By Toby Lanser
The last decade has brought unprecedented strides in the life sciences and medicine, ranging from ultra-specific gene editing to life-extending treatments. These fields seem to be at the verge of conquering all of the trials and tribulations encountered within life. Breakthroughs have led to a more comfortable ride through life and have even amounted to an extension of life itself. The parameter of life that these advances have dealt with is one that does not to budge, as it exists at one end of two extremes: life and no life. It has yet to, however, deal with the hurdle of restoring it. This notion of restoring life rests on the ability to reinstate what has seemingly ceased to exist, almost creating a time machine aimed at reversing the proverbial crossing of the Rubicon, and returning the die to the hand that cast it.
In biology, cell lines are routinely frozen in temperatures far below zero degrees Celcius for long-term storage and are thawed and grown with minimal effects on the cells’ viability. In a technique that’s essentially small-scale cryonics, known as cryopreservation, the anabolic and catabolic processes within cells are halted at extremely low temperatures and resume operation once thawed, like the dimming and brightening of the lightbulb of life. On a cellular level, the light within the cell flickers into darkness and restarts again with little-to-no hiccups. Biochemically, this makes sense if one views a cell as a glorified test tube housing chemical reactions. Processes stop when frozen, and pick back up when thawed. The technique of freezing cells has presented a wide variety of applications, but the technology has been limited to individual cells and relatively small groups of associated cells and tissues.
This begs the question: why can a reliable technique on a cellular level not be scaled up to freeze full organs or multicellular organisms, both of which are made of cells? Though there are a few known caveats that are innate with deep freezing cells, scientists are still stumped as to why individual cells can be rebooted, but multifaceted organisms and tissues can’t be. This failure has rejuvenated an idea that many scientists consider the bane of their existence: vitalism, which states that living beings contain an invisible, metaphysical glue that is vital for any living being to “be alive.” Understandably, vitalism has been disproven time and time again through rigorous experimentation. The experiments that have dealt the most significant blows have also become both historic, and seminal in the understanding of the relationship between life and its respective building blocks. Regardless of the overwhelming evidence to suggest otherwise, the vexing theory reemerges each time biologists fail to kickstart life and its physical constituents.
Vitalism, once again, has taken a new hit. In an ambitious study, researchers at Yale School of Medicine threaten both vitalism and our understanding of intelligent life by succeeding to restore both micro and semi-macro function of a pig’s brain hours after the animal was declared deceased. The paper that describes the researchers’ findings reads as a more esoteric, jargon-filled Mary Shelley novel that could pass as a study led by Dr. Frankenstein himself. Equipped with a self-designed contraption straight out of The Modern Prometheus (figure 1), the scientists mechanically pumped essential nutrients through the brain and closely monitored the temperature of the system. A pulse generator was used to emulate cardiac waveform and heart rate which was controlled by a researcher through a user-friendly computer interface.
Overall, an entire artificial circuit was erected to maintain homeostatic conditions. This, as we know from the thawing of cryopreserved cells, isn’t enough to magically reboot an entire organ. Except, in this case, it was. By supplying the correct amount and variety of nutrients in the correct intervals, the scientists were able to transform a heap of deceased tissue into a semi-functioning brain. This “semi-functioning” is key, however. Spontaneous activity of neurons and cell-specific functions were observed, but this isn’t much different from neurons thawed from a deep freezer growing in a petri dish, which are known to exhibit similar characteristics. The key to reviving an organ, it seems, is a multi-faceted delivery with the exact concoction of juices needed for complex systems to survive. Providing these juices in ways that mimicked the body’s own created a spark to restart the system. This lasted for just a moment, though. The few short hours of microcirculation and cellular functions that resulted from the procedure soon diminished, and the breath of new life became lost once again.
The restoration of neuronal activity within an intact brain hours post mortem is certainly no small feat. It is, however, far away from restoring a fully-functioning, conscious being. Aside from the logistical hurdles created by the contraption used in the experiment, much greater research is needed to understand the difference between spontaneous neuronal activity in a petri dish and the meticulously wired circuits with neurons primed for action present in our brains. This research also delivers another damaging blow to the constantly reemerging theory of vitalism, and shows us, once again, that biology truly is a well-oiled machine waiting for the ignition to spark with the turn of a key. What is needed now is to figure out where the oil goes and when, and we’ll all be one step closer to flipping the light switch of life on indefinitely.
References:
(n.d.). Retrieved from http://mechanism.ucsd.edu/teaching/philbio/vitalism.htm
Vrselja, Z., Daniele, S. G., Silbereis, J., Talpo, F., Morozov, Y. M., Sousa, A. M. M., … Sestan, N. (2019). Restoration of brain circulation and cellular functions hours post-mortem. Nature, 568(7752), 336–343. doi: 10.1038/s41586-019-1099-1
Farahany, N. A., Greely, H. T., & Giattino, C. M. (2019, April 17). Part-revived pig brains raise slew of ethical quandaries. Retrieved from https://www.nature.com/articles/d41586-019-01168-9.
Okamoto, K., Ishikawa, T., Abe, R., Ishikawa, D., Kobayashi, C., Mizunuma, M., … Ikegaya, Y. (2014). Ex vivo cultured neuronal networks emit in vivo-like spontaneous activity. The Journal of Physiological Sciences, 64(6), 421–431. doi: 10.1007/s12576-014-0337-4