Phenotypic Variation in Cancer Cells Often Not Due to Mutations

Jef Akst in The Scientist:

Most models of how tumors evolve have assumed that the process is based predominately on cancer cells’ genetics, and many cancer treatments are specifically targeted to mutations associated with disease. But comparing whole genome sequence data with RNA-seq data from samples of colorectal tumors revealed that the vast majority of gene expression differences among cancer cells cannot be explained by genetics, researchers report in Nature today (October 26).

“So far, a lot of the work that’s been done exploring cancer evolution in cancer development has focused very much on just the genetics,” says Nicholas McGranahan, a computational cancer researcher at the University College London Cancer Institute’s CRUK UCL Centre who was not involved in the research. But according to the new study, “there’s lots of these alterations that they can’t identify a clear [genetic] underpinning for. . . . It’s a nice study because it highlights some of the limitations of what we’ve been doing before.”

Computational biologist Andrea Sottoriva says that it’s those limitations that led him and his colleagues to consider the transcriptome in cancer evolution. “Basically, looking at the genetic evidence was not explaining everything that we were seeing,” says Sottoriva, a group leader at the Institute of Cancer Research, London, and the head of Computational Biology Research Centre at Human Technopole in Milan, Italy. For example, he explains, “if you just look at . . . mutations in genes that are involved in cancer, it’s not very easy to distinguish a benign cancer from a malignant cancer: In a benign cancer, there are as many cancer driver mutations as in a malignant cancer.”

More here.

The Rising Tide of Global Sadness

David Brooks in The New York Times:

Taylor Swift was quite the romantic when she burst on the scene in 2006. She sang about the ecstasies of young love and the heartbreak of it. But her mood has hardened as her star has risen. Her excellent new album, Midnights, plays upon a string of negative emotions — anxiety, restlessness, exhaustion and occasionally anger. “I don’t dress for women,” she sings at one point, “I don’t dress for men/Lately I’ve been dressing for revenge.”

It turns out Swift is part of a larger trend. The researchers Charlotte Brand, Alberto Acerbi and Alex Mesoudi analyzed more than 150,000 pop songs released between 1965 and 2015. Over that time, the appearance of the word “love” in top-100 hits roughly halved. Meanwhile, the number of times such songs contained negative emotion words, like “hate” rose sharply. Pop music isn’t the only thing that has gotten a lot harsher. David Rozado, Ruth Hughes and Jamin Halberstadt analyzed 23 million headlines published between 2000 and 2019 by 47 different news outlets popular in the United States. The headlines, too, grew significantly more negative, with a greater proportion of headlines denoting anger, fear, disgust and sadness. Headlines in left-leaning media got a lot more negative, but headlines in right-leaning publications got even more negative than that.

More here.

What Charles Darwin Saw in Tahiti

Diana Preston in Literary Hub:

The first Europeans to reach Tahiti were the crew of HMS Dolphin, commanded by Samuel Wallis, in June 1767. When the Dolphin approached the island and, like the Beagle, anchored in Matavai Bay, some Tahitians had thought the ship was “a floating island.” Others had recalled a prophecy that, as a result of the chopping down of a sacred tree, newcomers of an unknown kind would arrive and that “this land would be taken by them. The old order will be destroyed and sacred birds of the land and the sea will come and lament what the lopped tree has to dictate. [The newcomers] are coming upon a canoe without an outrigger.”

After some initial friction, Wallis’s crew and the Tahitians became so close that both were sad to see the Dolphin leave, not least on the sailors’ part because of the friendliness of the people, their willingness to trade, the fertility of their island, and most of all because of the ties between some of the crew and Tahitian women who had uninhibitedly made love to them.

More here.

The Beauty at the Heart of a ‘Spooky’ Mystery

John Horgan in Scientific American:

Studying quantum mechanics, which I’ve been doing for the last two-plus years, has served as an antidote to my tendency toward habituation, taking reality for granted. Wave functions, superposition and other esoterica remind me that this is a strange, strange world; there is a mystery at the heart of things that ordinary language can never quite capture.

I’m thus thrilled by this year’s Nobel Prize for Physics. John Clauser, Alain Aspect and Anton Zeilinger won for experimental probes of entanglement, a peculiar connection between two or more particles. The Nobel Foundation’s press release emphasizes the applications of this prize-winning work; researchers are building “quantum computers, quantum networks and secure quantum encrypted communication” based on entanglement. But I value the work of Clauser, et al., because it upends our commonsense notions about what is real and what is knowable. It rubs our noses in the riddle of reality.

More here.

The impasse of 2022 inflation politics

Adam Tooze in Chartbook:

The politics of inflation in 2022 are surprising.

Perhaps my priors were wrong, but as price indices surge by almost 10 percent I would have expected more talk about the losses inflicted on “small savers” and their vulnerable bank accounts, in other words the classic “petty bourgeois” politics of inflation.

Perhaps the relative lack of such talk points to the fact that no one actually believes that this inflation will be anything more than transitory, so that it amounts not to a landslide devaluation, but a one-off tax on savers and there is thus less reason for panic. Perhaps savers now have more diversified portfolios and are better protected. If so, the collapse in stock market prices hardly offers much comfort.

More here.

Face-to-Face: Diane Arbus at David Zwirner

Chris Murtha at Art in America:

Much has been written about Diane Arbus—the person and the images—in the 50 years since the Museum of Modern Art mounted its posthumous landmark retrospective of her photographs in November 1972. A recent restaging of that exhibition at David Zwirner, co-organized with Fraenkel Gallery in San Francisco, made visitors acutely aware of the work’s public reception even before entering the exhibition: An introductory note on the gallery windows recounted how the MoMA exhibition “precipitated an eruption of praise and outrage from critics and scholars, a war of words that continues to this day.” Inside, dozens of unattributed quotes wallpapered the lobby, ranging from acidic ridicule to ardent praise. In addition, the exhibition was accompanied by Diane Arbus Documents, a 500-page tome that assembles facsimiles of nearly 70 texts, including exhibition and book reviews, biographical profiles, scholarly essays, and even a master’s thesis. By foregrounding the literature on Arbus, the show acknowledged that the artist’s reputation has often overshadowed her images. Thankfully, it also allowed the photographs to speak for themselves.

more here.

Étant Donnés

Elena Filipovic at The Brooklyn Rail:

One bleary morning in a darkened art history classroom—think Modernism 101—a slide of the interior of Étant donnés: 1° la chute d’eau / 2° le gaz d’éclairage (1946-1966) flashed by. Its glimmering afterimage remained in my mind’s eye long after. One might say it never really left. I still remember how rattled I was as I tried to make sense of it. The odd installation didn’t fit into what was being taught as modern art at the time, yet conversely—perversely—it nominally coincided with enough of what art history syllabi then encompassed: female nudity mediated by a male gaze, corporeality framed by idyllic landscapes. What perhaps shook me most, however, was that it didn’t tally at all with what I was just learning about the art of its maker. Duchamp, the painter turned cool conceptualist. Duchamp, father of the readymade and chess-playing lover of puns. Duchamp, the sometime art dealer, occasional crossdresser, and elegant prankster who had definitively “retired” by the 1930s. Even if these myriad “Duchamps”already indicated a great flexibility regarding the concept of art and artist, it was Etant donnés, I thought, that didn’t fit. And I was not alone in thinking so.

more here.

Thursday Poem

An Appointment

Being out of heart with government
I took a broken root to fling
Where the proud, wayward squirrel went,
Taking delight that he could spring;
And he, with that low whinnying sound
That is like laughter, sprang again
And so to the other tree at a bound.
Nor the tame will, nor timid brain,
Nor heavy knitting of the brow
Bread that fierce tooth and cleanly limb
And threw him up to laugh on the bough;
No government appointed him.

by W.B. Yeats
Running to Paradise
Macmillan Company, 1962

Iran’s New Protest Generation

Robin Wright in The New Yorker:

In his fatwas and sermons, Iran’s revolutionary leader, Ayatollah Ruhollah Khomeini, commanded women to hide their bodies and hair from men and “lusting” prepubescent boys. “If this piece of clothing did not exist—the Islamic dress—women could not work in a useful and healthy way,” he said, in a testy exchange with the Italian journalist Oriana Fallaci, in 1979. (She promptly took off her chador, calling it a medieval rag.) Khomeini also recommended that girls be married off before puberty—or the onset of menstruation. “One of the blessings of man,” he said, “is to have his daughter experience her first period not in her father’s house but in that of her husband.” He ruled on sex and marriage and breast-feeding, too. A man who has had sex with his wife after her last menstrual period must wait until after her next one to divorce, although he could proceed if his wife had not yet reached her ninth birthday, was pregnant, or was menopausal. Any wet nurse, the Ayatollah said, should be a “faithful Shi’ite, intelligent, modest, and pretty,” and not “ugly or a bastard.” Every July, Iran officially marks the National Day of Hijab and Chastity.

More here.

Cancer drugs are closing in on some of the deadliest mutations

Heidi Ledford in Nature:

On 12 September, Amgen announced that the latest trial of sotorasib found that it extended progression-free survival — a measure of the time elapsed without the cancer worsening — only by about one month longer than standard chemotherapy. Only 28% of the participants treated with sotorasib responded to it. That’s roughly twice the number who responded to the standard chemotherapy, but a sign nonetheless that most people who have KRAS-positive lung cancers will not be helped by the new drug.

Even so, the pace of KRAS research and the pursuit of KRAS-targeting drugs has never been so energized, says cancer biologist Channing Der at the University of North Carolina in Chapel Hill. The first glimpse of success has shown that it is possible to drug the ‘undruggable’ KRAS, and now researchers in academia and industry are developing ways to improve their approach. “I have never seen this level of excitement and buzz in the entire history of the field,” he says. “The level now is insane.”

More here.

Mike Davis: 1946–2022

Jon Wiener at The Nation:

Mike Davis, author and activist, radical hero and family man, died October 25 after a long struggle with esophageal cancer; he was 76. He’s best known for his 1990 book about Los Angeles, City of Quartz. Marshall Berman, reviewing it for The Nationsaid it combined “the radical citizen who wants to grasp the totality of his city’s life, and the urban guerrilla aching to see the whole damned thing blow.”

And the whole thing did blow, two years after the book was published. When the Rodney King riots broke out in LA in 1992, frightened white people rushed home, locked the doors, and turned on the TV news. Mike, however, was driving in the opposite direction, with his old friend Ron Schneck at his side. They parked, got out, and started talking with the people in the streets about what was going on. Then he went home and wrote about it.

more here.


Otto Neurath’s Modern Man In The Making

Michael J. Golec at nonsite:

In 1939, the Viennese economist and sociologist Otto Neurath (1882–1945) released Modern Man in the Making to an American public. Published by Alfred A. Knopf, Neurath’s pictorial statistical history of human technological adaptation and social cooperation addressed a modern audience searching for optimistic narratives amid an economically, politically, and socially volatile era. If not actual members of the managerial class, readers of Neurath’s book were immersed in a “culture of management” that permeated many aspects of modern life. The concerns of the broader public were addressed by managerial commitments to profitable business and social betterment through the promotion of efficiency during the interwar years. Between 1917 and 1939 Neurath frequently referenced Scientific Management and its program for promoting cooperation through efficiency. Abandoning theology and enlightenment liberalism, he even went so far as to propose an ethics modeled on an extrapolation of Scientific Management which would take the form of the extension of convention and habit into new forms of life.

more here.

Diego Rivera’s Resolute Socialism Is on Full Display in His Mural “Pan American Unity”

Joel Whitney in Jacobin:

Diego Rivera painted Pan American Unity for the 1940 San Francisco World’s Fair in an airplane hangar, accompanied by an armed guard. Shortly before he commenced work on the mural, his wife — the artist Frida Kahlo — and Leon Trotsky began an affair. Though Rivera remained an admirer of the hero of the October Revolution, he expelled Trotsky from his home in Mexico. The security budget required to protect the former military leader had already been putting a strain on the household’s finances. This was the last straw.

Pan American Unity features no image of Trotsky. Stalin appears on the painting’s fourth panel as one set of a triad of ghouls cloaked in a gray ether, alongside Hitler and Mussolini. They are surrounded by portraits of actors, chief among them Charlie Chaplin, who assumes a number of his satirical personas. A single arm, tattooed with a swastika and holding a dagger tightly, emerges out of the cloud, but it is held at bay by another, much larger, arm draped in an American flag and flanked by bombers and paratroopers. This is Rivera’s ode to anti-fascist Hollywood.

More here.

Siddhartha Mukherjee on the Early Science Behind the Modern Microscope

Siddhartha Mukherjee in Literary Hub:

Modern genetics was launched by the practice of agriculture: the Moravian monk Gregor Mendel discovered genes by cross-pollinating peas with a paintbrush in his monastery garden in Brno. The Russian geneticist Nikolai Vavilov was inspired by crop selection. Even the English naturalist Charles Darwin had noted the extreme changes in animal forms created by selective breeding. Cell biology, too, was instigated by an unassuming, practical technology. Highbrow science was born from lowbrow tinkering.

In the case of cell biology, it was simply the art of seeing: the world measured, observed, and dissected by the eye. In the early seventeenth century, a Dutch father and son team of opticians, Hans and Zacharias Janssen, placed two magnifying lenses on the top and bottom of a tube and found that they could magnify an unseen world.

More here.

Considering a genealogy of birds

Jesse Russell in The Hedgehog Review:

In his classic book from 1990, Three Rival Versions of Moral Inquiry, the Marxist-turned-Catholic-Thomist philosopher Alasdair MacIntyre discusses three basic modern and postmodern approaches to philosophical inquiry: encyclopedia, genealogy, and tradition. The genealogical method, pioneered by Friedrich Nietzsche and elaborated by Michel Foucault, presents a historical narrative in which ideas develop and grow over time. According to this thinking, being and truth are conditioned by history (historicized) and thus develop in tandem with the twists and turns of science, technology, economics, language, and culture.

A method initiated by critical theorists writing primarily for other intellectuals and academics, the genealogical approach has found surprising success in an unlikely genre: coffee table books.

More here.

Wednesday Poem

The Water Wheel

The afternoon arrived
mournful and dusty

The water was composing
its countrified poem
in the buckets
of the lazy water wheel.

The mule was dreaming—
old and sad mule!
in time to the darkness
that was talking in the water.

The afternoon arrived
mournful and dusty.

I don’t know which noble
and religious poet
joined the anguish
of the endless wheel

to the cheerful music
of the dreaming water,
and bandaged your eyes—
old and sad mule . . .

But it must have been a noble
and religious poet,
a heart made mature
by darkness and art.

by Antonio Machado
Times Alone
Wesleyan University Press, 1989