Behind the bespoke cells of immunotherapy

From Nature:

It seemed like a very promising cancer immunotherapy lead. CHO Pharma, in Taiwan, had discovered that it was possible to target solid tumours with an antibody against a cell-surface glycolipid called SSEA-4.1 This antigen is present during embryonic development, but not seen on human cells again — until they turn into cancer cells.2 The company turned to Lan Bo Chen, a recently retired Harvard pathologist, to help develop this work into an anti-cancer therapy for solid tumours. “It is highly reasonable to imagine that we can use SSEA-4, overexpressed on cancer cells, as a target for CAR-T,” says Chen, now in his role as senior technology advisor for CHO Pharma.

CAR-T therapy works by genetically engineering a person’s own T cells in such a way that they recognize and attack cancer cells. This involves creating a chimeric antigen receptor (CAR) from an antibody against a target on the cell. But CAR-T therapy was designed for blood cancers so it needs several adaptations to make it suitable for the treatment of solid tumours.3 The cells need to be directed to the site of the tumour, survive in the tumour’s local microenvironment, and act only on tumour cells, not on healthy cells nearby. But, when Chen tried to create CAR-T cells against SSEA-4, he hit a few obstacles. First it took him a long time to get his hands on a humanized SSEA-4 antibody suitable for adaptation. When he finally had one, he still had to find a way to turn that antibody into a CAR. And then to insert the CAR into a human T cell using lentiviral transduction.

More here.

Hating Dave Eggers

Lisa Borst at n+1:

Eggers is hardly a systems novelist: his literary sensibilities, like his career, tend toward the monomaniacal. His writing in the past two decades has involved a suspiciously prolific series of smug morality tales fictionalizing or nonfictionalizing real people—a heroic Sudanese refugee, a heroic Yemeni coffee importer later accused of racketeering, Donald Trump—as well as novels about loners in perilous circumstances. He has also written children’s books, left-of-center comedic op-eds, and articles for the New Yorker about human rights and how much he loves wine. But evident throughout his literary output, as in his incoherent and self-congratulatory apparatus of publishing programs, bookselling platforms, and children’s literacy programs, is an ongoing fascination with epic, world-conquering ambition. The characters in A Heartbreaking Work of Staggering Genius, I was embarrassed to reread, are “sure that we are on to something epochal . . . sure that we speak for others, that we speak for millions”; in his 2006 foreword to Infinite Jest, Eggers lingers, enviously and, I think, not un-Bezosishly, on Wallace’s all-seeing book as an example of the “human possibility [for] leaps in science and athletics and art and thought.”

more here.

The Temptations Of Christopher Hitchens

Ross Douthat at The New Statesman:

Over the Thanksgiving holiday the Financial Times columnist Janan Ganesh expressed a sentiment I hear from time to time among connoisseurs of punditry – that our era, the age of Trumpism and wokeness and Covid controversy, badly misses the words and wits of Christopher Hitchens, who was taken from the stage before his time. Ganesh offered a particularly interesting version of this take, because he went halfway to conceding something that Hitchens’ critics (I was one of them) might say has become more palpable since his passing in 2011: that his great talents were expended on causes that have not exactly stood the test of time. But Ganesh framed this reality as an indictment of the somewhat-empty – dare one say, decadent – times in which Hitch lived:

“The trouble is, the artist dwarfed his canvas. Hitchens had the misfortune to peak during one of world history’s blander interludes.

more here.

Will Adam Smith’s Invisible Hand Fade Away?

by Michael Liss

Portrait of Adam Smith, artist unknown. National Galleries Scotland. Given by J.H. Romanes 1945.

Nearly 250 years is not quite Shakespeare, but if The Wealth of Nations were a play, we would say it has had a pretty good run. Is it a dusty old warhorse, to be read while sitting in a winged-back chair with a snifter of brandy, or still relevant today? Can it solve the (deep) problems of the present and future? Is our almost faith-bound devotion to market forces still justified, or are new approaches needed?

A heavy topic requires heavyweights, and I found them at this past November’s “Center on Capitalism and Society,” at Columbia University’s 20th Anniversary Conference. The topic: Economy Policy and Economic Theory for the Future

The two-day event assembled a formidable crew of speakers, headlined by three Nobelists for Economics: Joseph Stiglitz (2001), Eric Maskin (2007) and Edmund Phelps (2006). They were joined by a “supporting cast” of 15 others, also heavyweights in their field, including the sociologist and urbanist Richard Sennett, the financial journalist Martin Wolf, Finnish philosopher Esa Saarinen, Ian Goldin of Oxford, economists Roman Frydman and Jean-Paul Fitoussi, Carmen Reinhart of the World Bank, and Jeffrey Sachs of Columbia and the UN.

In short, there were a lot of credentials in the room (either in person or remotely) and a number of extremely compelling presentations, but it is Sachs whom I want to talk about. He spoke first, after opening remarks by the extraordinary Ned Phelps (nearing 90, still writing, still speaking, and still mentoring and inspiring), and I assume that the choice was a tactical one. The organizers clearly anticipated that Sachs would do what Sachs does: devote his time to lobbing a little hand grenade into the proceedings: Capitalism, to his way of thinking, particularly the Anglo-Saxon version of Capitalism practiced in the United States, was no longer capable of taking on the big, global challenges. Read more »

Which Scientific Bets Should Be Declined?

by David Kordahl

Imagine, if you will, that I own a reliably programmable qubit, a device that, when prepared in some standard and uncontroversial way, has a 50/50 probability of having one of two outcomes, A or B. Now imagine also that I have become convinced of my own telekinetic powers.

Suppose that the qubit has been calibrated within an inch of its life, and I have good reason to believe that the odds for the two possible outcomes, A or B, are in fact equally matched. My telekinetic powers, on the other hand, are weak—not strong enough to make heads explode like that guy in Scanners, nor strong enough to levitate chalk like in Matilda. Yet neither am I powerless. If I reign myself in—no more than a few attempts per night (I take care not to tire myself), and no counting tries when my juju’s off (remember, my gifts are unremarkable)—then I have been able, through intense concentration and force of will, to favor outcome A just slightly, just barely bumping its odds up, let’s say, from 50.0% to 50.1%.

Squinting, I claim statistical significance. But when I share these findings with you, my scientifically trained colleague, you are unimpressed.

Okay, but why not? I might insist that experimental controls have been properly implemented. I might even allow you to propose a list of criteria for a follow-up experiment. I might grow impatient, and thrust papers at you on meta-analyses of the para-psychological literature, and pass you a copy of Synchronicity—or at least my review of it—showing how the founders of quantum mechanics were themselves interested in psi effects. Look, I might huff, have you not read Freeman Dyson on the possibility of ESP? Have you not noticed that even critics suggest further study?

I hope this description does not describe the way that I actually behave. But why not? What about this response, rudeness aside, would be so bad? Read more »

Monday Poem

Uroboros

This image has an empty alt attribute; its file name is uroboros.jpg

new year, end day of a beginning,
two limits of an endless rope,
sunup/sundown, the day we split infinity
that lazy 8 napping on its side as time goes by,
the day we draw a deep breath
in belief that its undulant line may really be broken
regardless of the will of a universe to ever be
unsplittable in the extent of its being,
as if a year arbitrarily set to solar cycles
marks anything but a wish to apply human order
to a thing as opaque but terse as a snake biting its tail,
yet it can be done, and is
in love    by love

Jim Culleny
1/2/2022

The Alpha & The Omicron

by Rafaël Newman

Beginnings are a theme for sages,
For adepts of our Golden Ages:
When the victuals were prodigious,
And division un-litigious—
Since the stores, in their abundance,
Rendered striving a redundance;
Why in gardens Paradisal
Our ancestors scorned reprisal
As they supped upon the flower
That was bounty, boon, and bower;
How dread Rome was born from zero
When a hapless, vagrant hero
Laid the fundaments imperial,
Having shunned the charms venereal
Of a likewise diasporic
Queen of Carthage, prehistoric;
That the very Earth we tread on,
Raise our children, earn our bread on,
Once was spoken into being
By a deity all-seeing,
Whose division was prodigious—
Not, however, un-litigious. Read more »

Critique of IBM Apollo Study Report – 1 Oct 1963 – Eldon Hall

by R. Passov

Eldon Hall spent the first seven years of his life climbing hills alongside Oregon’s Snake River, trailed by a faithful Shepard dog. He and his father “…went fishing in the mountains…” and “… slept outdoors while his mother, safely residing at home, worried about the poisonous snakes that might bite [them.]” In 1926, when Eldon was seven, his father passed. If not for that, Eldon would have carried on farming alongside the banks of the Snake.

Unable to hold onto the farm, Eldon’s mother took her three children across the river to Paytte, Idaho. There she married a subsistence farmer. While Eldon was tempered working as a farmhand, she held his dream of getting an education.

The day before Pearl Harbor, Eldon defied the odds by enrolling at the University of Washington. The war dried up funding. On the verge of dropping out, he joined the ROTC. In 1943 he was called to active duty. The few college credits he brought along gained entry into a newly formed “Army Specialized Training Program” that led to City College, NY where his days were “…filled with lectures, testing, military instruction, calisthenics, and some free time to tour the Big Apple.”

After 18 months he was sent across another river to Rutgers University to begin a “training program” in electrical engineering. Of the two hundred or so men who started the program, 65 finished. The top four graduates joined the Manhattan Project. Eldon graduated in 5th position. Read more »

Dead Teachers, Live Pedagogies And The Reanimation Of Hope

by Eric J. Weiner

January, 2022. East End, Long Island, NY. It’s getting colder. I just recovered from a bout with COVID. I am sitting around the fire pit sipping tequila, drinking homemade bone broth from a mug, and watching lists of very important dead people, ripped from various newspapers and magazines, burn in the fire. Life is good.

It is curious to me that the ending of each calendar year should signal the production of these lists. Against the backdrop of so much death from COVID in 2021, they are exclusively brief and, in the Marcusian sense, one-dimensional. Commodify your nostalgia: the bad and ugly exchanged whole cloth for the good. Death as salve, all is forgiven or, at the least, quickly forgotten. Beck got it right: “Time is a piece of wax falling on a termite/Who’s choking on the splinters.” No one gets out alive. But for those of us who are teachers, the lessons we learned from our dead brothers and sisters, those intimates who have touched and transformed our lives in deep and meaningful ways, can be reanimated through our teaching.

From the pedagogical perspective, the lexicon of death is not about lore, myth-making, or some other practice of forgetting. Rather, it suggests a critical practice of recognition that is concerned with how they lived their lives; how they taught their own students; how they treated their colleagues; the way they represented their work; the way they situated themselves within and beyond the university and school; the way laughter informed their interactions; and the seriousness by which they undertook their various social/political/educational projects. Read more »

Black Lives Matter? #BlackFriendsMatter

by Akim Reinhardt

The white Southerners who fought US segregation - BBC NewsThree things we know about #BLM, two obvious, one a bit more subtle.

1. Activists originally created the Black Lives Matter slogan to point out and push back against the generally unstated truth that in American society, black lives do NOT matter as much as white lives. That in America, black lives have always been cheap. They were literally commodified for two and a half centuries; police, vigilantes, and mobs have beaten and even killed black people with relative impunity; and white people have, in general, always been safer around police. To say “Black Lives Matter” is to point out all of this, to assert the morality of black lives mattering as much as white lives, and to insist that we strive for that equality in America.

2. Reactionaries immediately attacked the slogan. They misinterpreted the slogan, sometimes intentionally, often myopically, claiming it meant that ONLY black lives matter, which it did not. They countered with the slogan “All Lives Matter” as if it were a different and better slogan, when in reality, “All Lives Matter!” is the core message of “Black Lives Matter!” Because “Black Lives Matter” is really shorthand for “Black Lives Matter Too!”

3. Many white liberals support the Black Lives Matter movement, either quietly, or with yard signs and bumper stickers. This allows white liberals to define themselves as “allies” without actually doing anything substantive. It provides white liberals an opportunity to publicly perform their politics, wrapping themselves in the slogan and proclaiming they are not racist. As if racism is only (or mostly) about what you believe and say. But of course all biases, including sexism, homophobia, and classism, are truly evil because of what people do. Read more »

When Hans Holbein Came to Town

by Leanne Ogasawara

Holbein, 1536 or 37. Walker Art Gallery, Liverpool

1.

What are the chances that one of the greatest painters alive– a genius of portraiture, no less– would arrive at the court of the most infamous king in British history at the precise moment when the king began sending his royal wives to the chopping block?

Henry VIII. Even today, we can close our eyes and conjure up his dazzlingly rotund image. Those shapely legs in their white hose, adorned with courtly garter. And what about his perfect eyebrows and soft cheeks? The only reason we can do this conjuring is the skill of the painter Hans Holbein the Younger, who arrived in London just when all the fun started.

Holbein painted Henry so vividly. So evocatively. Facing straight on, legs set wide apart, his eyes are locked on the viewer. This is a vision of power. A lion about to pounce. In his puffed sleeves and doublet, the king is dripping in silk, gold, and gemstones. Holbein’s Henry is not just a portrait of the King but is an icon of power and excess.

And I’m sure I don’t need to point out the codpiece.

It was not just Henry whom Holbein painted either; for as Franny Moyle says in her wonderful Holbein biography, The King’s Painter, which came out earlier this year, every aristocratic Tom, Dick and Henry wanted a portrait painted by the great German artist. Read more »

On the Road: Happy New Year. What Could Go Wrong?

by Bill Murray

2022 is alive, a babe come hale and hollering to join its sisters 2020 and 2021, siblings bound by pandemic. Everybody stood to see off 2022’s older sister 2021, like we all did 2020 before her. Out with the old. Quickly, please.

2022 debuts with a striking resemblance to her sisters, just more evolved. So that by now some Americans signal their freedom by avoiding vaccination while others seek freedom by staying indoors. Meanwhile Europeans ban each other, for a moment there the whole world tried to put southern Africans out of mind entirely, and every country tortures its airlines. Hi ho the derry-o a quarantining we will go.

The Die Welt UK correspondent lamented that should she visit her homeland this holiday, she couldn’t even test her way free. Test your way free.

Consider the world in which 2022 will make her mark. Look east from Kyiv and please find Russia issuing un-agree-to-able demands and backing them with the rattling of 100,000 human sabres. It would be utterly incredible if Putin were to start a land war in Europe. But those who claim knowledge of his inner thoughts cite a deep, consistent grievance. Indeed they find it in the public record, in his 5000 word ‘Ukraine is not a real country’ article back last summer.

As far back as 2008, at a NATO-Russia Council meeting in Bucharest, Putin declared to W. Bush, “George, do you realize that Ukraine is not even a state? What is Ukraine? Part of its territory is Eastern Europe but the greater part is a gift from us!” Read more »

My Early Jazz Education: From the Firehouse to Louis Armstrong

by Bill Benzon

I don’t remember just how I first became interested in jazz as a child growing up in Western Pennsylvania in the 1950s. There was always music in the house, but it was mostly classical music, often on big old 78s. My father had a particular affinity for Beethoven.

Walt Disney is part of the story. Not Uncle Walt himself, but a Dixieland jazz band, The Firehouse Five Plus Two, consisting of personnel from his animation studio. They’d show up regularly on “The Mickey Mouse Club” TV program back in the 1950s, and I’m sure I heard them there. Here’s a clip where they play “Muskrat Ramble”:

I have no recollection of having seen any particular performance of theirs, but I could well have heard them play this one.

Dixieland, as you may know, is a style closely based on traditional New Orleans jazz from the first quarter of the 20th century. It was enjoying a resurgence, perhaps in part as a reaction to bebop, and was sweeping college campuses. But me and my friends knew nothing of that. We just knew that we liked this music.

One of those friends, David Leffler, actually his mother, introduced me to Louis Armstrong. I was down the street visiting David late one afternoon when somehow or other his mother asked whether or not I’d heard Louis Armstrong. I’d never heard of him. She put a record on and I listened. I don’t remember what it was. All I remember is that it sounded a bit thin. But – and here’s the thing – I remembered it.

When my father joined a record club – you know, one of those deals where you could by records and they’d be mailed to you – I was allowed a selection in the first buy. I read through the little pamphlet and picked something called A Rare Batch of Satch. Again, lots of tinny sound. And a lot of what I would come to recognize as standard repertoire: “Basin Street Blues,” “High Society,” “St. James Infirmary” (which I loved), “When It’s Sleepy Time Down South” (Armstrong’s theme song), and others. Read more »

Charaiveti: Journey From India To The Two Cambridges And Berkeley And Beyond, Part 25

by Pranab Bardhan

All of the articles in this series can be found here.

At my ISI office there were several good economists. Apart from TN, there was B.S. Minhas, Kirit Parikh, Suresh Tendulkar, Sanjit Bose (my friend from MIT days), V.K. Chetty, Dipankar Dasgupta, and others. Of these in many ways the most colorful character was Minhas. A shaved un-turbaned Sikh, he used to tell us about his growing up in a poor farmer family in a Punjab village, where he was the first in his family to go to school. He went to Stanford for doctorate, before returning to India. He relished, a bit too much, his role as the man who spoke the blunt truth to everyone including politicians, policy-makers and academics. He illustrated his Punjabi style by telling the Bengalis that he had heard that in Bengal when a man had a tiff with his wife, he’d go without food rather than eat the food his wife had cooked; he said at home he did quite the opposite: “I go to the fridge, take out my food and eat it; then if I am still upset, I go to the fridge again and take out my wife’s food and eat it all up—serves her right!”

At ISI Bose, Dasgupta and Chetty were theorists; Minhas, TN, Parikh and Tendulkar did multi-sector planning models as well as quantitative studies of particular sectors like agriculture, water, energy, etc. TN, as probably India’s most versatile economist ever, did both theory and empirical quantitative work. (He and I started editing a new journal on Quantitative Economics, which later became the journal of Indian Econometric Society). To my great benefit, TN was also most knowledgeable about Indian data.

Without TN’s guiding hand at the beginning I’d have felt completely out of my depth in the data world. These were days when data were stored in boxes of computer punch-cards. Data storage was often in awful condition—I used to jokingly ask how we could be sure that some of the data in the form of holes in the punch-cards were not made by the insects that infested the store rooms. Read more »

Joyce Carol Oates on the lifelong obsessions of Fyodor Dostoyevsky

Joyce Carol Oates in Prospect:

Of all writers, Fyodor Dostoyevsky is the great artist of obsession. It is not surprising, therefore, that his monumental works—Crime and PunishmentThe PossessedThe IdiotThe Brothers Karamazov—are seeded in his shorter works of fiction, as if in embryo. From the wildly romantic and effusive “White Nights” (1848) to the parable-like “Dream of a Ridiculous Man” (1877), these tales explore themes taken up in minute detail in the novels, in which Dostoyevsky’s sense of the tragic predicament of humankind is given its fullest expression: that human beings recognise the good, but succumb to evil; that, though knowing that love is the highest value, they rejoice in their own wickedness, like the “ridiculous man,” a perverse saviour who corrupts the innocent:

“The dream encompassed thousands of years and left in me only a vague sensation… I only know that the cause of the Fall was I. Like a horrible trichina, like the germ of the plague infecting whole kingdoms, so did I infect with myself all that happy earth that knew no sin before me.”

Dostoyevsky is a fierce Christian visionary for whom “social realism” holds little interest, except as a backdrop for powerful dramas of good contending with evil. Unlike his fellow Russian Leo Tolstoy—whose prose evokes an astonishingly lifelike world of men and women of virtually every social class, who could write as vividly of a young girl’s first ball as of a young soldier’s first battle—Dostoyevsky is all foreground, his settings (cramped and febrile interiors, sweeping and anonymous cityscapes) incidental to the histrionic nature of his prose.

More here.

Beyond case counts: What Omicron is teaching us

Andrew Joseph and Helen Branswell in Stat News:

The Omicron wave in the United States is upon us.

If you were fortunate enough to tune out from Covid-19 news over the holidays, you’re coming back to startling reports about record high case counts and, in some places, increases in hospitalizations. The wave will crest, of course; the question is when.

For now, experts say, the country still has a ways to go to get through the Omicron surge. Below, STAT outlines what Omicron is already teaching us as this phase of the pandemic plays out.

A reminder: Scientists have known about this variant for just a little over a month. While a tremendous amount has been learned in a stunningly short amount of time, our understanding will continue to be refined as data pour in and key questions are answered.

More here.