Checkpoint inhibitors (which are the primary driver of improved cancer treatment over the last 15 years and generate > $50B/year in sales) generally don't look very good preclinically. Even their clinical data can be hard to interpret prior to a large scale trial, which led to them almost being shelved.

The catch here is that only two targets (PD(L)-1 and CTLA-4) turned out to work well in humans. All of the other immunotherapies that looked mediocre preclinically turned out to also be mediocre or entirely ineffective in humans.

This is an oft-refuted trope that does harm to patients. Numerous randomized phase 3 studies show meaningful survival advantages for modern treatments.

This isn’t really an issue in biotech since companies don’t have any revenue until late in their lives. Ie if I’m doing discovery work for a drug candidate today, it won’t generate revenue for 7+ years. So when if I have to amortize those costs over 5 years, that process will be complete by the time the project generates revenue.

I can’t speak to the pharma side as much, but since the 174 issue is most painful for companies with liquidity issues, I doubt it has a huge impact on them.

Does this article actually provide evidence for the headline claim?

Forested is not wilderness. Most forests have lots of roads, power lines running through them, etc. You're just trying to redefine a defined term.

Prior to 1946 there was no wilderness as the BLM didn't exist to define it as such.

Or they don't own the definition.

Congress owns the definition via the Wilderness Act, which are tracts of land with no human presence or impact.

Perhaps that will give you context in this discussion.

I don’t think he was ever offered a plea deal

I feel in the federal system, they'll offer pleas to everyone under you to get to you. But once they've got to you, you're the target, and there's little motivation to let you plead out.

Perhaps the only one (potentially, and not trying to derail this) might be Donald Trump (but I also have a hard time seeing him accepting a plea deal on the current raft of bullshit around him).

> Perhaps the only one (potentially, and not trying to derail this) might be Donald Trump (but I also have a hard time seeing him accepting a plea deal on the current raft of bullshit around him).

(Not sure what “current raft of bullshit around him implies” but derail ahead)

Trump is no stranger to settling cases and making deals with prosecutors(1)(2) but all cases he’s facing now having such face-losing punishments even on plea that he can’t afford to take any.

(1) https://www.reuters.com/article/us-trump-lawsuit-idUSKBN13D1...

(2) https://www.newyorker.com/news/news-desk/how-ivanka-trump-an...

My understanding is that he was, in fact, not offered a plea deal.

I wonder if a valid option could have been to plea guilty and throw himself at the mercy of the court to receive a lesser sentence.

Does that work? I mean, he could plea guilty just to save some lawyer expense for his parents but I don't think he had a better choice than going for a hail mary.

I think you actually do get credit for pleading guilty in the sentencing guidelines.

Western European countries are around 1 per 100,000 population per year. Seattle is 15x that rate based on those statistics. Seems bad.

Maybe my statement was a bit too broad. What I was trying to communicate was that statistically, the chance you get murdered in Seattle is still extremely low despite the headline that seems to be spreading fear.

And now I’m having the same experience

The comment you're responding to is incorrect. SBV was blown up by 10 year US bonds (ironically the quintessential safe investment):

https://www.npr.org/2023/03/19/1164531413/bank-fail-how-gove...

This is entirely correct.