Tag Archives: Genetic engineering

A Gigeresque melange

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Reading Cold People by Tom Robb-Smith for the Times, 14 January 2023

Harvard medical student Liza is on holiday in Lisbon with her parents and younger sister when gigantic alien fish-shapes descend from the sky and order all humans to vacate the habitable bits of their planet for Antarctica, the only continent humans have never been able to settle.

Twenty years on, in a ramshackle, endlessly retrofitted settlement on the Antarctic Peninsula called Hope Town, Liza — one of very few survivors — gives birth to Echo, a genetically engineered daughter whose modifications allow her to withstand the bitter cold. Echo is an early prototype of future human being designed in McMurdo City (the ramshackle, ice-bound, over-serious new capital of humanity) by the heroically unprincipled geneticist Song Fu, aided and abetted by her assistant Yotam Penzak, the book’s splendidly drawn antagonist. (The author of Child 44 knows how to tell a story; you know you’re in safe hands when your villain is motivated by love.)

Yotam, who attended her birth, thinks Echo and her posthuman kind are a worthy end in themselves: powerful and humane, capable of nurturing unengineered humanity in their impossible new environment, even as they succeed them over evolutionary time.

His boss disagrees. The remains of humanity will die out in not much more than a century, says Song Fu. A more radical succession is required if humans are to survive in any form.

Yotam’s unlucky love life leaves him vulnerable to browbeating by his boss, and then to seduction by Song Fu’s posthumous final creation, a Giger-esque melange of human, alligator and shark.

In this wasteland, “Eitan” and his kind are by far the dominant species — or will be, if Yotam lets them out of their cave.
Much as Roald Amundsen and his party consumed the husky dogs that had got him to the Pole in 1911, they will consume their human creators, not out of hate or revenge, but simply because they have no other use for them.

Can Yotam’s convictions be shaken? Can Eitan be stopped?

Cold People does not explore ideas; it animates them. Plot is king. Smith’s characters aren’t so much pretend people as they are admirable, animated types. The result is a page-turner that, without offering much by way of ordinary human feeling, reveals Tom Rob Smith’s view of the human condition: what he thinks about the plight of thinking, would-be ethical beings who still need to consume and burn and exploit in order to survive. In Smith’s vision, humanity’s reach so far exceeds its grasp that its downfall at its own hand seems more or less assured.

These are chewy and worthwhile themes, and Cold People cleverly distils them to the point where they play out, and reach a satisfying climax, at ordinary human scale. If Echo can protect her human family, there’s hope for humanity at large. If not, we’re all for the chum bucket.

Cold People will entertain and impress readers who enjoy novels that are containers for ideas. The rest of us may regret that Smith did not linger longer among the Polynesian navigators, seal hunters and stir-crazy researchers populating his largely irrelevant but wonderfully evocative prologue. Slow down, Smith! You were so set on your destination, you missed the scenery.

Citizen of nowhere

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Watching Son of Monarchs for New Scientist, 3 November 2021

“This is you!” says Bob, Mendel’s boss at a genetics laboratory in New York City. He holds the journal out for his young colleague to see: on its cover there’s a close-up of the wing of a monarch butterfly. The cover-line announces the lab’s achievement: they have shown how the evolution and development of butterfly color and iridescence are controlled by a single master regulatory gene.

Bob (William Mapother) sees something is wrong. Softer now: “This is you. Own it.”
But Mendel, Bob’s talented Mexican post-doc (played by Tenoch Huerta, familiar from the Netflix series Narcos: Mexico), is near to tears.

Something has gone badly wrong in Mendel’s life. And he’s no more comfortable back home, in the butterfly forests of Michoacán, than he was in Manhattan. In some ways things are worse. Even at their grandmother’s funeral, his brother Simon (Noé Hernández) won’t give him an inch. At least the lab was friendly.

Bit by bit, through touching flashbacks, some disposable dream sequences and one rather overwrought row, we learn the story: how, when Mendel and Simon were children, a mining accident drowned their parents; how their grandmother took them in, but things were never the same; how Simon went to work for the predatory company responsible for the accident, and has ever since felt judged by his high-flying, science-whizz, citizen-of-nowhere brother.

When Son of Monarchs premiered at this year’s Sundance Film Festival, critics picked up on its themes of borders and belonging, the harm walls do and all the ways nature undermines them. Mendel grew up in a forest alive with clouds of Monarch butterflies. (In the film the area, a national reserve, is threatened by mining; these days, tourism is arguably the bigger threat.) Sarah, Mendel’s New York girlfriend (Alexia Rasmussen; note-perfect but somewhat under-used) is an amateur trapeze artist. The point — that airborn creatures know no frontiers — is clear enough; just in case you missed it, a flashback shows young Mendel and young Simon in happier days, discussing humanity’s airborne future.

In a strongly scripted film, such gestures would have been painfully heavy-handed. Here, though, they’re pretty much all the viewer has to go on in this sometimes painfully indirect film.
The plot does come together, though, through the character of Mendel’s old friend Vicente (a stand-out performance by the relative unknown Gabino Rodríguez). While muddling along like everyone else in the village of Angangueo (the real-life site, in 2010, of some horrific mine-related mudslides), Vicente has been developing peculiar animistic rituals. His unique brand of masked howling seems jolly silly at first glance — just a backwoodsman’s high spirits — but as the film advances, we realise that these rituals are just what Mendel needs.

For a man trapped between worlds, Vicente’s rituals offer a genuine way out: a way to re-engage imaginatively with the living world.

So, yes, Son of Monarchs is, on one level, about identity, about how a cosmopolitan high-flier learns to be a good son of Angangeo. But more than that, it’s about personality: about how Mendel learns to live both as a scientist, and as a man lost among butterflies.

French-Venezuelan filmmaker Alexis Gambis is himself a biologist and founded the Imagine Science Film Festival. While Son of Monarchs is steeped in colour, and full of cinematographer Alejandro Mejía’s mouth-watering (occasionally stomach-churning) macro-photography of butterflies and their pupae, ultimately this is a film, not about the findings of science, but about science as a vocation.

Gambis’s previous feature, The Fly Room (2014) was about the inspiration a 10-year-old girl draws from visits to T H Morgan’s famous (and famously cramped) “Fly Room” drosophila laboratory. Son of Monarchs asks what can be done if inspiration dries up. It is a hopeful film and, on more than the visual level, a beautiful one.

Life at all costs

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Reading The Next 500 Years by Chris Mason for New Scientist, 12 May 2021

Humanity’s long-term prospects don’t look good. If we don’t all kill each other with nuclear weapons, that overdue planet-killing asteroid can’t be too far off; anyway, the Sun itself will (eventually) explode, obliterating all trace of life in our planetary system.

As if awareness of our own mortality hasn’t given us enough to fret about, we are also capable of imagining our own species’ extinction. Once we do that, though, are we not ethically bound to do something about it?

Cornell geneticist Chris Mason thinks so. “Engineering,” he writes, “is humanity’s innate duty, needed to ensure the survival of life.” And not just human life; Mason is out to ensure the cosmic future of all life, including species that are currently extinct.

Mason is not the first to think this way, but he arrives at a fascinating moment in the history of technology, when we may, after all be able to avoid some previously unavoidable catastrophes.

Mason’s 500-year plan for our future involves reengineering human and other genomes so that we can tolerate the (to us) extreme environments of other worlds. Our ultimate goal, Mason says, should be to settle new solar systems.

Spreading humanity to the stars would hedge our bets nicely, only we currently lack the tools to survive the trip, never mind the stay. That’s where Mason comes in. He was principal investigator on NASA’s Twins Study, begun in 2015: a foundational investigation into the health of identical twins Scott Kelly and Mark Kelly during the 340 days Scott was in space and Mark was on Earth.

Mason explains how the Twins Study informed NASA’s burgeoning understanding of the human biome, how a programme once narrowly focused on human genetics now extends to embrace bacteria and viruses, and how new genetic engineering tools like CRISPR and its hopeful successors may enable us to address the risks of spaceflight (exposure to cosmic radiation radiation is considered the most serious) and protect the health of settlers on the Moon, on Mars, and even, one day, on Saturn’s moon Titan.

Outside his specialism, Mason has some fun (a photosythesizing human would need skin flaps the size of two tennis courts — so now you know) then flounders slightly, reaching for familiar narratives to hold his sprawling vision together. More informed readers may start to lose interest in the later chapters. The role of spectroscopy in the detection of exoplanets is certainly relevant, but in a work of this gargantuan scope, I wonder if it needed rehearsing. And will readers of a book like this really need reminding of Frank’s Drake equation (regarding the likelihood of extra-terrestrial civilisations)?

Uneven as it is, Mason’s book is a genuine, timely, and very personable addition to a 1,000-year-old Western tradition, grounded in religious expectations and a quest for transcendence and salvation. Visionaries from Isaac Newton to Joseph Priestley to Russian space pioneer Konstantin Tsiolkowsky have spouted the very tenets that underpin Mason’s account: that the apocalypse is imminent; and that, by increasing human knowledge, we may recover the Paradise we enjoyed before the Flood.

Masonic beliefs follow the same pattern; significantly, many famous NASA astronauts, including John Glenn, Buzz Aldrin and Gordo Cooper, were Freemasons.

Mason puts a new layer of flesh on what have, so far, been some ardent but very sketchy dreams. And, though a proud child of his engineering culture, he is no dupe. He understands and explores all the major risks associated with genetic tinkering, and entertains all the most pertinent counter-arguments. He knows where 19th-century eugenics led. He knows the value of biological and neurological diversity. He’s not Frankenstein. His deepest hope is not that his plans are realised in any recognisable form; but that we continue to make plans, test them and remake them, for the sake of all life.

We may never have a pandemic again

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Reading The Code Breaker, Walter Isaacson’s biography of Jennifer Doudna, for the Telegraph, 27 March 2021

In a co-written account of her work published in 2017, biochemist Jennifer Doudna creates a system that can cut and paste genetic information as simply as a word processor can manipulate text. Having conceived a technology that promises to predict, correct and even enhance a person’s genetic destiny she says, not without cause, “I began to feel a bit like Doctor Frankenstein.”

When it comes to breakthroughs in biology, references to Mary Shelley are irresistible. One of Walter Isaacson’s minor triumphs, in a book not short of major triumphs, is that, over 500 pages, he mentions that over-quoted, under-read novel less than half a dozen times. In biotechnology circles, this is probably a record.

We explain science by telling stories of discovery. It’s a way of unpacking complicated ideas in narrative form. It’s not really history, or if it is, it’s whig history, defined by a young Herbert Butterfield in 1931 as “the tendency… to praise revolutions provided they have been successful, to emphasise certain principles of progress in the past and to produce a story which is the ratification if not the glorification of the present.”

To explain the science, you falsify the history.
So all discovers and inventors are heroes on the Promethean (or Frankensteinian) model, working in isolation, and taking on the whole weight of the world on their shoulders!

Alas, the reverse is also true. Telling the true history of discovery makes the science very difficult to unpack. And though Walter Isaacson, whose many achievements include a spell as CEO of the Aspen Institute, clearly knows his science, his account of the most significant biological breakthrough since understanding the structure of DNA is not the very best account of CRISPR out there. His folksy cajoling — inviting us to celebrate “wily bacteria” and the “plucky little molecule” RNA — suggests exasperation. Explaining CRISPR is *hard*.

The Code Breaker excels precisely where, having read Isaacson’s 2011 biography of Steve Jobs, you might expect it to excel. Isaacson understands that all institutions are political. Every institutional activity — be it blue-sky research into the genome, or the design of a consumer product — is a species of political action.

The politics of science is uniquely challenging, because its standards of honesty, precision and rigour stretch the capabilities of language itself. Again and again, Doudna’s relationships with rivals, colleagues, mentors and critics are seen to hang on fine threads of contested interpretation. We see that Doudna’s fiercest rivalry, with Feng Zhang of the Broad Institute of MIT and Harvard, was conducted in an entirely ethical manner — and yet we see both of them stumbling away, bloodied.

Isaacson’s style of biography — already evident in his appreciations of Einstein and Franklin and Leonardo — can be dubbed “qualified hagiography”. He’s trying to hit a balance between the kind of whig history that will make complex materials accessible, and the kind of account that will stand the inspection of academic historians. His heroes’ flaws are explored, but their heroism is upheld. It’s a structural device, and pick at it however you want, it makes for a rattlingly good story.

Jennifer Doudna was born in 1964 and grew up on Big Island, Hawaii. Inspired by an old paperback copy of The Double Helix by DNA pioneer James Watson, she devoted her life to understanding the chemistry of living things. Over her career she championed DNA’s smaller, more active cousin RNA, which brought to her notice a remarkable mechanism, developed by single-celled organisms in their 3.1-million-year war with viruses. Each of these cells used RNA to build their very own immune system.

Understanding that mechanism was Doudna’s triumph, shared with her colleague Emmanuelle Charpentier; both conspicuously deserved the Nobel prize awarded them last year.

Showing that this mechanism worked in cells like our own, though, would change everything, including our species’ relationship with its own evolution. This technology has the power to eradicate both disease (good) and ordinary human variety (really not so good at all).

In 2012, the year of the great race, Doudna’s Berkeley lab knew nothing like enough about working with human cells. Zhang’s lab knew nothing like enough about the biochemical wrinkles that drove CRISPR. Their rivalrous decision not to pool CRISPR-Cas9 intellectual property would pave the way for an epic patent battle.

COVID-19 has changed all that, ushering in an extraordinary cultural shift.. Led by Doudna and Zhang, last year most academic labs declared that their discoveries would be made available to anyone fighting the virus. New on-line forums have blossomed, breaking the stranglehold of expensive paywall-protected journals.

Doudna’s lab and others have developed home testing kits for COVID-19 that have a potential impact beyond this one fight, “bringing biology into the home,” as Isaacson writes, “the way that personal computers in the 1970s brought digital products and services… into people’s daily lives and consciousness.”

Meanwhile genetic vaccines powered by CRISPR — like the ones developed for COVID-19 by Moderna and BioNTech/Pfizer — portend a sudden shift of the evolutionary balance between human beings and viruses. Moderna’s chair Noubar Afeyan is punchy about the prospects: “We may never have a pandemic again,” he says.

The Code Breaker catches us at an extraordinary moment. Isaacson argues with sincerity and conviction that, blooded by this pandemic, we should now grasp the nettle, make a stab at the hard ethical questions, and apply Doudna’s Promethean knowledge, now, and everywhere, to help people. Given the growing likelihood of pandemics, we may not have a choice.

 

Pollen count

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Watching Jessica Hausner’s film Little Joe for New Scientist, 11 March 2020

THEY are red, they have stalks that look like eels, and no leaves. But Karl, the boss of the laboratory – played by the unsettling David Wilmot – has his eye on them for the forthcoming flower fair. He tells visiting investors that these genetically engineered creations are “the first mood-lifting, antidepressant, happy plant”.

Ben Whishaw’s character, Chris, smirks: “You’ll love this plant like your own child.”

Chris is in love with Alice, played by Emily Beecham, who is in love with her creations, her “Little Joes”, even to the point of neglecting her own son, Joe.

Owning and caring for a flower that, treated properly, will emit pollen that can induce happiness, would surely be a good thing for these characters. But the plant has been bred to be sterile, and it is determined to propagate itself by any means necessary.

Little Joe is an exercise in brooding paranoia, and it feeds off some of the more colourful fears around the genetic modification of plants.

Kerry Fox plays Bella, whose disappointments and lack of kids seem to put her in the frame of mind to realise what these innocent-looking blooms are up to. “The ability to reproduce is what gives every living thing meaning!” she exclaims. Her colleagues might just be sceptical about this because she is an unhappy presence in the lab, or they may already have fallen under the sway of Little Joe’s psychoactive pollen.

Popular fears around GM – the sort that dominated newspapers and scuppered the industry’s experimental programmes in the mid-1990s – are nearly as old as the science of genetics itself.

At about the turn of the 20th century, agricultural scientists in the US combined inbred lines of maize and found that crop yields were radically increased. Farmers who bought the specially bred seed found that their yields tailed off in subsequent years, so it made sense to buy fresh seed yearly because the profits from bigger crops more than covered the cost of new seeds.

In the 2000s, Monsanto, a multinational agribusiness, added “terminator” genes to the seed it was developing to prevent farmers resowing the product of the previous year’s crop. This didn’t matter to most farmers, but the world’s poorest, who still rely on replanting last year’s seed, were vociferous in their complaints, and a global scandal loomed.

Monsanto chose not, in the end, to commercialise its terminator technologies, but found it had already created a monster: an urban myth of thwarted plant fecundity that provides Jessica Hausner’s Little Joe with its science fictional plot.

What does Little Joe’s pollen do to people? Is it a vegetal telepath, controlling the behaviour of its subjects? Or does it simply make the people who enjoy its scent happier, more sure of themselves, more capable of making healthy life choices? Would that be so terrible? As Karl says, “Who can prove the genuineness of feelings? Moreover, who cares?”

Well, we do, or we should. If, like Karl, we come to believe that the “soul” is nothing more than behaviour, then people could become zombies tomorrow and no one would notice.

Little Joe’s GM paranoia may set some New Scientist readers’ teeth on edge, but this isn’t ultimately, what the movie is about. It is after bigger game: the nature of human freedom.