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    • Interview Part 2: Politics Thru Climate Change
      This second excerpt from my interview is more interesting and longer. This is the second clip from my interview with Ian Welsh (Ian blogs at ianwelsh.net). For this segment, we went on a wild ride discussing the big picture mess that is US politics and society more broadly. I asked Ian what might happen if […]
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He’s not demented. He’s just not very smart.

Trump is like a shark. Single minded. Driven to consume and rip to shreds for his own survival.

But you don’t need to be smart to do that. I don’t mean that you need a degree to be smart. I have met plenty of people with degrees that aren’t very smart. Everyone has deficits. I suck at math. It’s always been a struggle for me. I can’t leave home without my calculator.

No, the degree thing is not the problem. After all, Trump has a degree. Anyone can get one provided someone is willing to pay for it for you. Look at Lori Laughlin’s daughters. One of them didn’t even want to go to college and yet her parents lied her way into USC. A little palm greasing got her there. Same with Trump.

But I’m guessing that if Laughlin’s daughters were interested in college, they would have been able to get into one without much trouble. They didn’t have to go to USC.

The thing about Trump is he’s dangerously not smart. We’ve all watched him in the last three years. At first, his policies were just thuggish and mean, while the economy hummed along without much help. We didn’t see how unsmart he really was.

But little by little, his unsmartness has been exposed. All it took was a time and Trump’s inability to refrain from emoting all the time.

He doesn’t seem to know how unsmart he is. If he knew, he might have stepped aside whenever the science of coronavirus came up. He could have said… nothing. That would have been better. Nothing would have been refreshing. A slightly smarter guy would have said, “this is not my lane so I’m going to let my experts craft the proper strategy and I’ll do everything I can to implement their recommendations. Don’t worry. Our best and brightest will lead.” Why didn’t one of his advisors tell him to do that?? Probably because he is not bright enough to appoint the right advisors.

It’s gotten worse. His shark like behavior is getting in the way of making good decisions.

Virginia Heffernan wrote a review of Mary Trump’s book in the LA Times yesterday and pulled out these quotes that explain the phenomenon of Donald Trump:

He’s not demented. He’s not crazy. He’s just had someone pay his way and cover his mental deficiencies. I’m not sure what that deficiency is but it’s staring us in the face.

He’s not going to get smarter. It’s incredible that we, the greatest nation in the world, have managed to install a man so wholly unfit to lead or even think his way through this. Every move he makes is intended for short term fluffing of Donald Trump to the long term detriment of Donald Trump. He’s not even smart enough to save himself.

About Remdesivir

This is another installment of pharma related posts you guys will probably not read but I thought it was important enough to bring up.

Gilead pharmaceuticals presented findings from a limited study on severely ill Coronavirus patients using its anti-viral drug Remdesivir. The study shows that Remdesivir shows modest activity, reducing death rates by 62%. It’s not as impressive as it sounds but it’s not nuthin’.

For those of you who are mildly curious, this is the structure of Remdesivir:

Remdesivir’s modus operandi probably involves interfering with RNA in some way. Coronavirus is a retrovirus, meaning it only carries its RNA around with it for efficiency’s sake. It makes your cells do all the heavy lifting. The scaffold structure of this drug looks like a nucleotide (heterocycle A, sugar B, phosphate C). There are additional bits and pieces added to the scaffold that likely adds to its activity.

In regular non-Covid R&D, we would never do drug discovery this way. But this is an emergency. In regular time, we would identify a target protein of the virus and do high throughput screening (HTS) of a compound library against that target protein. The HTS would identify potential hits and the cheminformaticists and drug designers would mine bigger virtual compound libraries for compounds that look similar to it. Then we would go through a zillion iterations of optimizations with a project team with the biologists sucking up most of the meeting time talking about detergents and showing gels that are indistinguishable from last week’s gels. And all of that work is very important. I’m not trying to minimize it. But it does take a lot of time. It’s like everyone starting off blind and gradually seeing what they’re dealing with.

Ain’t nobody got time for that.

What we’ve done here is a little more direct. We’ve started with known anti-viral meds, given them to patients and seen if any of them helped. The good news is Remdesivir helps. The bad news is it’s like giving Tylenol to someone who has had major surgery. I mean, sure, it’s better than nothing but it’s not a cure. The activity of this type of drug needs to be optimized.

Would *I* take it if I had a severe case of Covid? Absolutely. I wouldn’t expect a miracle but it’s a hell of a lot better than hydroxychloroquine, which on top of being utterly ineffective is more likely to kill you. I’m putting that in my directives. Dexamethasone and Remdesivir, yes; hydroxychloroquine, no, non, Nyet

Anyway, back to the good news. Now that we know that this class of drugs works, we can mine the database directly and pass it on to medicinal chemists who will make slight modifications that can be tested in vitro (“in glass”, basically, a test that doesn’t require a live animal). If they look promising, they can be tested in vivo (in a live animal).

Will they give it straight to humans? Depends on what can be mined from the databases. If the mining shows up something that has already been tested for something else and has been found relatively non-toxic and easily available to the body, maybe? Well, hydroxychloroquine was hyped and fast tracked with less evidence so maybe. Otherwise, let’s just hope that med chem can crank out some compounds and get them tested.

So, get your hopes up but not too much over this announcement. I know that we are all breathlessly waiting for someone to announce a cure so things can get back to normal. That’s the way the media presents these things but the reality is much more realer. It’s going to take awhile.

In the meantime, cover your freakin’ face.

For more in-depth analysis on stuff like this, see Derek Lowe’s In The Pipeline blog.