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Cancer's invasion equation

newyorker.com

39 pointslb7219 comments

Honest question: Do many people read these entire New Yorker articles? This is what happens to me as I'm looking at HN:

From the main page, I open a bunch of tabs that look interesting. On some types of issues, I also open a tab on the HN discussion.

From there, I just wander through the tabs, reading stories and mostly just glancing at some of the top comments. My goal when I browse is to learn something new, and I try to remember that as I'm reading.

When I hit a New Yorker article's tab, I've often half-forgotten the subject line from HN... maybe it matches the article's title, but I just start reading regardless. Four or five paragraphs in, I start to think, "What the hell does all this setup have to do with the article title I clicked on?" Sure, on some level I know that it probably has something esoteric to do with the main article. These people must be paid by the word.

A couple paragraphs further and I start turning the mouse wheel to skim ahead. "Where do they start actually talking about the topic that looked interesting?" At that point, the New Yorker column has maybe mentioned the topic in an ancillary way, but oftentimes it's just warming up by bringing in some personality that they're going to focus on later in relation to the topic.

I get impatient.

I start scrolling faster, looking for some actual text to sink my mind into. At this point, I'm very conscious that I have a bunch of other potentially interesting tabs open in my browser and I've only allocated fifteen minutes or so before I need to get back to work. I scroll way down, hoping that I'll hit a paragraph that looks like it's full of information. Maybe I'll find one that looks interesting, but at that point I also don't have a whole lot of context to go on. It's like that endlessly long joke that you zone out on and then when they get to the punchline, maybe it sounds kind of funny, but you weren't paying attention to all the setup.

I close the tab and wonder how anyone has the time and patience to read these things. Maybe I'm just a slow reader.

In 1983 a girl in an esoteric dress stood in the rain outside the window of an appartment of a man named Why Do All TNY Articles Start Like This.

But this one starts with "Over the summer of 2011, the water in Lake Michigan turned crystal clear. Shafts of angled light lit the lake bed, like searchlights from a U.F.O.; later, old sunken ships came into view from above."... oh, I see... nevermind... :)

Yeah. That garden path caused me to elide a paragraph or two, but the rest of the story was worth my persistence.

Not going to lie, that made me laugh out loud.

But in all honesty, that's literally the only think I like about TNY articles... they start so prettily.

I completely agree the articles are just way to self-indulgent when it comes it to length... writing compelling and succinct prose makes a writer great.

Name one great author that wrote succinctly, besides Hemingway, Mark Twain, or Orwell. Or the Spartan poets. /s

thank you. yes. that nails it. it's ridiculous. so many of these 29 paragraph articles could be 3 paragraph articles.

writers paid by the word. doctors paid by the number of treatments.

this is why we can't have nice things.

I now always open tabs for the HN discussions first instead, hoping for a TLDR.... Not just because of New Yorker articles that never get to the point anywhere, but also because of the increasing pest of subscription gates and anti-adblockers...

I just read this NYer article in its entirety. It's brilliant.

As a CS-AI guy and biologist working in pharma (and on the margins of cancer), I found the article's thesis fascinating as a great look into the complexity of mining available bio data and as well as the limits inherent in mining only the signals that already exist.

It's clear now that between the immune system and the body's gene activation networks that regulate each person's biological "soil", we need to 1) look well beyond the cancer itself to how each of us responds to the arrival of cancer cells as well as 2) how therapists can judge the actual risk from cancer, and 3) how we help the immune system to kick cancer's ass.

After reading this piece, I finally bought both of Mukherjee's bestseller books. I already know a fair bit about both topics (cancer, genes), but it's now clear to me that the author's ability to focus my attention on the crux message while telling a great story makes the investment of my time in reading him easily worth the occasional revisit of material I already know.

I've read The Emperor of All Maladies. Overall I liked it a lot, but there are several long stretches with exceptionally boring material about the politics of competing philanthropic groups and things of that nature. While the fundraising side of cancer research is an important topic he spends far too much time on it. And he intersperses with contemporary "patient stories" from his practice that felt more like filler than relevant material. The book did not need to be 600 pages. That said the good parts are really good and it's worth putting up with the rest for them.

Mukherjee is like candy for me. I have no idea what it is but either his style or methodology just sucks me in.

I pretty much always read the entire thing, and I love them for the extensive context. I have the opposite problem these days, where shorter articles without much else going on fail to hold my attention. There are plenty of those out there, but far fewer longform pieces that give me a more complete picture of the topic at hand. I actually just clicked over here from finishing this article[1] which was fairly lengthy, but also informative, relevant, and interesting.

[1] https://www.nytimes.com/2017/09/06/magazine/the-resegregatio...

Yeah, I miss the epic length articles that used to beat the heart of WiReD Magazine too.

The New Yorker is for people interested in food / fashion / personalities / culture. Their readership isn't interested in technical details or technical subjects. So while they occasionally have an article about a technical subject they always fill it with information about the people involved and gloss over the details. That sells magazines among their core readership, but doesn't work well at all for HN. We're not the intended audience.

I do this all the time on HN, and I even did it with the article. For certain web sites, I even look at the HN discussion before looking at the web page is discusses. Even if nobody has written a specific TL;DR of the article, the tone and content of the discussion highlight the meatier parts.

>'“But, over all, would you say the temperature of the water was the key?” I asked. “The water temperature’s a factor. The water chemistry would also have contributed.” “So a combination of the temperature and the salinity?” “But also the calcium content. That’s absolutely important.” I added that to my list of drivers: “Temperature, salinity, calcium . . .”'

Of course... what is more important to determining the volume of a box? Is the height a key variable? Sure, but you also need to know the width. Not only that but also the height.

Surely irrelevant things like the color of the box, or material it is made of, will also have non-zero correlations with the volume. This is one reason why the NHST strategy of finding isolated "effects" will never lead to an "equation for cancer", but is very good at generating large numbers of red herrings.

You need a model of the process of carcinogenesis, and then to collect data allowing you to estimate (at least get some decent upper/lower bounds on) the parameters of the model (mutation rates, division rates, number of cells of each type, % aberrant cells that get cleared by the immune system, % that commit apoptosis, etc).

Armitage and Doll started this way back in the 1950s and had quite an effect on the current cancer paradigm (slow accumulation of genetic errors in a single cell lineage -> cancer), but since then it has been only a tiny minority of cancer researchers working on the actual problem.

>Malignancy wasn’t simply about cells spreading; it was also about staying—and flourishing—once they had done so.

>In the field of oncology, “holistic” has become a patchouli-scented catchall for untested folk remedies: raspberry-leaf tea and juice cleanses.

why some "juices", or more specifically just plain baking soda in a glass of drinking water, may actually help - at least for mice it doubled survival chances here https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2834485/figure/...

(it is pretty logical - metastatic invasion is based on acidic dissolution of ECM (which is collagen mostly) and cancer tumor local environment is acidic as a result of increased glycolysis and the resulting increased lactate production, so increasing the pH of the tumor environment naturally impedes metastatic invasion)

This article reminds me of all the things people talk about when they try and approach cell signaling from a systems approach. Modeling biological systems as an actual system probably does make sense in the long run. The problem is that it's far, far harder to study and generate that model.

And it's extremely hard to sell biologists on the idea that your model just happens to capture sufficient signal to be useful or to accomplish more than a simple regression line on one or two known-to-be-causal factors. But I do think the importance of context has become inescapable and any therapeutic approach that overlooks it will fail to deliver needed efficacy.

Personally, I believe the day of telling the patient, "Sorry, but since none of the existing drugs will work for you, we can't help further" -- that era of medicine is past. Using deep drills through the maze of each patient's relevant / causal / contextual data, it's nigh time for us to dig deeper and do better.

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