Stavroula Kousteni, is the Associate Professor of Medicine in Physiology and Cellular Biophysics at Columbia University Medical Center. The goal of her research is to understand the influence of the skeleton on various physiological processes, to uncover the pathogenesis of degenerative diseases and to suggest therapies for them. She is currently examining the role of osteoblasts in hematopoiesis with particular emphasis in myelodysplasia (MDS) and acute myeloid leukemia (AML). Her lab has discovered the skeletons role as an inducer of leukemogenesis, identifying a mutation in osteoblasts that disrupts hematopoiesis leading to leukemogenic transformation of hematopoietic stem cells (HSCs) and establishment of MDS progressing to AML. Additionally, she has helped establish the role of osteoblasts in the engraftment of leukemia blasts. She is currently characterizing the signaling pathway that mediates these actions to manipulate osteoblasts to make the hematopoietic niche hostile to residual leukemia cells.

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?

by Mary Hrovat

I think it was in the 1980s that I first saw t-shirts showing a drawing of a spiral galaxy with an arrow indicating “You are here.” They were amusing, and the image provides a bit of cosmic context. You may be here, looking at this screen, with your to-do list and personal problems and worries about the world, but you’re also here in the Orion arm of the Milky Way, about 25,000 light years from the center, in this solar system, on this planet.

One way to capture the most local part of your cosmic context is the 3D solar simulator at The Sky Live, which shows a simulated snapshot of the locations of all the planets relative to the sun at this moment. You can zoom in and out and add asteroids, near-Earth objects, and comets. You can also animate the simulation. At one week per second, you get a pretty good view of the tight circling of the inner planets, but the outer planets move at a very sedate pace. At one year per second, the inner planets move too quickly to follow easily, but the outer planets sweep along briskly.

Of course, you can also observe the solar system from the inside. One great way to broaden your horizons is to go out in the evening to see what other planets in the solar system are visible and to watch them moving along in their orbits over the weeks and months. There are a number of guides to what you can see on a clear night. Sky & Telescope provides a weekly update that tells you which planets will be visible, what phase the moon is in, and whether there will be any events such as eclipses or meteor showers. Space.com offers a monthly summary that covers a somewhat broader range of things to look for in the night sky, and EarthSky describes what you can see in the sky tonight.

In addition, space is not an unchanging backdrop but a place with its own weather (sort of) and events. Spaceweather.com posts news stories about solar activity, aurorae, meteor showers, fireball observations, and more. The sidebar on the left shows current data and images. Read more »

by Brooks Riley

by Charlie Huenemann

We find ourselves always in the middle of an experience. But it’s what we do next – how we characterize the experience – that lays down a host of important and almost subterranean conditions. Am I sitting in a chair, gazing out the dusty window into a world of sunlight, trees, and snow? Am I meditating on the nature of experience? Am I praying? Am I simply spacing out? Depending on which way I parse whatever the hell I’m up to, my experience shifts from something ineffable (or at any rate, not currently effed) to something meaningful and determinate, festooned with many other conversational hooks and openings: “enjoying nature”, “introspecting”, “conversing with God”, “resting”, “procrastinating”, and so on. Putting the experience into words tells me what to do with it next.

Buber claims that the deepest and most immediate setting we establish in characterizing our experience is whether it falls into one or another mode: that of the “I/It” or that of the “I/Thou”. (Think of a toggle switch at the base of your mind, with two settings.) On the I/It setting, I am experiencing It: “I perceive something. I feel something. I want something. I sense something. I think something.” A curtain is drawn between two countable collections, and typically there is one thing on one side (me, or you), and one or more things on the other. Toggling into this setting means you are getting serious about getting something done or making something known. You will see whether you have enough butter and eggs to make the cookies. You are an agent, one who does. And the entities you are doing unto are patients, or the pieces in your game.

We should resist any temptation to underestimate the scope of I/It. It underlies nearly everything we do – no, everything, since “we do it” is an I/It formulation. To the extent that we think, sense, know, understand, or do anything, it is on this setting. Indeed, we might well wonder what other setting there could possibly be. Read more »

Part of the housing in Franzensfeste, South Tyrol, for workers of the Brenner Base Tunnel project. Photo taken while on my evening walk in November of 2019.

by Joseph Shieber

It is a great shame that the authors of the recently released AAUP statement “In Defense of Knowledge and Higher Education” do not even know what it is that they are attempting to defend. And it is the height of irony that, in an essay attempting to defend the importance of expert knowledge, the authors of the AAUP would be so cavalier in their rejection of expert knowledge about the very subject of their defense, namely knowledge itself.

The authors of the AAUP report have a laudable goal in mind. They seek to defend the importance of, as they put it, “the disciplines and institutions that produce and transmit … knowledge”.

The authors correctly note that recent critics of higher education mistakenly confuse the teaching and research conducted at colleges and universities with indoctrination. They quote the current United States Secretary of the Department of Education, Betsy DeVos, who exhorted college students to “fight against the education establishment”. “The faculty, from adjunct professors to deans,” DeVos warned the students, “tell you what to do, what to say, and more ominously, what to think.”

Although they aren’t terribly clear, it would seem that the AAUP report authors push back against DeVos’s conflation of education with indoctrination on the basis of three important qualities of research and education at higher education institutions:

1. College and university professors develop and transmit valuable thinking methods and skills — examples that the authors cite include learning how to “solve differential equations”, “to predict the path of a hurricane”, “to track the epidemic of opioid addiction”, “to study the impact of tariffs on the economy”.
2. College and university professors discover and disseminate factual information — examples that the authors cite include “the principles of quantum mechanics”, “the somatic effects of nicotine”, and “the history of slavery and Jim Crow, or the history of the Holocaust”.
3. In addition to those discipline-specific thinking methods and bodies of factual information, college and university professors also inculcate in students an appreciation for the methods of investigation appropriate to knowledge-seeking, which the authors characterize as “informed, dispassionate investigation”.

So far, so good! If the authors of the AAUP report had stopped here, they would have done higher education — and, indeed, the general public who derive so much from the fruits of higher education — a great service.

Unfortunately, they didn’t stop here. Read more »

Banks

along a river its banks are set
and keep the river in the river

being in the river the river’s
in its being

within its banks, whole, astatic,
a river flows unbound, ecstatic
a falling river goes

within these banks, astatic,
this river grows unbound, ecstatic
this falling river flows

until, without banks,
this river goes

Jim Culleny
1/4/2020

Photo: S. Abbas Raza

Sughra Raza. “Living in the Mountain”, Yangshuo, China, January, 2020.

Digital photograph.

by Katie Poore

While waiting, shivering and jetlagged, for a train home from the Paris airport this week, I alternately stared into space and checked the train timetables. My train was an hour late. I later learned, thanks to the friendliness of a fellow traingoer, that the train had hit a deer.

Waiting on the platform, I happened upon an article in The Atlantic. The author’s name was Jedediah Britton-Purdy. I clicked the Instagram link with immediate fascination, not because of the notability of that name—it strikes me as so quintessentially American—but because I spent days and weeks with his book After Nature last year, slogging through an undergraduate thesis centered on the intersection of the environment and literature.

Purdy’s article is called “The Concession to Climate Change I Will Not Make.” In it, he explains his rationale for maintaining hope in a world that seems to be, quite literally, burning down around us. To him, this hope means, at least in part, continuing to have children.

This struck a chord with me, perhaps because it was eerily similar to a conversation I had with my mother over the holidays, where I professed a sense of hopelessness about the world and its seemingly impending expiration date. Sometimes it made me terrified to have children, I told her. Thinking about what they might inherit felt almost cruel. Read more »

Dr. Antonio “Tito” Fojo specializes in the management of patients with adrenocortical cancer, malignant pheochromocytoma, neuroendocrine malignancies, and thyroid cancer; his current laboratory efforts are focused on developing therapies to treat such patients. Dr. Fojo has worked to understand the molecular basis of drug resistance, he was involved in the original work relating to several ABC transporters and identified rearrangements involving the MDR-1 gene as a novel mechanism of drug resistance in several cancers. He has also been very involved in research on microtubule-targeting agents. In addition to his clinical expertise Dr. Fojo is involved in the design, conduct and interpretation of oncology clinical trials and his collaboration have helped to pioneer a novel method of analysis that dissects rates of tumor growth and regression as concurrent events.

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?

by Mindy Clegg

This past week has been a roller coaster in American foreign policy, as we quite nearly ended up in a hot war with Iran. A curious phenomenon reared its ugly head during the fallout of the assassination of Qasem Soleimani, one of Iran’s top generals—comparisons to the start of the First World War’s precipitating event, the shooting of the Archduke of the Austro-Hungarian empire Franz Ferdinand.¹ As we all seriously contemplated another war, some leaned into the notion of its inevitability. Many would have you believe a Third World War was history merely asserting itself once again.² Supporters of a war with Iran (and other wars) might tell you that war is a glorious thing, that our young will cut their teeth on violence and blood, coming out the other side battle hardened, ready to tackle the “real” world with both hands. At the very least, we’ll defeat our enemies and ensure our continued dominance of the world, which we deserve. They might also proclaim that war is the only racket in town that will get our economy jumping again, exciting innovation through shattered bodies. I could not agree less with these assessments, and history most certainly backs me up here. First, with a few exceptions, there is no inevitable path to conflict—history shows us there are always choices. Second, young people are often shattered by participation in war, as our homeless population still replete with veterans of various wars attest. Last, many things can jumpstart innovation. I argue that making parallels to events of the past in order to draw conclusions about the inevitability of particular outcomes (the ones that benefit the fewest and hurt the most, like a war) is to misread or even blatantly misuse history and what it actually tells us about humanity. Read more »

by Brooks Riley

A slow exposure photo from a bus window between Bruneck and Franzensfeste, taken in December of 2019.

by Eric J. Weiner

The allure of fresh and true ideas, of free speculation, of artistic vigor, of cultural styles, of intelligence suffused by feeling, and feeling given fiber and outline by intelligence, has not come, and can hardly come, we see now, while our reigning philosophy is an instrumental one. —Randolph Bourne

Schoolteachers across the grades are responsible for teaching their students how to write. Their essential pedagogical role is instrumental. With particular attention paid to format, grammar, spelling, and syntax, students ideally learn to write what they know, think, or have learned. It matters little if the student is in a class for “creative writing” or “composition,” writing is taught and practiced as a way to record thoughts, compose ideas in a coherent manner, and clearly communicate information. A student’s writing is then assessed for how well she adhered to these instrumental standards while the teacher is assessed for how well she adhered to the standards of instrumental teaching.

By contrast, writing to learn re-conceptualizes our relationship to writing from measurable outcomes to critical/creative processes. It moves the epistemological needle from instrumentality to exploration, innovation, imagination, and discovery. Writing to learn supports the development of what Randolph Bourne (1917) called “poetic vision.” Having poetic vision diverts our “creative intelligence” away from “the machinery of life” and redirects our “creative desires” toward enhancing the quality of life. “It is the creative desire,” Bourne writes, “…that we shall need if we are ever to fly” (from Twilight of Idols). Read more »

by John Schwenkler

What is the point of being courteous, kind, and otherwise well-mannered?

I suspect that most of us are inclined toward an answer that parallels Thrasymachus’ view of justice in the early books of Plato’s Republic. For Thrasymachus, what really matters to us where questions of justice are concerned is all on the side of self-interest. We care about justice in others only to the extent that it brings benefits to us and our friends, and we care about embodying justice in our own lives only to the extent that justice wins us friends, while unjust action carries the risk of punishment and social sanction. The attractiveness of this view comes out in Plato’s famous retelling of the myth of Gyges: given the power to act either justly or unjustly without being detected by others, any of us would choose the life of total injustice. In themselves, the demands of justice are at odds with the desires of naked self-interest, and the only thing that motivates us to respect them is the fear of what will happen to us if we don’t.

An analysis along these lines is even more attractive in connection with the traditional demands of courtesy. Many of us will have the sense that there is — or at least could be — something objectively, universally wrong with stealing, lying, murdering, or imprisoning a person without proper cause. By contrast, no such status accrues to the demand to wear a collared shirt to work or put a napkin on one’s lap while eating: customs like these are contingent, local practices a large part of whose purpose is to mark off the one who observes them as a member of polite society. Meanwhile, even those aspects of good manners whose justification seems more fundamental, such as keeping disparaging thoughts to oneself and refraining from interrupting one’s conversational partners, are all such as to be dispensable in certain situations. What force do they have, then, except as the impositions of an oppressive, socially stratified culture? Read more »