Marcela Maus in Nature:

The use of genetically engineered immune cells to target tumours is one of the most exciting current developments in cancer treatment. In this approach, T cells are taken from a patient and modified in vitro by inserting an engineered version of a gene that encodes a receptor protein. The receptor, known as a chimaeric antigen receptors (CAR), directs the engineered cell, called a CAR T cell, to the patient’s tumour when the cell is transferred back into the body. This therapy can be highly effective for tumours that express the protein CD19, such as B-cell acute leukaemias^1,2 and large-cell lymphomas^3,4. However, some people do not respond to CAR T cells, and efforts to optimize this therapy are ongoing. In a paper in Nature, Fraietta et al.⁵ report the fortuitous identification of a gene that positively affected one person’s response to treatment with CAR T cells.

Therapies involving engineered immune cells use viral vectors based on retroviruses or lentiviruses to insert a DNA sequence, such as one encoding a CAR, into a person’s T cells. However, given that there is no control over where the sequence inserts into the genome, it is possible that the engineered gene could insert at a location that disrupts another, important gene. In the early 2000s, a clinical trial⁶ enrolled people with immunodeficiencies arising from the lack of a functional copy of a particular immune gene. The trial used viral vectors to insert a wild-type copy of this gene into their stem cells. Unfortunately, however, several people developed uncontrolled T-cell proliferation that evolved into T-cell leukaemia. This event was linked⁷ to the gene inserting within the sequence of the LMO2gene, disrupting the normal regulation of LMO2.

The pattern of genomic integration sites for various viral vectors has been found to be specific for a given combination of vector and cell type⁸. In a study of people who had T cells modified using retroviral vectors, the integration events were not implicated as the cause of any cancers⁹. Lentiviral vectors integrate randomly into the genome but tend to preferentially locate at sites of transcriptionally active genes¹⁰. Although random integration is generally thought to be safe, any disruption of the genome nevertheless confers a risk of unwanted consequences.

More here.

James McElroy in The American Conservative:

Critics of Goldman Sachs love to say the investment bank highlights the failures of everything from capitalism and neoliberalism to democracy and socialism. Millions of words have been written depicting Goldman as the central villain of the Great Recession, yet little has been said about their most egregious sin: their lobby art. In 2010, Goldman Sachs paid $5 million for a custom-made Julie Meheretu mural for their New York headquarters. Expectations are low for corporate lobby art, yet Meheretu’s giant painting is remarkably ugly—so ugly that it helps us sift through a decade of Goldman criticisms and get to the heart of what is wrong with the elites of our country.

Julie Mehretu’s “The Mural” is an abstract series of layered collages the size of a tennis court. Some layers are colorful swirls, others are quick black dash marks. At first glance one is struck by the chaos of the various shapes and colors. No pattern or structure reveals itself. Yet a longer look reveals a sublayer depicting architectural drawings of famous financial facades, including the New York Stock Exchange, The New Orleans Cotton Exchange, and even a market gate from the ancient Greek city of Miletus.

What are we to make of this?

More here.

Natalie Elliot in The New Atlantis:

In Act V of Hamlet, after Hamlet has killed Polonius, Ophelia has died, and Hamlet has returned to Denmark from his murderous trip to England, he happens upon two gravediggers. It is an odd and puzzling scene, and a noticeable departure from the rising action of the play. At this juncture, we expect Hamlet to clash with his rivals. Instead, we get a deeply philosophical and darkly comic exchange on death, with the gravediggers singing as they toss around bones and Hamlet wondering about the lives of the skeletons before him:

That skull had a tongue in it and could sing
once….

There’s another. Why may not that be the
skull of a lawyer? Where be his quiddities now, his
quillities, his cases, his tenures, and his tricks? Why
does he suffer this mad knave now to knock him
about the sconce with a dirty shovel and will not tell
him of his action of battery?

Later, Hamlet turns from the unfeeling coarseness of the gravediggers to morbid curiosity about the bodies, asking, “How long will a man lie i’ th’ earth ere he rot?”

The question of what comes after death has been on Hamlet’s mind throughout the play. Considering suicide, he wonders “what dreams may come / When we have shuffled off this mortal coil.” He seems torn between Catholic and Protestant accounts of the afterlife: Soon after returning from the University of Wittenberg, a center of the Protestant Reformation, Hamlet encounters what appears to be a strikingly Catholic specter — the ghost of his father, claiming his earthly sins must be “burnt and purged away” in purgatory — but he vacillates on whether the ghost can be believed. By the time he meets the gravediggers, Hamlet’s questions about the afterlife, still unsolved, turn to the physical realm: He wants to know about the material nature of corpses.

Hamlet’s curiosity about bodies is significant not only because it recalls some of the materialistic ideas he entertained earlier in the play — that man is nothing more than a “quintessence of dust,” or that the dead Polonius is simply a bag of guts — but also because it suggests that Shakespeare was engaging with the science of his time.

More here.  [Thanks to Simon Dedeo.]

Michelle Starr in Science Alert:

Around 7,000 years ago – all the way back in the Neolithic – something really peculiar happened to human genetic diversity. Over the next 2,000 years, and seen across Africa, Europe and Asia, the genetic diversity of the Y chromosome collapsed, becoming as though there was only one man for every 17 women.

Now, through computer modelling, researchers believe they have found the cause of this mysterious phenomenon: fighting between patrilineal clans.

Drops in genetic diversity among humans are not unheard of, inferred based on genetic patterns in modern humans. But these usually affect entire populations, probably as the result of a disaster or other event that shrinks the population and therefore the gene pool.

But the Neolithic Y-chromosome bottleneck, as it is known, has been something of a puzzle since its discovery in 2015. This is because it was only observed on the genes on the Y chromosome that get passed down from father to son – which means it only affected men.

This points to a social, rather than an environmental, cause, and given the social restructures between 12,000 and 8,000 years ago as humans shifted to more agrarian cultures with patrilineal structures, this may have had something to do with it.

More here.  [Thanks to Steven Pinker.]

Caitlin Flanagan in The Atlantic:

Is it possible for two people to simultaneously sexually assault each other? This is the question—rife with legal, anatomical, and emotional improbabilities—to which the University of Cincinnati now addresses itself, and with some urgency, as the institution and three of its employees are currently being sued over an encounter that was sexual for a brief moment, but that just as quickly entered the realm of eternal return. The one important thing you need to know about the case is that according to the lawsuit, a woman has been indefinitely suspended from college because she let a man touch her vagina. What kind of sexually repressive madness could have allowed for this to happen? Answer that question and you will go a long way toward answering the question, “What the hell is happening on American college campuses?”

The substantive facts of the case come to us only through a lawsuit, one that has thus far implicated everything from Title IX, the Sixth Circuit Court of Appeals, and the United States Constitution to “slut shaming” and good old-fashioned horniness. But not super horniness, because—as with many high profile cases involving the infinitely expandable concept of “college sexual assault”—the actual encounter exists as merest prologue to the massive novel of ideas that followed it.

More here.

Kieran Healy:

Recently Tyler Cowen asked whether there has been progress in Philosophy. Agnes Callard wrote a thoughtful reply, saying amongst other things:

We don’t demand progress in the fields of fashion or literature, because these things please us. Philosophy, by contrast, is bitter, and we want to know what good it will do us, and when, finally, it will be over. It is not pleasant to be told that maybe you don’t know who you are, or how to treat your friends, or how to be happy. It’s not pleasant to have it pointed out to you that maybe nothing you have ever done matters, or that, for all you know, there is nothing out there at all.

So one way to hear the questioner is as asking:

“When will philosophy finally go away? When will they stop raising questions about whether my own will is free, or saying that I can’t tell whether I’m leading my life or it’s leading me? When will they stop telling me that I need to read this or that book in order to be fully human? When will they leave me alone?”

The answer is: never.

In the background of this exchange is an ongoing discussion in philosophy about whether the field is making progress, as exemplified in recent papers by Dave Chalmers (”Why isn’t there more progress in Philosophy?”) and Herman Cappelen (”Disagreement in Philosophy: an optimistic perspective”). Disciplines—including my own—periodically have debates about whether they are making as much progress as they once did, or as they should be making. There’s a strong connection between what those debates look like and the degree of “disciplinarity” in a given area.

More here.

Wajahat Ali in The Atlantic:

I grew up eating Hebrew National kosher hot dogs in my Fremont, California, home. Back then, halal meat was alien to the local supermarket, so Jewish dietary restrictions came to the rescue of an overweight Pakistani American kid. Straightforward anti-Semitism was not taught in my Muslim household or in weekend Koran classes. My father never dusted off The Protocols of the Elders of Zion from the living-room bookshelf. Instead, I carpooled to an all-male Jesuit high school with my Jewish neighbor Brian, with whom I never debated the implications of the wars of 1948 or 1967, but with whom I did regularly have heated exchanges about the merits of Star Trek: The Next Generation versus Star Trek: Deep Space Nine.

Growing up, I was taught that Christians and Jews were considered “People of the Book,” part of the same Abrahamic tradition as Muslims. But the specter of Israel, the suffering of Palestinians, and the occupation of Jerusalem in particular loomed large in conversations at home and in the religious teachings I received. When visiting Pakistan, I heard relatives and friends lament how “the Jews” oppressed “the Muslims.” In America, the Muslims I knew discussed their envy of Jewish power and influence: If only we Muslims were as organized and strategic as the Jews, we could replicate their success. Among my community, respect for the Jews’ mythical status as the magical minority was its own subtle form of anti-Semitism. Sometimes my dad would read aloud the credits at the end of a movie and say, “Spielberg … Jewish. Cohn … Jewish. Adelstein? Definitely Yehudi! See, Wajahat, if Jews can dominate Hollywood, there’s no reason you can’t!”

As an undergraduate at UC Berkeley, I was a member of the Muslim Student Association. I recall listening to more passionate khutbahs—Friday sermons—about the injustices in Palestine than stories about the Prophet Muhammad and his companions. The conflict in the Holy Land superseded all other Muslim suffering, including the ongoing occupation of Kashmir, the repression of Chechen Muslims, and the daily racism experienced by many African-American Muslims. I became a bit actor in a never-ending cosmic drama. I would parrot a script written by others, and serve as a proxy soldier for a tragedy happening across the Atlantic. The Jewish kids from the campus Hillel were my foil. We showed up to “debates,” predictable affairs where each side cheered and booed when appropriate but rarely engaged in a constructive dialogue.

We marched, chanted, rallied. We wore zionism is racism T-shirts. We thought we were differentiating Judaism from Zionism, the political ideology espoused by Theodor Herzl at the turn of the 20th century, which argued for the creation of a Jewish state in the Jews’ ancestral homeland of Israel. But too few of us Muslims bothered to ask how the many American Jews who consider themselves in some way Zionist felt upon hearing that Zionism was racism.

More here.

Love after Love

The time will come
when, with elation,
you will greet yourself arriving
at your own door, in your own mirror,
and each will smile at the other’s welcome,

and say, sit here. Eat.
You will love again the stranger who was your self.
Give win. Give bread. Give back your heart
to itself, to the stranger who has loved you

all your life, whom you ignored
for another, who knows you by heart.
Take down the love letters from the bookshelf,

the photographs, the desperate notes,
peel your own image from the mirror.
Sit. Feast on your life.

by Derek Walcott
from Sea Grapes
Farrar, Straus and Giroux

Michael Tye in Inference Review:

In an essay entitled, “Philosophy and the Scientific Image of Man,” the American philosopher Wilfrid Sellars argued that our allegiances are divided between the manifest and the scientific image of the world.¹ On the manifest image, the world comprises people, pains, and puzzles; on the scientific image, nothing more than various quantum fields. It is the scientific image that takes ontological pride of place. But if colorless quantum fields are really real, what are we to say about colored roses, which are really red?

There is an obvious gap between the manifest and scientific image of the world. How could roses be red?  One venerable philosophical answer is that roses are red in virtue of how they are experienced. But experience is itself no less mysterious than color. We are subjects of experience; quantum fields are not. Questions of this sort have persuaded David Chalmers tentatively to embrace what he calls naturalistic dualism. For all that, dualism is still dualism. Many philosophers have resisted following him into the badlands. The stay-behinds hope to make sense of consciousness in a way that does justice to its richness while somehow embedding it in the scientific side of things.

In his new book, Daniel Dennett argues that all parties to this discussion, while rarely in doubt, are nonetheless in error. There is no point in bridging the gap between the manifest and scientific image of the world because no such gap exists. The manifest image, Dennett argues, is a user illusion.

More here.

Peter Woit in Not Even Wrong:

Jim Holt has a new book out, a collection of essays entitled When Einstein Walked with Gödel. I wrote enthusiastically about his last book (Why Does the World Exist?) here and, if you have any interest at all in the overlap of mathematics, science and philosophy, I recommend this one just as highly. Holt is pretty much a unique example of someone able to regularly write about topics in this area in a manner that is both enlightening and entertaining.

This is a book of essays written on different topics for different venues, of too great a variety to try and itemize here. Most of them have some sort of connection to mathematics and philosophy, typically centering on one idea or one, often historical, figure. Holt loves to write about the most abstract of ideas (the subtitle of the book is “Excursions to the Edge of Thought”), but in the context of the particular very human qualities of the thinkers responsible for them.

More here.

Secunder Kermani at the BBC:

It was the night of 16 November 2016. Mr Haider has not been seen since. Despite the CCTV video evidence both the police and intelligence services have denied in court that he is in their custody.

Mr Haider is one of 140 Pakistani Shias to have “disappeared” over the past two years, according to community activists. Their families believe they were taken into custody by the intelligence services. Over 25 of the missing, including Mr Haider, belong to Pakistan’s largest city Karachi.

Mr Haider’s family say he had returned to the port city from pilgrimage in Karbala, Iraq, with his pregnant wife just two days before he was detained.

Uzma Haider has since given birth to a baby boy who has never seen his father.

“My kids are always asking me, ‘When will our dad come home?'” she told the BBC. “What answer can I give them? No-one is telling us where he is or how he is. At least tell us what he’s accused of.”

More here.

Jennifer Szalai at the NYT:

The photographer Arthur Fellig, better known as Weegee, lugged his enormous Speed Graphic camera around the nighttime streets of New York City in the 1930s and ’40s, cultivating a persona as stark and as memorable as his tabloid pictures. He was the wisecracking tummler in the rumpled suit, always on the lookout for a car crash or a dead gangster.

“I have no inhibitions, and neither has my camera,” he declared in a 1961 autobiography — a fascinating and problematic document if there ever was one, given Weegee’s compulsion for exaggeration and self-promotion. This, after all, was the man who titled his first solo exhibition “Murder Is My Business” and likened a picture to a blintz: “Eat it while it’s hot.”

more here.

Claire Messud at The Guardian:

All who have loved Lorrie Moore’s fiction since her first marvellous short story collection Self-Help (1985) will be keen to read See What Can Be Done, an anthology, albeit not comprehensive, of her critical writings and essays since the 1980s. Those who have not yet discovered her might best begin with the fiction and save this collection for later, not because it doesn’t merit attention but because Moore’s incisive, often mordant yet exhilarating pieces illuminate the trajectory of a literary artist’s aesthetic evolution, and enhance an understanding of her fiction. They give us a cumulative sense of how the frank, savvy, tragicomic sensibility so evident in her stories and novels reverberates in the wider context, whether she is discussing the fiction of Ann Beattie or Alice Munro, TV series such as The Wire or True Detective, or Hillary Clinton’s doomed presidential campaign.

more here.

Jesse Baron at Bookforum:

Country fans no longer resemble the characters in country songs; they are salaried accountants chewing Nicorette in Chevy Tahoes, not railroad linemen spitting Copenhagen through the shot-out windows of a Ford F-150. Their assimilation worries them, and they sometimes overcompensate. “If any of you tuned in to ABC tonight expecting to see the new show Black-ish,” said host Brad Paisley at the 2014 Country Music Association Awards, referring to the sitcom about assimilation anxiety in the suburbs, “this ain’t it. In the meantime, I hope y’all are enjoying white-ish.” The joke had another meaning, too, which Paisley probably didn’t intend: Despite the perception that country is white America’s music, it’s only ever been white-ish. “Country” descended from British and Celtic ballads that crossed the ocean into Appalachia and the South, where singers Americanized the names of the women and the rivers. It was stirred with Baptist hymns, black American folk songs, New Orleans jazz, and—crucially—the twelve-bar blues. Was the sound white? Was it native? The banjo derived from the African gourd-based banjar.

more here.

Personal

Don’t take it personal, they said;
but I did, I took it all quite personal—

the breeze and the river and the color of the fields;
the price of grapefruit and stamps,

the wet hair of women in the rain—
And I cursed what hurt me

and I praised what gave me joy,
the most simple-minded of possible responses.

The government reminded me of my father,
with its deafness and its laws,

and the weather reminded me of my mom,
with her tropical squalls.

Enjoy it while you can, they said of Happiness
Think first, they said of Talk

Get over it, they said
at the School of Broken Hearts

but I couldn’t and I didn’t and I don’t
believe in the clean break;

I believe in the compound fracture
served with a sauce of dirty regret,

I believe in saying it all
and taking it all back

and saying it again for good measure
while the air fills up with I’m-Sorries

like wheeling birds
and the trees look seasick in the wind.

Oh life! Can you blame me
for making a scene?

You were that yellow caboose, the moon
disappearing over a ridge of cloud.

I was the dog, chained in some fool’s backyard;
barking and barking:

trying to convince everything else
to take it personal too.

by Tony Hoagland
from: Poetry, Vol. 194, No. 4
July/August, 2009