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      MANDOS POST Take a look at Joe Biden—he appears to have, for now at least, considerable staying power in the Democratic primary opinion polls (although, of course, this may change as the actual primaries come through). If your model of political psychology can predict a strong core of popular support for Trump without also predicting […]
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Well, this is interesting. US Gov’t to dabble in drug discovery?

It looks like the NIH is going to start screening for new drugs.  Here’s a quick and dirty primer on how drug discovery works (via me):

There are two different paths to discovering a drug.  In the first path, a database of gene sequences are scanned for a potential “target”.  The target gene codes for a protein or receptor that is implicated in a disease state.  Biologists make the protein and use robots to test a library of potential “ligands”, drug compounds, against the target.  These libraries consist of hundreds of thousands and possibly millions of compounds.  When  a compound interacts with the target and elicits the right response, it is called a hit.  The hits are passed to a project team of biologists, chemists and drug designers who examine the hits, select the most promising ones, ie, the ones that look like they won’t be toxic or too hard to work with and which provide places for modification.  The team then engages in a years long struggle of iterations.  The drug designers propose modifications, the chemists make the modifications the designers suggest (or not, as the case may be.  Convincing a chemist to make a drug is the most challenging aspect of the whole endeavor, IMHO.) and the biologists test the new compounds and say “hotter” or “colder”.

There is a lot of other stuff going on in the background.  There are structural biologists who can sometimes crystallize the protein in question and make it a lot easier for the chemist and designers to see what the hell they’re doing.  Also, there are groups that test the compounds for properties other than how effective they are against the target.  Those things include toxicity, mutagenicity (how likely they are to cause cancer and birth defects), bioavailability (how easily they get into your system through the gut, stomach or blood-brain barrier), solubility (how easily they dissolve), metabolism (how your liver breaks them down and into what byproducts) and cardiotoxicity (does it make your heart spazz out).  Note that this list is not exhaustive.  The FDA is very strict about what goes into your body and drug discovery takes these regulations very seriously.

Once the potential new drug is ready, it gets passed to a development group for scale up and clinical trials.  This whole process takes a long, long, LONG time and there are many failures along the way.  It is also extremely expensive.

The other path is to bypass the gene target identification route and simply test a bunch of compounds, that are already sitting around, against a desired endpoint.  This is known as a phenotypic screen or high content screening.  In this case, the drug company does not know what the target is, well, not at first.  Instead, the tests that are conducted against cells and a desired outcome is noted.  After the phenotypic screen finds hits, it is sometimes possible to deconvolute the pathway that the compound affected and identify the targets.  In this scheme, the discovery process presumably starts out with drug compounds in the library that are already known to have desirable or promising safety profiles because they might have been worked on before for different projects but they weren’t active enough against the target they were made for.  But that doesn’t mean they can’t be used for something else.

The last pathway is what I think is going on with this new initiative at the NIH or at least that’s the way I interpret it.

There’s a lot of factual data in the NYTimes article about what the drug industry is up against.  It remains to be seen whether this new initiative will be good or bad for the industry or the public.  I can imagine many possible scenarios as to how it might turn out and some worry or encourage me more than others.

In any case, go read it and when you’re done, I’ll try to answer any questions you might have in a broad, general way.  I can’t speak for my industry or company and wouldn’t want to anyway.  But general information I can do.

Update:

Here’s a weird comment from the same article:

Great. So now taxpayers will be liable when there’s a problem. I hope there’s some kind of handoff program to private industry at some point in the program to avoid problems like that.

Soooo, let me get this straight.  The ability to sue is still of utmost importance.  Did I get that right?  Because, from where I sit, the class action lawsuits are part of the problem.  Everyone complains about not reining in the big finance guys but ambulance chasers looking for big bucks who glom onto adverse drug reaction reports like blood sucking ticks are all ticketyboo?  It’s *not* ok to curb the lawyers?  I mean, presumably, the government would not be interested in deliberate negligence and injury brought on by a joint venture, right?

Just curious.

Another commenter who doesn’t quite get how the industry works or didn’t check the graphs on the side of the page (they are pretty accurate):

Its about time. Our drug companies have lost focus on what is really important. All they concentrate on is profit and the FDA is complicit in its approval process. New drug application fees should be abolished also. One drug turns into 5 or 6 all with patents and huge costs are passed on to the US consumer. We do not need over half of these meds for they really do not benefit anyone other than the profits of big pharma. Do we actually need dozens of antidepressants or drugs for male impotence?

I’ve seen many good drugs taken off the market because of unexpected side effects.  It happens to all of the companies in the industry.  I’ve also seen drugs that the industry has spent billions of dollars and years to develop go before the FDA and get shot down.  There goes a huge investment.  It’s hard to justify taking that kind of risk with shareholders’ money, especially when money making drugs are going off patent and there’s nothing in the pipeline that can get approved.  If the FDA and the pharmaceutical companies are colluding with each other, you would expect a whole lot more drugs getting approved and the numbers simply don’t bear that out.  Sooo, I would safely ignore this commenter as dreadfully uninformed.

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Sunday: What to do, What to do?

Susie Madrak has her own radio show on BlogTalkRadio.  On January 17, her guests were Eric Boehlert and Nicole Sanders.  They took a call from a woman whose unemployment benefits ran out last March.  MARCH.  Of 2010.  For almost a year, this woman has had zero income.  No unemployment, no little job, nuthin.  She’s spent all of her savings and is now living on a home equity line of credit to pay her bills.  And she called Susie, who’s doing the best she can with what she has too since being out of work for some time now, and asks what she can do to get lawmakers’ attention?

Susie talked about how the Communist party started organizing back in the Great Depression, preventing people from getting evicted and feeding the poor.  And back then, it got a lot of attention.  There were tent cities and Hoovervilles in Washington.  Evidence of poverty was everywhere.  It was the threat of a public uprising the finally got things moving.

Susie gave the standard answers about what can be done.  Show up at a congressman’s office en masse, hang out in front of the restaurant where he/she and friends have lunch, throw a tent city or two and call the local paper or TV station about it.  Butcha know, I don’t think that’s going to work anymore and as one of them said: the right has the biggest megaphones and they simply won’t report it.

The right knows their voters.  They motivate their voters to vote by romanticizing the fetus, by appealing to their religiosity.  If bad things happen to other people, it’s because they weren’t as pious and good as the typical Fox News viewer.  That same religiosity prevents the religious conservative from doing too much to help the poor by contacting their representatives and demanding action.  It’s because there is so much evil and bad and pain in the world that mankind does not have the capacity to clean it up.  Only god does.  So, we need to just wait for Jesus to come back, which should be any day now.  If you’ve ever wondered what the apocalyptic messaging in right wing propaganda has to do with anything, there’s the reason.  It’s to keep the older conservative voter who sees disturbing things from taking any action.

If Susie wants to know what to do, she is going to have to target these viewers to get involved.  One thing that temporarily woke people up was the sight of so many people suffering in the wake of Katrina in New Orleans.  Which means that the news machine will be very careful to never do that again.  So, if you can’t bring the news to the people, maybe you have to bring the people to the news.

Don’t isolate your older, more conservative relatives.  Tell them what’s going on because you’ve seen it personally.  Tell them what is happening to your unemployed friends.  If they ask why they’re not willing to relocate, tell them the truth.  There are no jobs.  Anywhere.  Be harsh with them.  They won’t want to see you.  But they’ll call and ask why you haven’t come to visit.  Tell them you’re trying to help your friends- who are unemployed and that they just don’t get it.  They’ll go on about how God is the only one who can clean this mess up.  Tell them that’s bullshit and Jesus wouldn’t want them to ignore the poor.  If they tell you that you’re friends did something wrong, tell them the only thing they did wrong was being born in the wrong part of the 20th century.  If they say, yes, it’s true, the older generation has it good in comparison, tell them, great!  We’re moving in with you.  With the bird.  And the kid who likes to play Edith Piaf songs all. the. time. and refuses to speak to you in anything but French and eats like there’s no tomorrow.  When they express some hesitation about that, tell them to turn off the fricking TV news.

As for Susie, I think she has a future in broadcasting but she really has to ditch her propensity to glom onto left wing memes.  I’m not saying stop being liberal.  I’m saying stop letting the left do your thinking.  On one broadcast a couple of months ago, I think Athenae was on, they got so frustrated with it all that they want to just ditch everything and go rustic, which is great if you have no dependents.  But in some respects, it reminds me of the older religious person’s decision to just stay in the house away from the evil men and sexual predators until Jesus comes back.  You can’t run away from the world’s problems when they seem insurmountable.  If you do that, the bad guys win.  They want people to feel helpless.  Learned helplessness is their goal.

The only way to win is to get together and fight back.  And if Susie hasn’t figured this out yet, the left’s support of Obama in 2008 has resulted in thousands of sparkling shards of leftiness with the incapacity to reform itself.  I keep appealing to people like Susie to stop blowing us off and join with us and let’s do something together.  But the left hasn’t given up on the stuff that doesn’t resonate with their potential allies who work for the big corporations the left condemns.  It’s incomprehensible to me that for all the intelligence the left claims it has that it hasn’t figured out yet that the corporations are not the ogres here.  It’s the rulemakers they help elect.  If the rules weren’t bent or destroyed, the corporations would go back to playing by the rules and merely scheming like grinches instead of running around causing havoc like Thing 1 and Thing 2.   Then there are people like us who voted for Hillary and are still personas non grata.  We’re always going to think Obama was the wrong guy for the moment.  But why would the left cut off half of its strength if it really want to make a change?  Let me ask you this, Susie, why haven’t you asked any of US on your show yet?   Not that we can’t host our own shows but that’s hardly togetherness, is it?

The left’s obsession with perfection mirrors the right’s eschatological fervor.  Neither one addresses the causes and concerns of people in the middle who still bitterly cling to their FDR era programs with track records of success for those who participate.  Both sides insist that if they can’t have everything their way, no one will get anything at all.  In this respect, the left does as much damage to its cause as the right does with its huge megaphones.

If you want to know why no one hears your cries, it’s because you haven’t joined with other voices.  And the men in charge, and it’s ALWAYS men, like it that way.  Power is the ultimate drug and no one is going to wrest it from them without a fight.  As long as the left remains broken, Susie and her tent cities are no threat to the power brokers.

In other news:

So, about that FICA 2% tax break.  I was just talking to my colleague about this the other day.  She was planning to roll that money into her 401K.  Hold off on that, I said, you never know how they’re going to take it out of your hide.  After all, you’re income tax may go up instead.  Sure enough, Carissa at Corrente discovered what the catch is in Making Work Pay Clawback.  You’re not going to like it.  I probably won’t like it a whole bunch more.  As a single person who only gets to claim Head of Household every other year, while still retaining the blessings of parenthood and a healthcare policy that requires that I am the major source of support for the kid, I pay an outrageous amount in taxes already but I’m well below the top tax bracket that actually gets…

wait for it

a break! Yep, if you’re in the 35% tax bracket, the amount of money you can make before you are taxed has risen.  For everyone else, the amount you have to make before the taxes kick in has dropped. Isn’t that special?  So, hold off on adding to your 401Ks, which only people who have paid off their mortgages can afford to fund adequately.  Not only has Obama managed to not soak the rich, he has given them additional breaks, acquiesced to a plan that underfunds social security, transferring that money to the general fund where it will be spent in Iraq, and raised taxes on our income.  In summary, the 2% FICA tax break does absolutely NOTHING to stimulate the economy. Well done!  Is this really the one we were waiting for?

Les Leopold at AlterNet attempts to answer the perennial question, “Why Do People Who Work in Finance Earn So Much More Than the Rest of Us?” Yes, I would like to know the answer to that question, as well as why it is that people who work in the corporate offices make so much more than the people who do the innovation and the hands on work to produce the products that make all the money?  And why is their gym nicer and their cafeteria food better?  Why is it they can use the mail service to ship personal items to international destinations while the people in the facility down the road can’t?  Shit, did I say that out loud?  Well, why???  What is it about dressing up and sitting behind a desk makes the people who make sometimes incredibly bad decisions so much wealthier than the rest of us?  The answer, as far as I can tell is that if you delegate your authority to other people to keep track of the money so that you can get actual work done, you run the risk that those delegates will reward themselves handsomely at your expense, and at a certain level of wealth, you can’t live with them and you can’t live without them.  It’s extortion.  That’s my theory and I’m sticking with it.

Leopold does some calculations:

Let’s try a back-of-the envelope calculation of Wall Street’s net social value. Compare their bonuses and profits for roughly the last five years (about $500 billion) with the economic losses produced in the financial crisis the bankers caused (about $4 trillion in value destroyed, not counting the ongoing travails of the 22 million people who haven’t yet been able to find a full-time job). For every dollar “earned” on Wall Street, about 8 dollars were destroyed. (In case you’re suffering from financial amnesia and forgot how the financial sector single-handedly caused the economic crisis, please see The Looting of America. Chapter One can be found gratis on AlterNet.

I hate to break this to the educators but, it turns out if you really want your students to learn something, testing is one of the best ways to do it.  You know those endless stupid projects you have our kids doing where they have to map everything out on big pieces of expensive poster board with connections to all of the other concepts in the unit?  Turns out that might be a waste of parents time.  What researchers have discovered is that those projects impose an artificial organization and categorization system on students that is more easily and naturally achieved by simply testing them on the material as soon as possible after they learn it.  Go back to the pop quizzes, teachers.  Save yourself and your kids and their families a nights of exhaustion and despair.  From the NYTimes article:

Why retrieval testing helps is still unknown. Perhaps it is because by remembering information we are organizing it and creating cues and connections that our brains later recognize.

“When you’re retrieving something out of a computer’s memory, you don’t change anything — it’s simple playback,” said Robert Bjork, a psychologist at the University of California, Los Angeles, who was not involved with the study.

But “when we use our memories by retrieving things, we change our access” to that information, Dr. Bjork said. “What we recall becomes more recallable in the future. In a sense you are practicing what you are going to need to do later.”

It may also be that the struggle involved in recalling something helps reinforce it in our brains.

It makes sense.  If you impose a little bit of stress on the student in the form of a quiz or test, they are forced to rapidly organize the information and discover where they are deficient so they can revisit the information later.  If you impose too much stress on them by forcing them to adopt another organization method, you not only screw up their intrinsic method but you create a life long hatred of projects.  JMHO.

Anyway, it’s in the journal Science, which is a stickler for peer review and details and stuff like that so as much as you may dislike the concept of testing for retention, you can’t completely dismiss this paper.  Well, you *could*, but it would be pointless.

Another article from the NYTimes proclaims that Obama is to press a centrist agenda in his SOTU address.  So, it looks like after three years of playing the political philosophical mystery man, Obama has finally found a place to dig in his heels and plant his flag — right down the middle.  Which has moved significantly rightwards since he became president.  Uh-huh.  I see this as a way to head off Bloomberg and his silly No Limits soiree.  Which means, the vast majority of people who are not making $200K a year and have to work for a living without a safety net are still screwed and unrepresented by this President.  Obama has finally found his constituents:

Mr. Obama previewed the themes in a video e-mailed Saturday evening to supporters who had helped in his election campaign. But the video made plain that his speech would be geared more broadly toward the political center, to independent voters and business owners and executives alienated by the expansion of government and the partisan legislative fights of the past two years.

The rest of you scientists and airline pilots and mathematicians turned uber programmers and burger flippers and unemployed journalists and part time morticians can go take a hike.

Lovely.  By the way, NYTimes reporters, the economy is *not* “picking up steam”.  My friends are just as unemployed as ever and the rest of us are in danger of joining them.

I’m so glad that I can say with pride that “I didn’t vote for him”.

About that abortion clinic from hell, Alternet has a followup.  Well, there are a lot of articles on this subject.  The story is very gruesome but just goes to show you that desperate women will overlook unsanitary conditions, illegality and their own health to get abortions when they decide they need them.  There is nothing that a senior citizen mainlining Fox News can do about it.  These women are never going to bond with or have any warm and fuzzy maternal instincts for the fetuses they carry.  There’s no amount of shame or inconvenience you can foist on them that will deter them.  The only thing you accomplish by stigmatizing abortion and forcing poor women to “Chase the Fee” is that you end up risking two deaths instead of one.

This is the first but certainly not the last legal clinic that resembles a back alley abortion mill.  There will have to be a lot more of them before the anti-choice contingent starts feeling the weight of all of the deaths and destruction and infertility it has visited on women.  They will have to feel it and be made to take the blame for it.