Tag Archives: biology

This is not how science is done!

Posted on by

Reading J. Craig Venter & David Ewing Duncan’s Microlands for the Telegraph

Scientists! Are you having fun? Then stop it. Be as solemn as an owl, or else. Your career depends on it. Discoveries are all very well for the young, but dogma is what gets you tenure. Any truths you uncover must be allowed to ossify through constant poker-faced repetition. And Heaven forbid that before your death, a new idea comes along, forcing you to recalculate and re-envision your life’s work!

Above all, do not read Microlands. Do not be captivated by its adventures, foreign places and radical ideas. This is not how science is done!

Though his book edges a little too close to corporate history to be particularly memorable, it is clear that science journalist David Duncan has had an inordinate amount of fun co-writing this account of ocean-going explorations, led by biotechnologist Craig Venter between 2003 and 2018, into the microbiome of the Earth’s oceans.

While it explains with admirable clarity the science and technology involved in this global ocean sampling expedition, Microlands also serves as Duncan’s paean to Venter himself, who in 2000 disrupted the gene sequencing industry before it was even a thing by quickly and cheaply sequencing the human genome. Eight years later he was sailing around the world on a mission to sequence the genome of the entire planet — a classic bit of Venter hyperbole, this, ”almost embarrassingly grandiose” according to Duncan — but as Duncan says, “did he really mean it literally? Does it matter?”

It ought to matter. Duncan is too experienced a journalist to buy into the cliche of Venter the maverick scientist. According to Duncan, his subject is less a gifted visionary than a supreme and belligerent tactician, who advances his science and his career by knowing whom to offend. He’s an entrepreneur, not an academic, and if his science was off by even a little, his ideas about the microbial underpinnings of life on Earth wouldn’t have lasted (and wouldn’t have deserved to last) five minutes.

But here’s the thing: Venter’s ideas have been proved right, again and again. In the late 1990s he conceived a technology to read a long DNA sequence: first it breaks the string into readable pieces, then, by spotting overlaps, it strings the pieces back into the right order. A decade later he realised the same machinery could handle multiple DNA strands — it would simply deliver several results instead of just one. And if it could produce two or three readings, why not hundreds? Why not thousands? Why not put buckets of seawater through a sieve and sequence the microbiome of entire oceans?

And — this is what really annoys Venter’s critics — why not have some fun in the process? Why not gather water samples while sailing around the world on a cutting-edge sailboat, “a hundred-foot-long sliver of fiberglass and Kevlar”, and visiting some of the most beautiful and out-of-the-way places on Earth?

It is amusing and inspiring to learn how business acumen has helped Venter to a career more glamorous than those enjoyed by his peers. More important is the way in which his ocean sampling project has changed our ideas of how biology is done.

For over a century, biology has been evolving from a descriptive science into an experimental one. Steadily, the study of living things has given ground to efforts to unpick the laws of life.
But Venters’ project has uncovered so much diversity in aquatic microbial worlds, the standard taxonomy of kingdom, phylum, and species breaks down in an effort to capture its richness. At the microbial scale, every tiny thing reveals itself to be a special and unique snowflake. Genes pass promiscuously from bacterium to bacterium, ferried there very often by viruses, since they survive longer, the more energy-producing powers they can “download” into their host cell. We already know microbial evolution takes place on a scale of hours. Now it turns out the mechanisms of that evolution are so various and plastic, we can barely formalise them. “Laws of biology” may go some way to explain creatures as big as ourselves, but at the scale of bacteria and viruses, archaea and protozoa, wild innovation holds sway.

The field is simply overwhelmed by the quantity of data Venter’s project has generated. Discovering whether microbes follow fundamental ecological ‘laws’ at a planetary scale will likely require massive, monolithic cross-environment surveys — and many further adventure-travel vacations posing as expeditions by provoking tycoons who love to sail.

Here’s the capping irony, and Duncan does it proud — that Venter, the arch-entrepreneur of cutting-edge genetic science, is returning biology to a descriptive science. We are just going to have to go out and observe what is there — and, says Venter, “that’s probably where biology will be for the next century at least.”

Two hundred years of electro-foolery come good

Posted on by

Reading We Are Electric by Sally Adee for the Times, 28 January 2023

In an attempt to elucidate the role of electricity in biology, German polymath Alexander von Humboldt once stuck a charged wire up his bum and found that “a bright light appears before both eyes”.

Why the study of biological electricity should prove so irremediably smutty — so that serious ”electricians” (as the early researchers called themselves) steered well clear of bodies for well over a century — is a mystery science journalist Sally Adee would rather not have to re-hash, though her by-the-by account of “two hundred years of electro-foolery”, during which quacks peddled any number of cockeyed devices to treat everything from cancer to excessive masturbation, is highly entertaining.

And while this history of electricity’s role in the body begins, conventionally enough, with Volta and Galvani, with spasming frog’s legs and other fairly gruesome experiments, this is really just necessary groundwork, so that Adee can better explain recent findings that are transforming our understanding of how bodies grow and develop, heal and regenerate.

Why bodies turn out the way they do has proved a vexing puzzle for the longest while. Genetics offers no answer, as DNA contains no spatial information. There are genes for, say, eye colour, but no genes for “grow two eyes”, and no genes for “stick two eyes in front of your head”

So if genes don’t tell us the shape we should take as we grow, what does? The clue is in the title: we are, indeed, electric.

Adee explains that the forty trillion or so cells in our bodies are in constant electrical communication with each other. This chatter generates a field that dictates the form we take. For every structure in the body there is a specific membrane voltage range, and our cells specialise to perform different functions in line with the electrical cues they pick up from their neighbours. Which is (by way of arresting illustration) how in 2011 a grad student by the name of Sherry Aw managed, by manipulating electrical fields, to grow eyes on a developing frog’s belly.

The wonder is that this news will come as such a shock to so many readers (including, I dare say, many jobbing scientists). That our cells communicate electrically with each other without the mediation of nerves, and that the nervous system is only one of at least two (and probably many more) electrical communications systems — all this will come as a disconcerting surprise to many. Did you know you only have to put skin, bone, blood, nerve — indeed, any biological cell — into a petri dish and apply an electric field, and you will find all the cells will crawl to the same end of the dish? It’s taken decades before anyone thought to unpick the enormous implications of that fact.

Now we have begun to understand the importance of electrical fields in biology, we can begin to manipulate them. We’ve begun to restore some function after severe spinal injury (in humans) regrown whole limbs (in mice), and even turned cancerous tumours back into healthy tissue (in petri dishes).

Has bio-electricity — once the precinct of quacks and contrarians — at last come into its own? Has it matured? Has it grown up?

Well, yes and no. Adee would like to deliver a clear, single message about bioelectricity, but the field itself is still massively divided. On the one hand there are ground-breaking researches being conducted into development, regeneration and healing. On the other, there are those who think electricity in the body is mostly to do with nerves and brains, and their project — to hack peoples’ minds through their central nervous systems and usher in some sort of psychoelectric utopia — shows no sign of faltering.

In the 1960s the American neurophysiologist Warren McCulloch worked on the assumption that the way neurons fire is a kind of biological binary code. this led to a new school of thought, called cybernetics — a science of communications and automatic control systems, both living and mechanical. The idea was we should be able to drive an animal like a robot by simply activating specific circuits, an idea “so compelling” says Adee, “there wasn’t much point bothering with whether it was based in fact.”

Very many other researchers Adee writes about are just as wedded to the idea of the body as a meat machine.

This book arose from an article Adee wrote for the magazine New Scientist about her experiences playing DARWARS Ambush!, a military training simulation conducted in a Californian defence lab that (maybe) amped up her response times and (maybe) increased her focus — all by means of a headset that magnetically tickled precise regions in her brain.

Within days of the article’s publication in early 2012, Adee had become a sort of Joan of Arc figure for the online posthumanist community, and even turns up in Noah Yuval Harai’s book, where she serves as an Awful Warning about men becoming gods.

Adee finally admits that she would “love to take this whole idea of the body as an inferior meat puppet to be augmented with metal and absolutely launch it into the sun.” Coming clean at last, she admits she is much more interested in the basic research going on into the communications within and between individual cells — a field where the more we know, the more we realise just how much we don’t understand.

Adee’s enthusiasm is infectious, and she conveys well the jaw-dropping scale and complexity of this newly discovered “electrome”. This is more than medicine. “The real excitement of the field,” she writes, “hews closer to the excitement around cosmology.”

A normal process

Posted on by

Reading What Is Regeneration by Jane Maienschein and Kate MacCord for New Scientist, 30 March 2022

Some animals are able to regrow lost or damaged parts. Crabs and lobsters regenerate whole tentacles and claws. Many more animals have lifecycles that involve the wholesale shedding and regrowth of certain tissues. (Unlike hydras and some worms, we humans cannot regrow our heads; but we can regrow our fingernails.)

Regeneration is such a peculiar property, it is surprisingly often ignored or discounted. The 18th-century French naturalist René-Antoine Réaumur spoke to people who made their living by fishing and was surprised when they dismissed stories of limb regeneration as mere “fables”. (His own somewhat bloodthirsty experiments on the local crayfish showed otherwise.)

So is regeneration a mere oddity? Is there any underlying logic to it? And what does it have to do with the grander mysteries of birth, death and development?

Jane Maienschein directs the History and Philosophy of Science Project at the Marine Biological Laboratory in Woods Hole, Massachusetts. Kate MacCord administers the centre’s effort to study how regeneration works across the scales of complex living systems. This book is their collaborative effort to understand why regeneration occurs when it does, and whether the regeneration of communities (the gut flora in your intestines after a course of antibiotics, say, or the regeneration of woodland after a forest fire) bears anything more than a semantic relationship with the kind of regeneration those crayfish enjoyed in the weeks following their unlucky encounter with M. Réaumur.

Regeneration turns out to be one of those simple, discrete, observable phenomena that, the closer we look at them, seem to vanish into thin air. For instance, when we think about regeneration, are we thinking about regeneration of structure, or regeneration of function, or both? How we think about regeneration impacts whether and where we think it occurs.

The authors’ history of regeneration begins with Aristotle and ends with Magdalena Zernicka-Goetz’s current work on cellular signalling. Their account pivots on Thomas Hunt Morgan (better known as a pioneer of chromosomal genetics) and in particular on his book Regeneration of 1901. Morgan, more than anyone before or since, attempted to establish clear boundaries around the phenomenon of regeneration. The terminology he invented remains useful. Restorative regeneration occurs in response to injury. Physiological regeneration describes replacement, as when a bird moults its feathers or an elk its antlers and a new structures grow in their place. Morphallaxis refers to cases of reshaping, as when a hydra, cut to pieces, reorganises itself into a new hydra without going through the normal processes of cell division.

Morgan’s observations and analysis established that the mechanisms of regeneration are not (as our authors put it) “a special response to changing environmental conditions but, rather, an internal normal process of growth and development. Nor is regeneration an evolutionary adaptation to external conditions, even though the process may be useful.”

So here’s the problem: if the mechanisms of regeneration cannot be distinguished from the mechanisms of growth and development, what’s to stop everything regenerating all the time? What dictates lawful regrowth, and why does it happen only in some tissues, only in some species, and only some of the time?

Far from being an interesting curio, regeneration turns out to be a window through which we glimpse the tightly imbricated (if not impossibly entangled) feedback loops from which the living world, at every scale, is composed. The words of geneticist François Jacob, writing in 1974 and quoted here, barely conveys the scale of the challenge the authors reveal: “every object that biology studies is a system of systems.”

No wonder that regeneration remains largely a mystery; that hopeful regenerative therapies using stem cells usually fail (and usually for unfathomable reasons); and that even the simplest ecosystems elude our control.

Maienschein and MacCord take fewer than 150 pages to anatomise the complexities and ambiguities that their simple question throws up. It is to their further credit that they do not make the biology any more complex or ambiguous than it has to be.

“A moist and feminine sucking”

Posted on by

Reading Susan Wedlich’s Slime: A natural history for the Times, 6 November 2021

For over two thousand years, says science writer Susan Wedlich, quoting German historian Richard Hennig, maritime history has been haunted by mention of a “congealed sea”. Ships, it is said, have been caught fast and even foundered in waters turned to slime.

Slime stalks the febrile dreams of landlubbers, too: Jean-Paul Sartre succumbed to its “soft, yielding action, a moist and feminine sucking”, in a passage, lovingly quoted here, that had this reader instinctively scrabbling for the detergent.

We’ve learned to fear slime, in a way that would have seemed quite alien to the farmers of ancient Egypt, who supposed slime and mud were the base materials of life itself. So, funnily enough, did German zoologist Ernst Haeckel, a champion of Charles Darwin, who saw primordial potential in the gellid lumps being trawled from the sea floor by various oceanographic expeditions. (This turned out to be calcium sulphate, precipitated by the chemical reaction between deep-sea mud and alcohol used for the preservation of aquatic specimens. Haeckel never quite got over his disappointment.)

For Susan Wedlich, it is not enough that we should learn about slime; nor even that we should be entertained by it (though we jolly well are). Wendlich wants us to care deeply about slime, and musters all the rhetorical at her disposal to achieve her goal. “Does even the word “slime” have to elicit gagging histrionics?” she exclaims, berating us for our phobia: “if we neither recognize nor truly know slime, how are we supposed to appreciate it or use it for our own ends?”

This is overdone. Nor do we necessarily know enough about slime to start shouting about it. To take one example, using slime to read our ecological future turns out to be a vexed business. There’s a scum of nutrients held together by slime floating on top of the oceans. A fraction of a millimetre thick, it’s called the “sea-surface micro-layer”. Global warming might be thinning it, or thickening it, and doing either might be increasing the chemical transport taking place between air and ocean — or retarding it — to unknown effect. So there: yet another thing to worry about.

For sure, slime holds the world together. Slimes, rather: there are any number of ways to stiffen water so that it acts as a lubricant, a glue, or a barrier. Whatever its origins, it is most conspicuous when it disappears — as when overtilling of America’s Great Plains caused the Dust Bowl in 1933, or when the gluey glycan coating of one’s blood vessels starts to mysteriously shear away during surgery.

There was a moment, in the 1920s, when slime shed its icky materiality and became almost cool. Artists both borrowed from and inspired Haeckel’s exquisite drawings of delicate maritime invertebrates. And biologists, looking for the mechanisms underpinning memory and heredity, would have liked nothing more than to find that the newly-identified protoplasm within our every cell was recording, like an Edison drum, the tremblings of a ubiquitous, information-rich aether. (Sounds crazy now, but the era was, after all, bathing in X-rays and other newly-discovered radiations.)

But slime’s moment of modishness passed. Now it’s the unlovely poster-child of environmental degradation: the stuff that will fill our soon-to-be-empty oceans, “home only to jellyfish, algae and microbial mats”, if we don’t do something sharpish to change our ecological ways.

Hand in hand with such millennial anxieties, of course, come the usual power fantasies: that we might harness all this unlovely slime — nothing more than water held in a cage of a few long-chain polymers — to transform our world, providing the base for new materials and soft robots, “transparent, stretchable, locomotive, biocompatible, remote-controlled, weavable, wearable, self-healing and shape-morphing, 3D-printed or improved by different ingredients”.

Wedlich’s enthusiasm is by no means misplaced. Slime is not just a largely untapped wonder material. It is also — really, truly — the source of life, and a key enabler of complex forms. We used to think the machinery of the first cells must have risen in clay hydrogels — a rather complicated and unlikely genesis — but it turns out that nucleic acids like DNA and RNA can sometimes form slimes on their own. Life, it turns out, does not need a substrate on which to arise. It is its own sticky home.

Slime’s effective barrier to pathogens may then have enabled complex tissues to differentiate and develop, slickly sequestered from a disease-ridden outside world. Wedlich’s tour of the human gut, and its multiple slime layers, (some lubricant, some gluey, and many armed with extraordinary electrostatic and molecular traps for one pathogen or another) is a tour de force of clear and gripping explanation.

Slime being, in essence, nothing more than stiffened water, there are more ways to make it than the poor reader could ever bare to hear about. So Wedlich very sensibly approaches her subject from the other direction, introducing slimes through their uses. Snails combine gluey and lubricating slimes to travel over dry ground one moment, cling to the underside of a leaf the next. Hagfish deter predators by jellifying the waters around them, shooting polymers from their skin like so many thousands of microscopic harpoons. Some squid, when threatened, add slime to their ink to create pseudomorphs — fake squidoids that hold together just long enough to distract a predator. Some squid pump out whole legions of such doppelgangers.

Wedlich’s own strategy, in writing Slime, is not dissimilar. She’s deliberately elusive. The reader never really feels they’ve got hold of the matter of her book; rather, they’re being provoked into punching through layer after dizzying layer, through masterpieces of fin de siecle glass-blowing into theories about the spontaneous generation of life, through the lifecycles of carnivorous plants into the tactics of Japanese balloon-bomb designers in the second world war, until, dizzy and gasping, they reach the end of Wedlich’s extraordinary mystery tour, not with a handle on slime exactly, but with an elemental and exultant new vision of what life may be: that which arises when the boundaries of earth, air and water are stirred in sunlight’s fire. It’s a vision that, for all its weight of well-marshalled modern detail, is one Aristotle would have recognised.

Citizen of nowhere

Posted on by

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.

We may never have a pandemic again

Posted on by

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.

 

“Some only appear crazy. Others are as mad as a bag of cats”

Posted on by

unnamed

Stalin’s more eccentric scientists are the subject of this blogpost for Faber & Faber.

Stalin and the Scientists describes what happened when, early in the twentieth century, a handful of impoverished and under-employed graduates, professors and entrepreneurs, collectors and charlatans, bound themselves to a failing government to create a world superpower. Envied and obsessed over by Joseph Stalin — ‘the Great Scientist’ himself — scientists in disciplines from physics to psychology managed to steer his empire through famine, drought, soil exhaustion, war, rampant alcoholism, a huge orphan problem, epidemics and an average life expectancy of thirty years. Hardly any of them are well known outside Russia, yet their work shaped global progress for well over a century.

Cold War propaganda cast Soviet science as an eccentric, gimcrack, often sinister enterprise. And, to my secret delight, not every wild story proved to be a fabrication. Indeed, a heartening amount of the smoke shrouding Soviet scientific achievement can be traced back to intellectual arson attacks of one sort or another.

I’ll leave it to the book to explain why Stalin’s scientists deserve our admiration and respect. This is the internet, so let’s have some fun. Here, in no particular order, are my my top five scientific eccentrics. Some only appear crazy; others have had craziness thrust upon them by hostile commentators. Still others were as mad as a bag of cats.

1. Ilya Ivanov
Ilya Ivanov, the animal breeding expert who tried to mate humans with chimpanzees

By the time of the 1917 revolution, Ilya Ivanov was already an international celebrity. His pioneering artificial insemination techniques were transforming world agriculture. However, once he lost his Tsarist patrons, he had to find a research programme that would catch the eye of the new government’s Commissariat of Education. What he came up with was certainly compelling: a proposal to cross-breed humans and chimpanzees.

We now know there are immunological difficulties preventing such a cross, but the basic idea is not at all crazy, and Ivanov got funding from Paris and America to travel to Guinea to further the study.

Practically and ethically the venture was a disaster. Arriving at the primate centre in Kindia, Ivanov discovered that its staff were killing and maiming far more primates than they ever managed to capture. To make matters worse, after a series of gruesome and rapine attempts to impregnate chimpanzees with human sperm, Ivanov decided it might be easier to turn the experiment on its head and fertilise African women with primate sperm. Unfortunately, he failed to tell them what he was doing.

Ivanov was got rid of during the Purges of the late 1930s thanks to a denunciation by an ambitious colleague, but his legacy survives. The primate sanctuary he founded in Sukhumi by the Black Sea provided primates for the Soviet space programme. Meanwhile the local tourist industry makes the most of, and indeed maintains, persistent rumours that the local woods are haunted by seven-foot-tall Stalinist ape-men.

2. Alexander Bogdanov
whose Mars-set science fiction laid the groundwork for the Soviet Union’s first blood transfusion service — and who died of blood poisoning

Alexander Alexandrovich Bogdanov, co-founder of the Bolshevik movement, lost interest in politics, even as control came within his grasp, because he wanted more time for his writing.

In his novels Red Star and Engineer Menni, blood exchanges among his Martian protagonists level out their individual and sexual differences and extend their lifespan through the inheritance of acquired characteristics.

These scientific fantasies took an experimental turn in 1921 during a trade junket to London when he happened across Blood Transfusion, a book by Geoffrey Keynes (younger brother of the economist). Two years of private experiments followed, culminating in an appointment with the Communist Party’s general secretary, Joseph Stalin. Bogdanov was quickly installed as head of a new ‘scientific research institute of blood transfusion’.

Blood, Bogdanov claimed, was a universal tissue that unified all other organs, tissues and cells. Transfusions offered the client better sleep, a fresher complexion, a change in eyeglass prescriptions, and greater resistance to fatigue. On 24 March 1928 he conducted a typically Martian experiment, mutually transfusing blood with a male student, suffered a massive transfusion reaction and died two weeks later at the age of fifty-four.

Bogdanov the scientist never offered up his studies to the review of his peers. In fact he never wrote any actual science at all, just propaganda for the popular press. In this, he resembled no-one so much as the notorious charlatan (and Stalin’s poster boy) Trofim Lysenko. I reckon it was his example made Trofim Lysenko politically possible.

3. Trofim Lysenko
Stalin’s poster-boy, who believed plants sacrifice themselves for their strongest neighbour — and was given the job of reforesting European Russia.

Practical, working-class, ambitious and working for the common good, the agrobiologist Trofim Lysenko was the very model of the new Soviet scientist. Rather than studying ‘the hairy legs of flies’, ran one Pravda profile in August 1927, this sober young man ‘went to the root of things,’ solving practical problems by a few calculations ‘on a little old piece of paper’.

As he studied how different varieties of the same crop responded to being planted at different times, he never actually touched any mathematics, relying instead on crude theories ‘proved’ by arbitrary examples.

Lysenko wanted, above all else, to be an original. An otherwise enthusiastic official report warned that he was an ‘extremely egotistical person, deeming himself to be a new Messiah of biological science.’ Unable to understand the new-fangled genetics, he did everything he could to banish it from biology. In its place he championed ‘vernalisation’, a planting technique that failed dismally to increase yields. Undeterred, he went on to theorise about species formation, and advised the government on everything, from how to plant oak trees across the entire Soviet Union to how to increase the butterfat content of milk. The practical results of his advices were uniformly disastrous and yet, through a combination of belligerence, working-class credentials, and a phenomenal amount of luck, he remained the poster-boy of Soviet agriculture right up until the fall of Khrushchev in 1964.

Nor is his ghost quite laid to rest. A couple of politically motivated historians are even now attempting to recast Lysenko as a cruelly sidelined pioneer of epigenetics (the study of how the environment regulates gene expression). This is a cruel irony, since Soviet Russia really was the birthplace of epigenetics! And it was Lysenko’s self-serving campaigns that saw that every single worker in that field was sacked and ruined.

4. Olga Lepeshinskaya
who screened in reverse films of rotting eggs to prove her theories about cell development — and won a Stalin Prize

Olga Lepeshinskaya, a personal friend of Lenin and his wife, was terrifyingly well-connected and not remotely intimidated by power. On a personal level, she was charming. She fiercely opposed anti-semitism, and had dedicated her personal life to the orphan problem, bringing up at least half a dozen children as her own.

As a scientist, however, she was a disaster. She once announced to the Academic Council of the Institute of Morphology that soda baths could rejuvenate the old and preserve the youth of the young. A couple of weeks later Moscow completely sold out of baking soda.

In her old age, Lepeshinskaya became entranced by the mystical concept of the ‘vital substance’, and recruited her extended family to work in her ‘laboratory’, pounding beetroot seeds in a pestle to demonstrate that any part of the seed could germinate. She even claimed to have filmed living cells emerge from noncellular materials. Lysenko hailed Lepeshinskaya’s discovery as the basis for a new theory of species formation, and in May 1950 Alexander Oparin, head of the Academy of Sciences’ biology department, invited Olga Lepeshinskaya to receive her Stalin Prize.

It was all a fraud, of course: she had been filming the death and decomposition of cells, then running her film backwards through the projector. Lepeshinskaya made a splendid myth. The subject of poetry. The heroine of countless plays. In school and university textbooks she was hailed as the author of the greatest biological discovery of all time.

5. Joseph Stalin
whose obsession with growing lemons in Siberia became his only hobby

Stalin, typically for his day, believed in the inheritance of acquired characteristics – that a giraffe that has to stretch to reach high leaves will have long-necked children. He assumed that, given the right conditions, living things were malleable, and as the years went by this obsession grew. In 1946 he became especially keen on lemons, not only encouraging their growth in coastal Georgia, where they fared quite well, but also in the Crimea, where winter frosts destroyed them.

Changing the nature of lemons became Stalin’s sole hobby. At his dachas near Moscow and in the south, large greenhouses were erected so that he could enter them directly from the house, day or night. Pruning shrubs and plants was his only physical exercise.

Stalin shared with his fellow Bolsheviks the idea that they had to be philosophers in order to deserve their mandate. He schooled the USSR’s most prominent philosopher, Georgy Aleksandrov, on Hegel’s role in the history of Marxism. He told the composer Dmitry Shostakovich how to change the orchestration for the new national anthem. He commissioned the celebrated war poet Konstantin Simonov to write a play about a famous medical controversy, treated him to an hour of literary criticism, and then rewrote the closing scenes himself. Sergei Eisenstein and his scriptwriter on Ivan the Terrible Part Two were treated to a filmmaking masterclass. And in 1950, while he was negotiating a pact with the People’s Republic of China, and discussing how to invade South Korea with Kim Il Sung, Stalin was also writing a combative article about linguistics, and meeting with economists multiple times to discuss a textbook.

Stalin’s paranoia eventually pushed him into pronouncements that were more and more peculiar. Unable to trust even himself, it came to Joseph Stalin that people were, or ought to be, completely readable from first to last. All it needed was an entirely verbal theory of mind. ‘There is nothing in the human being which cannot be verbalised,’ he asserted, in 1949. ‘What a person hides from himself he hides from society. There is nothing in the Soviet society that is not expressed in words. There are no naked thoughts. There exists nothing at all except words.’

For Stalin, in the end, even a person’s most inner world was readable – because if it wasn’t, then it couldn’t possibly exist.

 

 

Just how much does the world follow laws?

Posted on by

zebra

How the Zebra Got its Stripes and Other Darwinian Just So Stories by Léo Grasset
The Serengeti Rules: The quest to discover how life works and why it matters by Sean B. Carroll
Lysenko’s Ghost: Epigenetics and Russia by Loren Graham
The Great Derangement: Climate change and the unthinkable by Amitav Ghosh
reviewed for New Scientist, 15 October 2016

JUST how much does the world follow laws? The human mind, it seems, may not be the ideal toolkit with which to craft an answer. To understand the world at all, we have to predict likely events and so we have a lot invested in spotting rules, even when they are not really there.

Such demands have also shaped more specialised parts of culture. The history of the sciences is one of constant struggle between the accumulation of observations and their abstraction into natural laws. The temptation (especially for physicists) is to assume these laws are real: a bedrock underpinning the messy, observable world. Life scientists, on the other hand, can afford no such assumption. Their field is constantly on the move, a plaything of time and historical contingency. If there is a lawfulness to living things, few plants and animals seem to be aware of it.

Consider, for example, the charming “just so” stories in French biologist and YouTuber Léo Grasset’s book of short essays, How the Zebra Got its Stripes. Now and again Grasset finds order and coherence in the natural world. His cost-benefit analysis of how animal communities make decisions, contrasting “autocracy” and “democracy”, is a fine example of lawfulness in action.

But Grasset is also sharply aware of those points where the cause-and-effect logic of scientific description cannot show the whole picture. There are, for instance, four really good ways of explaining how the zebra got its stripes, and those stripes arose probably for all those reasons, along with a couple of dozen others whose mechanisms are lost to evolutionary history.

And Grasset has even more fun describing the occasions when, frankly, nature goes nuts. Take the female hyena, for example, which has to give birth through a “pseudo-penis”. As a result, 15 per cent of mothers die after their first labour and 60 per cent of cubs die at birth. If this were a “just so” story, it would be a decidedly off-colour one.

The tussle between observation and abstraction in biology has a fascinating, fraught and sometimes violent history. In Europe at the birth of the 20th century, biology was still a descriptive science. Life presented, German molecular biologist Gunther Stent observed, “a near infinitude of particulars which have to be sorted out case by case”. Purely descriptive approaches had exhausted their usefulness and new, experimental approaches were developed: genetics, cytology, protozoology, hydrobiology, endocrinology, experimental embryology – even animal psychology. And with the elucidation of underlying biological process came the illusion of control.

In 1917, even as Vladimir Lenin was preparing to seize power in Russia, the botanist Nikolai Vavilov was lecturing to his class at the Saratov Agricultural Institute, outlining the task before them as “the planned and rational utilisation of the plant resources of the terrestrial globe”.

Predicting that the young science of genetics would give the next generation the ability “to sculpt organic forms at will”, Vavilov asserted that “biological synthesis is becoming as much a reality as chemical”.

The consequences of this kind of boosterism are laid bare in Lysenko’s Ghost by the veteran historian of Soviet science Loren Graham. He reminds us what happened when the tentatively defined scientific “laws” of plant physiology were wielded as policy instruments by a desperate and resource-strapped government.

Within the Soviet Union, dogmatic views on agrobiology led to disastrous agricultural reforms, and no amount of modern, politically motivated revisionism (the especial target of Graham’s book) can make those efforts seem more rational, or their aftermath less catastrophic.

In modern times, thankfully, a naive belief in nature’s lawfulness, reflected in lazy and increasingly outmoded expressions such as “the balance of nature”, is giving way to a more nuanced, self-aware, even tragic view of the living world. The Serengeti Rules, Sean B. Carroll’s otherwise triumphant account of how physiology and ecology turned out to share some of the same mathematics, does not shy away from the fact that the “rules” he talks about are really just arguments from analogy.

“If there is a lawfulness to living things, few plants and animals seem to be aware of it”
Some notable conservation triumphs have led from the discovery that “just as there are molecular rules that regulate the numbers of different kinds of molecules and cells in the body, there are ecological rules that regulate the numbers and kinds of animals and plants in a given place”.

For example, in Gorongosa National Park, Mozambique, in 2000, there were fewer than 1000 elephants, hippos, wildebeest, waterbuck, zebras, eland, buffalo, hartebeest and sable antelopes combined. Today, with the reintroduction of key predators, there are almost 40,000 animals, including 535 elephants and 436 hippos. And several of the populations are increasing by more than 20 per cent a year.

But Carroll is understandably flummoxed when it comes to explaining how those rules might apply to us. “How can we possibly hope that 7 billion people, in more than 190 countries, rich and poor, with so many different political and religious beliefs, might begin to act in ways for the long-term good of everyone?” he asks. How indeed: humans’ capacity for cultural transmission renders every Serengeti rule moot, along with the Serengeti itself – and a “law of nature” that does not include its dominant species is not really a law at all.

Of course, it is not just the sciences that have laws: the humanities and the arts do too. In The Great Derangement, a book that began as four lectures presented at the University of Chicago last year, the novelist Amitav Ghosh considers the laws of his own practice. The vast majority of novels, he explains, are realistic. In other words, the novel arose to reflect the kind of regularised life that gave you time to read novels – a regularity achieved through the availability of reliable, cheap energy: first, coal and steam, and later, oil.

No wonder, then, that “in the literary imagination climate change was somehow akin to extraterrestrials or interplanetary travel”. Ghosh is keenly aware of and impressively well informed about climate change: in 1978, he was nearly killed in an unprecedentedly ferocious tornado that ripped through northern Delhi, leaving 30 dead and 700 injured. Yet he has never been able to work this story into his “realist” fiction. His hands are tied: he is trapped in “the grid of literary forms and conventions that came to shape the narrative imagination in precisely that period when the accumulation of carbon in the atmosphere was rewriting the destiny of the Earth”.

The exciting and frightening thing about Ghosh’s argument is how he traces the novel’s narrow compass back to popular and influential scientific ideas – ideas that championed uniform and gradual processes over cataclysms and catastrophes.

One big complaint about science – that it kills wonder – is the same criticism Ghosh levels at the novel: that it bequeaths us “a world of few surprises, fewer adventures, and no miracles at all”. Lawfulness in biology is rather like realism in fiction: it is a convention so useful that we forget that it is a convention.

But, if anthropogenic climate change and the gathering sixth mass extinction event have taught us anything, it is that the world is wilder than the laws we are used to would predict. Indeed, if the world really were in a novel – or even in a book of popular science – no one would believe it.

How the forces inside cells actually behave

Posted on by

animal electricity

Animal Electricity: How we learned that the body and brain are electric machines by Robert B. Campenot (Harvard University Press) for New Scientist, 9 March 2016.

IF YOU stood at arm’s length from someone and each of you had 1 per cent more electrons than protons, the force pushing the two of you apart would be enough to lift a “weight” equal to that of the entire Earth.

This startling observation, from Richard Feynman’s Lectures on Physics, so impressed cell biologist Robert Campenot he based quite a peculiar career around it. Not content with the mechanical metaphors of molecular biology, Campenot has studied living tissue as a delicate and complex mechanism that thrives by tweaking tiny imbalances in electrical charge.

If only the book were better prepared. Campenot’s enthusiasm for Feynman has him repeat the anecdote about lifting the world almost word for word, in the preface and introduction. Duplicating material is a surprisingly easy gaffe for a writer, and it is why we have editors. Where were they?

Campenot’s generous account ranges from Galvani’s discovery of animal electricity to the development of thought-controlled prosthetic limbs. He has high regard for popular science. But his is the rather fussy appreciation of the academic outsider who, uncertain of the form’s aesthetic potential, praises it for its utility. “The value of popularising science should never be underestimated because it occasionally attracts the attention of people who go on to make major contributions.” The pantaloonish impression he makes here is not wholly unrepresentative of the book.

Again, one might wish Campenot’s relationship with his editor had been more creative. Popular science writing rarely handles electricity well, let alone ion channels and membrane potentials. So, when it comes to developing suitable metaphors, Campenot is thrown on his own resources. His metaphors are as effective as one could wish for, but they suffer from repetition. One imagines the author wondering if he has done enough to nail his point, but with no one to reassure him.

Faults aside, this is a good book. Its mix of schoolroom electricity and sophisticated cell biology is highly eccentric but this, I think, speaks much in Campenot’s favour. The way organic tissue manipulates electricity, sending signals in broad electrical waves that can extend up to a third of a metre, is a dimension of biology we have taken on trust, domesticating it behind high-order metaphors drawn from computer science. Consequently, we have been unable to visualise how the forces in our cells actually behave. This was bound to turn out an odd endeavour. So be it. The odder, the better, in fact.