Talking us down from the glyphosate ledge

Glyphosate. Not keeping me up at night.

Glyphosate is now the new cyclamate and we’re all supposed to be terrified to use it in agriculture.  Oh, please.  Check out this analysis of the glyphosate study by Derek Lowe at In the Pipeline, Is Glyphosate Poisoning Everyone?.  Here’s the money quote:

Now, that presumably sounds extremely detailed and impressive if you don’t know any toxicology. What you wouldn’t know from reading through all of it is that their reference 121 actually tested glyphosate against human CYP enzymes. In fact, you wouldn’t know that anyone has ever actually done such an experiment, because all the evidence adduced in the paper is indirect – this species does that, so humans might do this, and this might be that, because this other thing over here has been shown that it could be something else. But the direct evidence is available, and is not cited – in fact, it’s explicitly ignored. Reference 121 showed that glyphosate was inactive against all human CYP isoforms except 2C9, where it had in IC50 of 3.7 micromolar. You would also not know from this new paper that there is no way that ingested glyphosate could possibly reachlevels in humans to inhibit CYP2C9 at that potency.

In the pharma lab, if a compound had an IC50 of 3.7 micromolar against a target, we’d have to be desperate to call it a “hit”.  That level of activity means you’d have to choke down a lot of chocolate cookies before you’d be even mildly affected.

So, you can stop worrying about glyphosate poisoning.  That doesn’t mean everything in the world is safe to consume.  It’s just that glyphosate is no dioxin and you won’t have to superfund site a farm that uses it.

Lowe also has a post on the cost of cancer drugs that is worth reading.  It gems fairly nicely with my cynical theory of the current pharma business model, which goes like this: Once upon a time, big pharma made drugs for all kinds of ailments, like heart disease, schizophrenia, depression, reproductive health, antibiotics, diabetes, pain, inflammation, etc.  But over the last 30 years, it has become increasingly more difficult to get those drugs to market for a variety of reasons I won’t go into here.  Suffice it to say that the FDA doesn’t approve very many small molecule drugs anymore.  Like virtually none.  A pharma can spend a lot of money on research only to have a drug shot down at the approval stage.  So, how does a drug company make money if it can’t sell drugs?

Easy.  It concentrates on cancer and orphan drugs.  Orphan drugs are for diseases that are relatively rare.  For cancer drugs, the path to profit is pretty straightforward.  The patients are desperate. They’ll pay what the market will bear and then some.  Will they mortgage their houses?  Yeah, probably.  So, the market is there.  But it gets better.  Cancer drugs are fast tracked for approval and no one is overly concerned with toxicity.  In other words, there won’t be class action lawsuits because patients are grateful for any extension of life they get.  Even if the patient dies, their families are likely to consider their treatment as advancing the knowledge of science.  No one complains.  If you’re a bean counter, oncology drugs are as good as it gets.  They’re profitable, quickly approved, they don’t have to be perfect and no one will hold you accountable.  It’s probably the same situation for orphan drugs.

This is the financier’s mindset at work.  R&D people don’t think like this.  But in the end, there is a ceiling to the amount of money we as a society are willing to pay for potentially lifesaving drugs and  we are now up against it.  Meanwhile, if you are suffering from any other ailment, like bipolar disease or osteoporosis or some flesh eating bacterial infection, you’re going to be stuck with older drugs that are quickly becoming generics.  The good news is that the generics will be cheaper, well, at least for a little while longer.  I don’t think that can last as there won’t be enough profit in generics to keep the production facilities up to FDA standards. I can easily imagine some production facilities being taken offline a la the rolling blackouts of the California energy crisis 10 years ago.  Some jerk generics traders are going to be yucking it up about Granny not being able to afford her cholesterol lowering drugs.  Call me paranoid but as far as I know, there’s nothing to stop such scenarios from taking place and I wouldn’t be surprised if it’s already happened.

At some point, the price of generics will start to rise and in some cases, they haven’t really dropped all that much yet.   There won’t be a steady stream of new and improved drugs coming from the pipeline.  It will be more of a thin trickle.  The public has spoken.  It doesn’t want me-too drugs even if they are better than what’s already on the market, and it doesn’t want any drug that’s less than 100% perfect and free from all side effects.  Whether this combination of financier morality and public skittishness is good for medicine, science or society are questions we haven’t even considered yet.  No one, it seems, except the displaced scientists from Pharmageddon seem to be discussing those issues.  Someday, the Ezra Kleins and Duncan Blacks will wonder how that happened but it’s already almost too late to do anything about the coming Dark Ages of pharmaceutical medicine.

So, if you’re rich and you have cancer, you’re probably going to be Ok.  If not, well, it’s just another symptom of being in the 99%.

Monday: Structural unemployment is a lie

It’s bullshit.

For those of you scratching your heads, it’s the idea that the reason so many people are unemployed is because they don’t have the right skills, education and technological training or they’re located in the wrong places in the country.

I can only imagine the titans of industry at the job junkets where they go to speak to former presidents and cabinet members, whining about how if they could only find more graduates in STEM fields, they wouldn’t have to send all this work overseas or import so many H1-B visa workers.  Woe is they, crocodile tears, wringing of hands.  It’s just pathetic.

And it’s a lie.  It’s the biggest lie in the country these days.  Lie, lie, lie.

Paul Krugman doesn’t believe it and has been writing about it for the past couple of weeks.  He thinks unemployment is a problem caused by lack of demand.  But even that doesn’t tell the whole story.  In the STEM fields, unemployment is a deliberate, calculated, psychopathic and destructive strategy for reducing costs at the expense of the research industry and consumer health.  It’s just a way of extracting wealth.  There’s no demand problem.  There are more than enough projects to keep every scientist alive busy for the rest of their lives.  And there certainly is no shortage of people suffering from diseases.

And now, here comes Zachary Karabell in Newsweek who disagrees and says that we have a structural unemployment problem and who has apparently not been following Pharmageddon:

Distressingly, this framing of the debate limits so many options. You can view the waves buffeting society as structural and long-term and then argue for cogent government action—and yes, spending—that acknowledges and addresses that reality. But where can that view be found in the current policy framework? You could argue for aggressive government action to manage a generational shift, to seek productive employment for the unemployed à la the Works Progress Administration and the Civilian Conservation Corps of the 1930s. After all, if we are going to spend tens of billions a year on unemployment benefits, and if those benefits make people feel simultaneously helpless and worthless, why not spend the same money allowing those people some gainful use of what skills they have? And if there truly is a generation lost in the transition, then we owe that generation a solid net—but we do not owe that to the generation now emerging. Instead, they deserve the opportunities to acquire the skills and training that they will need in a post-manufacturing world as surely as those farmers in 1900 needed new skills in a 20th-century manufacturing world.

Ok, he’s got the first part right.  We need a WPA program for unemployed scientists so we can use the skills we already have.

But he totally fails when he ignores the reason for the generational shift (greedy bankers and shareholders) and says that we need more skills and training.  We have hundreds of thousands of people who are plenty skilled and trained in science and technology who can’t find jobs or can find jobs and are willing to move, or have moved and find themselves laid off again.

What we really need is a leader who is determined to put his or her foot down with the finance guys and has a vision of the future of American recovery where we use the people we already have.  Otherwise, when the finance guys have done drinking the milkshake of pharma and come to the realization that they need American researchers just like the good old days, there won’t be *any* STEM workers because the next generation won’t be caught dead in a lab in a dead end job and no job security.  Then structural unemployment will have become a self-fulfilling prophecy.

STEM students aren’t stupid, you know.  Well, not anymore they’re not.

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For those of you who haven’t been following the saga of Trustus Pharmaceuticals, here’s a recap of the chocolate cookie of the apocalypse:

First, the bad news that the company is going with throttle up on the alpha12 project:

Second, the sign of the endtimes for the alpha12 project- the project polo shirts (I’ve been there but on our case, it was shirts and color changing coffee mugs with comic book character graphics and ads that would have made Don Draper proud.  And that compound looks very familiar, probably a HTS screening hit I threw out.):