Research into Reanimation
Research into Reanimation
Briefly examining the history of our attempts at turning back the clock at that crucial hour and bringing back the recently dead.
It’s late August, and raising the dead is in the air, maybe even literally. Our proclivity for trying to live longer is just about matched with our fascination with returning from the undiscovered country, mind and body intact. I won’t wax lyrical about humans expressing this desire through mythology, art, and religion; there are more than enough to read about that. Nor will I broach the psychology of the desire, the broad strokes of which are likely intuitive for anyone to understand. I will instead discuss biological research on the matter of reanimating dead tissue, briefly surmising our efforts thus far and where we can go next.
Specifically, we will discuss several recent pieces of news: a group of researchers using hydraulics to reanimate a spider, another using microRNAs to regenerate heart tissue, and another group using a system involving an artificial blood substitute to restart function on a cellular and even organ level in the body of a pig, and discuss how these tie into a growing of body of research in biologically reanimating dead tissue, and the implications of these developments.
The experiments I did on the hanged criminal did not aim at reanimating the cadaver, but only to acquire a practical knowledge as to whether galvanism can […] override other means of reanimating a man under such circumstances.
Giovanni Aldini (1804)
In the early 1800s, Bolognese physicist Giovanni Aldini was obsessed with proving that muscles contract because of electricity intrinsic to the body. This line of thought was developed by his uncle, Luigi Galvani, who had previously discovered that stimulating the sciatic nerve of dead frog would cause its leg to twitch. Following a retirement from the scientific pursuits due to personal matter, Aldini had conducted numerous experiments on animals and cadavers in his uncle’s stread, using electricity to stimulate their muscles. Allesandro Volta, a contemporary physicist and scientific peer, named this quasi-mystical “animal electricity” and its study galvanism in the man’s honour.
At the turn of the 19th century, the whole of Europe was gripped with a zeitgeist steeped in spirituality and the clash of emergent scientific disciplines and old-school mysticism. Even the eminent empiricists of the time had difficulty pinning down exactly what made the ox’s tongue twitch when a current was applied to it; the aforementioned theory of animal electricity was plausibly linked to the movement of the body, and the vital force behind life itself. Indeed, when Aldini was posed to perform his infamous experiment on recently hanged convict George Forster, several “uninformed bystanders” in attendance truly believed they were about to see a dead man brought back to life. It’s all but a certainty that galvanism (which can be interpreted from our 21st century vantage point as a precursor to modern electrophysiology) was never intended to be used for literally reanimating the dead; indeed, its early proponents pointed to its supposed powers to treat mental health issues as its donum to humanity. But, the seed of using an extraneous power source to mobilise an otherwise immobile body was well and truly planted, and while a fantastic source for the stuff of fiction, it’s only in our 21st century that we may begin to see it sprout.
Earlier this year, graduate student Faye Yap and assistant professor Daniel Preston of Rice University were likely taking a well-deserved break from their work on materials research when they noticed a dead spider, curled up in a hallway. Naturally, being scientists, such a curious natural phenomenon piqued their interest - why do spiders curl up like that? The answer is that when humans beings move, it is by mechanically synchronising opposing muscles in antagonistic muscle pairs. This is different in spiders, which use hydraulics. Situated within their heads is a chamber, the prosoma, which contracts to force blood into the limbs and causing them to extend, contracting when the pressure decreases. Knowing this fact, they immediately sought to apply this knowledge to the dead spider.
Using a simple rig consisting of a syringe and an air hose, the researchers deftly turned the spider into a miniature gripper which could pick up small objects, up to 130% the weight of the spider. The spider was able to run through 700 open-close cycles, and the pair plan to optimise further by applying polymeric coatings to the joints to overcome the dehydration that occurs there. Raising the excellent point that taking advantage of an existing mechanical system circumvents necessity for complex fabrication, they point out that reanimating a dead organism in this purpose-drive manner would allow us (the necrobiomancer?) to potentially make use of most of the physical traits the organism boasted in life; the researchers highlight “biodegradability and camouflage […] to potentially deploy them in nature to grip small and delicate samples in an unobtrusive and ecofriendly manner”.
In a statement made to the press, Preston elaborated:
We use all kinds of interesting new materials like hydrogels and elastomers that can be actuated by things like chemical reactions, pneumatics and light […] this area of soft robotics is a lot of fun because we get to use previously untapped types of actuation and materials.
Daniel Preston (2022)
And why not take advantage of what’s already there? Biomimcry is founded on the principle of approximating the characteristics of organisms and elements of nature into human design; elastomers and hydrogels have always been adjacent to the edge of biomimetics, and now we see first for using biological matter itself as the starting point. Next research steps in the short term (>10 years) could focus on increasing the sum of actuators in a single necrobot, allowing for independent movement and fine motor control, and trials of other insect necrobot platforms; proposed by the authors are necrbiotic Patu digua (famous for their diminutive size) and whip scorpions for their speed, favoured as actuators for their speed. I, for one, would love an undead cybernetic spider-pet that fetches me my slippers and newspaper; having a dog do it is so passé. Possibilities include:
Cuttlefish, their camouflage ability lending itself to a post-mortem role as stealthy undersea wildlife camera mount
Gekko-bots that could adhere to walls and move around in uneven locations, e.g. burned or collapsed houses
Necrobot spy-drones based on winged insects such as dragonflies, wasps and even flies that would give micro drones such as the Piccolissimo a run for their money.
Stretching that idea further, bringing the branch of swarm robotics back around by using necrobiotic insects in lieu of insect-inspired robots.
Those snake-bots you’ve heard about a few years ago, designed for search and rescue? Well… why not actual snakes?
And so on. It is only slightly ironic that the concept of necrobots is, in a sense, itself a form of biomimicry as what the Preston group achieved in 2022 is not too far from the type of cross-species mind control Cordyceps fungi has been engaged in for almost 50 million years.
Martin Kaltenbrunner’s team at Johannes Kepler University Linz in Austria recently published a paper detailing a new kind of “bio-inspired” ultrafast robot which clocks in at an impressive 70 BL/s (body lengths per second, a measurement of speed relative to the size of the object’s body) on a corrugated, sawtooth-like surface (pictured above) and 35 BL/s on arbitrary planar substrates - metal, glass, that sort of thing. For comparison, a cheetah's top speed is approximately 16 BL/s. This ultrafast bot is fast - but significantly less so than R. hudsoni1, the Australian tiger beetle that clocks in at a brisk 125 BL/s. The holy grail of such a school of thought in necrobiotics would be to harness the mite P. macropalpis, which clocks in at a whopping 323 BL/s.
One proposed thesis behind the development of such small-scale, fast robots is operating with high responsiveness in small, enclosed and dynamic environments, such as in the human body during surgery, or for the purpose of targeted drug delivery. Could a mite necrobot move fast through the vascular system to deliver a drug? At least, such a biological chassis would fulfil the aim of a biodegradable robot for invasive operations. Assuming we can scale the amount/size of actuators in either direction, the question then becomes when we should stop. Necrobot insects would likely be accepted - as Dr. Manhattan tells us, a living body and a dead one share the same amount of particles, and we are more than happy to kill insects at arbitrary scales for our gain, what with them lacking consciousness and all. Reptiles too, most likely - and any pest animals such as rats. We will likely tolerate them dead as much as we tolerate them alive. But what about larger mammals?
Would a trapped earthquake survivor be disturbed by a boa slithering through the rubble to find her, as opposed to a roboboa? Would she care? Our understanding of and response to death threads its way out of our deepest, most evolutionarily conserved and visceral responses to a massive sprawl of cultural and social norms. I made a point about not leaning too heavily into philosophy, but it is worth highlighting that one who returns from the grave intact is a saviour, and one who returns with some critical part missing is a monster. Strong taboos around death will prevent any work on necrobiotic dogs or cats anytime soon, and our general revulsion with insects will likely confine them to edge cases for aesthetic reasons.
For now, working on cadavers to elucidate the neural pathways which can be artificially controlled to stimulate muscle contraction will give us workable knowledge that could pay dividends in BCI (brain-computer interface) research. Of course, the two main barriers to adoption of necrobiotics would be keeping the body of the organism intact, and being able to effectively control multiple functionalities in a quick and responsive manner. The limitation is obvious: whatever organism you are “reanimating” is still very much nonfunctional and unstable on a cellular level. Even the most advanced portfolio of actuators will still be racing against the clock as the organism succumbs to decay. The obvious issue is that rejuvenating a dead cell is far from rejuvenating a dead organism; there are orders of magnitude of difficulty due to the innate complexity of the systems in question.
Regeneration isn’t a complete novelty for us mammals; researchers found that newborn mice (and therefore possibly humans) are capable of regenerating damage to their heart tissue for one day or so after birth, without any resultant scars or lasting damage; this amazing capacity, however, is entirely lost by approximately one week later. However, what was once lost can be regained, and the field of regenerative medicine is evidence of that. In 2019, Mauro Giacca’s team at King’s College London used a microRNA treatment through an adeno-associated viral vector to regenerate tissue damage in the heart after a myocardial infarction. They are currently working on using a lipid nanoparticle platform, similar to the Pfizer and Moderna vaccines, to deliver the microRNAs in a safer and more efficient manner.
We are using exactly the same technology as the Pfizer and Moderna vaccines to inject micro RNAs to the heart, reaching surviving heart cells and pushing their proliferation. The new cells would replace the dead ones and instead of forming a scar, the patient has new muscle tissue.
Mauro Giacca (2022), source
Academics aren’t the only ones looking for ways to reanimate dead tissue. In 2017, a Philadelphia based startup opined its plans to inject stem cells into the spinal cords of people who have been declared clinically brain-dead, followed up with a protein serum, electrical nerve stimulation (Aldini would be proud) and laser therapy to the brain, along with the kitchen sink no doubt. While ambitious, it was lambasted by researchers for being “unethical […] quackery”. After falling afoul of regulatory authorities and failing to attract a single enrolment, as of 2022, there have been no updates on any progress and trying to access their website at bioquark.com gives a 404 error. Oh well. Likely the technology simply wasn’t there, and even if they had received permission from regulatory bodies, it’s doubtful that such a multi-pronged approach would’ve paid immediate dividends for humans.
However, a more conservative effort to use re-circulation as a method of rejuvenating dead cells has seen more success earlier this year. In 2019, a group of researchers at the Yale School of Medicine piloted a study using a perfusion system dubbed BrainEx to recover function in the brains of pigs who had been dead for four hours. Essentially a dialysis machine, BrainEx supplied a cocktail of antibiotics, vitamins, amino acids, inorganic salts, metabolic factors, and cellular protective agents over a time period of six hours through the brain vasculature of the dead animal. After determining that flow throughout the brain was restored, they sought to identify the recovery of cellular structure and function; staining the brain’s cells showed they looked more like cells from a brain that had been dead for 1 hour rather than 10. Next, they treated the brain cells with inflammatory which would precipitate an immune response in living cells… which is what occurred (to some extent) in the BrainEx treated cells.
It fundamentally challenges existing beliefs in neuroscience. The idea of the irreversibility of loss of brain function clearly isn’t true.
Nita Farahany (2019), Source
OrganEx was the logical progression, applying the system to multiple organs instead of just the brain. Delivered in a 1:1 ratio with the animal’s own blood, this solution prevents inflammation and cell death. Results were similar to the findings in BrainEx, with less cell death in the treated animals, and even signs of cellular repair associated gene expression in the kidneys. Following injection of a contrast dye, the OrganEx rated animals exhibited “complex … movements of the head, neck and torso”. Galvani’s frogs, anyone? While the cause of the movement is undetermined, this is at least evidence of motor function being preserved and potentially re-started even after death.
The history of medicine’s attempt to define death has been rocky, moving from cardiopulmonary approach to the so-called Harvard criteria; now, the higher brain standard (brain stem activity such as breathing, circulation, and digestion doesn’t count) rules, and restoring full brain activity will likely remain the litmus for our ability to truly bring one back from the dead. Our interpretation of what constitutes death is pushed back further and further as our capability to treat the most grievous damage grows. Cryonics, the low temperature freezing of a human that has been declared legally and clinically dead, is a process hedging its bets on future humans pushing back this understanding even further. Suppose that a perfusion platform like OrganEx could indeed do the heavy lifting on reviving a recently deceased individual, though only in a procedure overseen by specialists in a hospital setting. In this case, we wouldn’t need to extend the time during which the perfusion could still function; simply cryonically freeze the deceased individual, freezing him in a state of 1 hour post-mortem.
Perhaps one day we will have the power salvage all short-term and long-term memories, as well as personality at any time post mortem if appropriate care is taken with the remains. Maybe such a process would see streams of research merge; a recently deceased victim of an accident receiving a transfused cocktail similar to OrganEx, including microRNAs delivered in lipid sheaths to kick-start cell proliferation while a BCI-like, Galvanic skin response module stimulates the nervous system. The mistake that Bioquark made w CPR will seem as archaic as smelling salts, and the undiscovered country will be ours to safely return from.
This article uses the nomenclature of Cicindela hudsoni, as opposed to the now accepted Rivacindela hudsoni - this is due to a reclassification of hudsoni as being part of the Rivacindela subgenus of Cicindela due to divergent habitation and characteristics. See Flightlessness and Rapid Terrestrial Locomotion in Tiger Beetles of the Cicindela L. Subgenus Rivacindela van Nidek from Saline Habitats of Australia (Coleoptera: Cicindelidae) at: jstor.org/stable/4009161#metadata_info_tab_contents