers an additional dose of pragmatic realism. “We have embraced every technology,” he says, “ – from explosives to nuclear energy to anabolic steroids to plastic surgery – that promises to improve our lives despite the potential downsides, and this will be no exception. The very idea of altering our genetics calls for an enormous dose of humility, but we would be a different species if humility, not hubristic aspiration, had been our guiding principle.”

Indeed, space exploration is, in a sense, the ultimate act of human hubris. Think of Icarus daring to strap wings on to his arms so he could fly, or Da Vinci dreaming up mechanical flying machines. We would defy our very nature, were we to ignore the incredible potential bioengineering holds in helping us transcend our existing physical and physiological boundaries.

Researchers like Dr. Chris Mason, Dr. George Church and a few others like them who straddle the scientific and public domains are at the forefront of wielding bioengineering as a tool for space exploration, and as the space industry’s focus shifts from ‘how to build reliable spacecraft’ to ‘how to reliably put live people on Mars’, their ideas and methods are likely to get increased traction and more adherents.

Yet the path they’re on is going to be long and winding. Human bioengineering is and will remain a controversial subject, as much social and political as scientific. The dangers of meddling with the foundational bricks of life have become part of the public discourse, where everyone is entitled to an opinion.


Featured illustration "Prosperous Universe - Asteroid Day" .   Credit Mac Rebisz.  

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