by Jalees Rehman

Two scientific papers that were published in the journal Nature in the year 2000 marked the beginning of engineering biological circuits in cells. The paper “Construction of a genetic toggle switch in Escherichia coli” by Timothy Gardner, Charles Cantor and James Collins created a genetic toggle switch by simultaneously introducing an artificial DNA plasmid into a bacterial cell. This DNA plasmid contained two promoters (DNA sequences which regulate the expression of genes) and two repressors (genes that encode for proteins which suppress the expression of genes) as well as a gene encoding for green fluorescent protein that served as a read-out for the system. The repressors used were sensitive to either selected chemicals or temperature. In one of the experiments, the system was turned ON by adding the chemical IPTG (a modified sugar) and nearly all the cells became green fluorescent within five to six hours. Upon raising the temperature to activate the temperature-sensitive repressor, the cells began losing their green fluorescence within an hour and returned to the OFF state. Many labs had used chemical or temperature switches to turn gene expression on in the past, but this paper was the first to assemble multiple genes together and construct a switch which allowed switching cells back and forth between stable ON and OFF states.

The same issue of Nature contained a second land-mark paper which also described the engineering of gene circuits. The researchers Michael Elowitz and Stanislas Leibler describe the generation of an engineered gene oscillator in their article “A synthetic oscillatory network of transcriptional regulators“. By introducing three repressor genes which constituted a negative feedback loop and a green fluorescent protein as a marker of the oscillation, the researchers created a molecular clock in bacteria with an oscillation period of roughly 150 minutes. The genes and proteins encoded by the genes were not part of any natural biological clock and none of them would have oscillated if they had been introduced into the bacteria on their own. The beauty of the design lay in the combination of three serially repressing genes and the periodicity of this engineered clock reflected the half-life of the protein encoded by each gene as well as the time it took for the protein to act on the subsequent member of the gene loop.

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by Lisa Lieberman

In the memoir he was writing at the time he died, my friend Avresh described returning to the Czechoslovakian town of Sevlush, his birthplace, in the winter of 1946. He'd left some fifteen years earlier to attend a Jewish gymnasium in a larger city, stayed on to study engineering at the university and never looked back. This was his mother's wish for him: that he enter the great, free, secular world, liberate himself from the narrowness of his tradition. Escape.

When the Germans occupied Czechoslovakia in 1939, Avresh joined the Communist resistance. Captured and tortured by the Gestapo but inexplicably released, he made his way to the Soviet Union, expecting to be welcomed with open arms, a comrade in the fight against Nazism. Instead he was arrested at the border and charged with espionage—the fate of most Jewish refugees from Eastern Europe. Avresh spent two and a half years in the Gulag, shuffled from one prison camp to the next, but ended up an artillery officer in a Czech unit of the Russian army;
by the time he was discharged, he'd earned four medals for his service on the Eastern front. His favorite featured a picture of Stalin.

So it was as a decorated officer in a Russian army uniform that he returned to his town after the war. All the Jews were gone, rounded up and deported to Auschwitz. A Slovak family was living in his childhood home and not a trace of Avresh's own family remained. Looking for answers, he went to the neighborhood synagogue and peered in the door. The sanctuary, the balcony, the corridors and stairways were cluttered with belongings: furniture, pots and pans, bedding, books, knickknacks and photographs. A policeman stood watch over the household goods of the departed Jews of Sevlush. Town officials had collected the Jews' possessions and stored them in the synagogue to prevent looting. No Jews had returned to claim their things. Was there something he wanted from the collection, the policeman asked, some memento?

Avresh said he took nothing when he left Sevlush, but this is not strictly true. He carried no objects away from the synagogue, no material belongings, pointedly refusing the money the officials offered as “rent” on his family's house. What he took, along with the burden of guilt he carried—”I share the usual remorse of most Holocaust survivors lamenting why they are alive and why they did not try harder to save their perished family,” he wrote in his memoir—what he took, I would say, was a sense of spiritual belonging, the token that remained of his Jewish inheritance.

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by Ahmed Humayun

(This is the first post in a series on Pakistan's struggle against militancy).

Almost a decade in, the rebellion by the Pakistani Taliban against Islamabad shows no signs of flagging. Tough, savvy, and agile, the insurgents have expanded their campaign from the isolated northwestern tribal regions all the way to urban centers in the south such as the port city of Karachi. Their declared agenda has grown with each success: they first demanded acceptance of their control over large swathes of the tribal areas; they then denied the authority of Islamabad across Pakistan altogether; today, influenced by Al Qaeda's rhetoric, they boast of sending fighters to wars in Arab lands and attacking the United States.

We need not accept all their grandiose declarations at face value. When it comes to global terrorism, in particular, there is a chasm between their rhetoric and their capacity. The only terrorist plot on American soil they can claim is of the failed Times Square Bomber in 2010. The evidence of Taliban involvement in Middle Eastern battlefields is ambiguous at best. And their operations are constrained by an overall pool of fighters that is small: estimates vary because data is hard to collect and the definition of an active fighter is murky but at any given time there may only be between ten and twenty thousand rebel fighters.

But the insurgents have substantially expanded their campaign within Pakistan itself. They have strategic clarity where Islamabad does not and their aspirations have been whetted by the confusion of the state. In recent years the rebels have complemented their fight against Pakistani armed forces in the tribal areas with a systematic campaign of terrorism in towns and cities across the country. To this end the insurgents have leveraged and expanded a vast ‘infrastructure of extremism', which originates in decades of state sponsorship of non-state militant groups.* The network includes combat trainers, militant recruiters, funders, suicide jacket makers, indoctrinators and foot soldiers who have access to training camps, safe houses, telephone getaway exchanges, madrassahs (some, not all) and highly sophisticated media communications facilities across the length and breadth of Pakistan. The insurgents are not cave dwellers: they are adept organization builders who have institutionalized the production of terrorism as one weapon in their broader war against the state.

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by Alon Levy

There's a genre of shows, above the level of House or Friends and below that of The Wire, that exude high quality even if the actual level of characterization and plot isn't deep. Julian Fellowes' Downton Abbey is one of the prime examples of this genre. It's beautifully done and acted, has enough characters and plots to keep anyone's interest, and is full of references that seem smart.

It just so happens that none of these references is particularly intellectual or obscure. Instead, they're the sort of history that everyone knows. The first episode discusses the Titanic; we do not live in an alt history in which James Cameron chose to make more Terminator sequels in the 90s. Every time Lord Grantham's American wife's mother comes, we're treated to the usual tropes of differences between British and American culture. In the season that just concluded with its Christmas special, two additional common references are added: a rich English expat goes to Munich in 1922 and is killed by the early Nazi party because he vocally disagreed with them; and there's a subplot regarding Edward VIII's playboy philandering. This is about as smart as an American mid-18th century period drama inserting a reference to Washington not being able to tell a lie.

The problem is that even the stronger points of symbolism on the show are like this. The biggest is the analogy between the upstairs and the downstairs. The servants form a tight group (except Thomas and O'Brien) in which Carson is the father, Hughes is the mother, and the rest of the servants have a hierarchy in which valets and lady's maids are above the rest. Bates/Anna is of course parallel to Matthew/Mary, and the stronger parts of the show are the ones that showcase the differences between their relationships, with Matthew/Mary having more resources and more clout than Bates/Anna so that they face more rich-people problems rather than a possible execution.

The only problem is, the show didn't really invent this view of the butler as the father, the housekeeper as the mother, and the other servants as lesser members of the house. It was common in that era. I don't think it's as well-known a reference, but that symbolism is still a trope, and the servants' order of precedence within the great houses reflected it. It works well enough as a reference, but as symbolism, it's trite.

Everywhere else, Fellowes' Tory baron biases show. The show can't write women well, and descends to a virgin/whore/mother trichotomy. The only man who is as conniving as the median woman is gay. The treatment of race is facile. Lord Grantham is self-consciously written as an upper-class twit, but he doesn't suffer any consequences for it and is always saved by more competent family members, nor does he have interesting moral dilemmas. The characters are never shown to engage in any effort – they do some work and succeed, without any of the failures that are associated with actual effort. The show wants to be about the aristocracy's struggles with its decline after WW1, but it's instead about an aristocratic family that weathered all the troubles, which is about as interesting as any riches-to-riches story could be.

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SHOCK AND STOICISM

A doctor in tailcoats

Makes a house call.

He straps her ankles,

Shoves a buffer in her mouth.

Her husband kisses her eyes closed,

Pins down her fleshy arms.

The doctor pads her temples,

Inserts wires into a black box.

Bulbs flicker as he smoothes

Moonlight back in her throat.

Doctor unplugs his machine.

A boy with birthmark on forehead

Tiptoes to his mother’s bed

Where she calmly asks my name.

by Rafiq Kathwari, the first non-Irish winner of the Patrick Kavanagh 2013 Poetry Award, representing Ireland Literature Exchange at the Hyderabad Literary Festival January 23-25, 2014.

by Rishidev Chaudhuri

One of the main aims of modern science is finding mathematical expressions to describe the relationships between observed quantities. For example, Newton's law of gravitation tells us that the force of gravity between two bodies depends in a certain way on their masses and the distance between them; thermodynamics tells us that the pressure of a gas depends in a certain way on its volume and temperature; and an economist studying income might conclude that income increases with educational level according to some functional form.

Sometimes these mathematical relationships emerge from an underlying model. We might model a gas as made up of molecules that collide with each other and the walls of the container, think that pressure is a measure of collisions with the walls and temperature a measure of kinetic energy, and then our functional form is a result of mechanistic insight into pressure and temperature. In other cases, the relationships serve to provide a summary representation of the data (instead of giving you a list of pressures at various temperatures, I could say pressure=3*temperature) and, even without providing an explanation of how the relationship came to be, allow us to make predictions about new data (for example, I might have observed the pressures at temperatures of 30 degrees and 60 degrees and want to predict the pressure at 90 degrees).

As we choose a relationship (or hypothesis) to explain a given set of data, the two goals of accounting for the existing data and making predictions for new data are often in conflict. Look at the graph below, which plots the simultaneously measured values of two quantities, X and Y.

Say we're trying to describe this relationship in a way that allows us to predict the values of Y at unobserved points (for example, we haven't measured the value of Y when X is 0.25 and we want to predict this). A common thing to do is to draw a line along the middle of this scattered cloud of points and use this as an approximation of the underlying relationship.

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by Ryan Seals

We are in the position, unique in human history, of possessing the knowledge of how to alleviate much of the unnecessary suffering in the world. What we lack is the knowledge of how to deliver and disseminate that knowledge, and of how to encourage its uptake. In an eerily prescient article of the sort at which he excelled, John Maynard Keynes wrote in The New Republic in 1932:

At present the world is being held back by something which would have surprised our fathers—by a failure of economic technique to exploit the possibilities of engineering and distributive technique; or, rather, engineering technique has reached a degree of perfection which is making obvious defects in economic technique which have always existed, though unnoticed, and have doubtless impoverished mankind since the days of Abraham.

Replace engineering technique with scientific understanding and economic technique with, well, some broadly defined sociopolitical will to implement our understanding, and Keynes's point is precisely applicable to the current state of health and longevity around the world.

Whether you read into modern medicine an amazing ability to deflect and defer nature's slings and arrows, or you bemoan the failed ‘War on Cancer' and the much-delayed genomic revolution, the fact remains that we now know the major ways for the majority of people to lead long, healthy, lives. It isn't medical technology that allows people to live into old age; with the exception of vaccines, the causes of good health aren't to be found in hospitals and medical clinics. Nutrition, sanitation, and hygiene are the keys to population health, and it isn't too great an exaggeration to say that health depends, above all else, on where you live, eat and excrete. The solutions are, for the most part and in a strictly technical sense, rather simple and well understood.

Keynes wrote that statement in 1932, before modern vaccines and antibiotics, without much (successful) interventional surgery, and with scant knowledge of the mechanisms of disease. The 80 years before he wrote had seen a revolution in human health – maximum life expectancy had long been on its steep upward trajectory, and infant mortality in the Western world was fast becoming a rarity.

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by Debra Morris

Until my grandmother—whose 100^th birthday we celebrated this year—took up residence first with my parents and then at the care center where three of her sisters also spent their last years, she lived independently and, in many ways, unconventionally. (Whereas she is content to describe her long life as “good,” my grandmother deviated from the norms of small-town Texas just enough, and in enough domains of her life, for that life to seem quite remarkable to me. That nearly everyone calls the lady “Morris”—a long story, but it originated when I was very young and couldn't replicate my mother's polite “Mrs. Morris,” so I shortened it and the name stuck—is only the first of many odd details that I'd need to explain to anyone meeting her for the first time.) When her husband suffered a fatal heart attack after a morning spent plowing, she inherited a prosperous family farm and kept it that way for four decades more. She hosted retired teacher banquets, a duty (though certainly not a grim one, my grandmother was the type to understand it as a duty nonetheless) born of a storied 40-year career as teacher and principal in the Quail Rural Consolidated School District (the largest such district in the country at the time). To this day, she is my family's only elected official, having served a term as the County Superintendent of Education. For many years she split her leisure time between a full slate of daytime TV dramas—what she called her “stories”—and virtually any televised sporting event. Whenever I asked, she could catch me up on the tangled relationships and intrigues of any given soap opera, somehow managing to dignify the most idiotic plot or one-dimensional character. She could conjure the same remarkable effect with sports; normally oblivious, I would suddenly understand the beauty and depth of a sport (who knew golf could be anything but tedious?), envying her effortless command of baseball stats and NFL playoff hopes, and sharing her quiet marvel at a beautiful swing.

And, on top of all this, every two years or so she would vote a straight Democratic ticket. This, at least, is how her only son, my father, tells it. About ten years ago—or it could have been fifteen, or five; it hardly matters because this stunning revelation came when Morris was already quite old, and long after Texas had turned solidly Republican—my father referred to my very proper grandmother as a “yellow dog Democrat” (meaning, to any Southerner, someone who would sooner vote for a yellow dog than a Republican). He said it with what seemed like mild exasperation, as if he couldn't make sense of, or fully commend, this irrational allegiance to a political party. But I remember being secretly thrilled (I think he could have told me that Morris was an avid day-trader and I would have been less surprised). Maybe I felt vindicated, too; apparently the Democratic gene can skip a generation, but obviously it was there, deep in me, ensuring that a family's rich history would continue to bind, and instruct. Perhaps most surprising of all, I discovered that I was proud—suddenly proud of a party that could have earned my dear grandmother's life-long support.

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by Mara Jebsen

While I do not like the phrase, “at the height of her powers,” it comes to mind when I think of Taymor directing this comedy. I don't like the phrase because it seems to anoint the critic with a false sense of her own fortune-telling powers, and has an undue emphasis on the importance of being urgent–as if I were saying, “run, don't walk” to this play. But perhaps you should run–or, more accurately, sit. I had to sit in the stand-by line for a long time, because the play, now running at the Polonsky Shakespeare Center is officially sold out. Sit, and wait, for a long time for this production, because the images it gives you will delight at first, and then, over time, will resolve themselves into a sort of important pastiche that helps you think about love, madness, and Shakespeare.

I had to go because my mother made me. She was a theatre student, a mime, a theatre-director, and a folklorist before she became the director of a k-12 school in West Africa, where she finds an outlet for her enormous creative energy by putting on plays. This year it is Midsummer Night's Dream. “I can't get a feel for it, yet,'' she said. “But Julie Taymor directed it, and I love her, and they're putting it on in a theatre six blocks from your house. I read all about her troubles with Spider-man and had been following her before I had the idea to do Midsummer.It means something. Go. Find out what she's up to.”

I had no idea that my mother loved Julie Taymor. Or that she 'followed” anything that had anything to do with the internet. I promised to do it, but procrastinated, and when I saw that the tickets were sold out, I nearly panicked.

Anyway, here is the gist: initially, even if you are not compiling a list of directorial choices for your mother's use, you will be startled and awed by the choices Taymor makes. There is a stunning mixture of expensive technology and simple stagecraft, and a viewer feels safe the whole while–safe because they are in the hands of a person who will not bore them, who seems to have an exact sense of rhythm, scale and color scheme-and who presents recognizable character 'types' that amuse without degrading the people who make that type.

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by Tom Jacobs

Years ago an earnest young student entered his professor’s office for a brief chat about a paper topic he had been turning around in his head. The professor was esteemed and well-dressed and famous for being a cool and political yet accessible writer about cool and political things. The student was spangly mediocre, wildly intimidated by his professor because he knew that he (the professor) was indifferent to this object/student before him that/who didn’t know enough about the world or the past or theory to challenge him on any level that he might recognize.

They shook hands limply and then sat down across from each other, the power differential radiating out in all directions, but it was mainly felt by the beleaguered student. The student fumblingly explained that the paper was to be about the nature of emergent electronic communities (this was the mid-nineties). He babbled and referenced a few novels and sociological and philosophical works that seemed to him potentially useful.

The professor, un-noddingly and somewhat socially autistically stared at him from across his desk with a mixture of curiosity, interest, and pity, giving the student neither quarter or shelter. After a few moments of squirming awfulness he asked a depth-charge question: “What do we mean when we say “’community?’” The question exploded in the student’s mind, and the shockwaves resonated well into the future. To this very day, this very moment, to speak truthfully.

It’s not necessary to go into the student’s flummoxed response. What’s important is the question: what the fuck do we mean when we say “community?” Because we say it all the time, the media says it all the time, politicians say it all the time, and it does an enormous amount of work for us even if none of us know quite what we mean when we say it.

I know, I know, there are many sociologists and philosophers and so forth who have considered this very question, and I will refer to some of them below. But the feeling precedes the concept, and that’s what makes it so interesting. We all know that there is such a thing as a community, even if we can’t put our finger on it. In that regard it’s a bit like pornography or (as has been said, I’m told) the clitoris. So what’s important is to figure out how really smart people who have thought long and hard about what “community” means maps on to what it means to the rest of us. How might we make these two disparate worlds sing in harmony?

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by Omar Ali

Polio is an ancient scourge that spreads only within human populations and can cause paralysis, most frequently of the lower extremities, but can also be fatal when the paralysis extends to the muscles of breathing. For reasons that are not completely clear, the disease erupted in huge epidemics from the late 19^th century onwards, causing millions of victims to die or become paralyzed for life. Once a virus had been identified as the cause, the race was on to develop a vaccine. Finally, in 1952, Jonas Salk and his colleagues developed the first effective inactivated vaccine for this disease. Within a few years, mass vaccination decreased the number of victims in developed countries from hundreds of thousands to just a few hundred per year. In the mid-fifties, Albert Sabin and colleagues developed an effective live vaccine that was cheaper, easier to adminster and provided better immunity and that was then adopted by the WHO as the main vaccine for use in endemic areas. Thanks to mass immunization campaigns, the number of victims dropped precipitously and by 1988 the WHO was ready to launch a well-coordinated international initiative to completely wipe out wild polio from the planet. Like smallpox, polio does not have an animal reservoir, so if human to human transmission is completely blocked by mass vaccination the disease can be effectively wiped out.

Initially, the campaign proceeded well, with the Americas being declared polio-free in 1994 and Europe in 2002. Today, there are only 3 countries where polio still remains endemic: Pakistan, Afghanistan and Nigeria. Unfortunately, the reason in all three is the same; the moronic wing of the international Jihadist movement has somehow picked up bits and pieces of chatter about risks from oral polio vaccine, combined it with pre-existing paranoia about modern international institutions, and created a robust anti-vaccine meme that is able to draw upon the ruthless killing power of Jihadi militias to effectively stop polio eradication campaigns in their area of influence.
I would like to clarify this a bit further:

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by Dave Maier

Last month in this space I discussed physicist Lawrence Krauss's suggestion that in advancing certain cosmological theories (concerning the early universe, dark matter, dark energy, and so on) he had thereby put to rest the age-old philosophical question “why is there something rather than nothing?”. I agreed for the most part with those who think Krauss misunderstands the question if he thinks a physical theory – any physical theory – can answer or dispel it. There were a lot of interesting comments on the post (go read them), but I think people were sometimes talking past each other. Some of the confusion and/or disagreement concerns the concept of metaphysics, so that's today's topic.

We often see “metaphysics” or “metaphysical” used as a term of abuse. (I myself use it this way sometimes.) But not all such abuse amounts to the same thing. What exactly is metaphysics “in the bad sense”? And why is there also a “good” (or at least not necessarily bad) sense of the term as well? How does the latter devolve into the former, and how can we avoid such a thing? Or must we part ways with “metaphysics” entirely, leaving only a “bad” sense of the term?

A good place to start is the entry on “Metaphysics” in the Stanford Encyclopedia of Philosophy. Its author might give us critics pause, since if there is such a thing as metaphysical Kool-aid, Peter van Inwagen has drunk as deeply of that toxic draught as any philosopher alive. However, except for the perfunctoriness of its final section, which grudingly examines (or at least mentions) the question “Is Metaphysics Possible?”, most of the article is perfectly uncontroversial, as is appropriate given the venue (really, check it out for a good introduction). Metaphysics has always been part of philosophy, whether in the ancient form of a “science of being as such”, or the modern welter of rather more specific questions about causation, modality, personal identity, mind and body, space and time, and so on.

Naturally this does not mean that such things must be unobjectionable. Maybe philosophy first barked wrongly up a single ancient tree (The Tree of Being?), turning in the modern period to bark equally wrongly up a number of related trees, and maybe what we should do now is cut out such barking altogether. But as van Inwagen points out, to say that the ancient “science” (as pursued, for example, in Aristotle's Metaphysics) was wrong-headed because there are no things that do not change is itself a “metaphysical” assertion in the modern sense; and the same is often true of contemporary dismissals of “metaphysics” broadly construed.

On the other hand, the Catch-22 nature of this defense of metaphysics, if that's what it is, should arouse our suspicions. It sounds like a “gotcha,” like the blithe, infuriating assertion that “it takes a lot of faith to be an atheist.” Indeed, it's the broader cultural spat between science and religion which provides a lot of the heat and lack of light (dark energy?) for most discussions of “metaphysics.” We have to detach, or at least locate, the latter discussion to see it properly – if not to resolve it, at least to see who the players are.

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Say Something Obvious

The geometry of moonlight is triangular
Its pallid glow is whole, homogeneous and crisp,
never granular. Moon, mating with Sun
cries out like a bell, her rings are ecstatic and annular

Under a condensing cloud you’ll be singing in the rain
if you carry a tune while following your bliss
If it falls upon the skin of lovers it will hiss

We had a Harley once, too small to ride
to Champaign from N J, but we went anyway
Later, not even a kiss

The forearm muscles of the young,
their Palmaris Longus and Carpis Ulnaris,
are means to an end
they’re not there for show, but to work
In the old they sometimes give sharp hints
of what’s left to spend

Behind a blower in the snow
if the wind whips the plume just so
(colder bitter cheeks with every flake)
you may as well have been with Scott’s expedition
in Antarctica freezing in determination
dying from mistake

There’s good to be said for caution
and brashness too
…………………………….. reticence or passion
—you’ll only know which one was called for
when the day is through

.
by Jim Culleny
12/22/13

by Brooks Riley

It is difficult to talk about metaphors without talking in metaphors: Metaphors are birds, around us all the time, but unnoticed unless we take the time to look at them. Or, metaphors are apples on the tree of life, the fruits of our search for meaning. You get the idea.

Here’s a riddle: What can a human being see that no other creature on earth can see? A metaphor. We and the creatures all see the same objects, in the literal sense. But humans are able to see those objects as providers of meaning, a tree as a symbol for family or immutability. a puddle as a small inconvenience on the path of life. A pothole? Life is full of them in the metaphoric sense.

What are metaphors anyway except a parallel way of looking at things—like stepping into a second life to explain the first one.

Some people are happy just to beat a dead metaphor: ‘Life is a bowl of cherries’, ‘All the world’s a stage’, ‘No man is an island’ (not true!) or Pedro Calderón de la Barca’s exquisite ‘. . . life is a dream, and the dreams are dreams.‘ La vida es sueño, y los sueños, sueños son. Others look for unexpected analogous connections in unusual places or events.

Some metaphors are so parasitic, they kill the host–so deeply imbedded into the language of certain events that they have lost their role as metaphor. In America we don’t ‘stand’ for office, we ‘run a race’ for it, hence the image of two candidates at the starting line, Obama in his track suit, Romney in a body stocking, in the distance a tiny White House. When you pry the metaphor out of the electoral process, there are not enough words to describe it.

For reasons having nothing to do with literary endeavor, I have been searching for metaphors. Unlike Brad Leithauser’s metaphor (in his recent, lovely piece in the New Yorker ‘Meet my metaphor’), which simply came to him while he waited in an airport, mine are the result of an active search.

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