Heidi Ledford in Nature:

The stunning failure of a once-promising cancer drug has got some researchers arguing that the field has moved too fast in its embrace of therapies that unleash the immune system. The drug, epacadostat, blocks a protein called IDO that hobbles immune cells if left unchecked. Early trials suggested that the drug could be a powerful weapon against some advanced cancers when paired with existing therapies that bolster the body’s immune response to tumours. But a large, controlled study of epacadostat was halted in April after the drug failed to show benefits. Now, a researcher who helped to conduct some of the first trials of the drug says that it was pushed into large clinical studies too soon — and that the same could be true of other cancer immunotherapies in development. “People ask me right now, ‘What are you excited about?’” says Jason Luke, an oncologist at the University of Chicago in Illinois who aired his concerns last week at a meeting of the Society for Immunotherapy of Cancer in Washington DC. “And I say, ‘Unfortunately, little to nothing,’ because almost none of this is done properly.”

Early data from small trials of epacadostat, which is made by Incyte of Wilmington, Delaware, excited researchers. Luke recalls one trial participant with advanced cancer who was so weak that it was difficult for him to travel to the clinic. From the first dose, the man showed improvement. But Luke now attributes those gains to the treatment given alongside epacadostat in the trial: an approved immunotherapy called pembrolizumab, made by Merck of Kenilworth, New Jersey.

After Incyte and Merck reported in April that a larger trial of epacadostat and pembrolizumab had failed, other companies announced that they were halting their own programmes to develop cancer drugs that block the IDO protein. “The field has completely evaporated,” says Luke, who notes that more than 1,000 participants were once enrolled across various studies of IDO-inhibiting drugs. This failure should be a wake-up call for other cancer researchers, says Felipe Campesato, a cancer immunologist at Memorial Sloan Kettering Cancer Center in New York City. “We can take that challenge as an opportunity for improvement, and maybe a turning point in the field.”

More here.

Kelly and Zach Weinersmith in Delancyplace:

Let’s talk about mirror humans: “Oh, you haven’t heard of mirror humans? Let’s back up a moment.

“Life is made of lots of little molecules, and these molecules make up import­ant bigger molecules, like DNA, RNA, and proteins. Some molecules exhibit what is called chirality, from the Greek word for ‘hand.’ If a molecule has chirality that basically means there is a mirror version of it. “To wrap your head around ‘mirror versions’ of things, think about your hands. They look exactly the same, but no matter how you rotate your left hand, it won’t be exactly the same as the right. If you have your palms up, your left thumb will point left and your right thumb will point right. Each hand has all the same parts, but they are flipped, as if through a mirror. “When you have two molecules that are mirror images of one another, one of these molecules is designated as the left-handed version and the other as the right-handed version. Intriguingly, life seems to favor a certain handedness for particular tasks. For example, almost all amino acids (which you may remember from previous chapters are the building blocks of proteins) are in the left-handed form. Why nature abhors right-handed amino acids is a topic of debate, but even the amino acids we find in space tend to be left-handed.

“But screw nature. Whatever her reasoning is, there is no known physical reason we couldn’t create an organism out of completely opposite-handed molecules in the lab — a ‘mirror organism,’ if you like. Some scientists, including Dr. [George] Church­ [of Harvard], are working to create (simple) mirror organisms, with the hope creating larger and larger such creatures. Why exactly would we want this? Well, for one, it’s awesome. You create something that looks like a nice little kitty, but is totally incompatible with the rest of the life on the planet, perhaps even the universe. For example, mirror-opposite organisms would need to eat mirror food in order to be able to digest it. They would also be undigest­ible to all predators. Best of all, a mirror-opposite organism would be com­pletely immune to all diseases, because all living parasites and pathogens evolved to infect organisms with normal chirality.

“And if it worked, hey, we could scale up to making mirror-opposite humans.

More here.

February 11

The moon is out. The ice is gone. Patches of white
lounge on the wet meadow. Moonlit darkness at 6 a.m.

Again from the porch these blue mornings I hear an eagle’s cries
like God is out across the bay rubbing two mineral sheets together
slowly, with great pressure.

A single creature’s voice—or just the loudest one.
Others speak with eyes: they watch—
the frogs and beetles, sleepy bats, ones I can’t see.
Their watching is their own stamp on the world.

I cry at odd times—driving, or someone touches my shoulder
or has a nice voice on the phone.

I steel myself for the day.
.
by Nellie Bridge
from Echotheo Review

Bianca Bosker in The Atlantic:

One afternoon in the summer of 2013, Anna Todd was in the checkout line at Target when, as most of us do, she pulled out her phone. Then she propped her elbows on her shopping cart and began to type.

Todd was 24 years old and living near Fort Hood, Texas, with her husband, a soldier she had married a month after graduating high school, and their newborn, who suffered daily seizures. While caring for her son and taking online community-college courses, she helped support the family by babysitting for a neighbor and working the beauty counter at Ulta. For fun, she read. Wuthering Heights, Twilight, The Things They Carried. Since the previous fall, she’d also indulged an addiction to One Direction fan fiction—stories featuring the boy band in imagined scenarios. After blazing through all that she could find online and then tiring of waiting for updates from erratic authors (many of them teens juggling writing and school), Todd decided to attempt her own series. She called it After and wrote on her smartphone whenever she could steal a moment—while shopping for groceries, waiting to get her teeth cleaned, riding in friends’ cars. She used a pseudonym (imaginator1D) and hid her alter ego from family and friends. “My husband just thought I had a phone addiction or something,” she has said.

More here.

Kevin Hartnett in Quanta:

Elliptic curves seem to admit infinite variety, but they really only come in two flavors. That is the upshot of a new proof from a graduate student at Harvard University.

Elliptic curves may sound exotic, but they’re unspectacular geometric objects, as ordinary as lines, parabolas or ellipses. In a paper first posted online last year, Alexander Smith proved a four-decade-old conjecture that concerns a fundamental trait of elliptic curves called “rank.” Smith proved that, within a specific family of curves, and with one qualification, half of all curves have rank 0 and half have rank 1.

The result establishes baseline characteristics of objects that have intrigued mathematicians for centuries, and that have increased in importance in recent decades.

“We’ve been thinking about this for over 1,000 years, and now we have some probabilistic sense about [elliptic curves]. That’s super important,” said Shou-Wu Zhang, a mathematician at Princeton University who advised Smith at the outset of the work, when Smith was an undergraduate at Princeton.

More here.

Barry Latzer in the National Review:

New York’s governor, Andrew Cuomo, just announced a bail-reform program. Details were not yet available at press time, but it’s clear that Cuomo intends to release thousands of arrested persons, even suspected felons, without bail.

Meanwhile, across the Hudson, New Jersey has already launched its bail-reform plan. It replaces money bail with an algorithm that scores recently arrested defendants on dangerousness plus the likelihood of their appearance at court hearings. In the first three months of operation, three-quarters of the state’s defendants were released. After six months, New Jersey’s non-sentenced jail population declined 20 percent and was 35 percent lower than it had been two years earlier.

That’s good for the defendants, who don’t have to spend time in jail in the event that they’re unable to make bail. But is it safe for the public? As with virtually every other criminal-justice reform, these experiments increase public risk. Any reform that keeps parolees, probationers, or pretrial defendants out of jail or prison, either by making their sentences shorter or by replacing incarceration with release to the community, is risky.

More here.

The Cutting Reason

I go back to the island,
see the house, no longer home,
breathe the sea, to breathe the sea.

Walking the streets, Belfast on Orange
Eve. The two of you, sipping tea. Bewley’s.
Pane of glass, the glass between –

and when my skinned heart finally stops
beating and beating, a lambeg drum,

I know, having walked away,
the cutting reason why I came.

by Catherine Graham
from  Pupa
Insomniac Press, Toronto 2003

Micah Meadowcroft at The New Atlantis:

Hannah Arendt reflected on the significance of humanity’s desire for the stars in her 1963 essay “The Conquest of Space and the Stature of Man.” Man, she said, has not found a new place for himself after his self-displacement in modernity’s rejection of old orders. We stand alienated from ourselves and nature. And as we see deeper into the firmament, and account for more of nature, we only better know the scale of our disorientation, the smallness of our vision. Science cannot bound the cosmos into a comfortable domain, for “this observed universe, the infinitely small no less than the infinitely large, escapes not only the coarseness of human sense perception but even the enormously ingenious instruments that have been built for its refinement.” But neither does modern science really wish to find a place for man in all this space, for the questions that would require would produce answers for man that act “as definitions and hence as limitations of his efforts.”

This alienation calls for some kind of transcendence — a need to find ourselves and discover where we are.

more here.

Philippa Snow at The Baffler:

It occurred to me, when thinking about Ronnie’s bathroom scene, that this is not McQueen’s first time depicting the repressed, deep-seated trauma of a wealthy but unhappy individual on film: that Shame, whose central character appeared to have developed sex-addiction in the wake of some unspecified, formative trauma—maybe psychic, maybe physical—addressed a similar, if not entirely symmetrical, ache. The sex addict, Brandon, as played in the key of Patrick Bateman by the Irish actor Michael Fassbender, also contained his introspection and his self-injurious anger within the confines of the bathroom. Often, his releases there were masturbatory. So, on some level, was the movie; lacking detailed and elucidating background information, Brandon’s tragedy became the tragedy of a successful, very handsome white man tortured by the need to regularly have sex with one or more women who resemble fashion models. (Brandon’s kookily sad sister, Sissy, is so white that she is played by Carey Mulligan, and is called Sissy. His apartment, in what might be seen as a reflection of his inner turmoil, is white and expensive, but lit so that above all else, it looks blue.)

more here.

Matthew Aucoin at the NYRB:

For modern listeners, Debussy practically defines French music, by which I mean that the essential qualities of his music—not only his sensuous delicacy but also his aversion to the harmonic behavior characteristic of late-nineteenth-century German music, a dense chromatic motion that tends to constantly, restlessly build to orgiastic climaxes, as in Wagner and Strauss—have come to be seen as also essentially “French” qualities. Walsh makes clear, however, that Debussy, far from simply amplifying or exemplifying the dominant tendencies of his musical milieu, consciously and stubbornly swam against the current, especially when it came to the heavy influence of German music on French composers. Wagner was the unavoidable presence in late-nineteenth-century Paris, but Debussy traced the blame for that influence further back, to Gluck. Debussy was quietly radical in his preference for Rameau’s “delicate and charming tenderness” over what he perceived as the Germanic “affectation of profundity or the need to double underline everything.”

more here.

Nicholas Smith in IAI:

If we were to stop and ask ourselves how our lives might be improved, one likely answer that might occur to us is that we should spend less time at work. At least that is what the statistics suggest.

…In her book The Human Condition (1958), Arendt argued that most of what we now do when we say we ‘work’ has the essential character of what she calls ‘labour’. Labour resembles the artisanal work of previous times in that it is a means to an end, but unlike work in its true sense, which leaves some enduring useful object behind, it produces something to be consumed, and is done for the sake of empowering one’s consumption. Labour is our ‘metabolism with nature’, a phrase Arendt borrows from Marx, which ties us to the eternally recurring cycle of life. Labouring activity, no less than the behaviour of any other living organism, inherently lends itself to scientific measurement and enhancement. For this reason, well-meaning efforts to humanise labour were, in her view, futile and ill-conceived. But labour, however highly valued it is in the modern world, represents only one aspect of the human condition. Human beings are also capable of what Arendt calls ‘speech and action’, in which they deliberate over matters of common concern and act together. It is only through action in this true sense, Arendt believed, that human beings show themselves to be more than members of a species, or cogs in a machine, and appear to themselves in their uniqueness and plurality. When we act, in this sense, we break out of the cycle of endless repetition and bring about something genuinely new, something unpredictable. In the making and retelling of history, Arendt thought, we attain a kind of immortality, or at least some redemption of our earth-bound, life-bound condition, our condition qua labouring animal. 

More here. 

Denise Grady in The New York Times: