Cryopreservation, Genes, and Space Travel

This blog article highlights some of the findings and extrapolates from the review paper written by John Larson (J Exp Biol. 2014 Apr 1;217(Pt 7):1024-39).

Ever wondered about what is being done in the study of cryopreservation? Well, much of the work has focused on the systems of how animals are able to withstand zero oxygen or low temperature environments. The most important systems studied are oxygen storage and conservation, hibernation physiology, and ice crystal formation inhibition.

Diving animals like whales, seals, and penguins evade their zero oxygen environment by storing large quantities of oxygen in myoglobin in their muscles and higher concentrations and volumes of hemoglobin in their blood. Penguins slow their heart rate when they dive to further conserve oxygen use. Similarly, naked mole rats, which live in very low oxygen environments, have strong hemoglobin adaptations. These moles are able to use and store oxygen more efficiently by binding to what little oxygen there is more tightly. However, just storing oxygen won’t help with long term cryopreservation since those stores eventually run out, forcing the subject to be revived.

Hibernation physiology on the other hand couples adaptations to low temperature with low oxygen environments. Some animals can live completely without oxygen for extended periods of time. For example, the red-eared slider turtle, Trachemys scripta, is able to survive without oxygen for 24 hours at room temperature and several weeks in winter hibernation temperatures. After extended periods of low oxygen, these turtles have no apparent loss of neuron cell function. Although turtles are fascinating in of themselves, their cold-blooded physiology is much further removed from the human than our fellow species in the mammal kingdom. The mammalian arctic ground squirrel, Spermophilus parryii, is similar to turtles in that during hibernation, their core body temperature is lower than the freezing point of water. Even during the summer, arctic squirrels can go 10 minutes without oxygen before brain damage occurs. Low oxygen causes the bodies of vertebrates to move from aerobic to anaerobic respiration. Anaerobic respiration works to create energy and lactic acid from glucose. If lactic acid builds up too high it can create a pH imbalance in blood and tissues which is deadly. Hibernating animals move in and out of anaerobic respiration easily with better pH buffering capacity. They are also very resistant to oxidative damage that can occur when an animal goes from long term low oxygen environments to oxygen rich environments. This resistance to low oxygen is built in at the molecular level through gene adaptations which are constantly active and switched on further during hibernation. Some examples of protein family adaptations are to heat shock chaperones which facilitate folding and refolding of deformed proteins during cell stress. Other examples are neurological gene adaptations which slow firing rates to conserve energy and reduce oxygen requirements. It is likely that many of the same hibernation gene modifications active in turtles and arctic squirrels could be modified for use in humans.

Ice crystal formation is one of the biggest problems that animals in frozen climates encounter. When ice crystals form in and around cells during freezing they cause breaks in lipid cell membranes which are forced open during thawing. Leaky membranes are very deadly to all species. Insects like the sleeping chironomid fly, Polypedilum vanderplanki, are capable of surviving the shedding of nearly all of their water. In the desiccated state, this fly larva can be frozen to extremely low temperatures since there is little water left to form ice crystals. After the larva is heated and rehydrated, it goes back to its normal lifecycle. Unfortunately, human physiology is too far removed to make water shedding a part of a cryogenic storage protocol. Other animals like the spruce bud worm, Choristoneura hebenstreitella, have antifreeze proteins in their blood. This protein helps keep their cells safe from ice crystals by reducing their ability to form in even -30०C weather. More importantly, these antifreeze proteins work at fairly modest concentrations and do not impact an animal’s internal water pressure.

So, let us think practically about space travel. Without faster than light travel technology, it would take many years to get to the nearest stars. For moving out farther into space, just slowing down metabolism of oxygen or storing it more efficiently (like in the whale or mole) isn’t going to do the trick because the extremely long travel time. We will need to freeze people deeply enough to stop metabolism altogether. To create the perfect human popsicle one would need to induce compatible low oxygen/temperature protection systems from animals like the freshwater turtle, arctic ground squirrel, and spruce bud worm. These systems would need to be programmed into every cell in the body. The human would then need to be placed into a chemically induced coma and very slowly frozen. At the other end of the space voyage the human would need to be thawed. Thawing presents problems when considering the size of the human body versus the speed of heat transfer. For example, if different parts of the brain warm at different speeds it would create a potentially deadly disaster once those neurons try to talk to one another. A heat transfer system would need to be engineered to transfer warmth more evenly.

Anyway, if you can set up all of these genetic systems to run in parallel it should be possible to freeze a human being and thaw them again without much damage. But one would need to be able to deliver the required genes to every cell in the human body, which we are developing using synthetic viruses.

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