From here: Pfaller, W. & Jennings, P. Frankenstein’s followers. Maintenance of human cells outside the body. Issue 1. Toxicol. Vitr. 82, 105387 (2022).

Frankensteins Followers. Maintenance of human cells outside the body. Issue 1.
Walter Pfaller and Paul Jennings

Medical University of Innsbruck, Christoph-Probst-Platz 1, Innrain 52 A, Fritz-Pregl-Straße 3,
Innsbruck A6020, Austria.
Email: Walter.pfaller@i-med.ac.at or Walter.Pfaller@gmail.com

Division of Molecular and Computational Toxicology, Department of Chemistry and Pharmaceutical Sciences,
AIMMS, Vrije Universiteit Amsterdam, De Boelelaan, 1108, 1081 HZ Amsterdam, The Netherlands.
Email: p.jennings@vu.nl

Abstract:
Although science can endeavour to do a great many things, unachievable thus far, these activities should be, but seldom are, tempered with the question, should we really do it? This is not necessarily implying a moral code to scientific activity, but at least suggests that we probably should consider the long-term consequences of certain scientific activities to human society and the environment. Indeed, scientists have struggled with the consequences of their discoveries, not least Nobel himself, who set up the Nobel prize as a reaction to being called “The father of death”, due to his discovery and financial success with dynamite. Here, we set out the basis for a series of articles entitled, Frankenstein’s Followers, Maintenance and propagation of human cells outside the body.

Main
In April 1815, the largest volcanic eruption during historic times occurred on the island of Sumbava in the Dutch East Indies. Roughly 200 cubic kilometres of lava and hot particulate matter was ejected during the eruption of mount Tambora. The consequence for our planet was a severe change of the global weather. The year 1816 entered history as the year without summer.  During this wet and cold summer, a group of eccentric British upper-class people resided with George Gordon Noel Byron (Lord Byron) at Villa Diodati, a mansion he rented on the shore of Lake Geneva in Switzerland. Annoyed by the bad weather which prevented excursions into the alpine surrounding, Byron suggested to his guests to write up a spine-chilling story each. This idea had consequences for world literature. "The vampyre" written by Byron's friend and personal physician John Polidori became the inspiration for the famous Dracula novel, later written by the Irishman Bram Stoker (Dublin 1897). The most influential story, however, was conceived by Mary Wollstonecraft, who visited Byron's villa together with her Stepsister Claire Clairmont and her lover and later husband Percy Bysshe Shelly.  Percy may have inadvertently influenced the contents of Mary's novel, as he was a student of the Scottish physician James Lind. Lind was influenced by Galvani’s work on frog leg experiments like many others at the beginning of the 19th century. These activities were preceded with the invention of the first battery by Alessandro Volta. His batteries could generate electrostatic potential differences of up to 100 Volts, which was sufficient to cause muscle twitches in dead animals and humans. These observations might have triggered the imagination that electricity could be a crucial factor to resurrect the function of animal and human tissues and in the end even whole bodies. Most influential in this context were the experiments of Galvani’s nephew Giovanni Aldini, who publicly zapped the heads of decapitated criminals in an attempt to reanimate them. He imagined this could be used to resuscitate people who had drowned or suffocated and possibly to help the insane. These and other developments of biological sciences at those times have definitely influenced the origin of Mary Shelley´s story: “Frankenstein, or the modern Prometheus”. Impressed by the work Byron persuaded Mary to expand her short story to a novel and publish it.
Although the novel "Frankenstein, or the modern Prometheus" was not well accepted when published, it gained remarkable popularity as the hubris of science in form of the human derived monster, who became a murderer, much later via the stage play and specifically by the 1931 film where Boris Karloff was portraying the monster and the 1994 film with Robert de Niro as the creature (Taschwer 2018). In 2015, a consortium of 82 international literature critics chose Mary Shelley's novel as one of the best British novels (“The 100 best novels written in English: the full list | Books | The Guardian,” n.d.).  Meanwhile, both the novel and the films are utilised to depict the danger which potentially may arise from certain scientific approaches.  
An article in Surgical Neurology International 2013 proposed recreating Aldini’s experiments with decapitated human heads. The authors of “HEAVEN (HEad Anastomosis VENture): The Frankenstein effect,” noted that Aldini ultimately aimed to transplant a human head, using electricity to spark it back into awareness. The authors wrote, “On the whole, in the face of clear commitment, HEAVEN could bear fruit within a couple of years,” they write (Cohen, 2018). Many scientists have called the project unfeasible and unethical, but two of the co-authors recently announced to the media that they had performed a head transplant on a human corpse and soon plan to publish the details.Although this activity seems to be an outlier and the general scientific consensus is that “the mad scientist playing God the creator will cause the entire human species to suffer eternal punishment for their trespasses and hubris“. “Mary Shelley, Frankenstein, and The Dark Side of Medical Science,” a 2014 essay published in the charmingly incongruous Transactions of the American Clinical and Climatological Association, ticks off a diverse list of recent experiments that have drawn the “Franken-” label, to name but a few: the maintenance of viable small pox, the cloning of Dolly the sheep, the engineering of a highly lethal H5N1 bird influenza that could more easily infect mammals, the synthesizing of an entire bacterial genome, and genetic engineering of the human genome using CRISPR-CAS9. Other triggers of Frankenstein-ish fears have included in vitro fertilization, proposals to transplant pig organs into humans, and tomatoes endowed with genes from fish to make them freeze-tolerant (Cohen 2018). Craig Venter, a pioneer in genomics based in San Diego, California, has been called a Frankenstein for his effort to create cells with synthetic DNA and generate the smallest possible genomes. Still, he is proposed to be a fan of Shelley’s tale. “I think she’s had more influence with that one book than most authors in history,” says Venter, who owns a first edition. “It affects a lot of people’s thinking and fear because it represents this fundamental of ‘You don’t mess with Mother Nature and you don’t mess with life because God will strike you down.’” “Obviously, I don’t buy into that theme,” he adds.
The Frankensteinmyth endures, he says, because “fear is easy to sell”—even when unwarranted. “Most people have a fear of what they don’t understand,” he says. “Synthetic cells are pretty complicated and putting a new gene into corn sounds scary.” But by throwing around labels like Frankenfood and Frankencells to rally the public against potentially valuable innovations, he says, the “fear-based community will potentially do more damage to humanity than the things they .” Unlike Frankenstein, who initially didn’t consider how his work might go wrong, Venter says he recognises that editing and rewriting genomes could “contaminate the world” and cause unintended harm. “I think we need to be very smart about when we do it, and how we do it,” he says. He thinks Shelley “would highly appreciate” his work. Henk van den Belt, a philosopher and ethicist at Wageningen University (WUR) in the Netherlands, who wrote a paper about Frankenstein and synthetic biology, applauds Venter for fighting back against the Frankenslur. “Very often  scientists are afraid to take this position, but I think it’s better to be defiant,” Van den Belt says (Cohen 2018).
We write this series not to create any kind of angst but simply to inform the scientific community and the public as a whole of both the opportunities and the potential dangers of the utilisation and further manipulation of human cells in culture. We feel that the journal in vitro toxicology and its readership is a perfect outlet for this article series.

 

List of References FrankensteinMAIN:

  1. Klaus Taschwer 200 Jahre Frankenstein:der Horror der Forschung https://www.derstandard.at/story/200007217916/200-jahre-frankenstein-der-horror-der-forschung
  2. Jon Cohen Science 359 (6372), DOI: 10.1126/science.359.6372.148 How a horrorstory haunts science
  3. https://www.theguardian.com/books/booksblog/2015/dec/08/best-british-novel-of-all-time-international-critics-top-100-middlemarch
  4. Henk van den Belt Frankenstein lives on. Science 359, 6372, 137 DOI 10.1126/science.aas9167