On the Origins of Modern Biology and the Fantastic — Part 17: Iain M. Banks and Genetic Engineering

“Just doing nothing is a statement, don’t you understand that? What is all your studying worth, all your learning, all your knowledge, if it doesn’t lead to wisdom? And what’s wisdom but knowing what is right, and what is the right thing to do?” —Cheradenine Zakalwe in Use of Weapons

Where does the moral boundary of a society lie, and at what point can utilitarian reasoning based in the concept of “the greater good” justify intervention in the affairs of other civilizations?” And if an individual is used as a mercenary of such a society, where does their humanity stop and their weaponhood begin? Use of Weapons (1990) is the third book in Iain M. Banks’ Culture series, which uses the trappings of a liberal anarchist utopia to examine politics, philosophy, morality, religion, and human psychology from the perspective of an ultimate mercenary on the side of such a “greater good.” It is a Gothic tale of split identity, fast-paced bloodshed, and galactic excess, told through two converging storylines and informed by a critique of traditional space opera tropes.

New Wave critics took issue with the traditional space opera of the ’30s and ’40s, viewing the subgenre as a conservative expression of the “Great Man” theory of history, in which a heroic figure (a man) set right all wrongs while defeating the other (aliens) and preserving the status quo. Decades later, space opera remained hierarchical, militaristic, and imperialist, influenced by the popularity of Star Wars, and echoed the increase in political conservatism of the 1970s and ’80s. It was within this milieu that a notable member of the next generation of science fiction writers would blend his literary and science fictional influences to examine the conservative morality of space opera—bringing about a sea change in what would become New Space Opera, while also becoming a prominent member of the Scottish Fantastic literary movement in the process: Iain Menzies Banks.

A similarly impactful sea change would take place in the realm of biology, which would bring long-standing moral dilemmas back into public consciousness, thanks to advances in tools for genetic engineering. From the moment genes were discovered to be responsible for traits, ideas and theories involving eugenics began to spread, evolving from questionable theory to a (thankfully limited) period of crude and horrific practice in the United States and Nazi Germany. But the advent of recombinant DNA technology, PCR, cloning and sequencing in the 1970s and ’80s, along with the development of prenatal tests for genetic disease and the ability for genetic information to become actionable thanks to Roe v Wade (1973), the theoretical once again became practical. Through trial and error, a guiding moral rubric evolved around what situations genetic information should be acted on: 1) Genetic testing should be restricted to gene variants guaranteed to cause a disease that 2) causes extraordinary suffering, and that 3) a justifiable intervention, such as abortion or medical intervention, is governed by complete freedom of choice. But where is the line drawn with interventions? Would you discard embryos with some types of mutations and not others? What if you had the capacity to fix any mutation in such an embryo? In terminally differentiated somatic tissues? In germline/reproductive cells? The technology that enabled genetic editing to become possible with an unprecedented level of precision, as we’ll see, is CRISPR.

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Banks, born in Scotland on February 16, 1954, was the only child of a professional ice skater and an Admiralty officer. He grew up in North Queensferry in the shadow of the Forth Bridge, which gave him a lifelong awe of engineering, before moving to Gourock at nine. Banks read lots of SF, deciding to become a writer at eleven, and writing his first novel at thirteen—a Catch-22-like satire packed with puns and Terry Gilliam-esque collages. In high school he met Ken MacLeod, a fellow science fiction fan and editor of the school magazine. MacLeod asked Banks for a story, and though he rejected it for profanity, the two became lifelong friends. Their mutual love of SF criticism led them both to read a 1971 essay by John Clute and M. John Harrison that called out science fiction as “a literature of shoddy programmed pap,” and inspired them to think about how they could write a space opera—the subgenre of bright and open-ended futures—that Clute and Harrison would approve of. Banks was already collecting publisher rejections when he enrolled at the University of Stirling to study English literature, philosophy, and psychology. He wrote more seriously and further developed his space opera ideas into what would become the Culture—a communistic space civilization of “pan-sentient utilitarian hedonism,” according to MacLeod, in which the greater good means greater pleasure for everyone.

Meanwhile, the pipe dream in biology has always been to bring about the greater good through the ability to affect specific genetic changes. It was traditionally limited by 1) not knowing which genes were responsible for which traits, and 2) the lack of a broadly applicable and specific technique to edit genes. The first hurdle was cleared thanks to DNA mapping and sequencing, but the solution to the second has remained elusive. Irradiation-inspired early efforts at gene editing came along, followed by chemical mutation, until it was discovered that certain viruses could stably integrate their genetic material into a host’s genome. The first transgenic mouse capable of passing its transgene down through its germline cells was created in 1981, winning a 2007 Nobel Prize. The first disease model for cancer came soon after in 1984, when an oncogene was introduced that predisposed mice to cancer. Researchers soon created mouse lines for a variety of diseases, but mouse lines took years to create, and genes could only be inserted, leaving the endogenous genes intact.

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After university, Banks continued to pursue his own dreams of becoming a writer while soaking up the influences that would inform his work for his lifetime—one job near Inverness influenced the setting of his first published novel. In 1979, Britain undermined Scottish efforts to establish an assembly, and the rise of the conservative U.K. government made Scots feel like they’d lost control of their destiny. These sentiments rippled through Scottish fiction, sparking the Scottish Fantastic literary movement, of which Banks became an important part. The work of writers associated with this milieu, including Alastair Gray and Irvine Welsh, featured characters struggling with helplessness, with fractured identities, and lives deformed to fit external power structures. In fact, Gray’s experimental novel, Lanark (1981), profoundly impacted Banks’ ideas of literary structure.

Banks, who had by then to London and met his future wife, Annie Blackburn, was growing frustrated by rejections for his science fiction. He pivoted to the mainstream with The Wasp Factory (1984), which was pulled from the Macmillan slush pile and published on Banks’ 30th birthday. It is a darkly funny and disturbing story of the ritualized existence of a teenage boy on the remote Scottish coast, which garnered equal acclaim and derision from critics, and marked Banks as a rising star in Scottish fiction. Thereafter he wrote full-time, channeling his astute societal observations into his second mainstream novel, Walking on Glass (1985), which featured entwined stories of a contemporary lovesick  London college student and two war criminals playing games in a far-future Gothic castle. He followed that up with his first masterpiece, The Bridge (1986), about an amnesiac trapped on a bridge of his own mental construction.

Biology’s first big break in gene editing came from a set of similarly astute observations, in this case from researchers working with transgenic plants. RNA interference (RNAi) was observed in 1986, when researchers noticed when transgenes randomly integrated beside promoters running the opposite direction, it would create an “antisense” transcript complementary to their “sense” strand, thus forming double-stranded RNA, which was preferentially degraded. By 1997, researchers discovered the degradation mechanism was mediated by short-complementary sequences, known as microRNAs, which act not only in plant immunity to viruses, but to broadly regulate gene expression. Within a year, Andrew Fire and Craig Mello conducted the first RNAi experiment, and discovered the mechanism also existed in C. elegans, earning them a 2006 Nobel Prize. The technique’s power was in its ability to target specific genes in a broad range of species. Soon enough, its limitations became apparent. Sequence similarity to other places in the genome led to off-target effects, and frequently the target genes wouldn’t be completely knocked out, but only had their expression turned down a bit.

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The same year RNAi was discovered, Banks moved home to North Queensferry. Despite the SFnal elements in his work and his mainstream success, Banks remained unnoticed in SF. He used his clout to convince Macmillan to publish his science fiction novel, Consider Phlebas (1987) under the name “Iain M. Banks” (whereas his previous work was credited to Iain Banks). His first Culture novel, it’s a straightforward adventure in which his liberal, atheist utopia fights a war against the Idrians—a race of religious zealots. While the space opera angle surprised readers, the book was full of rich worldbuilding, Banks’ characteristic dark humor, and philosophical subtexts. He quickly published three more Culture books: Player of Games (1988), Use of Weapons (1990) and short story collection The State of the Art (1991). The Culture became an instant hit. Banks’ depiction of his ideal post-scarcity society—where people can become anything they wish in terms of race, shape, sex, or cyborg elements through near-magical feats of genetic engineering, while living whatever life they choose—demonstrated how, even in such a liberal utopia, humans (and their machine creations) are inherently hypocritical and self-destructive, as seen through the eyes of their enemies, bored citizens, and adopted outsiders as the Culture engages with societies actively or ideologically opposed to them. In the end, the Culture’s urge to not feel useless trumps the urge to do no harm—creating fertile grounds for explorations of the contemporary morality of benevolent colonialism. Player and Weapons would both win various European awards.

The genetic engineering successes of the early 1990s inspired clinicians to join in the fun, deciding on retroviruses as the delivery mechanism. The first proof of principle clinical trial in 1994 saw two patients transfused with their own T-cells transfected with a copy of an enzyme involved in immune response in which they were deficient. With no observed ill effects, the flood gates quickly opened, then shut again following multiple deaths caused by poorly designed trials, including eighteen year-old Jesse Gelsinger, whose body mounted a massive immune response to an adenovirus vector, which is related to the virus that causes the common cold. The excitement in the scientific community had proved premature, as researchers returned to the drawing board.

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Following the success of the Culture books, Banks too returned to the drawing board, releasing a series of standalone SF novels, citing a fear of becoming too comfortable in the Culture universe. Against a Dark Background (1993) explored an exaggeratedly capitalist world, and Feersum Endjinn (1994), followed the remnants of an abandoned humanity as they squabble in the shadow of a deserted space elevator as an existential threat closes in from the cosmos. But Banks couldn’t stay away from the Culture for long: Excession (1996), Inversions (1998), and Look to Windward (2000), instead of looking at the Culture from the outside, examine how the Culture deals with the unknown, the practical applications of its morality, the consequences of its imperialistic missteps, and how it grapples with death.

In the realm of biology, the need for better tools became a prerogative following the clinical deaths of the 1990s, and the first discovery with the required specificity came with the discovery of nucleases’ ability to cut double-stranded DNA. Cellular repair mechanisms were discovered to use nearby complementary templates to repair such breaks, therefore eliminating the need to insert genetic material randomly into the genome with a virus. The first attempts using a randomly cutting nuclease and a complementary template containing gene repair were made in 1994 at Memorial Sloan Kettering, resulting in an unprecedented 10% success rate. Then, in 1996, a group at Johns Hopkins joined a nuclease to a Zinc Finger protein, which could recognize specific DNA sequences, thus only cutting the sequence you wanted to cut in a single spot of your choosing. Incremental improvements to specificity were made, but the constructs were difficult to make and prohibitively expensive.

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In 2002, Banks was able to undertake an otherwise prohibitively expensive tour of Scotland’s distilleries when he wrote Raw Spirit (2003), his only nonfiction book, which is about Scotch, friends, fast cars, and the burgeoning Iraq War, before returning to fiction with the standalone SF novel The Algebraist (2004). It was an unfocused and infodump-rich space adventure, and the first book released after the 2003 death of his longtime friend and editor, James Hale. Banks then took a brief step away from fiction as his life became more turbulent before publishing what would be his final Culture novels: Matter (2008), Surface Detail (2010), and The Hydrogen Sonata (2012). The three books deal with secular examinations of religious morality, godhood, afterlives, and the Culture’s own hesitancies when it comes to the next step in its evolution. He also released Transition (2009), a complex blend of mainstream fiction and SF, with multiple characters transitioning between multiverses.

Around the same time Banks was touring Scottish distilleries, researchers noticed among the sequences of bacterial genomes that were piling up that some contained clustered, regularly interspaced, short palindromic repeating (CRISPR) sequences, and that the unique sequences between these repeating elements were complementary to known bacterial viruses. Upon further study, it was found that when transcribed, the short, complementary RNAs bound to their target viruses, and a Cas (CRISPER-associated) protein would then degrade that double-stranded RNA. The system was simple—requiring only a guiding RNA sequence that matched what you wanted to cut, and the Cas9 protein to cut that sequence. The first publication to mention CRISPR/Cas9’s utility for genome editing (from Jennifer Doudna’s group at Berkeley) appeared in 2012, and the first experiment using it to edit human cells was published in 2013. CRISPR was specific, broadly applicable, as well as being cheap and fast, enabling mouse disease models to be created in months instead of years. It could be used not only to repair defective genes, but could be used to knock genes out, or change them to study their component parts. It took biology by storm, leading to a call for a temporary moratorium in 2015, following reports of it being used (unsuccessfully) on human embryos in China. But progress has been made, and the first CRISPR-based therapies entered human clinical trials in 2019. With this unprecedented level of control, the kinds of justifiable interventions have dramatically increased, and gene editing interventions now seem to be pushing us from discussions of what circumstances we should intervene in to discussions focused on the circumstances in which we should not.

Iain Banks was diagnosed with inoperable cancer in late 2012, and would die at the age of 59, just two weeks before his final book, The Quarry, was released in June 2013. While celebrated in Europe, Banks’ literary influence was somewhat spottier in the United States, but his works are now beginning to receive more critical attention, as is his influence on the British Boom, which helped opened up space opera to become a more diverse and politically and socially progressive subgenre.

In our next and final installment, we’ll look at the further diversification of voices and perspectives within science fiction, as well as the impact of genetic engineering on the understanding and control of cellular diversification in stem cell biology.

Kelly Lagor is a scientist by day and a science fiction writer by night. Her work has appeared at Tor.com and other places, and you can find her tweeting about all kinds of nonsense @klagor

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