The Cancer Questions Project, Part 14: Larry Norton

Dr. Larry Norton, a breast oncologist, is well-known as a leader in the development of drug treatments for breast cancer. His research has established the importance of using sequential combinations of drugs — a strategy aimed to overcome different drug sensitivities among the cells in a tumor. He has served in leadership positions in several national cancer-related organizations, including serving as president of the American Society of Clinical Oncology (ASCO) in 2001-2002, and is chairman of the board of directors of the ASCO Foundation. Currently, Dr. Norton is serving as the Senior Vice President at Memorial Sloan Kettering Cancer Center and a Professor of Medicine at Weill-Cornell Medical College with over 350 published articles and book chapters to his name.

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?

Where Does Domenico Scarlatti Belong?

by Anitra Pavlico

Vivi felice (live happily)” —Domenico Scarlatti, in the introduction to his Essercizi per Gravicembalo (Exercises for Harpsichord), 1738

Domenico Scarlatti (1685-1757) refuses to be put into any particular category, despite generations of music historians’ efforts. Scarlatti scholar W. Dean Sutcliffe begins his 2003 book The Keyboard Sonatas of Domenico Scarlatti and Eighteenth-Century Musical Style with the blunt statement, “Domenico Scarlatti does not belong.” Scarlatti was born in Italy, but spent the last thirty years of his life in Spain. He was not quite Baroque, not quite Classical. In his review of the Sutcliffe book, Michael Talbot describes Scarlatti as a “cult figure” who is “neither inside nor outside the canon. He is not seminal in the sense of forming a link in a historical chain either of composers or of performers, but his influence is clearly perceptible in the literature of keyboard instruments from Haydn to Ligeti.” As disparate as their styles might appear, Franz Liszt was an early champion of Scarlatti’s sonatas, and was perhaps the first to perform them publicly. Chopin was also an admirer. Talbot says that Beethoven must have written the second movement of his Op. 54 piano sonata with the ghost of Scarlatti looking over his shoulder. 

Sutcliffe views the concept of “disdain” as central to Scarlatti’s approach: the term, first applied to the composer by Italian musicologist Giorgio Pestelli, connotes a deliberate rejection of convention. Scarlatti is well-versed in, but does not fully adopt, the conventions of the galant musical language in vogue at the time. In short, the galant style was a response to the complexity of the Baroque period and featured simpler melodies, phrasing, and harmonies. Rules are well and good for lesser composers, apparently, but Scarlatti reportedly was of the opinion that his deviations from the rules were “sanctioned by the pleasure that they gave the ear.” Janet Schmalfeldt writes that Scarlatti is “intriguing” in his evasion of stylistic classification, a “smart move” on his part: he was seemingly ahead of his time, given the modern disillusionment with stylistic categories and sharp boundaries between historical periods. Read more »

How can psychology change the ‘algorithm’ for morality in bioethics?

by Michael Klenk

Moral psychology has shaken up moral philosophy in recent years (see, e.g., here and here). The upheaval is welcome. Understanding better how ethical judgements work should eventually lead to positive behaviour change. For example, we might hope for more altruism to solve collective action problems like climate change, and less in-group vs out-group thinking, to curb racism.

So far, however, moral psychology’s impact on ethical conduct has mostly been within the narrow confines of academic journals. The philosophers who took up moral psychological findings mainly focus on rather abstract questions about the theory of knowledge and methodology in ethics. For example, a significant debate concerns the question of whether moral judgments remain warranted given evidence of their psychological origin (see, for example, some of my previous blogs here and here).

Notwithstanding the fascinating nature of such meta-ethical questions, it is a long way from progress in these theoretical debates to effecting positive behavioural change in people. Indeed, moral psychology’s practical impact has not been a focus of much academic work yet.

Our hope may rest on what we can call ‘trickle-down ethics,’ where the revelations of ethicists trickle down to all of society eventually. Moral psychology may impact moral philosophy, and so the impact of moral psychology on moral philosophy may finally be felt in practice, too. However, there is no clear evidence for the success of trickle-down ethics, and blindly trusting it can be frustrating. After all, engaging in moral philosophy is a way to understand what ought to be done, and why, and then to do it – not merely hoping that something eventually gets done. Even if moral philosophy as a discipline has illuminated the ‘understanding’ part, we leave the ‘practice part’ almost entirely to an ill-founded hope in trickle-down ethics. So, blind trust in trickle-down ethics is probably up for a displeasing reality check, especially if the frail prospect of trickle-down economics is any indicator. Read more »

Crying like a Girl

by Shadab Zeest Hashmi

One autumn I’m suddenly taller than my mother. The euphoria of wearing her heels and blouses will, for an instant, distract me from the loss of inhabiting the innocence of a child’s body—the hundred scents and stains of tumbling on grass, the anthills and hot powdery breath of brick-walls climbed, the textures of twigs and nodes of branches and wet doll hair and rubber bands, kite paper and tamarind-candy wrappers, the cicada-like sound of pencil sharpeners, the popping of coca cola bottle caps, of cracking pine nuts in the long winter evenings— will blunt and vanish, one by one.

That the sensory life is dulled just as the cerebral life is intensified, is no accident; at school, boys and girls are separated for a special talk on how the changing body requires a set of rules, a sense of restraint. The talk is grave and ends with alarming details of the impending burden of academic work that will make or break us. As if the process of adapting to a new life in a new body were not hard enough, we are told that we are under scrutiny for following the prescribed path of success as well as for containing the challenges that gender poses.

The body is as unforgiving as the social norms it finds itself in the clutches of; it is more often a tempest than a temple. Growing pains, at least for girls, must be strictly private. How you decipher and piece together the physical, emotional and social puzzle of your life is entirely and urgently your own responsibility and never without open and free scrutiny and judgement. The present is a perpetual shore to an ocean of future anxiety; there is no turning back. Without sisters or close female company, I am alone now in this space of being a girl and I always will be as a woman. Read more »

The Moral Robot

by Chris Horner

The question of how to program AI to behave morally has exercised a lot of people, for a long time. Most famous, perhaps, are the three rules for robots that Isaac Asimov introduced in his SF stories: (1) A robot may not injure a human being or, through inaction, allow a human being to come to harm; (2) A robot must obey orders given it by human beings except where such orders would conflict with the First Law; (3) A robot must protect its own existence as long as such protection does not conflict with the First or Second Law. These have been discussed, amended, extended and criticised at great length ever since Asimov published them in 1942, and with the current interest in ‘intelligent AI’ it seems they will be subject for debate for some time to come.  But I think the difficulties of coming up with effective rules of this kind are more interesting for what they tell us about the difficulties of any rule or duty based morality for humans than they are for the question of ‘AI morality’. 

Duty based – the jargon term is ‘deontological’ – morality seem to run into problems as soon as we imagine them being applied. Duties can easily seem to clash or lead to unwelcome outcomes – one might think that lying would be justified if it meant protecting an innocent person from a violent person set on harming them, for instance. So which duties should take precedence in the infinite number of future situations in which they might be applied? Answering a question like that involves more than coming up with a sequence of rules, as there seems to be something one needs to add to any would-be moral agent for them to really exercise an adequate moral judgment. Considering the problems around this is more than a philosophical parlour game as it should lead us into more realistic ways of thinking about what it takes to act well in the real world. What we are looking for, I think, is an approach that takes into account the need for genuinely autonomous moral thinking, but also connects the moral agent to the the complicated social world in which we live. Read more »

The Being of Grief

by Adele A Wilby

It is unlikely that any of us will escape the experience of grief during the course of our lifetime. Throughout that experience, many of us will struggle to find the words that adequately convey what happens to us during that period, and the disruption to our lives that grief brings will be understood as normal in the circumstances. Unable to console the bereaved, and with good intentions, ‘time’ they reassure us, ‘is a great healer’, and there is some truth in that adage.  But ‘time’ itself can also be the very source of confusion in grief, although most of us fail to recognise it as such throughout a bereavement, and we are left wondering what it is about that feeling of being out of the world that I, for one, experienced following the death of my husband. Why, apart from all the other manifestations of grief, did I feel ‘suspended’ from life, yet still alive and living, as I stood and stared out the window of my sitting room, and watched the world go by? I considered myself to be a competent person capable of ordering my life, yet I was impotent in my ability to change what was happening to me. Why did I find it so impossible to act, and get back ‘into’ the world? Read more »

Equality Now

by Tim Sommers

We are all in some sense equal. Aren’t we? The Declaration of American Independence says that, “We hold these Truths [with a capital ‘T’!] to be self-evident” – number one being “that all Men are created equal.” Immediately, you probably want to amend that. Maybe, not “created”, and surely not only “Men” – and, of course, there’s the painful irony of a group of landed-gentry proclaiming the equality of all men, while also holding (at that point) over 300,000 slaves. But don’t we still believe, all that aside, that all people are, in some sense, equal? Isn’t this a central and orienting principle of our social and political world? What should we say, then, about what equality is for us now?

In September, Professor Elizabeth Anderson was awarded a MacArthur Fellowship, a so-called “genius grant”, for her work in political philosophy. Though the Foundation specially cited the way she applies her views, pragmatically, to “problems of practical importance and urgency” (most recently with books on race, “The Imperative of Integration”, and work, “Private Government”), the theoretical backbone of her view is a new, original account of social equality – relational or democratic egalitarianism. In a seminal 1999 article, “What is the Point of Equality?”, Anderson asked rhetorically, “If much recent academic work defending equality had been secretly penned by conservatives, could the results be more embarrassing for egalitarians?” Her point was that at the same time that new egalitarian social movements, or at least newly reinvigorated egalitarian movements, focused on race, gender, class, disability, sexual orientation, and gender expression, the dominant form of academic egalitarian political philosophy (“luck egalitarianism”) spent a lot of time arguing about lazy surfers, people “temperamentally gloomy, or incurably bored by inexpensive hobbies”, and those who couldn’t afford the expensive religious ceremonies they wanted to perform. Granted, the characters that inhabit philosophical hypotheticals are bound to be a quirky lot, nonetheless, Anderson wondered what had happened to oppression as the main subject of political philosophy?

Well, here is one way, probably the dominant way in political philosophy, of thinking about equality before Anderson. The notion of equality seems to demand a quantitative comparison. To be equal is to have an equal amount of something. An egalitarian society, then, is one where (certain) things are distributed equally. Call this distributive justice. Read more »

The personal diet has become not only a cult, it has become a political statement

James McWilliams in The Hedgehog Review:

In the summer of 2016, James and Becca Reed, a lower-income couple living in Austin, Texas, decided it was time to save their lives. The Reeds, married more than twenty-five years, had become morbidly obese, diabetic, and depressed. They were taking a combined thirty-two medications. Only in their early fifties, they had arrived at this condition via a well-trod path: They ate their way into it. They did no more than consume what the American food industry not only offers in abundance—salt, starch, and sweetness—but also encourages us to eat.

As nearly 40 percent of the adult US population can attest, it doesn’t take a lot of time, effort, or expense for the consequences of the American way of eating to add up.1 A steady diet of processed and fast food, oversized restaurant meals, and “favorited” takeout options can quickly make the average American a victim of the growing obesity epidemic. Considering that the Reeds live paycheck to paycheck, and given what we know about the strong link between economic disadvantage and poor eating choices, I was especially intrigued when a friend, who knew James and Becca from church, told me about this really interesting couple getting ready to reclaim their health in a dramatic way.

With disarming generosity, the Reeds opened their lives to me as they undertook their mission.

More here.

The socialization of intelligence: A talk by Seth Lloyd

Seth Lloyd at Edge:

We haven’t talked about the socialization of intelligence very much. We talked a lot about intelligence as being individual human things, yet the thing that distinguishes humans from other animals is our possession of human language, which allows us both to think and communicate in ways that other animals don’t appear to be able to. This gives us a cooperative power as a global organism, which is causing lots of trouble. If I were another species, I’d be pretty damn pissed off right now. What makes human beings effective is not their individual intelligences, though there are many very intelligent people in this room, but their communal intelligence.

More here.

Sean Carroll’s Mindscape Podcast: Katie Mack on How the Universe Will End

Sean Carroll in Preposterous Universe:

Cosmologists are always talking excitedly about the Big Bang and all the cool stuff that happened in the 14 billion years between then and now. But what about the future? We don’t know for sure, but we know enough about the laws of physics to sketch out several plausible scenarios for what the future of our universe will hold. Katie Mack is a cosmologist who is writing a book about the end of the universe. We talk about the possibilities of a Big Crunch (and potential Big Bounce), a gentle cooling off where the universe gradually grows silent, and of course the prospect of a dramatic phase transition, otherwise known as the “bubble of quantum death.” Which would make a great name for a band, I think we can all agree.

More here.

Zadie Smith Experiments With Short Fiction

Rebecca Makkai in the New York Times:

To consider yourself well versed in contemporary literature without reading short stories is to visit the Eiffel Tower and say you’ve seen Europe. Not only would monumental writers be missing from your literary tour, but entire angles and moves and structures of which the novel, in its bulk, is incapable. The quirky neighborhood, the narrow cobblestone alley, the stray cats and small museums and the store that sells only butter.

Since the publication of “White Teeth” in 2000, readers have known Zadie Smith as a novelist of tremendous scope, a maximalist with a global eye and mind. Those who’ve been paying attention have also caught her stories along the way in our better magazines and journals — stories that until recently have, for the most part, followed a linear narrative, taking advantage of the shorter form but not its more eccentric powers.

Some of these more traditional stories have landed in Smith’s first collection, “Grand Union,” and while still brilliant on the level of the sentence, the paragraph, the often hilarious skewering of humanity, they’re the least successful ones here, sour notes in a collection in which the best pieces achieve something less narrative and closer to brilliance.

More here.

Sunday Poem

Bull Song

For me there was no audience
no brass music either,
only wet dust, the cheers
buzzing at me like flies,
like flies roaring.

I stood dizzied
with sun and anger,
neck muscle cut,
blood falling from the gouged shoulder.

Who brought me here
to fight against walls and blankets
and the gods with sinews of red and silver
who flutter and evade?

I turn, flies rise and settle,
I exit, dragged, a bale
of lump flesh.
The gods are awarded
the useless parts of my body.

For them this finish,
this death of mine is a game:
not the fact or act
but the grace with which they disguise it
justify them.

by Margaret Atwood
from
The Poetry Foundation

How Trump Reshaped the Presidency in Over 11,000 Tweets

Shear et al in The New York Times:

In the Oval Office, an annoyed President Trump ended an argument he was having with his aides. He reached into a drawer, took out his iPhone and threw it on top of the historic Resolute Desk:

“Do you want me to settle this right now?”

There was no missing Mr. Trump’s threat that day in early 2017, the aides recalled. With a tweet, he could fling a directive to the world, and there was nothing they could do about it.

When Mr. Trump entered office, Twitter was a political tool that had helped get him elected and a digital howitzer that he relished firing. In the years since, he has fully integrated Twitter into the very fabric of his administration, reshaping the nature of the presidency and presidential power. After Turkey invaded northern Syria this past month, he crafted his response not only in White House meetings but also in a series of contradictory tweets. This summer, he announced increased tariffs on $300 billion worth of Chinese goods, using a tweet to deepen tensions between the two countries. And in March, Mr. Trump cast aside more than 50 years of American policy, tweeting his recognition of Israel’s sovereignty in the Golan Heights. He openly delighted in the reaction he provoked.

“Boom. I press it,” Mr. Trump recalled months later at a White House conference attended by conservative social media personalities, “and, within two seconds, ‘We have breaking news.’”

Early on, top aides wanted to restrain the president’s Twitter habit, even considering asking the company to impose a 15-minute delay on Mr. Trump’s messages. But 11,390 presidential tweets later, many administration officials and lawmakers embrace his Twitter obsession, flocking to his social media chief with suggestions. Policy meetings are hijacked when Mr. Trump gets an idea for a tweet, drawing in cabinet members and others for wordsmithing. And as a president often at war with his own bureaucracy, he deploys Twitter to break through logjams, overrule or humiliate recalcitrant advisers and pre-empt his staff.

“He needs to tweet like we need to eat,” Kellyanne Conway, his White House counselor, said in an interview.

More here.

Can You Overdose on Happiness?

Lone Frank in Nautilus:

It is a good question, but I was a little surprised to see it as the title of a research paper in a medical journal: “How Happy Is Too Happy?” Yet there it was in a publication from 2012. The article was written by two Germans and an American, and they were grappling with the issue of how we should deal with the possibility of manipulating people’s moods and feeling of happiness through brain stimulation. If you have direct access to the reward system and can turn the feeling of euphoria up or down, who decides what the level should be? The doctors or the person whose brain is on the line?

The authors were asking this question because of a patient who wanted to decide the matter for himself: a 33-year-old German man who had been suffering for many years from severe obsessive-compulsive disorder and generalized anxiety syndrome. A few years earlier, the doctors had implanted electrodes in a central part of his reward system—namely, the nucleus accumbens. The stimulation had worked rather well on his symptoms, but now it was time to change the stimulator battery. This demanded a small surgical procedure since the stimulator was nestled under the skin just below the clavicle. The bulge in the shape of a small rounded Zippo lighter with the top off had to be opened. The patient went to the emergency room at a hospital in Tübingen to get everything fixed. There, they called in a neurologist named Matthis Synofzik to set the stimulator in a way that optimized its parameters. The two worked keenly on the task, and Synofzik experimented with settings from 1 to 5 volts. At each setting, he asked the patient to describe his feeling of well-being, his anxiety level, and his feeling of inner tension. The patient replied on a scale from 1 to 10.

The two began with a single volt. Not much happened. The patient’s well-being or “happiness level” was around 2, while his anxiety was up at 8. With a single volt more, the happiness level crawled up to 3, and his anxiety fell to 6. That was better but still nothing to write home about. At 4 volts, on the other hand, the picture was entirely different. The patient now described a feeling of happiness all the way up to the maximum of 10 and a total absence of anxiety.

More here.

‘My Mother Laughs’ by Chantal Akerman

Lauren Elkin at The Guardian:

In a scene in No Home Movie (2015), the last film from the celebrated film director Chantal Akerman, which is a documentary of her elderly mother’s daily life as she recovers from an operation, Akerman says while they are eating dinner: “In Judaism a child doesn’t have to love his parents, but he does have to respect them. Which is a very good idea!” she adds, waving her knife in the air. Her mother, Natalia, laughs.

Her mother laughs often, Akerman recalls in her memoir, in which the present day seems to be about a year before the film was made. “Often she laughs in the middle of her moans.” “I listen to her laugh,” Akerman writes. “She laughs over nothing. But this nothing means a lot. She even laughs in the morning sometimes … I like the sound her laugh makes. She sleeps a lot, but she laughs. She enjoys herself. Then she sleeps.”

more here.