Hacks and thwaks

Yesterday, for some bizarre, unknown reason known only to Yves Smith, I was accused of spouting PR for the pharmaceutical industry.  It appears that it goes against left of center dogma to say that the NIH does not just hand over perfect drug entities to the drug industry, already tested and bioavailable and efficacious, and that all the industry “R&D” divisions (well, what’s left of them) do is add a few finishing touches and charge everyone an arm and a leg for them.  Yes, that is what pharmas do.  They don’t really do research.  We just accept these gifts of government largess and when they arrive on our front door steps all glistening with ingenuity and brilliance, we stand around and marvel at them like they are alien creations.

Ok, the chemists can stop laughing now.  No, really, you’re going to hurt yourselves.

The truth is that NIH grants allow for some good science and many new discoveries.  But very rarely do they get to the stage where a new drug is delivered to a pharmaceutical company as a fully formed entity that requires no modification.  My experience (>20 years in the industry) is that NIH grants fund a lot of basic science on targets.  Then, if those targets (not drugs, protein targets) look interesting, they’re picked up by a pharmaceutical R&D, or more likely, several pharmaceutical R&Ds because the information is public, and all those different companies work on the target at the same time.  That’s how you get “me too” drugs. Just because someone beat you to market doesn’t mean you can trash all your hard work. Besides, your drug might actually be better.  It is strange that it is only in the pharmaceutical industry that “new and improved” is looked on as a bad thing.

Now, I am not going to argue that the pharmaceutical industry doesn’t charge an outrageous amount of money for new drugs these days.  And I won’t argue that they haven’t done much of anything to put new drugs on the market.  Or that they haven’t gone back into their old compound libraries  or that they reformulate things.  Sometimes, those reformulations are meaningful and sometimes they are not.

But I do know that research is expensive.  Ridiculously expensive.  That’s why big pharma has been cutting back on research as a counterintuitive business model.  That’s why there’s nothing coming out of the labs.  They are spending less money these days and they are relying on academic groups more often now.  The reasons are many but chief among them is that after having spent many billions of dollars on research, very few new drugs were approved by the FDA.  And that could be a result of higher safety standards that didn’t exist when the project was started or the constant mergers and acquisitions and bad management and the explosion in biology in the past couple of decades and the new and trendy things that snake oil salesmen corporate ladder climbers sold to their bosses as the next big thing that weren’t ready for prime time.  In fact, if Yves had been reading the posts I have written in the past several years on the pharmaceutical industry, or Derek Lowe at In the Pipeline has been writing (check the archives, Yves) or even someone like Anthony Nicholls at Openeye has been writing, she would have gotten a more complete picture of what is really going on.

What is really going on is that the big pharmas are going “weightless”.  They think they can exploit little start up companies and academic groups and turn those compounds into drugs.  And they want a cheap workforce.  I mean REALLY cheap.  Like $37K/year is their ideal top of the salary band for post docs who will never find a job in industry.  So they have been pushing this nonsense to the White House and Congress that what we need is more students who will sacrifice themselves to STEM professions and forget about having a stable job or family life because it is the patriotic thing to do.

Meanwhile, there really are academic groups that are trying to create new drugs.  They consist of former industry professionals who have taken incredibly steep cuts in their salaries and work in facilities where their resources are vastly reduced compared to their formerly corporate lab environments.  The pharma industry has them right where they want them, using their decades of expertise to cobble together drugs out of shoestrings and bubblegum.  And those dedicated scientists spend a lot of time applying for grants from the NIH but the money is very hard to come by and can’t pay for all the things and people they need to do their jobs.  These people are amazing and I can’t say enough good things about them.

But they are the exceptions, not the rules.  The rule is that the vast majority of NIH funded research provides germs of ideas.  They are hints of possibilities, a bunch of gel slides and some correlations.  I have been on many projects that started with a few interesting papers from NIH funded research.  We spend a lot of time on these shiny little nuggets setting up assays and crystallizing proteins and screening millions of compounds and synthesizing new compounds only to find out that the NIH funded studies did NOT have all of the answers.  The initial studies had only part of the answers and didn’t know about all of the other pathways and upregulation or the initial study was just off and the assays don’t work like they should and the project has to solve a different problem before it circles back to the original problem.  In the process, the industry research uncovered many aspects of the biology that the NIH scientists didn’t have the time, money or urgency to discover by themselves.  Many millions of dollars have been spent chasing NIH beginnings that ran into brick walls and had to be abandoned.  In any pharmaceutical company, there were dozens and dozens of these kinds of projects going on all at the same time.  Many projects are started but bloody few succeed and the vast majority of drugs that are produced from the germ of an idea that came out of an NIH study originated in the compound library of the pharmaceutical company itself.

Those are just the facts, Yves.  You can talk to anybody who has ever worked in pharma in the past 20 years and they will confirm this.  Yes, some remarkable things have come out of academia but very few of them  came directly from some academic lab untouched.  All of the other drugs were industry generated.

The reason why drugs are so expensive and are going to get more expensive is because more companies are abandoning their small molecule drug discovery efforts, because they couldn’t get approvals and recoup their investments before the patent clock expired, and are now moving into biologicals, the next big thing.  Oh sure, there will be some small molecule efforts in areas like oncology but this is due to a very cynical calculation on the part of the bean counters.  Oncology drugs are fast tracked and the safety profile is relaxed. People with death sentences on their heads are more than willing to become human guinea pigs and put up with a lot more toxicity than average non-sick people. They’re less picky about formulations.  Sure it would be great if the drug is oral and easily bioavailable but if you have to take it by IV, that’s OK too. If the drug extends life by even a few months, some families would consider that a success and they’d be willing to pay whatever the market wants.  And best of all, patients don’t complain and file class action lawsuits.  If the treatment succeeds, everyone is happy no matter how much the liver is shot.  If it fails, well, the patient was going to die anyway.  The relatives chalk it up to fate. The shareholders are happy.

Biologicals are a whole different animal with their own share of problems from humanizing mouse antibodies and aggregation problems to all kinds of new and different things that no one even knew about the cell.  It’s going to be interesting and very expensive.

The rest of the non-wealthy people will have to live with generics, which are bound to get more expensive.  Yves is smart enough to figure out why because she understands scarcity, supply and demand.  But these will be older, less efficacious drugs.  Well, the public put it’s foot down about “me too” and demanded a higher level of perfection than any small molecule drug is likely to ever deliver and this is what happens.  No more new small molecule drugs.

There are many facets to this problem.  Everyone sees the issue they are closest to.  If you only consult one “expert”, you only see one part of the problem.  There is no reason to distrust those of us former industry professionals who have a different version of events.  Believe me, we are not going to tell you a lot of flattering things about the pharmaceutical industry that stupidly laid off all of its expertise.  But unless you find out what is really going on and who is doing what with which resources and how successful those resources are, you can’t develop a complete picture of the landscape of this problem.  And more importantly, you can’t *solve* the problem. That smacks of a very unscientific approach to solving problems and, in the end, it doesn’t serve the patients or American citizens well at all.  In fact, not gathering as much information as you can from different sources is precisely what Big Pharma wants you to do.  It’s asymmetrical information at its best.  You only have one part of the picture and they just sit back and laugh at your righteous indignation while you rail against them.  How is this different from the finance industry?

By the way, I am no finance person and I didn’t much care for economics.  But I took the time to read books and ethnographies and visited wonky sites and read Yves and waded through all this money crap that interests me not even in the slightest.  And although I don’t know everything, I know much more than I did four years ago.  I know what motivates the bastards now and what incentives need to be changed to make the system function again.  That’s a positive step, right?

So, maybe closing your ears to differing points of view is not a good thing, Yves.  You’re not helping us beat this thing.  And that is something no pharma PR rep would ever say.

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And now for some IKEA hacks!

This first one is from one of my new favorite YouTubers, goodbrowngravy, who despite being a white southern male with an accent, appears to be not the ignorant redneck that some lefties think all white southern men are.  (Do we condescend and stereotype much?  I think we do.)

Here’s goodbrowngravy’s IKEA hack of a Rast dresser into a campaign style side table.  Nice work!

And here is a hack of an Expedit unit turned into a stereo system from Apartmenttherapy.

Speaking of IKEA, if you are in the area tomorrow of the Elizabeth, NJ IKEA, you can drop off some badly needed items for the NYC/NJ survivors of Hurricane Sandy. IKEA is teaming up with the RedCross and other organizations to provide furniture and funds and also to collect items from customers who are shopping on Sunday. Check here for a list of items that would be much appreciated.  The collection will start at 11:00am.  And I really need a Rast…