This book should transform your outlook on cancer research

by Ashutosh Jogalekar

A few days ago I finished watching a new documentary on Bill Gates’ life and work. One of the episodes narrated the sad story of the death of his mother in the mid 1990s from late stage breast cancer. She was a great philanthropist and a doting parent who managed to see Bill get married just before she died. At that point her son was already one of the most successful and wealthiest individuals in the world, but with all his resources and wealth, her life could not be saved. Steve Jobs, another person who had access to every medical treatment that money can buy, died early from cancer. These two stories tell us how great the leveling effect of cancer is, taking poor and rich alike without discrimination. Like war, cancer is the father of us all.

Today breast cancer can be treated much better than it was in the 1990s. There are better drugs and better radiation treatment options available, but for resistant late stage breast cancer the prognosis isn’t much better. In fact, as Dr. Azra Raza who is a distinguished oncologist at Columbia University tells us in this eloquent, thought-provoking and immensely sobering book, what’s true for breast cancer is true for most other kinds of cancer except for a few rare exceptions. The hard hitting truth is that in spite of tens of billions of dollars fueled into research around the world done by some of the smartest people in the field, the truly relevant endpoint for cancer – the increase in someone’s life span – has not changed much even after thirty years. For instance, a study of FDA-approved drugs from 2002 to 2014 showed that these drugs extended people’s lives by an average of only 2 months. Dozens of Nobel Prizes have been given out for basic cancer discoveries, cancer ‘moonshots’ have been promoted by politicians, startups and hospitals working on cancer continue to spend countless dollars and hours on a cure for the disease, but the two things that matter most for patients and their loved ones – extension and quality of life – haven’t changed much.

To know why this depressing scenario persists, Raza offers a simple reason with a hard answer: we are focusing too much on late stage cancer treatment, when the disease has already progressed and spread throughout the body, and much less on early stage detection and prevention. In spite of purported cancer breakthroughs in the media, the treatment is essentially the same as it has been for decades – slash (surgery), poison (chemotherapy) and burn (radiation), a triad of interventions sounding like they have been imported from the Stone Age, used because we can’t use anything better. Read more »

The Cancer Questions Project, Part 9: Ellin Berman

Ellin Berman is a board-certified medical oncologist and hematologist with a clinical and research focus on new drug development in acute and chronic leukemias, including acute myelogenous leukemia (AML) and chronic myelogenous leukemia (CML). As a member of the multidisciplinary Leukemia Disease Management Team at Memorial Sloan Kettering Cancer Center (MSKCC), she works closely with the many individuals who make up the clinical and research programs there. Along with other members of the Leukemia Service, she is involved in clinical trials of new drugs that hopefully will lead to new treatment approaches for these diseases. She has also worked closely with the Food and Drug Administration in this regard, and for the last 20 years have helped review new drug applications for the treatment of leukemia. She is a member of KSKCC’s Institutional Review Board (IRB), the committee that approves, monitors, and reviews research studies at the Center. She is an Associate Editor for the journal Leukemia Research, and reviews articles for a number of other journals including Blood, the Journal of Clinical Oncology, Cancer Research, The Lancet, and the New England Journal of Medicine.

Azra Raza, author of the forthcoming book 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?

The Beginning of the Beginning: Impeachment in the Air

by Ali Minai

Sometimes, history moves faster than thought. Something like that is happening in the United States in these early days of fall. Though the season is taking longer than normal to turn, the political season has changed more quickly than anyone expected. The opinions of last week – such as the long article I had written for 3QD on the prospects of Donald Trump and the Democrats in 2020 – have suddenly become irrelevant, and I find myself writing this wholly surprising piece on the possible impeachment of Donald Trump. As these lines are being written, 223 Democrats and one Independent in the US House of Representatives – a clear majority – have announced on the record that they support opening an impeachment process against the President. That number was 120 at the beginning of September, and below hundred just a couple of months ago. We are at a hinge moment in the Trump presidency and in American history.

In critical situations with severely limited options, timing is almost always critical. If a fearsome beast is charging to attack you and you have a single bullet in your gun, when you fire that bullet is as important as whether you aim right. If you fire too soon, the bullet falls to the ground ineffectually and you are at the mercy of the beast, and if you hold your fire too long, the beast will already be upon you.  Nancy Pelosi, expert huntress that she is, seems to have got her timing on impeachment exactly right.

The Democratic base has wanted to impeach Donald Trump virtually since the minute he was elected. That fervor persisted as the so-called “Resistance” grew in the wake of the Muslim Ban and other inhumane, ill-advised, and outright cruel Trump Administration policies. However, while the intensity of this fire grew every day, it did not spread beyond the base, and all those who wished to check Trump’s reckless administration came to see winning back the House of Representatives for the Democrats in 2018 as the primary goal. Fed by this passion, the Democrats duly captured the House, decimating the Republicans in cities and suburbs from Wisconsin to Texas. After eight years in the minority, the Democrats were back in charge. Read more »

Time Out

by Joan Harvey

a skilled
Vigilant, flexible,
Unemphasised, enthralled
Catching of happiness

from Born Yesterday by Philip Larkin, quoted in Adam Phillips, One Way and Another

But the fear’s so strong it leaves you gasping
No way to last out here like this for long
‘Cause everywhere I go, I know
Everywhere I go, I know
All my happiness is gone
All my happiness is gone
It’s all gone somewhere beyond
All my happiness is gone

—David Berman, All My Happiness is Gone

It’s tied to that word we were talking about this morning—ebbrezza. There is a sort of wondrous fever that can go on, and that is very near a feeling of happiness. The Sanskrit word tapas, “ardor,” is deeply connected with this. —Roberto Calasso

In Microhabitat, a film by Korean Jeon Go-woon, a young woman who cleans houses for a living goes to an elegant bar after work each day where she sits alone and contemplatively drinks a glass of good whiskey and smokes a cigarette. When her rent goes up, rather than give up this daily bit of relief she gives up her apartment, and moves nomadically around the city, staying with friends when she can. Some of her friends in the film are morally outraged at her choice, especially as neither cigarettes nor whiskey are considered healthy. I found the film striking in showing a woman taking care of herself, in a way not socially acceptable, knowing what she needed to get through the day. Men are often filmed in bars, but we rarely see women just pausing, not unhappy, not looking for anything but time alone for themselves, in a place where, for a change, they are waited upon. I saw in this a woman’s way of allowing herself some daily respite, an achievement of a space of happiness. Read more »

On Not Knowing: Story About That

by Emily Ogden

Humpty Dumpty had a great fall.

When Donald Trump was elected, I was pregnant with twins. My sons were born after the 2017 inauguration, under what I cannot help but feel is an ill star—though in themselves they are privileged and want for nothing. Nothing, that is, except a planet whose future is secure and a nation that does not “reign without a rival” for “revolting barbarity and shameless hypocrisy”—words of Frederick Douglass’s whose restless sound wave has kept propagating itself. My sons were learning to crawl when white supremacists marched in downtown Charlottesville, a mile from our house. They started walking at about the time that NPR played recordings of children wailing in detention centers. No crisis that has come, has passed. Another election is approaching; talk of impeachment grows serious. And my sons, oblivious to all of this, are asking for stories.

“Story bout that,” they say, when some event, or more commonly some non-event, captures their attention. In the dark, Beckettian world of their fictions, little happens except for a persistent breaching of bodily integrity. Here are some of the stories; judge for yourself (L. and N. are my sons, and Zeke is one of our dogs):

When L. got stung by a bee

When N. got stung by an ant

When N. got a splinter in his foot

When a wheel fell off the neighbor’s pickup truck

When Zeke broke [killed] the snake

When Zeke broke the lizard

When the weather broke

When a bowl broke

When L. had broken skin

When the red balloon went up to the ceiling and we couldn’t reach

When Zeke got out the front door

When N. was coughing so hard he gagged

When the red baby cried

Things break and people break and we, the tellers of stories, survive. That is the common burden of these monotonous, unstructured downers, each of which I have been ordered to tell at least fifty times. My sons listen, calm as sucklings. Why such an appetite for damage? It reflects their reality, I suppose. Toddlers fall and they destroy things. I understand the appeal of Humpty Dumpty without the need to search for royalist intimations. An egg, who is at once a fragile person and a fragile object, shatters beyond repair. Welcome to my household. My sons have had several great falls each, and they have broken literally dozens of literal eggs. Read more »

Stoicism in the 21st century

by Jeroen Bouterse

I remember the first time I thought I might be able to get on board with Stoicism. I read a passage in Aulus Gellius’ Attic Nights, about a distinguished Stoic philosopher on a ship crossing the Ionian sea. The ship finds itself in a violent storm, catches water and seems to be on the verge of being overpowered by the elements. The narrator describes how everybody is working to keep the vessel afloat, all the while lamenting their situation.

In the midst of all the chaos, he looks for the Stoic – perhaps to anchor his own courage in the idea that the truly wise are unperturbed even by this seemingly dire situation. “And then”, he remembers later, “I beheld the man frightened and ghastly pale, not indeed uttering any lamentations, as all the rest were doing, nor any outcries of that kind, but in his loss of colour and distracted expression not differing much from the others.” Whether the philosopher at least manages to make himself useful at the pumps remains unclear.

To add evident insult to apparent injury, a rich man then heckles the Stoic, remarking that he himself showed no fear whatsoever. The philosopher’s retort is something to the effect that apparently the man doesn’t have as much to lose by his death as has the philosopher. We can hardly expect that witticism, expressed in a convoluted way and apparently after some hesitation, to have saved his face.

Now that’s my kind of Stoic – the kind of hero who still jumps at loud noises, and who still gets bullied by obnoxious social superiors. Read more »

Dil Dil Pakistan

by Claire Chambers

Image result for Kashmir

I’m just back from a short trip to Lahore and, while the colours, tastes, and sounds are still vibrant in my mind, I want to write it all down.

On my way to Pakistan I got talking to someone at Manchester Airport. We were both eager to charge our phones before the long flight and ended up taking turns with our plugs at the socket as we engaged in desultory chat. This young woman hailed from London and, like me, was unusual in travelling alone. She told me she was on a visit to her Pakistani husband. They had met on their degree courses at the University of Nottingham, and while they waited for his UK spousal visa to come through she was making regular trips to Lahore to see him. A British Indian Sikh, she still hadn’t told her family, even though the couple had been married for almost two years. His family in Lahore also had no knowledge of their nuptials, for the couple believed that their relatives on either side would never accept this marriage across borders and faith groups

Indeed, this is a tense time for Indo-Pak relations. In Lahore, friends would from time to time reveal their heightened awareness of how long it had been since Narendra Modi’s abrogation of Kashmir’s semi-autonomous status. At the time of writing it is fifty days since this decision was passed by the Rajya Sabha. Aghast as I am at Modi’s lockdown of the valley, before this trip I would not have thought of counting days (like a prisoner, aptly enough). Read more »

A Few Instances of Alphabet Reform

by Gabrielle C. Durham

Do you remember when the Irish playwright and critic George Bernard Shaw suggested significant changes to English spelling so that it would make more sense? Probably not, because it was more than 70 years ago. According to him and, likely, some predecessors, English spelling was so goofy that ghoti could be manipulated to sound like fish. (Gh as in “enough,” o as in “women,” ti as in “action.”) He had an admittedly excellent point about the, um, esoteric spelling rules of English.

Often alphabets reform during times of great social and political upheaval as an issue of nationalism. For instance, many of the languages and alphabets in Europe underwent serious changes to uphold and distinguish themselves from other similar languages in the second half of the 19th century, amidst all sorts of revolutions.

For example, one Serbian hero is Vuk Karadžić, who updated the Serbian Cyrillic alphabet in 1818, which was officially adopted in 1868 in Serbia, Bosnia, and Herzegovina. He removed many letters from the old alphabet and added a few new letters to better match how people actually spoke. If you have ever heard of Saints Cyril and Methodius, you may be familiar with the two brothers creating the alphabet that led to modern Cyrillic in or around 900 (Cyrillic being named for St. Cyril). The alphabet they created was actually Glagolitic, which in its original form has been found in parts of modern Croatia. The alphabet that the brothers created was intended to for transcribing the liturgical language Old Church Slavonic. Its strongest predecessor was ancient Greek, with elements of Old Bulgarian and Old Macedonian. Read more »

We Contain Multitudes

by Marie Gaglione

Things are changing. Always, everywhere, immensely and minutely, the history of mankind unfolds as we rotate around a grand burning star (also, everything everywhere else changes; the history of mankind may be of the least consequence on a cosmic scale, but I digress). I digress too early; I include parentheticals too soon; I stall with flowery descriptions of the sun. Because – ugh – I’m going to talk about “how divided we are as a nation.” It’s such a tired phrase; I don’t want to write about it. It’s stale because it’s static, and anyway, the declaration is often accompanied by divisive rhetoric. Wherever one may fall on the political spectrum (and here I’m being gracious; how often do we now identify with a “side”), they likely have established opinions of those who lie elsewhere. It does seem increasingly difficult to imagine a sweeping reconciliation when we continue to pour our definitions in concrete and defend our positions by reason of consistency. Inflexibility begets inability to listen, and thus to understand, which is why we find our differences so baffling and allow our prejudices to influence our opinions. So, finally, here it is: my own personal take on how we can get people to stop saying how divided we are. Bear with me, because I’m going to try and sell contradictions as potential energy for unity. Read more »

Silence! The Fado Must Be Sung

by Thomas O’Dwyer

One of the few pleasures left in modern travel is to visit an unfamiliar place and to attempt to feel its historical and cultural pulse – if it still has one. The British author Lawrence Durrell endlessly sought the “spirit of place” in his travels. He developed the rare talent of being able to transmit that spirit to his readers – the long-dead voices of Alexandria, or the mythical deities riding the breezes of the Greek islands and Cyprus.

Pena Palace, Sintra, Lisbon.
Pena Palace, Sintra, Lisbon, Portugal.

Two weeks ago I went to Lisbon for the first time. By accident rather than design, Portugal had been the only European country I had never visited. If I had to produce a few keywords to summarise my knowledge of the country, I might have come up short. There was Vasco de Gama, a Carnation revolution against a dictator named Salazar, the writer José Saramago, port, cork trees, Fatima, and fado music. I might even have mentioned Brazil. Sorry Portugal, that was about it.

I was appalled by my ignorance of the ancient, imperial, and cultural history of a European nation. Some of my travelling companions were American, reminding me of another dreary fact of modern travel. Wherever you go, you can’t escape America. Perhaps in the 50s BCE, some lone travellers felt the same when they visited remote Celtic Britain. They found they still couldn’t avoid Roman garrisons and bathhouses. Read more »

The antidote to endless, thoughtless consumption lies not in purging ourselves of the stuff we own, but rather, redefining our relationship with stuff altogether

Benjamin Leszcz in The Globe and Mail:

Several years ago, while living in London, England, my wife met Prince Charles at an event associated with the Prince’s Foundation, where she worked. She returned with two observations: First, the Prince of Wales used two fingers – index and middle – when he pointed. Second, Charles’s suit had visible signs of mending. A Google search fails to substantiate the double-barrelled gesture, but the Prince’s penchant for patching has been well documented. Last year, the journalist Marion Hume discovered a cardboard box containing more than 30 years of off-cuts and leftover materials from the Prince’s suits, tucked away in a corner at his Savile Row tailor, Anderson & Sheppard. “I have always believed in trying to keep as many of my clothes and shoes going for as long as possible … through patches and repairs,” he told Ms. Hume. “In this way, I tend to be in fashion once every 25 years.”

As it happens, double-breasted suits are rather on-trend. But more notable is Charles’s sartorial philosophy, which could not be timelier. The Prince comes from a tradition of admirable frugality – the Queen reuses gift-wrap – but his inclination to repair rather than replace, to wear his clothes until they wear out, is an apt antidote to our increasingly disposable times. Most modern consumers are not nearly so resourceful: The average Canadian buys 70 new pieces of clothing each year, about 60 of which ultimately wind up in a landfill.

More here.

On the Evolution of Animal Consciousness

Michael S. A. Graziano in Literary Hub:

Self-replicating, bacterial life first appeared on Earth about 4 billion years ago. For most of Earth’s history, life remained at the single-celled level, and nothing like a nervous system existed until around 600 or 700 million years ago (MYA). In the attention schema theory, consciousness depends on the nervous system processing information in a specific way. The key to the theory, and I suspect the key to any advanced intelligence, is attention—the ability of the brain to focus its limited resources on a restricted piece of the world at any one time in order to process it in greater depth.

I will begin the story with sea sponges, because they help to bracket the evolution of the nervous system. They are the most primitive of all multicellular animals, with no overall body plan, no limbs, no muscles, and no need for nerves. They sit at the bottom of the ocean, filtering nutrients like a sieve. And yet sponges do share some genes with us, including at least 25 that, in people, help structure the nervous system. In sponges, the same genes may be involved in simpler aspects of how cells communicate with each other. Sponges seem to be poised right at the evolutionary threshold of the nervous system. They are thought to have shared a last common ancestor with us between about 700 and 600 MYA.

More here.

How The U.S. Hacked ISIS

Dina Temple-Raston at NPR:

The crowded room was awaiting one word: “Fire.”

Everyone was in uniform; there were scheduled briefings, last-minute discussions, final rehearsals. “They wanted to look me in the eye and say, ‘Are you sure this is going to work?’ ” an operator named Neil said. “Every time, I had to say yes, no matter what I thought.” He was nervous, but confident. U.S. Cyber Command and the National Security Agency had never worked together on something this big before.

Four teams sat at workstations set up like high school carrels. Sergeants sat before keyboards; intelligence analysts on one side, linguists and support staff on another. Each station was armed with four flat-screen computer monitors on adjustable arms and a pile of target lists and IP addresses and online aliases. They were cyberwarriors, and they all sat in the kind of oversize office chairs Internet gamers settle into before a long night.

“I felt like there were over 80 people in the room, between the teams and then everybody lining the back wall that wanted to watch,” Neil recalled. He asked us to use only his first name to protect his identity. “I’m not sure how many people there were on the phones listening in or in chat rooms.”

More here.

How Boeing’s Managerial Revolution Created the 737 Max Disaster

Maureen Tkacik in The New Republic:

Nearly two decades before Boeing’s MCAS system crashed two of the plane-maker’s brand-new 737 MAX jets, Stan Sorscher knew his company’s increasingly toxic mode of operating would create a disaster of some kind. A long and proud “safety culture” was rapidly being replaced, he argued, with “a culture of financial bullshit, a culture of groupthink.”

Sorscher, a physicist who’d worked at Boeing more than two decades and had led negotiations there for the engineers’ union, had become obsessed with management culture. He said he didn’t previously imagine Boeing’s brave new managerial caste creating a problem as dumb and glaringly obvious as MCAS (or the Maneuvering Characteristics Augmentation System, as a handful of software wizards had dubbed it). Mostly he worried about shriveling market share driving sales and head count into the ground, the things that keep post-industrial American labor leaders up at night. On some level, though, he saw it all coming; he even demonstrated how the costs of a grounded plane would dwarf the short-term savings achieved from the latest outsourcing binge in one of his reports that no one read back in 2002.

More here.

Misunderstanding Susan Sontag

Merve Emre in The Atlantic:

To experience a thing as beautiful means: to experience it necessarily wrongly,” Friedrich Nietzsche wrote in The Will to Power. It is a line that Susan Sontag quotes toward the end of her 1977 essay collection, On Photography, about how photographs aestheticize misery. It is a line that Sontag’s authorized biographer, Benjamin Moser, quotes to describe Sontag’s susceptibility to beautiful, but punishing, lovers. And it is a line that I am quoting to summarize how Moser’s monumental and stylish biography, Sontag: Her Life and Work, fails its subject—a woman whose beauty, and the sex appeal and celebrity that went along with it, Moser insists upon to the point of occluding what makes her so deeply interesting.

The fascination of Sontag lies in her endurance as a cultural icon, the model of how a woman should think and write in public, even though her thinking and writing weren’t very rigorous. What is intriguing about Sontag is less who she was than how we understand our desire for her, or someone like her, to occupy a rare position in American literary culture: that of a dark-haired, dark-eyed, apparently invulnerable woman capable of transforming intellectual seriousness into an erotic spectacle. What need does such a presence and performance satisfy?

More here.

Yes, capitalism is broken. To recover, liberals must eat humble pie

Richard Reeves in The Guardian:

Capitalism reigns. But capitalism is in trouble. Therein lies the paradox of our age. For the first time in human history, a single economic system spans the globe. Of course there are differences between capitalism Chinese-style, American-style and Swedish-style. Close up, these differences can seem significant. But viewed through a wider lens, the distinctions blur. As the economist Branco Milanovic writes in his new book, Capitalism Alone, “the entire globe now operates according to the same economic principles – production organized for profit using legally free wage labor and mostly privately owned capital, with decentralized coordination”. After the fall of Soviet communism in 1989, and China’s embrace of the market, crowned by the nation’s entry into the World Trade Organization in 2001, it seemed, for a brief flicker of human history, that the world was converging on a political economy of free markets in liberal democracies. As it turned out, markets spread, but without necessarily bringing more democracy or liberalism along with them.

Capitalism without democracy was assumed to be at most a passing phase. Eventually, so western liberal thinking went, China and other Asian nations adopting what Milanovic calls “political capitalism” – free markets, but authoritarian politics – would have to adopt liberal political institutions, too. But, so far, the liberalization thesis remains unproven. China has successfully adopted a market system – and, even more importantly, a market culture – without liberal democratic institutions.

More here.