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Ballet as full body workout

This clip from the Royal Ballet’s rehearsal of The Rite of Spring looks exhausting.  Monica Mason directs Artist Claudia Dean in the dance of the Chosen One. The choreography is by Kenneth McMillan but I see a lot of Nijinsky poses in this piece, especially with the arms straight out as if the dancer was plucked from the side of a Grecian urn.

Dean was picked for this role because of her ability to jump. She says she cross trains for this dance. I can see why you would have to. At the end of the day, I’d be completely knackered.

Anyway, spring is only 22 days away. It can’t come soon enough.

Fox News viewers are perfectly OK with being lied to; they really just hate non-conservatives

In the morning, he’ll be talking in word salads and punching the unemployed.

That’s really what this comes down to.

According to Gawker, Fox News doesn’t feel it needs to defend Bill O’Reilly anymore:

Update, 5:40 p.m.: Two hours after this post was published, Fox provided the following statement to Mediaite (without addressing the substance of the Media Matters report):

Bill O’Reilly has already addressed several claims leveled against him. This is nothing more than an orchestrated campaign by far left advocates Mother Jones and Media Matters. Responding to the unproven accusation du jour has become an exercise in futility. FOX News maintains its staunch support of O’Reilly, who is no stranger to calculated onslaughts.

Bill has addressed the lies about the Falklands, although there are new lies now about his involvement in the JFK assassination conspiracy. Plus, he claims he witnessed nuns being executed in El Salvador when records show he wasn’t even in the country at the time the events happened.

It’s more important to fling poo at those institutions that are trying to keep Bill O’Reilly honest than to force Bill O’Reilly to actually be honest.

But no matter. I never expected Fox would censure O’Reilly in the same way that NBC disciplined Brian Williams. Part of this is because NBC still clings tenaciously to the concept of being a news organization while Fox News does not.

Come to think of it, wasn’t it Fox News that won a Supreme Court victory several years back that made it Ok for it to lie? Yeah, it was something like, it doesn’t have to tell the truth. There’s nothing in the constitution that says that a media outlet that purports to report the news has to do so honestly or something to that effect. They all might lie but Fox News takes pride in being audaciously dishonest and getting away with it. It’s that audacity to flout the rules, while demanding everyone else adhere to some purity test, that I suspect is the real attraction for the Fox News viewer. It’s the thrill of making everyone else march to Fox’s drummer.

So, it doesn’t really matter what you throw at Bill O’Reilly, Fox is going to stand by him and they’ll pretend that they have addressed all of the accusations adequately and it’s only the left wing media and enemies that are going for Bill.

But it would be wrong to assume that it’s only MMFA or some radical Decembrist faction of a commie left that wants to bring down Bill O’Reilly and Fox News. Hey, I didn’t vote for Obama-twice! I have been called a racist for not sticking with my tribe when what *I* saw in 2008 was an inexperienced but ruthlessly ambitious opportunist hired to carry out the wishes of the financial services industry that was about to lose its shirt in the worst financial crisis since the 1930’s. My objection to Obama is he is really a country club moderately conservative Republican and he’s governed like one. So, how does the Fox News conditioned viewer handle people like me? I’ve seen the confusion in their eyes when they try to reconcile what they’ve been told with the fact that I am standing there saying I am a liberal who loathes Obama for purely non-racial reasons. It’s like watching Fembots about to explode. They can’t quite grasp it.

(Now that I think of it, I’ve seen some lefties have the same reaction. There’s a nugget of a problem there that the left has not accepted about its own side.)

No, the fighters against Fox extend beyond the usual suspects. It includes anyone who has to sit with brain dead relatives at dinner who have become mean spirited, crotchety, vile, bigots robotically spitting ultra-conservative nonsense in a garbled illogical word salad. Those people go out and vote, because they’re angry, and they don’t sound like they know what they’re supposed to be angry about. Nothing they say makes any damn sense. And it’s very difficult to want to be around them because they behave as if they’ve had a lobotomy. You can’t construct a logical argument with people who have had conditioned responses and thought-stopping reactions to anything you say. Seriously, they can contradict themselves several times in the same sentence and never even realize it. They are operating in pure fearful, emotional, enraged mode, thinking there is a child molester behind the potted plants and that the Muslims are going to kill them in their beds while they unknowingly support the most regressive economic theories the conservative right has to offer because God, or something.

The John Birch Society ain’t got nothing on Bill O’Reilly and Fox News. John Birch was fringe until Fox came along. And Bill has a single talent. He is extremely effective at turning perfectly ordinary people into obnoxious right wing Archie Bunker types who actively celebrate their willful ignorance and call themselves holy. That is a gift to the ultra wealthy. The rich and powerful will fight tooth and nail to protect Bill O’Reilly. He is their golden goose. His distortions and ability to provoke irrational anger keeps his audience in a state of poised suspension, ready to hurl themselves like zombies at the first fresh brains O’Reilly shakes in front of them. As informed citizens, they’re useless to the rest of us and, in most cases, actively harm their families and friends by their inability to see when they’ve been flimflammed. It’s pure gold to the small evil group that runs the world and to whom no one we know belongs.

The true Fox News watcher will joyfully accept their role as a minion to the corrupt. They will tell you that there is nothing you can do to change a corrupt system except pray for the second coming. How this justifies joining the army of corruption, I’ll never understand, unless it is to bask in the glory of being on the side of the powerful, especially those corrupt powerful who masquerade as godly. It sort of reminds me of the people who are flocking to the middle east to join ISIS. We all know ISIS is brutal, totalitarian and mindless but some people are attracted to that. Fox News only beheads people metaphorically. Its enemies still suffer the same fate, and the meanness, misogyny and cruelty is still there, but there’s less blood.

Oh sure, things were different when the typical Fox News view was younger. People were more helpful, there was a real sense of community, labor was stronger and public education was better and well funded. But they seem incapable of figuring out how we got to this place where we have gone back to the economic conditions that lead to the Great Depression. They do not see the role of Fox News in the process.

And that’s just the way Fox likes it. So, no need to draw further attention to itself. Defending Bill is just going to make it look like it needs to defend Bill and that’s not the kind of face Fox wants to present to the world. That shows a sense of vulnerability. The Fox News viewer doesn’t want to feel vulnerable. Fox wants to look impregnable, a mighty fortress against the commie left even if it’s more like a prison for the gullible.

Ok, we all know it. There are things we can not change in this world. So we must continually chant the serenity prayer as we watch Fox, and media like it, tear the fabric of our country apart. There’s nothing we can do about Fox News and it’s ability to lie, distort, mislead and destroy. We can only wait until the vulnerable reduce in numbers and the younger, less religiously motivated internet era demographic matures. Fox News will just become another niche channel for the unhinged. Then we will start the long, hard slog to recovery, reversing all the crap it has flung at us.

Blarney Bill O’Reilly

Bill O’Reilly lies about his war stories, just like Brian Williams. Actually, he’s worse than Williams because CBS has footage of what happened and who was there and Bill O’Reilly was no hero.

Butcha know, the people who watch Bill O’Reilly aren’t interested in the truth. They are interested in being flattered by a tall guy who went to Harvard. He’s the church lady’s crush. She will stand by her man no matter what he does or how much he lies. He’s the authority figure they crave even while they protest too much that they don’t need a man.

At least now, we can dispense with the pretense that he’s journalist with any kind of integrity. This is a shock to no one. Fox News is going to rally around his flag. He won’t get disciplined or fired. No, that’s for the liberal media that’s trying to take him down. Fox News operates under a different set of standards. And that’s fine as long as everyone is in on the joke.

Stupid Drug Discovery Advice, $2 Billion dollar prizes and Antibiotics.

The NYTimes posted a column from Ezekiel Emmanuel, Vice Provost at the University of Pennsylvania, on the subject of antibiotic resistance and how to encourage more companies to develop antibiotics. He wants to reward the successful researchers with a $2B prize. BUT, he says: “no payment for research that fizzles. Researchers win only with an approved product.” Oh, and he says that the bragging rights would be great! Yes! That would make the starvation diet so much more meaningful. Funny, we don’t expect any other employed person to live on nothing for close to a decade on something that might not pan out or may need to be sold to a big company to keep our little startup from declaring bankruptcy.

He’s identified the problem. Companies don’t want to invest a ton of money in a treatment that’s only going to be used for a short period of time. By the way, that’s the new business model. Back in the olden days when I first started working in pharma, we had all kinds of therapeutic areas to choose from. But during the mergers and acquisition years during the 90’s to the mid Naughties, those therapeutic areas had to be eliminated to make room for shareholder value. Ok, I don’t want to get into this too deeply because it’s territory I’ve covered before but I might touch on it towards the end.

As I’ve discussed before, the antibiotic shortage problem was bound to come up. Bacteria mutate. It’s what they do. They are masters of natural selection, if you believe in evolution. If you don’t, an infection might just be one of those mysterious things that happen to people who do not pray enough. See, there’s another topic I don’t want to get into right now.

Here’s the problem: as Derek Lowe at In the Pipeline has pointed out, the molecule space around the typical antibiotic therapy has been exhausted. There are other targets than beta lactamases but they are not low hanging fruit anymore. There are new mechanisms that we have to learn, like quorum sensing for example.

When a new target is identified, it takes many years for that project to reach any semblance of what Silicon Valley industries would call fruition. In fact, the most promising project I was ever on started back in 2006. I don’t know what its status is at this point. It was promising enough that I think there was a drug there. But I’m betting it is still in the early phases of clinical development even now. That’s almost 10 years later.

This is the problem that a $2B prize does not solve. You can’t incentivize research like this. The reason is that the money has to be spent up front. That is the problem that almost all R&D, both academic and industrial, is grappling with right now. The scientists have to be hired and paid, the reagents have to be ordered and paid, the equipment has to be bought and maintained, and the people funding all of this have to have the patience of saints while the scientists churn through iteration of iteration of assays, high throughput screening, medicinal chemistry and drug design, pharmacology, ADME/T optimization and scale up. It takes a long time and it’s expensive. What will the R&D staff live on in the meantime? What are they supposed to use to get their work done? It’s like marooning a bunch of scientists on a desert island and telling them to come up with a drug using sand and chewing gum. Or hitting their “friends, families and fools” up for early funding as the American Chemical Society encouraged us to do when we first got laid off.

There are ways to reduce costs. For example, don’t make everyone live in Cambridge, MA or San Francisco. That right there would save the funding agent a bunch o’cash. Move people back to the mid-west from whence they came 25 years ago. You know, those places like Kalamazoo and Cinncinatti or even Pittsburgh. It’s cheap to live here and there is such a thing called the internet. We might even use web meetings to interact with each other. Wow, I believe I even used to do that with my colleagues in France and Germany once upon a time about 5 years ago! Let’s face it, there is not a big melting pot of exchange going on in Cambridge when everyone has signed confidentiality agreements. The only reasons to relocate there is 1.) it allows the MBAs who were once bio majors but sold out for the big bucks to live vicariously and 2.) I have absolutely no idea. No one I know actually wants to relocate to Cambridge. But I’m getting off topic.

My point is that the investment has to be made up front. It doesn’t do much good if it comes afterwards, especially if there are side effects and litigation that need to be covered. This is the case with all drugs. To get the drug discovery mechanism rolling, the fuel has to come early in the process and be committed to seeing the process through. That’s what we don’t have anymore. Once the drug is discovered and marketed, the profits can be reinvested in the next drug. That’s what used to happen.

Note that in this scenario, it is the R&D professionals who are important, not marketing, finance or shareholders. The researchers aren’t in it for the big bucks. You will have to take my word for this. Almost no one I ever worked with went into chemistry or biology with the intention of becoming an entrepreneur or cashing in big on their first blockbuster. Pushing us to become what we are not may be hampering the drug discovery process. Do you want someone in the lab making discoveries or do you want that person negotiating with contractors and venture capitalists? You can’t have both. There may be a few people who have the energy for both but they are exceedingly rare or exceptionally lucky.

And here is where I revisit the cause for why antibiotics, and other therapeutic areas like CNS, Cardiovascular and reproductive health, have been abandoned. It was the frenzy to merge that caused this to happen. All of those mid-size labs were joined and then a purging went on when the executive bonus class and shareholders took their cut. They created “efficiencies” by cutting out R&D and imposing cost cutting measures on research. They made research departments compete with outside vendors for services. They destroyed the collaboration between departments and exacerbated the complexity of the problem to be solved. They looked at their post-merger portfolios and said, “Antibiotics are not chronic therapies. We can’t make money on those. Let’s cut them.”. That’s what happened, Mr. Vice Provost.

And THEN, to top it all off, the mergers and acquisitors decided that academic researchers were so much less expensive. Why not scrap the R&D group altogether and let grad students do it?? Not that I have a problem with grad students but realistically, you have to do industrial research and follow a project from start to finish (if that’s possible without being interrupted by a merger or layoff) before you actually “get it”. Solving a drug discovery problem is one of the most difficult problems in science. Pretending it can be done on the cheap or rewarded afterwards when the vulture capitalists are going to demand their cut is not really understanding the nature of the problem.

A $2B prize is not a solution. It is the definition of success from a country that thinks the only reward is money. THAT is the bigger problem that we have not solved and the reason why new antibiotics are in short supply.

State of The Confluence and Request for Input

At first I was like…

Yesterday, I locked myself out of my house. Yup, just pure stupidity. I picked up the wrong set of keys as I was leaving and checked them just as the door went *click!* behind me. Getting back in was painful, as in, painful to the money supply. I’m still in job search mode. I HAVE a job, but it is a bad one. That is to say, the money is seriously low, the hours ridiculous and the benefits close to non-existent.

Fortunately, I have some professionals helping me find a new job. Unfortunately, it is taking a lot, LOT longer than I had anticipated, even with my “worst case scenario” pre-planning. I mean, this is so long, drawn out and fruitless that I am beginning to think that I will be trapped in this hellish job forever. My career counselors assure me that this is not the case and I must persevere but even they must be getting worn out.

and then…

Fortunately, I own my own home! Yup, free and clear. All mine, mine, mine! It’s nice and comfy and I had the money when I bought it to make some major repairs. (It was foreclosed for about a year) Unfortunately, I have property taxes, and while they are less than half of what I paid in NJ, they’re still significant and at this moment, I will have to dip into some previously off limit funds to pay for them.

So, locking myself out of the house yesterday was not on my “things to do with my money this month” list. What I had actually planned was replacing my upstairs toilet before the crack in the tank that is being held together with epoxy finally gives on me. Ahhh, the joys of home ownership. Why didn’t I buy a new toilet when I moved in???

Anyway, this is a long winded way of saying that I am contemplating a fundraiser, like just about every other blog in the world. If you have been a long time reader of this blog, chime in and tell me whether you think this would go over like a lead balloon or not. I don’t usually ask for money except for special events, like when I asked for train fare to cover the Occupy Wall Street protests. Also, Katiebird has been nagging me to rewrite the website for the upcoming presidential campaign. I think this would be a good idea and I have some things I would like to add to this here place. A fundraiser would allow me to pay my property taxes as well as invest in some server time, Dreamweaver licenses and other training materials. If you have an opinion on what you would like to see at a new Confluence, put it in the comments below.

Having the money to pay my taxes and train myself to develop a high end web site would give me a great deal of peace of mind as well as some potentially marketable skills. I’ve been using WordPress and can install and maintain CMS’s but I feel the need to work on design skills and coding. Katiebird has been very encouraging in this respect and she says i can do it so I believe her.

What I should have done, or “in emergency, break glass”

Anyway, thanks to all of you for your support over the last seven years. We have had over 12 million comments. Can you believe it? I never thought anything I wrote would get that much attention. And really, attention was not what I was looking for. The purpose of this blog was to be a refuge from the consensus reality that was being manipulated during the 2008 presidential primary and general campaign. I’d like to keep that focus for the upcoming presidential campaign. That is, I’d like to cover topics in a way that is true to the liberal spirit of this blog but remains free of the dogma that plagues so much of the left.

I’ve been considering starting a regular podcast featuring guest interviews. Some topics I would like to cover are the problems of the pharmaceutical industry, employment and labor issues, infrastructure (net neutrality, mass transit), the impact of religion on our current culture, GLBT and feminism issues, and, of course, a discussion of the candidates and their policies. If this sounds interesting to you, or something you could support, let me know in the comments below.

Finally, there is a “Tip Jar” in the upper left hand corner of this blog. It goes to the PayPal account for this blog. I don’t check it very often because we don’t do fund raisers very often. But if you feel so inclined, or just want to help defray the costs of a locksmith, just hit that link. Today’s date is 2/22/15. May I suggest a contribution in the form of a multiple of $2.22.

Thanks!

#Pharma: Gobstopping Greed

Researchers are mostly a non-ideological lot. I sometimes wonder if we had been a little more ideological whether we would have kept our jobs but that’s for another post, someday down the road.

But some “capitalists” take greed to such an unbelievable level that even we are left almost completely speechless by the sheer audacity and (dare I say it?) evil.

Take the case of Martin Shkreli. I’ll let Derek Lowe at In the Pipeline tell this story:

He went on to form Turing Pharmaceuticals, whose business plan, by contrast, was (at least at first) to find some small-market drugs, buy them from their obscure producers, and raise their prices into geosynchronous orbit. As reported here by Adam Feuerstein, his first target was praziquantel (Biltricide), the antihelmenthic made by Bayer:

Shkreli is negotiating with the German drug giant Bayer to purchase marketing rights to Biltricide, a drug used to treat infections caused by worm-like parasites called liver flukes. A course of treatment with Biltricide typically involves taking six to nine pills in a single day and costs around $100. 

If Shkreli acquires Biltricide from Bayer, he plans to raise the price of the drug to $100,000 for a single-day course of treatment, according to people briefed on Turing’s business plans. No other changes or improvements to the drug will be made by Turing. The extra revenue generated by Biltricide is expected to earn Turing a fast profit for its investors and help defray the cost of developing other, experimental drugs, sources said.

We shouldn’t be surprised by this. This is just plain supply and demand economics. The number of small molecule drugs has fallen precipitously since the salad days of the 90’s. That means there are fewer blockbuster drugs to make money on and fewer drugs overall getting approved. Lowe reported a few weeks ago that the number of FDA approvals had gone up in 2014 but that represents work that happened about a decade earlier and now that we’ve been furloughed for the sake of “shareholder value”, that might be a high tide mark. The shift is from small molecule drugs to biologicals. This is not necessarily a bad thing but it does turn a whole generation of researchers into the equivalent of steelworkers while vastly reducing the output of small molecule drugs.

The consequence of not discovering new small molecule drugs is that even though they are going off patent and should be cheaper, there are no “new and improved” drugs to replace most of them. So, when they become generic, that’s it. There is no higher end model to compete with. Therefore, the cost of generics has to increase. I mean, where else are you going to go?

Now, in comes someone like Shkreli who sees a vast landscape of obscure generic drugs that could get a new life through retesting or new indications. He scoops up what he can and, without any R&D, he can cash in hugely. He still has to account to the FDA on production and quality standards. This is not insignificant. Think about what happened to the Today Sponge. But in general, this is a pure profit business model on the backs of ordinary people who may need these previously cheap medications. He is the ultimate MBA.

Give that man a bonus.

Believe it or not, researchers are not heartless tools of the pharmaceutical industry. We’re also consumers, and some of us are rather poor now that we’ve been kicked out of the field. R&D is incredibly expensive. Don’t let lefties tell you differently. And companies do have a right to recoup those costs and make a profit- that they can plough back into R&D (note: this was the old business model). But Shkreli’s model is shocking. One of Derek’s commenters summed it up nicely:

I wish people would learn to distinguish two types of capitalism:

1. Social capitalism: Create long-term value for customers with innovation, and then distribute the value created among all contributing stakeholders, including customers, employees, suppliers, distributors, payers & providers, tax payers, and yes, also managers and shareholders.

2. Anti-social / psychopathic capitalism (aka greed): Screw everone and take value from others while destroying it, in order to make a quick profit for management and shareholders.

There is far too much of the latter, and its rapidly destroying society as we know it. And ironically, managers and shareholders will also pay the price, ultimately, as part of the same broken society and economy.

I swear I didn’t write that.

In another sign of the times, I am starting to see some slight indications that the industry is falling out of love with academic research. A couple of postings I’ve seen for drug design support are specifically requesting industrial experience and one went so far as to say that academic modelers are not preferred. (And oh my golly, what a difference industrial experience makes, It really is amazing.) Of course, a PhD is still maniacally important so the wait continues…

It’s -2 Fahrenheit. Time to put the baby outside for a nap.

In Finland.

It’s tradition there to stick the kid outside in the pram for a brisk 2-3 hour nap in subzero temps. Check out this BBC Soundcloud for all the facts.

Of course, if you are in Finland, you will have received a Baby Box when your kid was born, containing snowsuit, mittens, hats, sleeping bag, etc, so you can safely leave it outside without worrying about it turning into a totcicle.

Here are the contents of a typical official Finnish Baby Box that every Finnish kid gets just for being born. Yes! Even the rich babies get them. They have no idea whether they’re going to grow up to be parasites on society.

article

Americans are cautioned not to do this. The neighbors will report you to CPS.

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