New Gene-Editing Tool Could Fix Genetic Defects—with Fewer Unwanted Effects

Tanya Lewis in Scientific American:

The gene-editing method CRISPR has transformed biology, giving scientists the ability to modify genes to treat or prevent genetic diseases by correcting dangerous mutations and to create a host of new genetically modified plants and animals. But the technique, which involves using an enzyme called a nuclease that acts as molecular scissors to “cut” DNA, can cause unintended effects. Making such double-stranded breaks in DNA can result in unwanted genetic material being inserted or deleted, which can have consequences including activating genes that cause cancer. Most mutations cannot be corrected easily without creating these undesirable genetic by-products.

In 2016 a team led by David Liu at the Broad Institute of Harvard University and the Massachusetts Institute of Technology developed another method, called base editing, which allows scientists to make precise edits to single DNA letters without relying on double-stranded breaks. This technique, however, can only be used to fix four out of the 12 types of “point” genetic mutations, which include insertions, deletions and combinations of the two.

Now Liu, Andrew Anzalone—a postdoctoral researcher in Liu’s laboratory—and their colleagues have developed a new gene-editing tool that avoids these double-stranded breaks and can correct all 12 types of point mutations.

More here.

Capitalism is modernity’s most beguiling and dangerous form of enchantment

Eugene McCarraher in Aeon:

Perhaps the grandest tale of capitalist modernity is entitled ‘The Disenchantment of the World’. Crystallised in the work of Max Weber but eloquently anticipated by Karl Marx, the story goes something like this: before the advent of capitalism, people believed that the world was enchanted, pervaded by mysterious, incalculable forces that ruled and animated the cosmos. Gods, spirits and other supernatural beings infused the material world, anchoring the most sublime and ultimate values in the ontological architecture of the Universe. In premodern Europe, Catholic Christianity epitomised enchantment in its sacramental cosmology and rituals, in which matter could serve as a conduit or mediator of God’s immeasurable grace. But as Calvinism, science and especially capitalism eroded this sacramental worldview, matter became nothing more than dumb, inert and manipulable stuff, disenchanted raw material open to the discovery of scientists, the mastery of technicians, and the exploitation of merchants and industrialists. Discredited in the course of enlightenment, the enchanted cosmos either withered into historical oblivion or went into the exile of private belief in liberal democracies. As Marx put it, all that was solid melted into air, and the most heavenly ecstasies drowned in the icy water of egotistical calculation.

With slight variations, ‘The Disenchantment of the World’ is the orthodox account of the birth and denouement of modernity, certified not only by secular intellectuals but by the religious intelligentsia as well.

More here.

Meet the Bloodsuckers

James Gorman in The New York Times:

It has been a big year for leeches. A new species was discovered near Washington and announced in August by Anna Phillips, who may have the world’s best job title: curator of parasitic worms at the Smithsonian National Museum of Natural History. The new leech, Macrobdella mimicus, has three jaws and 59 teeth, and is quite literally a creature of the Washington swamp: It drinks your blood and drops off when it’s full. This particular parasite is not registered as a foreign lobbyist. And there’s more leech news: In May, a man was charged in what may be the first case of leech smuggling in Canadian history. He had flown into Toronto with almost 5,000 leeches in a grocery bag — for personal use. At least, that’s what he said. What kind of personal use could that be? Well, leeches are good for bait, although fake ones are cheaper. There’s D.I.Y. bloodletting. And you can keep them as pets. (They’re not cheap, though: If you buy them online, you could pay $18 for a jumbo leech.)

Still, 5,000 is a lot of personal leeches. Suspicious officials called in Sebastian Kvist, curator of invertebrates at the Royal Ontario Museum, to identify the smuggled contraband. He said that dried leeches can be ground into a powder that is reputed in Chinese traditional medicine to have a variety of benefits. It’s a leech-intensive process. Dr. Kvist, who also helped identify Macrobdella mimicus, is co-designer of a new museum exhibit called “Bloodsuckers: Legends to Leeches,” a celebration of the sucking, sipping, drinking and lapping of the blood of mammals, birds, reptiles, fish and amphibians in real life as well as the imagination.

More here.

Tuesday Poem

A Greeting on the Trail

Turning fifty, at last I come to understand,
belatedly, unexpectedly, and quite suddenly,
that poetry is not going to save anybody’s life,
least of all my own. Nonetheless I choose to believe
the journey is not a descent but a climb,
as when, in a forest of golden-green morning sunlight,
one sees another hiker on the trail, who calls out,
where are you bound, friend, to the valley or the mountaintop?
Many things—seaweed, pollen, attention—drift.
News of the universe’s origin infiltrates atom by atom
the oxygenated envelope of the atmosphere.
My sense of purpose vectors away on rash currents
like the buoys I find tossed on the beach after a storm,
cork bobbers torn from old crab traps.
And what befalls the woebegotten crabs,
caged and forgotten at the bottom of the sea?
Are the labors to which we are summoned by dreams
so different from the tasks to which the sunlight of reality
enslaves us? One tires of niceties. We sleep now
surrounded by books, books piled in heaps
by the bedside, stacked along the walls of the room.
Let dust accrue on their spines and colophons,
let their ragged towers rise and wobble.
Of course the Chinese poets were familiar with all this,
T’ao Ch’ien, Hsieh Ling-yün, Po Chü-i,
masterful sophisticates adopting common accents
for their nostalgic drinking songs and laments
to age and temple ruins, imperial avarice,
autumn leaves caught in a tumbling stream.
As the river flows at the urging of gravity, as a flower
blooms after April rain, we are implements
of the unseen, always working for someone else.
The boss is a tall woman in a sky-blue shirt
or a man with one thumb lost to a cross-cut saw
or science or art or the emperor, what matter?
We scrabble within the skin of time
like mice in the belly of a boa constrictor,
Jonah within leviathan, pacing the keel, rib to rib,
surrounded by the pulse of that enormous, compassionate heart.
Later we dance in orchards of guava and lychee nuts
to the shifting registers of distant music,
a clattering of plates as great fish are lifted from the grill,
seared black with bitter orange and lemongrass.
Orchid trees bloom here, Tulip trees and Flame trees,
but no Idea trees, no trees of Mercy,
for these are human capacities, human occasions.
Because it has about it something of the old village magic,
the crop made to rise by seed of words,
by spell or incantation—
because it frightens and humbles us to recall
our submission to such protocols—
for this do we fear poetry, for the unresolved darkness
of the past. Where are you bound, friend,
on this bright and fruitful morning—to the valley
or the mountaintop?
To the mountaintop.
.
by Campbell McGrath
from the
Kenyon Review

Coping with Resurgent Nationalism

by Pranab Bardhan

Einstein had called nationalism ‘an infantile disease, the measles of mankind’. Many contemporary cosmopolitan liberals are similarly skeptical, contemptuous or dismissive, as its current epidemic rages all around the world particularly in the form of right-wing extremist or populist movements. While I understand the liberal attitude, I think it’ll be irresponsible of us to let the illiberals meanwhile hijack the idea of nationalism for their nefarious purpose. Nationalism is too passionate and historically explosive an issue to be left to their tender mercies. It is important to fight the virulent forms of the disease with an appropriate antidote and try to vaccinate as many as possible particularly in the younger generations.

Populists advocate a culturally narrow, narcissistic, nostalgic, xenophobic form of ethnic nationalism—from the Christian nationalism of evangelicals in the US or the Catholics in Poland or the Slavic Orthodox-church followers in Russia to the Islamic nationalism in Turkey or Indonesia to the Hindu nationalism in India. The alternative, more inclusive, form of nationalism often counterposed to this is some variant of what is called ‘civic’ nationalism.

But first a brief historical note. As a form of community bonding on the basis of some tribal or ethnic-territorial roots proto-nationalisms of different kinds have been quite old and durable in different societies. But as Ernest Gellner, one of the foremost theorists of nationalism, pointed out, nationalism in the form as we know it is of relatively recent origin. Of course, historical memories and myths (mythology is often blurred into historical facts and legends), symbols and traditions are constantly invoked in the name of ethnic nationalism, even though, as the distinguished historian, Eric Hobsbawm famously pointed out, many of the so-called traditions are actually of recent ‘invention’. The influential 19th-century French scholar, Ernest Renan had pointed out how ‘historical error’ is used in the creation of a nation. Gellner even points to cases of nationalism based on not a great deal of history: “The Estonians created nationalism out of thin air in the course of the 19th century”.

But it is often overlooked that there is a clear distinction between nationalism based on some social bonding principle and the nation-state that became a predominant political unit, at least in Europe since the Treaty of Westphalia (1648). The former refers to a sociological community based on some homogeneous binding element like religion, language, ethnicity or culture, whereas the latter is a political community which need not contain a singular sociological nationality. Read more »

Monday Poem

Darkroom, 6:44 AM

.
sun’s not up but imminent,
trees in the window are emerging
shades in a darkroom bath

three boys sleep in a room downstairs
near mother; in another a girl sleeps
with another mother—
all still new as if just born
on this darkroom raft

I look up again,
sun trumps umbra
as light is cast

two window-worlds:

an outside one in its frame
urged to deciduous existence,
forms of leaves and limbs
distending the borders
of impossible, billowing
from indistinct shadow,
pressing itself into being
upon the glass

the other, inner world (instead)
a lamp’s reflection in a pane,
a wall, a door, a backlit head
.

Jim Culleny
10/20/19, 6:44 am

Making far out the norm: Or how to nurture loonshots

by Ashutosh Jogalekar

Vannevar Bush – loonshot pioneer (Picture credit- TIME magazine)

What makes a revolutionary scientific or technological breakthrough by an individual, an organization or even a country possible? In his thought provoking book “Loonshots: How to Nurture the Crazy Ideas that Win Wars, Cure Diseases and Transform Industries”, physicist and biotechnology entrepreneur Safi Bahcall dwells on the ideas, dynamics and human factors that have enabled a select few organizations and nations in history to rise above the fray and make contributions of lasting impact to modern society. Bahcall calls such seminal, unintuitive, sometimes vehemently opposed ideas “Loonshots”. Loonshots is a play on “moonshots” because the people who come up with these ideas are often regarded as crazy or anti-establishment, troublemakers who want to rattle the status quo.

Bahcall focuses on a handful of individuals and companies to illustrate the kind of unconventional, out of the box thinking that makes breakthrough discoveries possible. Among his favorite individuals are Vannevar Bush, Akira Endo and Edwin Land, and among his favorite organizations are Bell Labs and American Airlines. Each of these individuals or organizations possessed the kind of hardy spirit that’s necessary to till their own field, often against the advice of their peers and superiors. Each possessed the imagination to figure out how to think unconventionally or orthogonal to the conventional wisdom. And each courageously pushed ahead with their ideas, even in the face of contradictory or discouraging data. Read more »

Batty

by Joan Harvey

Mojiganga from the Mexic-Arte Museum in Austin

Nightfall. Outside a low elongated cave entrance a small group of humans sit waiting on stone ledges facing the dark aperture. Kestrels begin to soar close in the late evening sky. Snakes too are gathering below, we’re told, but they aren’t in view. This is Bracken Cave, 20 miles from San Antonio, where 20 million bats, females and their pups, literally hang out. We’ve come from Austin, through miles of pick-up truck dealerships and mini-malls. At first our driver couldn’t find the cave, which is not open to the public, but eventually, guided by people from Bat Conservation International, the nonprofit that owns and protects the cave, we arrived. At dinner we were filled with Texas barbecue and many bat facts, and now everyone is quiet. Waiting. A strong odor permeates the air. Slowly small dark beings emerge, then more and then more, thousands shooting off, darkening the sky. So many they can be seen on radar, and a nearby Air Force base has to shut down each evening as the bats would interfere with flights. We watch the procession very quietly, each feeling in their own way this strange life form that is connected to us and yet so different, familiar and yet unfamiliar, this webbed mammal, this flying thing that has so engaged our imaginations.

Bats are beings who go too high, shooting up into the air — the species from this cave, the Mexican free-tailed bat, can fly at altitudes over 10,000 feet— but also too low, swooping down to face level, or, when they return from their nocturnal hunt, diving like furry missiles into the low entry of the cave to avoid the waiting predators. They’re fast, faster than birds, holding the horizontal speed record at over 160 kilometers (99 miles) per hour. As mammals they’re more closely related to us than birds, and they live almost everywhere we live, yet we rarely see them, and most of us know almost nothing about them. They’re nocturnal, dusty, silent, though when they fly by us in the thousands we can hear a low rush of wings like the rumble of water over rocks. Read more »

The Cancer Questions Project, Part 13: Bruce Chabner

Dr Bruce Chabner has had immense experience in the discipline of cancer drug discovery and development. During his career at the National Cancer Institute, he worked as a Senior Investigator in the Laboratory of Chemical Pharmacology, Chief of the Clinical Pharmacology Branch, Director of the Clinical Oncology Program, and Director of the Division of Cancer Treatment. His research significantly added to the development of high dose chemotherapy regimens and standard therapies for lymphoma. Additionally, his research led to the development of Taxol. He currently serves as a Professor of Medicine at Harvard Medical School and Director of Clinical Research at the MGH Cancer Center at Massachusetts General Hospital.

Azra Raza, author of The First Cell: And the Human Costs of Pursuing Cancer to the Last, oncologist and professor of medicine at Columbia University, and 3QD editor, decided to speak to more than 20 leading cancer investigators and ask each of them the same five questions listed below. She videotaped the interviews and over the next months we will be posting them here one at a time each Monday. Please keep in mind that Azra and the rest of us at 3QD neither endorse nor oppose any of the answers given by the researchers as part of this project. Their views are their own. One can browse all previous interviews here.

1. We were treating acute myeloid leukemia (AML) with 7+3 (7 days of the drug cytosine arabinoside and 3 days of daunomycin) in 1977. We are still doing the same in 2019. What is the best way forward to change it by 2028?

2. There are 3.5 million papers on cancer, 135,000 in 2017 alone. There is a staggering disconnect between great scientific insights and translation to improved therapy. What are we doing wrong?

3. The fact that children respond to the same treatment better than adults seems to suggest that the cancer biology is different and also that the host is different. Since most cancers increase with age, even having good therapy may not matter as the host is decrepit. Solution?

4. You have great knowledge and experience in the field. If you were given limitless resources to plan a cure for cancer, what will you do?

5. Offering patients with advanced stage non-curable cancer, palliative but toxic treatments is a service or disservice in the current therapeutic landscape?

Why on Earth Should It Mean That It Is Not Real?

A Conversation with Joan Giroux

by Andrea Scrima

Joan Giroux, born 1961 in Syracuse, New York, moved to the East Village in the early eighties to attend Parsons School of Design. After graduation, she began traveling back and forth between New York and Berlin, first as a guest student with Shinkichi Tajiri at the Hochschule der Künste, then to take part in a graduate program at the Milton Avery Graduate School of the Arts in Annandale-on-Hudson, NY. With a focus on sculpture, Giroux moved from interactive objects and kinetic sculpture into installation, performance, social practice, and community engagement. She has shown internationally at venues including the Museum of Contemporary Art Chicago, Weinberg/Newton Gallery, American Academy in Rome, Munson-Williams-Proctor Institute, Artists Space, BACA Downtown, and Künstlerhaus Hamburg, and has participated in international symposia for the arts and the environment in Korea, Japan, and Germany. She also shows her work in a number of public, alternative, and nontraditional venues, such as in the exhibition memory marks at the Hospice of Santa Barbara’s Leigh Block Gallery. Grants and awards include the Marie Walsh Sharpe Studio Residency, a Research Fellowship at the University of Michigan, and artist’s grants from Berlin’s Senate for Cultural Affairs and the Pollock Krasner Foundation, as well as residencies at the Squire Foundation and the MacDowell and Millay colonies. She teaches at Columbia College in Chicago. Read more »

Poem

Driving Lolita in the World’s Most Militarized Zone

A boy, I hid
in grandpa’s study.

An art dealer
he loved books

with gilded edges,
Aristotle to Zola

all stuck together
in the humidity.

I snuck Lo out
to his black Chevy

rifled for the dirty bits
(should ’ve looked harder, I guess),

drove her away for a spin
teen tunes swirling in my head

I Want to Hold Your Hand.
A crackdown in downtown ‑—

mothers hid their young sons.
“We fear they’ll take them away.”

A soldier rained pellets
on a nymphet’s face,

light of her mother’s eye.
“Moji,” nymphet said,

“Nothing can be seen,
as far as the eye can see.” Read more »

Cathedrals, Trees, And Humans

by Mary Hrovat

Photograph of tall trees lining a pathThe roof of Notre-Dame de Paris, lost in the fire of April 15, 2019, was nicknamed The Forest because it used to be one. It contained the wood of around 1300 oaks, which would have covered more than 52 acres. They were felled from 1160 to 1170, when they were likely several hundred years old. It has been estimated that there is no similar stand of oak trees anywhere on the planet today.

Even in the twelfth century, sourcing the wood for cathedral construction was not always easy. When the Basilica of Saint-Denis was under construction in the mid-twelfth century, it was assumed that the nearby forests could not supply the wood needed for the project because they were depleted. Abbot Suger reportedly found a local stand of timber suitable for the job and attributed his discovery to faith and divine intervention. Causes of medieval deforestation include clearing of land for agriculture and the expansion of urban areas. Read more »

‘Joyce Usurped My Splendid Name Of Bloom’

by Thomas O’Dwyer

Harold Bloom

The outpouring of words after the passing of literary critic Harold Bloom on October 14th was astonishing. Who knew that an 89-year-old American academic who still muttered about things like great literary canons and dead white male Victorian-era poets could cause such a ripple in self-absorbed 21st-century space-time? However, the eulogies, obituaries, and memoirs haven’t all been launched on a sea of love and regret. They seem equally divided between affection and snark. Most of the vinegar appears to drip out of academia, or what’s left of the battered and deconstructed humanities departments where Bloom made his name in those bygone days when literary snobs looked down their noses at such vulgar faculties as science, computers and (ugh!) business studies.

It’s no surprise that the academic journals and commentators are so sniffy. When one of the tenured pack moves from writing papers that are read by five people to producing books that top the bestseller lists, the green rot of envy and disapproval spreads like bindweed. One professor commented in an article, “Lest we forget, Bloom was also a bad scholar. His Shakespeare book is written horribly and says nothing.” Meow!

“He’s a wandering Jewish scholar from the first century,” Cambridge Professor Sir Frank Kermode, the English literary critic, once wrote of Bloom. “There’s always a pack of people sitting around him to see if any bread or fishes are going to be handed out. And I think there is in him a lurking sense that when the true messiah comes, he will be very like Harold.” Kermode was once labelled “distinguished;” now he too is merely deceased and forgotten.

It’s not only humanities professors – the late physicist Stephen Hawking was regularly scorned by his peers from the day A Brief History of Time hit the pop charts. It was as if his physicist’s brain had lost ten IQ points merely by addressing the hoi polloi who bought paperbacks. Forming your bubble outside the tenured bubble inevitably invites pinpricks. Read more »

‘Theologians and other fuzzy people’: two 20th-century Dutch novelists on the sciences and humanities

by Jeroen Bouterse

Willem Frederik Hermans

For better or worse, Dutch 20th-century postwar literature comes with a canon of three authors: Gerard Reve, Harry Mulisch, and W.F. Hermans. There, you learned something today. Other than this factoid, however, this post is not going to be a lecture about the landscape of Dutch literature, or even the literary qualities of these authors. I am introducing them because I am going to use two of them, and one in particular, to illustrate a point about discourse involving the landscape of science – that is, the distinction between the sciences and humanities.

The notion of a separation between the sciences and humanities usually revolves (again, for better or worse) around C.P. Snow’s famous Rede lecture. In this lecture, Snow tentatively suggests that what he calls the ‘scientific culture’ is probably more left-wing than the ‘literary culture’, as well as more progressive (scientists “have the future in their bones”). In his time, he saw his technocratic ideals represented best by the Labour party, to which he served as scientific advisor. In the 1970s, however, Snow (as chronicled by historian Guy Ortolano)[1] would drift away from the Labour party, and express himself in increasingly negative terms about all the nonsense one had to put up with as a liberal these days. Before his death in 1980, he expressed his sympathy for neo-conservative ideas.

According to Ortolano, Snow was one of multiple Anglophone intellectuals who reconsidered their political alignments in the 1970s. Nor does this necessarily imply that Snow betrayed or radically revised his own previous opinions. These, it seems, remained technocratic and meritocratic, and precisely therefore problematic in the face of a more egalitarian and anti-elitist ‘New Left’. Read more »

Mario Kart Mobile is Ruining My Life (and other tech-phobias)

by Marie Gaglione

I’m freaking out almost all the time, I’d say. I wouldn’t even limit my angst to my waking hours, because lately my dreamscapes have been rife with post-apocalyptic battle royale scenarios. I’m not writing this with any kind of proposed solution or discernible purpose beyond adding another frightened voice to the void, I just don’t think I can write about anything else until I work through some of this. I find that crafting my fears into essays works as a kind of filing system: I’m still afraid of the thing, but now there is a title and and my thoughts are at least ordered by paragraphs. 

This essay is about technology, probably. I waffle on the theme only because I think blaming existential panic on cell phones is stale, but I’m pretty sure it’s accurate! Let me make my case. I’ve opened Mario Kart Mobile Tour on my phone three times since starting to write this and I’m not yet on my third paragraph. And I’ve already raced all the races and gotten enough stars to pass each cup. And I still keep opening the app. This week it’s Mario Kart, but before that it was Love Island The Game and before that it was Tamagotchi (and Solitaire and Candy Crush and and and). I don’t have a Twitter and I rarely open Instagram so presumably the games are just the most enticing apps I have, but it’s still gross how long I spend with my shoulders tightened, neck tensed, and thumbs exercising. I feel like a loser. And I justify all the time, pretending like I’m having such deep thoughts in the background as I throw red turtle shells. I try to map life onto the racing track; I look for metaphors as I complete a lap and am satisfied with exercising the poetic side of my brain for the day. 

We’re living in a world of infinite content. I tire of one game, there are eight hundred more with subtle variations. I finish a TV show, the streaming network has thirty more recommendations. Every movie, every show, every clip or song or soundbite – it’s all within reach if you can connect to the internet. Which now you can do even on an airplane. I’m worried about it. Read more »

Reunions

by Carol A Westbrook

Fall is almost over and, thankfully, so is homecoming season. I’ve never been to a college homecoming weekend, and hope I never have to go to one. I can sit through a football game, but I can’t abide the class reunion party.

Most people love reunions. Me… not so much. Especially school reunions.  There are those who look back longingly at their school years as the best time of their lives. Many keep in touch with their former classmates. They remember all of their friends, and who sat next to whom in 5th grade, that horrible gym teacher, and their high school crushes. They enthusiastically volunteer to organize the next reunion.  Reunions let them see how the drama of their school years finally played out. Did that really smart boy become a doctor? Who finally married my high school sweetheart? Is my old best friend is still the same?

I certainly enjoyed my school years, but they weren’t the best years of my life by any stretch. Frankly, I don’t remember much of my primary and secondary school years because I was happy to move on. I couldn’t wait to leave my sheltered background and enter the real world. Read more »