For one year, Scott Kelly has been confined to living in a 338-cubic meter tube, while his identical twin brother, Mark, has been poked and prodded by government scientists. No, this isn’t an episode of Black Mirror (although I wonder if I can sell that to them). It’s a ground-breaking study performed by NASA, who just happened to have a set of identical twin astronauts, who were willing to be Hypothesis Human and Control Human.
The Twin Study is ten separate investigations comparing changes between the Kelly twins, coordinated into one research team. They are investigating differences in physiology, behavioral health, the microbiome, and genetic activity caused by extended amounts of time in space. Earlier this year, the press release about the preliminary findings resulted in many headlines implying that 7% of Scott’s genetic code had changed, and that Mark was no longer his genetic twin. If this were the case, the best-case scenario would be that Scott was a monkey. The far more likely result of 7% of your genetic code changing would be a severe case of deadness. What changed instead was Scott’s gene expression, so despite having the same genetic code, the stressors of space travel had caused different genes to switch on and off. And 6 months after returning to Earth, 93% of the expression changes had returned to normal, while 7% persisted. This is not insignificant, and has implications for the health of humans in space for extended periods of time, such as on a trip to Mars.
This ability to switch genes on and off is fundamental to the ability for a zygote to turn into a complex animal. Neurons, skin cells, muscle cells, liver cells, and kidney cells all have a nucleus containing the same genetic code, but have wildly different functions, resulting from the different proteins they produce. Simplistically, a neuron has all the genes to encode proteins that would allow it to contract like a muscle, and a muscle cell has the blueprints for nerve firing. But in each specialized cell, the extraneous functions it doesn’t need to perform are turned off via two main mechanisms: DNA methylation and histone modification.
DNA methylation is one of those things that is exactly what it sounds like; a methyl group (one carbon and three hydrogen atoms) is attached to DNA at the start of a gene, which doesn’t allow the transcription machinery to bind and instruct the ribosomes to construct the protein. No really, that’s pretty much it.
Histone modification is a little more complicated. Histones are a component of chromatin, which is the stuff that DNA is wrapped around to keep it orderly when stored, so it doesn’t end up looking like your headphones in your bag. The histones can be modified to keep the DNA wrapped around the chromatin, which doesn’t allow the part of the DNA with the gene of interest to be accessed by the cell. Ok, I said a little more complicated.
Changes to gene expression rather than to the genes themselves is called “epigenetics.” It had previously been demonstrated that epigenetic modifications occur in response to stressful environments, functionally (although not literally) changing your genetic code to become better adapted to a new environment—an increase in red blood cells in response to low oxygen climate, for example. While the fact that epigenetic changes occurred while in space is not surprising, which changes and the possible inability to revert to the original expression is a valuable finding. It is unclear what, if any, health risks will arise from the persistent changes to Scott’s immune system, bone formation, oxygen metabolism, and DNA repair. But we know the question needs to be investigated to prepare future long-term astronauts travelling to Mars and beyond.