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    • A word on Abenomics, QE and doing Stimulus right
      Quantitative Easing, to put it simply, no matter what form you do it in, is only marginally effective. Most of the money goes to the rich, you may or may not get a technical win in GDP, and in many cases the money may flow out of the country. If you want to improve the [...]
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Thursday: Here it comes

UpdateII: If you’re an ex-pharma scientist who has been laid off recently (and who in central NJ isn’t?) you really have to read this post on In the Pipeline about what Pharmaceutical CEOs really think of you.  It’s about Chris Viehbacher of Sanofi (waving “Hi!” to all the ex-sanofi people).  I’m past the stage where this kind of thing strikes me as anything but unintentional humor.  But people who actually care about preserving what’s left of research in this country and how long and hard researchers work only to be misused and discarded by the bonus class, should take note.  Pretty soon, all you’re going to be able to buy are overpriced generics.  No new drug entities will be coming out of drug discovery because there won’t *be* any drug discovery.  No one will want to work under these conditions.  This is the clearest explanation of how the bonus class wants to turn professionals into precariats that I’ve ever read and it’s coming to a workplace near you.

Update: Andrew Breitbart is dead.  He was 43.  Fox News is reporting that he died of natural causes but there’s nothing natural about dying at 43.  I’m going with apoplexy.  This must be very unexpected and sad for his family.  Or maybe not.  Rageaholics tend to be difficult.  Maybe his blood vessels just refused to cooperate any longer.  Let this be a lesson to Glenn Beck.

The Republicans have us in a vise and now they’re going to start turning the screws.  The NY Times reports today that speculators are going to push gas prices to over $5/gallon this summer. That’s going to wreck further havoc on the economy:

HOUSTON — Gasoline for $5 a gallon? The possibility is hardly far-fetched.

With no clear end to tensions withIran and Syria and rising demand from countries like China, gas prices are already at record highs for the winter months — averaging $4.32 in California and $3.73 a gallon nationally on Wednesday, according to AAA’s Daily Fuel Gauge Report. As summer approaches, demand for gasoline rises, typically pushing prices up around 20 cents a gallon.

And gas prices could rise another 50 cents a gallon or more, analysts say, if the diplomatic and economic standoff over Iran’s nuclear ambitions escalates into military conflict or there is some other major supply disruption.

“If we get some kind of explosion — like an Israeli attack or some local Iranian revolutionary guard decides to take matters in his own hands and attacks a tanker — than we’d see oil prices push up 20 to 25 percent higher and another 50 cents a gallon at the pump,” said Michael C. Lynch, president of Strategic Energy and Economic Research.

For the typical driver who pumps 60 gallons a month of regular unleaded gasoline, a 50-cent increase in price means an extra expense of $30 a month.

Ooo, can’t you just feel Michael Lynch squirming with delicious anticipation at the prospect of explosions in the Strait of Hormuz?  Hey, kiddies, do you remember the first oil crisis in the 70s when people were stealing gas from each others cars and gas was rationed?  Remember the line of cars around the block to the gas station early in the morning?  Remember when Daylight Savings Time was extended into the winter and we trudged to school in the snow in the dark?  Were those good times or what?

Now, before people go off half cocked about Iran, understand that this has absolutely nothing to do with Iran.  Iran is just an excuse to push up gas prices.  The oilmen need some kind of cover for the politically motivated cruelty they’re about to impose.  They’re probably counting on the left to take the bait and have a shit fit over Iran, because lefties don’t think this out any better than average Americans who just want to get to work without spending half of the grocery budget.  The average American doesn’t have time to investigate all of the causes of the spike in gas prices that is severely impacting their lives.  Who are they going to believe anyway?  You can’t trust the NY Times.  Remember what they did on the Iraq War.  No, it’s just going to look bad for Obama.  Why can’t he *do* something?

But gas is just part of it.  There are all of the downstream industries that rely on transportation.  The price of everything is going to go up, particularly food.  And since the Lesser Depression started, there are a lot more people struggling on smaller incomes and significantly smaller salaries.  It’s going to hurt.

What *is* Obama going to do?  He wasn’t particularly good at dealing with the bankers when they threatened domestic terrorism.  They pretty much got everything they wanted.  We footed the bill to bail them out.  And Obama’s going to be dealing with a Congress that’s going to be campaigning during the summer.  A hostile House isn’t going to want to cooperate by punishing the speculators.  They’ll just point to Iran and Obama when their constituents start screaming about gas prices.  And it will work.

It doesn’t matter who is in charge when the pain is inflicted, it’s going to look bad for them.  Gas prices are just the tip of the iceberg.  You can bet the Republicans have a lot more up their sleeves.  And in a way, you can’t really blame voters for reacting as they will.  Obama is in charge and he’s shown over and over again that he’s completely useless in alleviating misery.  Maybe another president would have handled this differently but we’re stuck with Obama.  And voters are bound to feel like they were betrayed.  They went to the polls in 2008 to elect a Democrat and instead got a guy who’s not really comfortable with party labels.  He’s into conciliation and negotiation with the interested parties in private conference rooms away from the public.  Let’s not get the legislative process involved here.  It’s too messy and real people will get involved.

Just because I can see what the Republicans are up to doesn’t mean I approve of Republicans.  But politics has devolved from public service to a vicious “winner takes all” game.  And in this kind of environment, it doesn’t help that your champion is a guy who has no idea how to play.

As Olympia Snowe suggested yesterday about her retirement, these kinds of maneuvers are meant to corner the opposition:

“Everybody’s got to rethink how we approach legislating and governance in the United States Senate,” Ms. Snowe said in an interview on Wednesday. She shook her head at how “we’ve miniaturized the process in the United States Senate,” no longer allowing lawmakers to shape or change legislation and turning every vote into a take-it-or-leave-it showdown intended to embarrass the opposition.

The target is Obama, the rest of us are collateral damage.  I’m sick of this game and ready to take my ball and go home.

**********************

Speaking of that Times article on Olympia Snowe’s retirement, we have the writers lamenting the demise of the centrists in the Senate:

Ben Nelson of Nebraska, the senator often considered the most conservative Democrat, and Ms. Snowe, seen as the most liberal Republican, will both be gone next year, as will Senator Joseph I. Lieberman of Connecticut, an independent who left a Democratic Party that would not tolerate his pro-Iraq war stand. They follow a parade of centrists out the Senate doors in recent years, including the Democrats Blanche Lincoln and Evan Bayh; a Republican-turned-Democrat, Arlen Specter; and two Republicans-turned-independents, James M. Jeffords and Mr. Chafee.

You know, none of us Democrats or Democrats in Exile are wasting any sleep on the imminent departure of Joe Lieberman, Ben Nelson or recent departure of Blanche Lincoln and Evan Bayh.  They were part of the problem, always trotted out to broker a deal just before some vote where Democrats were expected by their constituency to take a principled stand.  And for years now, Democratic voters have been fighting with their party leadership about what direction the party is going to go.  Arlen Specter is a perfect example of this.  The Democrats would rather back a former Republican than put all of their resources backing the guy who actually won the primary.  A similar thing happened with Hillary in 2008 where she was constantly undermined by her own party apparatus who very clearly had its thumb on the scales for Obama.  The party leadership has a bad habit of punishing the voters who insist on actually, you know, voting. As the years roll on, they’re giving us fewer and fewer reasons to go to the polls.

This health care amendment of Blunts should be an interesting one to watch.  How many Democrats are going to defect to pass it, allowing religious employers to start making exemptions for things they don’t like?  Will the Jehovah’s Witnesses stop covering life saving blood transfusions?  Will Christian Scientists stop covering everything?  What about Scientology’s conscience when it comes to psychology?  Will bipolar, schizophrenic and depressed patients now have to get their engrams expunged in place of prescription drugs?

Blunt’s bill is just another wedge issue.  It’s a way to test the Democrats and separate them from one of their constituent bases.  Will they cave to the religious and screw women or will they uphold the principle of separation of church and state in favor of the hussies?  Stay tuned.

********************

Jay Ackroyd praises Amanda Marcotte’s defense of women’s sexuality even though it is inconsistent with Amanda’s well known toadying for Barack Obama, a man who thinks women should have their menfolk and pastors weigh in on whether or not to have an abortion.  Let’s remember that Amanda passed on the woman in 2008 who was the staunchest defender of women’s rights and sexuality.  Delusions of hipness and loyalty to a party tends to override Amanda’s loyalty to her own sex no matter how much lip service she gives.  If Barack Obama and the Democrats think they can win this election by appealing to the religious and limiting women’s sexuality, they’ll do it in a heartbeat.  If you want progress on defending women’s sexuality from unwanted intrusion, it’s not the Republicans you have to warn people against.  They already know THAT enemy.  It’s the wishy washy, compromising pols of the Democratic party who are our worst enemies.

How much do you want to bet that if Obama signs a bill that includes Blunt’s amendment, Amanda will think up some excuse to deflect anger over Obama’s capitulation to the religionists at the expense of women’s sexuality?  It’s only meaningful if Amanda turns her back on Obama and Democrats like him, which she will never do.  She’s just a cowardly apologist whose actions do not match the power of her prose.

Jay, don’t be a Doormat Democrat like Amanda.

********************

This new Trustus Pharmaceuticals episode would be funnier if job counselors weren’t advising laid off scientists to get certification in all of this trendy MBA nonsense. This is the wave of the future:

Domo ariegato, Bitch!

************************

It has come to my attention that the forces of evil are spreading rumors that this site originated the birther movement.  I don’t particularly care for having to climb the water tower with a bucket of paint in order to defend our honor but nothing could be farther from the truth where birtherism is concerned.  We have always said that birtherism had no basis in reality and that people who insisted that it did were not welcome here.  It’s true.  You can comb through our archives.  We’ve told birthers that they’re wasting their time and that it doesn’t matter if your father was Osama bin Laden himself, if you were born in the US, you have a shot at the Oval Office.  Anyone who says otherwise is cracked.  And anyone who refuses to believe that the birth certificate that Obama produced was sufficient evidence of his natural citizenship without having a similar shit fit about any other politician they don’t like, is a hypocrite.  We asked PUMAs to focus on policies and behaviors that we could actually measure because there was plenty of material to work with in that regard that didn’t require an elaborate conspiracy theory.  Sorry, that’s the way I see it and have always seen it.

By the way, PUMA just means Party Unity My Ass.  It was an expression of disgust with the way the 2008 primaries were conducted to eliminate more than half of the Democratic base from participation.   It wasn’t ultra leftist at this site.  We’ve always said we’re FDR style Democrats in Exile.  I’m not sure there are any ultra leftists left in politics these days. I mean, what is that?  Pol Pot?

I’m betting that there are a lot of Democrats who have watched the last four years of anemic “leadership” from Obama who regret getting on our case in 2008, though they will never admit it in a zillion years.  As the saying goes, “One step ahead makes you a leader, two steps ahead makes you a martyr”.

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85 Responses

  1. I’m really sorry to post this link to DailyKos but, apparently Tom Tomorrow has starting posting his stuff there.

    Take a look at this one…. it’s totally on topic.

  2. In 2008 Barack Obama gave Chris Matthews a thrill down his leg, since then he’s been giving the rest of us the shaft up our butt.

    I guess I won’t be reading Tom Tomorrow, k-bird.

    • Tom Tomorrow may still have his own blog, I believe; where one can see his cartoons without validating the Koswipes.

  3. Cannon has some good stuff up on oil, including the assertion that we are currently exporting more fuel than we are importing. Now that’s a chunk of lava if the admittedly stupid GenPop actually hears of it. Oh, and what Mr. Mike said.

  4. Speculation may have some part in the run up of gas prices, but the real culprit is the devaluation of the dollar through quantitative easing. The dollar is worth a lot less so the price of commodities especially those imported or exported rise. The shakeout of the real value of the dollar has been working itself out for a while and this this probably the earliest and most observable result. The WH will spin this as hard as they can but the real culprit is QE.

    • Funny how it’s only affecting the price of oil. You would think that inflation would be popping up everywhere…

      • According to Reuters 64% of all oil futures contracts are now held by those who can never take delivery of the product, namely speculators.

        The Houston Chronicle had a story last week which said the current working oil rig count in the US is higher than it’s been in almost 40 years and domestic production was higher than it’s been in decades. This when energy demand is at 1998 levels in the US and also down in Europe due to recession. Even China’s demands are not growing wildly now.

        So, hell yes it’s speculation driving up the price of oil with the attendant rise of gasoline prices.

      • well actually it has been, just not so much domestically. World food staple prices have been skyrocketing beginning due to both the now legal speculation on commodities by investment banks (thanks Bill C.) and exacerbated by the devaluation of the dollar globally.

        • Um, the dollar has been devalued for quite a while now. I was in France in 2008 on a business trip and couldn’t buy a damn thing. It’s only looking good these days because the euro is taking a beating.

          I’m not buying it.

        • Agreed and it takes a while for commodity prices to catch up especially if a super power just keeps up the printing of money. Domestic production will be exported unless the US will pay world market prices in rapidly devaluing dollars. More commodities will see sharp rises in prices.

          • At the personal level, it sounds like a good time to start stockpiling semi-storable food.
            Okay-ish Stokely Van Camp sardines are now a dollar a can at the Dollar Store. Not totally fun to eat straight from the can, but good enough to cook with. Aldi’s has some okay-ish sardines called Northern Harvest at 83 cents a can, or so. Brunswick sardines were $1.49/can at K-Mart, last I checked. They are okay to eat straight from the can. For those who “don’t like” sardines, its never too late to learn to like sardines. And that’s just one example, for example.

  5. Re: A. Breitbart’s death…stroke does seems like a good bet. I would not be surprised at all if he had high blood pressure, given his personality. And if his doctor prescribed medicine for it, how well was he complying with treatment?

    • I feel like the only person on the planet who’s never heard of the guy until this morning. I wonder how much else I’m missing?

    • Something as benign sounding as a congenital defect (hole in the heart) can cause a stroke…my husband had one in his 40′s – no high blood pressure.

    • I would be wondering about drugs…. cocaine, poppers, crack. Was he gay? Heart attacks usually occur in morning. Walking in LA? Unheard of from my experience. He did look old for his age. Midnight death makes me wonder about partying with a “friend”. How about needing those little blue pills for extra staying power? Who was he with? It all seems a bit mysterious! I have known several young men who died or nearly died from using stuff to enhance the experience during playtime.

      • Occupy. Wait and see. You heard it here first. It will another conspiracy theory based on nothing but Fox News will eat it up.

      • The tragedy is not in Breitbart’s early death. The tragedy is in his ever having lived. ( Mean-spirited? Why yes, thank you. Monster from the Id can tell you what a mean spirited crasshole I could be over on the Hullabaloo).

        With Breitbart gone, who will the Democratic Officeholders resort to as their excuse for things like defunding ACORN, for firing Shirley Sherrod, etc.? Who will they designate at the next Breitbart who “made them do it”?

        • He might not have been a crasshole in real life. Maybe he just played one on TV. Anyhoo, his kids are probably distressed by it so, I kinda feel badly for them.

          • Well, you’re a nicer person than I am. Good thing I don’t have a blog
            (mwah ha ha ha ha ha ha ha . . . . )

          • Actually, I’m not a very nice person but I do have a soft spot for kids. Unless he was a totally brutalizing bastard at home, they probably don’t deserve to have their father’s memory smeared by a snarky blogger who didn’t even know him.

            OTOH, his crazy rant at those Occupiers did not look staged…

        • Actually, RUR, I bear much mean-spirited crassholery in my soul. I just try to stifle it, because I think it’s what my Invisible Friend who lives in a higher level of existence (not in the sky, that’s only metaphor) would want me to do. ;)

        • back in the mid 90s I dated a young man who was (still is probably) African American and democrat. He worked about two weeks for Acorn before he quit in disgust. He said the organization’s methods were corrupt borderline illegal and immoral. He wanted no part of it.
          I don’t think democrats need a reason to defund Acorn. They should have done it long ago.

          • So in part the organization self-destructed from internal decay? Unfortunate. So the Federal Officeholders might well have had a good longstanding reason to seek an opportunity to defund them?

            One wonders if they were semi-corrupt on purpose or so undeducated and ignorant about internal controls and standards and stuff that they did corrupt things without corrupt intent, or just what?
            I only saw tiny snippets of Dr. Breitbart’s videoshop video of the elderly ACORN office ladies and the O’Keefe Pair. The naivete and total unpreparedness of the elderly ACORN office ladies seemed shocking to me.

            Perhaps the non-corrupt parts of the post-ACORN personnel wreckage can come together into a more internally-controlled ACORN 2.0 .

      • Alibe, I don’t know whether you are gay or not, either way I am finding your comment kind of offensive. I have too many gay friends who are no longer with us, to find that kind of speculation okay.
        Don’t mean any offense. It’s just still so sad to me, some of the most creative talented people I knew and loved gone and I don’t get to grow old with them.

  6. Every time I saw Breitbart’s perpetually angry, sneering visage and his bulging face and neck veins, my uppermost thought was, “There’s a heart attack waiting to happen.” Not at all surprised that it did. His expression was so offensive and his tone so whining that I have no idea what it was he was so angry about.

  7. So who are the tin foil hatters going to blame for Breitbart’s untimely departure? Obama, or are they going to reach back to the Clinton Chronicles?
    I’m betting they’ll go with Clinton; either one will do.

    • Nope, I’m betting the Occupiers are going to get the blame for this one. Obviously, a man this young just doesn’t die spontaneously. There must be a conspiracy by Occupy to take him out. Now, if we can only concoct some crazy theory about how they induced a stroke in him. Or maybe they’ll say that the coroner isn’t releasing all of the evidence and he was secretly poisoned.
      Just wait. This is a gift to the right wing who hate Occupy.

  8. stroke most likely.

  9. Love this:

    • OOOOooo! I <3 Bernie. This is what a feminist looks like. Gosh, I wish he would run for President.

    • I love Bernie Sanders. He should be Hillary’s Veep.

      • If they ran on a no-nonsense no-compromise platform and were ready to lose, I would be prepared to vote for them.

        Especially if they got elected AFTER saying that “bi-partisanship” is just a big bedpan full of unformed stool and there would be no such “reaching-out” nonsense in a Clinton-Sanders Administration.

  10. I remember the Carter-era Seventies. One other thing we did then was pass Federal Interstate Highway speed limits of 55 mile per hour. The reason for that was that as a car or anything else goes faster through the air, the air-resistance to its passage increases at some kind of cube to the speed of its passage. Above 55mph, the air-resistance to a car’s passing through the air goes higher and higher-er
    at a faster and faster-er rate. That “drive 55″ law helped reduce gasoline consumption right there. Sometimes it helps to have an engineer for a President. Here is a little website article about the possibilities of fuel conservation through slowing transport down. People could drive just as much as now, but by driving slower (55 or less) they would spend less gasoline by spending more time . . . to get just the same distance as before.http://www.lowtechmagazine.com/2008/09/speed-energy.html

    Before I read the link to the “this site started the Birther movement” entry, may I just say that the first place I ever saw Birtherism was on Larry Johnson’s “No Quarter” websump; where it was featured Very VEry prominently.

    • I remember when I was in a daily commute “race” before I started working at home. It seemed that drivers took a lot of risks to get home a few minutes early. I figured most of them were going to spend more time on the couch watching TV than they spent on their frantic commute.

  11. My Internet connection totally sucks today. I have to wait forever for each page to load. So, please forgive me for not posting this as a reply to the right comment — I’ll never get there again at this rate (and I’ll be lucky if THIS comment posts)

    Anyway…. I just checked Tom Tomorrow’s blog and his link to that cartoon points to dKos as well. I haven’t checked Salon (he was posting them there for a while) because I just can’t take the stress.

    I’m REALLY sorry he made that move!

    • I remember feeling bad about him leaving Salon. I think the reason he gave is that DailyKos would get him a bigger audience, or something. So his own blog links to DailyKos to let us see his cartoons?

      Well . . . I’ll just wait for his next book or books to get remaindered, and buy them then.

    • Hey, MY internet connection totally sucks today too. I wonder what the heck is going on? Maybe it has something to do with google’s new privacy policy.

      • Maybe, I think with me though, our router just needed to be turned off & on. At least it seems better now.

        That Google thing kind of freaks me out but, what can I do? Even if I switched my email, most messages probably go through their servers (ex: if anyone getting my message has a google account)

        so I don’t know….

        • I wiped my history clean last night. Not sure there’s all that much to worry about. I think it was Jeff Jarvis who said recently that you get an awful lot of free stuff with google and what they ask of you in return is data so they can sell you ads. It seems fair but there’s no need to give them more information than you need to.
          What I worry about is the data miners who know all about you, your likes and dislikes, your socioeconomic status etc, who will craft carefully worded and imaged push ads to persuade you to do things you might not have considered. I was gigantically pissed off at the political ads that were invading YouTube a couple of weeks ago. As a political junky, I knew they were misleading but I’m not so sure that everyone knows that.

  12. U.S. Was Net Oil-Product Exporter for First Time Since 1949

    The U.S. exported more gasoline, diesel and other fuels than it imported in 2011 for the first time since 1949, the Energy Department said.

    Shipments abroad of petroleum products exceeded imports by 439,000 barrels a day, the department said today in the Petroleum Supply Monthly report. In 2010, daily net imports averaged 269,000 barrels. U.S. refiners exported record amounts of gasoline, heating oil and diesel to meet higher global fuel demand while U.S. fuel consumption sank.
    [...]
    Gasoline futures for March delivery on the New York Mercantile Exchange settled at $3.0423 a gallon today, up 11 percent in the past year.

    Interesting information on petroleum product usage and prices around the world.

  13. 25 People Who Think President Obama Killed Andrew Breitbart

    Looks like the Right’s conspiracists are blaming Obama instead of Occupy for Breitbart’s death. At this point anyway.

    • REally? I could have sworn they were going to blame Occupy. Obama wasn’t going to be threatened by Breitbart. But we have Breitbart on video acting like a completely unhinged lunatic at an Occupy event.

  14. Every so often you need the exception for the general rule — here it was, “Only the good die young.”

    • For a proper sendoff, see Matt Taibbi at Rolling Stone. He doesn’t hold back.

      • Good, I’m glad to hear it because watching Donna Brazile on CNN wax -get it,a Brazile wax?-on about what a good guy Brietbart was and how they chatted on the phone for hours made me want to hurl.
        She was more fulsome than Mary Matlin in her praise of him.
        I thought I couldn’t dislike old Cooking with Grease more than I did already, but I can.
        I feel about Brietbart’s death, the way I felt about Barbara Olsen and Christopher Hitchens–I’m sorry that he died and glad that he’s gone.

        • I wonder if Donna Brazile is especially proud and pleased about Breitbart’s instigatory role in getting Shirley Sherrod fired from USDA.

        • I said a long time ago that the one thing which would keep me from voting for a woman candidate would be old Donna B. working for her campaign.

          • I will second that thought. And don’t forget that Donna and Karl Rove were/are such good buddies. Talk about wanting to hurl! I always suspected that the planning between those two had a lot to do with Obumma getting the nomination. Rove had already ruiined the GOP brand so had to have himself a DINO to step in to continue Bush’s insane policies. Voila! Obumma. The third and maybe the fourth term of George W.

      • Wow, just wow — thanks for pointing out Taibbi’s send off, send up, send down.

        • The vile comments on his post are amazing. Matt has guts!

          • While I’m sure someone much smarter will have thought of it, IMHO a much more effective message would be, “This will be what modern political discourse is missing…” followed by some of Mr. Breitbart’s own bile-filled, caustic quotes. Since he was rewarded in life by his mordacity, his quotes certainly shouldn’t be forgotten in his death.

      • I just read Breitbart’s greatest hits and I gotta say that if there was any foul play, it’s going to resemble something out of Murder on the Orient Express. Everyone wanted him dead.

      • Yeah. As a response, “Good! Fuck him!” is pretty succinct.

  15. Gallup Builds The GOP Narrative

    It’s amazing what can be done with a single poll’s results.

  16. Re: the Pipeline…It is quite amazing the way Viehbacher went out of his way to diss all the scientists in his own company. And I’m sure Viehbacher would say that, while there will be no drug discovery in the U.S. in the future, there will still be new drugs. They will just be discovered and developed elsewhere (mostly in the Far East), and the U.S. drug companies will serve as importers, marketers and distributors of those drugs.

    Speaking of innovation and brainstorming innovative ideas, in a start-up it usually happens as part of an in-house “encounter” session. In a university, it usually happens at a lab group meeting or local bar. How does it happen in a large company?

    • It has changed over the years. Back in the olden days, ie the 90s, sometimes it was just a department head in chemistry who saw a publication on a viable target, like PTP1B or BACE. Then they would get biologists onboard. Those should have been easy because the structures were available but the 90s were learning years.
      Nowadays, it’s more systematic. A genomics group proposes a target. Some biologists verify the target and present it to a committee. The committee looks at the data available and decides whether to form a team of biologists, chemists, structural biologists, screeners and pharmacologists to determine whether the target is druggable. Criteria for druggability have to do with selectivity issues, potential tox issues, synthetic issues, that kind of thing. If the target is determined to be druggable, screening can begin. The biologists work with the HTS group to prepare an assay. Meanwhile, biologists also create a couple of validation assays and secondary assays. These are usually cell based where the pathway is known and a desired endpoint determined. The chemists scour the patent literature to see if there’s anything they need to stay clear of and they consult the lawyers for Freedom to Operate. Once they get the go ahead, they may decide to start making R-group changes to any literature compounds to get a feel for the dimensions of the SAR or the binding mode, if available. Modelers start virtual screens. If they have a structure, this is the best starting point. If not, they create homology models. If they have nothing but small molecules from the literature, they create pharmacophores and can use those for shape based or feature based screeing. Virtual screening of the compound database using docking on a known structure takes a few days. Analyzing the results takes a couple of weeks. At that point, the modeler hands off the virtual hits to the chemist who makes the selection and orders them from a commercial vendor. They get added to the screens during HTS. And then, everyone waits for HTS to finish. The actual HTS hits are processed and registered in some kind of database like ActivityBase and then handed off to the modeler and chemist. The modeler analyzes the experimental data, fingerprints and clusters compounds into series, pulls up any other data related to the compounds, calculates some preliminary ADME and ranks the series by structure activity relationships. The HTS data is usually just single point Ki. If resources are available and there is enough compound in the compound room, they do IC50s on the actives. The modeler goes over the series with the chemistry team and they eliminate series they aren’t interested in. The modeler takes the remaining series and does similarity and substructure searches on the corporate and commercially available databases. I like to do shape searches at this point as well and develop a preliminary pharmacophore. Selections are made from the searches for promising followup compounds to fill out the SAR as much as possible. A second round of screening occurs to test these search results. More data analysis occurs to narrow the series based on the second screening round. A third set of searches and screening may occur at this point to followup on the second round of screening. Meanwhile, the biologists are verifying the hits in their secondary assays. This may cause some series to be eliminated at this point. Then we all get together and determine if there’s anything worth pursuing. If there is, the chemists and biologists present to committee and resources are assigned. Or they present to the committee and the bastards say, “We need more data”.

      • Given your description of how things work now (systematic), it’s pretty clear that Viehbacher perceives innovation as working best when it happens within the context of “the olden days”, when things operated more like it does in the university (the individual professor reading a paper while flying to a conference and having a “eureka” moment, and putting together a collaborative group to work on it either at the university or in a start-up company he/she sets up at a local incubator). He doesn’t like “systematic”, both because of the expense and because he sees it as rigid, inflexible, rules-bound, and fostering “narrow-minded” (non-innovative) thinking. Viehbacher also doesn’t think that “systematic” is fun compared to the exciting, chaotic, adreneline-pumping atmosphere of a start-up, or the “deep-thinking”, ivory-tower atmosphere of the university laboratory. It’s a completely different way-of-thinking.

        • What Viehbacher fails to realize is that there are many moments along the systematic approach that are a lot like the eureka moment days. And we’ve learned from bitter experience that not every target in a paper is druggable. But what he really doesn’t seem to understand is that persistent grinding and multiple failures are what leads to those eureka moments. If you haven’t learned anything through exposure and experience, you won’t recognize a good idea when it happens.
          There are a lot of things big pharma could do differently to improve the drug discovery process. For example, they could stop hiring consultants and they could disconnect R&D from the business procedures. We just work differently and some of those processes and procedures get in the way of progress and slow things down. But Viehbacher’s crew is notorious for coming up with the most research strangling procedures, like making departments bid for work against outside companies. That is just an insane waste of money and time.
          Another thing pharma could do from the research side is to change it up a bit. I know my modeling benefitted from my year making and crystallizing proteins in structural biology and I wanted to do it not knowing it would have this effect. I think there is a cognitive science paper in here somewhere about the value of exercising different parts of your brain to facilitate new connections and spark creativity and I’m convinced that if more people did it, you would get the more flexible and innovative biotech atmosphere that shareholders are looking for. After all, in small biotechs, one person is expected to do multiple tasks. Encouraging scientists to do the same thing, even just temporarily, would be a good thing, IMHO. That is, provided they aren’t already in the zone on another project. You don’t want to interrupt flow states unnecessarily. But for scientists who are missing that flow, changing things up is highly recommended.

          • I think the bottom line is that Viehbacher doesn’t think that the current fully-integrated, systematic system is the way forward for future drug discovery (though he does seem to believe that systematics is still useful for validation and regulatory work). Part of the reason why is that he doesn’t believe that Big Pharma can attract the “best scientists” out of the universities necessary to keep the systematic system vibrant and innovative anymore (he says that such people now all want to start their own companies–or also perhaps remain within academia–as the reason why).

            But I suspect that he’s also not very confident that Big Pharma can continue to generate the kind of revenue necessary to keep the integrated, systematic system up and running for much longer. So he’s pushing the drug discovery onto start-ups, while retaining validation. Instead of analyzing 10,000 different drug candidates in-house, he wants to (in the extreme case), follow the fortunes of 10,000 start-ups as each one tries to develop one of those candidates, and then buy up the start-up(s) who turn out to have one of the golden tickets.

            This may explain his overall attitude towards research in sanofi.

          • From what I know, Sanofi lost one of its best and brightest recently. He got fed up with sanofi’s executive branch undermining him.

            There’s nothing wrong with either approach. As I said before, just getting together and having a show back in the 90s wasn’t entirely successful either. I worked on a couple of those projects, protein-protein interactions and stuff like that. It’s not a bad idea to verify your target.
            And when you’re looking for starting points, it’s not a bad idea to comb through databases looking for similars. Systemizing doesn’t necessarily lead to a bloated, inefficient discovery effort. Having insufficient human resources does. I’ve never been on a project that had enough chemists. I’ve never been on a project that didn’t have to join a queue to get some analysis done. The weird thing is that Viehbacher sounds like he’s funding lab buildings that are stuffed with fat and lazy scientists and that’s never been the case as far as I know. Not even close.
            There’s nothing wrong with academic collaborations and there’s nothing wrong with making things integrate better so there’s a smooth flow of information. They are not mutually exclusive. I just think Viehbacher doesn’t know anything about the labs he runs.

    • And, yes, Viehbacher is an ass. He got rid of some of his more experienced oncology people. For all I know, they’re going to make shareholders very rich someday and save some lives. That should be some consolation to the scientists who will never get their careers back.

      • Doesn’t he need such people to properly evaluate the quality of the science behind all of those “one-trick pony” biotech/pharma start-ups that he’s now relying for sanofi’s early-stage drug discovery work?

        • Speaking of start-ups, have you found a good corporate lawyer yet for yours? The lawyer is often “Employee # 2″ in any properly organized start-up, and very important for making sure that the wording of the NDAs everyone subsequent signs is iron-clad.

  17. RD,

    In 21st Century American politics, Barry Goldwater would be an “ultra-leftist”.

    HTH,

    P.

  18. It looks like Olympia Snowe retired before she had to compromise on reproductive rights . Good to know there’s a line she will not cross. Bad that we’re going to lose a woman from the senate.

    Democrats saw the issue tilting politically in their favor in recent days and forced the Senate vote even as some Republicans indicated unease about pressing the matter. One Republican, Senator Olympia J. Snowe of Maine, joined 48 Democrats and two independents in opposing the plan, days after she announced she was retiring from the Senate. Three Democratic senators — Bob Casey of Pennsylvania, Joe Manchin III of West Virginia and Ben Nelson of Nebraska — voted for the proposal, along with 45 Republicans. Mr. Casey and Mr. Manchin are up for re-election this year. Mr. Nelson is retiring.

    It was close. Too close. We need more women.

    BTW, what happened to Susan Collins? She is supposedly a hardliner on reproductive rights. I guess Snowe gave her just enough cover.

    • I can’t see where this ends. There’s no logical limit to the language these guys. I know there are women who voted for this madness but, they aren’t speaking up. Are they?

      They keep saying that these are moral decisions. But, aren’t they personal opinions? It seems like a conflict of interest for someone to legislate based on personal opinions.

      • Moral decisions depends on whose morals. The right wing political class are trying to define morals as biblically defined morals. The problem is, there are not proscriptions against contraceptives or abortion in the bible- anywhere. The right wing religious are broadly interpreting scriptures like “be fruitful and multiply” and some passages in the pentateuch as prohibiting these things but it’s a nebulous connection at best.
        But in a way, the pols on the left and middle are giving the right wing religious waaaaaay too much consideration. Because as I demonstrated last night, the right wing religious are very concerned about their own numbers. They are dwindling. They make it sound like they’re being outbred by muslims but they are really being replaced with non-believers. It is the non-believers who are increasing at a very rapid rate and they don’t give a rat’s ass what the bible says. To the non-believer, the bible is a 3000 year old book written by bronze age shepherds. Their world is completely different from ours. They had reasons for writing the rules as they did that do not carry over to the 21st century. There is nothing wrong with female sexuality. There is no reason why we should put a price on some virgin’s honor. These days, genetic testing keeps everyone honest and contraception makes sure that there are not more mouths to feed than there is food. There’s no need for all of these stupid rules. Men and women should be able to share equally in sexuality and planning of their family size and timing.
        The only reason we are stuck with biblical morality is because some people have been conditioned to be ashamed. They are older women who missed out on the sexual revolution by only a few years. But these taboos are so firmly ingrained that political operatives can push their buttons and trigger that guilt and shame and get them to the polls. It’s all tradition and conformity and making sure you’re tidy and clean. It’s very 50s.
        But I have no idea why Democrats are still falling for this crap. They could have the entire non-believer community eating out of their hands. There is such a thing as responsible sexuality. Why aren’t Democrats latching on to it and telling the religious right that their time has passed and that they should put their efforts towards more safety net related things? It’s because the religious are granted an inordinant amount of respect in this country. We are constitutionally separated but in reality, the state bends over backwards to kiss the ass of the religious. That’s the part that has to change. We can respect the person without having to respect their belief system. There is nothing wrong with saying, “I disagree with your belief system and do not put them on a plane higher than my own just because they were written in a piece of historical fiction.” Until we empower people to do that and assert their own worldview and personally developed morality, whatever that might be, we will not make any progress in pushing the religious out of our bedrooms. But I have hope. I am really astonished at the number of non-believers and freethinker sites that have come into being in the past couple of years. They’re coming out of the woodwork. The internet has made it possible to finally climb over the taboo of admitting you don’t believe in the bible. And now, I think, they have reached a tipping point. These are the people that the democrats should be reaching out to.

        • RD, someone pointed this article out to me. Can you tell if the authors are serious or is this some sort of sick joke. I just don’t see how it could be published in a credible journal.

          • I’m assuming that JME stands for the Journal of Medical Ethics. If this is a peer reviewed journal, then it probably shouldn’t be at all surprising that they publish on subjects that to the rest of us seem distasteful and barbaric. I guess it’s their job to consider every possible situation that could come up in a healthcare setting and discuss it.
            Every discipline has its own special subjects. Once upon a time, we had cold fusion and polywater. Ethicists talk about what sounds like infanticide. It kinda makes sense that this would show up in a peer reviewed journal. And there is nothing wrong with talking about it. You, the reader, are always free to disagree with the authors’ conclusions. You are also free to publish a counter argument that others would find more compelling. So, this paper is not the definitive word on the subject and *should* be challenged. I can think of an argument to refute them.
            But in the end, talk is cheap. It’s what happens in the medical setting between all of the interested parties that count and they have to make their decisions based on the circumstances they are presented with.

          • Oh, I could see that… but, one of their underlying premises is that there is no logical difference between a baby and a fetus. That both are helpless.

            But, that’s so clearly not true. For example, fetus’s don’t even breath on their own. Shouldn’t they be expected to have a sound basis for their peer reviewed discussions?

          • I don’t know what their criteria is for peer review. But you are allowed to disagree with them. I’m in your camp. I think there’s a difference. There are countries that are a lot more liberal than ours that have established guidelines about when the fetus becomes a person on its own.
            I have no problem with the ick factor of an abortion before 16 weeks. But there is a gray area. I’d much prefer it if women and girls weren’t guilted into denial so that they wait too long to have an abortion. It’s really a sad situation when that happens. But I would let the doctor make the final call on it, and if the fetus is able to be sustained on it’s own independent of its carrier, it’s barbaric to me to kill it. We need to develop compassion for the woman at this point and tell her its ok to wait it out without guilt or shame. And without guilt or shame, she should be able to walk away from her parental responsibilities. I’d like to see what happens when everyone knows the rules up front.

          • Strange, I saw it linked by a friend on Facebook then just now stopped by John Smart’s place and found this post. So, it must be making the rounds. I was wondering how my friend found it.

          • Yeah, I agree about the guilt/shame/denial thing. And there’s also pure ignorance. It’s amazing how many people don’t listen to the signals their body is sending. REALLY obvious signals sometimes.

          • Is polywater what parrots drink? :mrgreen:

    • We’re watching Abraham Lincoln’s party destroy itself. History in the making. Whee.

      • If I were you, I wouldn’t get cocky. I thought they were finished in 2008. Then they went on to sweep 2010. Never turn your back on the dead lady in the bathtub.

        Republicans ain’t playin’ with a full deck.

    • Well she will be senator until next january. I hope she raises hell. She doesn’t have to go all liberal on their a$$es or anything, just all ethical. That aught to shake up both sides.

  19. Wasn’t Abraham Lincoln’s party destroyed during the Ulysses Grant presidency? Didn’t it become Mark Hannah’s party at that time? And so now it is Mark Hannah’s party which may finally be destroyed, despite Barak Obama’s best efforts and the combined best efforts of the whole DLC ThirdWay Goldman-Sachs Rubinite Democratic Party to save the Mark Hannah Republican Party and restore it to power.

    Well, all I can say is . . . thank God, halleLUjah, and Praiiiiize the
    Lord!

  20. About finding Tom Tomorrow: On the left side of his blogpage are some tiny words. One of those words is “comics”. Clicking that will bring up some of his archived cartoons. They will show up here a little later than they show up on the koswipe site, no doubt. But if one doesn’t mind waiting, here they are.http://thismodernworld.com/tmw-2012

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