Once upon a time…

Merck chemists go into exile

Once upon a time in New Jersey about 20 years ago, there was a company called Merck that everyone I knew wanted to work for.  The streets of Rahway were paved with gold.  We jokingly referred to our own company as a training facility for Merck and Bristol Myers.  The best of the best worked there for two years and then went to Merck.

At local conferences, the Merck people showed up in a pack, smug, condescending, and cast an otherworldly pool of light around them.  THEY wrote their own proprietary modeling software.  Even as late as two years ago, when Pharmageddon got its groove on, there was something magical about Merck people.  They were like fading elves.

Alas, all good fairy tales come to an end and so it was with Merck this week where the rumor is that medicinal chemistry, that is the research part that makes your drugs from scratch, oh best beloveds, has been decimated at Merck.  The rest of the story at Merck is unclear at this moment.  We’re still trying to piece together whether Merck is going to outsource their synthesis to poorly paid foreign PhDs or whether management, who hasn’t synthesized anything but performance standards and political fantasy baseball for years, is going to don their too tight lab coats and nitrile gloves and go back to the lab.  That should be interesting.

Once upon a time, the US had world class public research.  Then the big companies decided they didn’t want to do research anymore and they would pharm out their research to academic labs.  And they wrote policies about how this would be accomplished and the politicians said it was good because many of them didn’t know what the heck they were voting for.  And then the Republicans decided to “drown government in a bathtub” and because they are like Godzillas in Tokyo, they were pretty indiscriminate about what they were knocking down.  It turns out that the NIH keeps getting hit pretty hard and grants are harder and harder to come by with higher and higher bars to jump over and endless hours slaving over documents.  That time could be used to invent new techniques but research is very expensive and someone has to pay for it.  So the academic scientist spends much of his or her time begging to keep the reactions going and the lab rats paid.

Recently, during the government shutdown, Francis Collins, the head of the NIH, said this about the sequester and the tragedy of what is happening to this country’s life sciences infrastructure:

The sequester hitting as it did in the middle of the year meant that about 640 grants that would have been supported and highly regarded by peer review are now not going to receive funds. And those ideas are not going to happen. And breakthroughs that they might have represented will not occur. We will not know what we’ve missed because it’s gone. Imagine 640 bright, motivated scientists on the brink of doing something powerful that could have changed the way in which we diagnose, treat, and cure cancer or influenza or diabetes or some rare disease that desperately needs an answer; it’s just not going happen. I would argue with anybody who says that’s a minor consequence. It’s not; it’s a major negative outcome and a tragedy for what had been the world’s most successful search-engine in biomedicine.

Other countries, meanwhile, have read our play book and see their future in trying to do what we used to do. As we seem to be backing away, they are increasing their support. And if people care about American leadership, they should be worried.

Unless something (it’s called C-O-N-G-R-E-S-S) stops the next set of cuts in the sequester, the problem is going to get a lot worse.

I don’t see a happily ever after ending to the story right at this minute but, you know, I’m a Tolkienist so I’m not ready to give up hope yet. The situation at the present time is this. We have private industry pulling out of research because the shareholders are like opium addicts who expect bigger and bigger quarterly hits.  Long term investment doesn’t play nicely in the sandbox with an “ownership society” where everyone and their grandma is expected to put their savings into mutual funds that analysts and managers can gamble with.  And we have idiots like Rush Limbaugh who yee-haw that the sequester is the best thing since sliced bread because liberals are sucking on it.  I wouldn’t wish a Charlotte Corday situation on my worst enemy but I wouldn’t think twice about wishing a drug resistant version of Fournier’s Gangrene on Rush Limbaugh.

In the meantime, some of us still can’t quit science.  After two years in the desert, I have to pinch myself because I now have access to all the journal articles I can eat.  I’m afraid to click on the “Full Journal Article” button sometimes.  It’s almost not real, like ruby slippers.  {{Oh, wow, oh, wow!}}  But it’s almost cruel too because it’s so uncertain these days.   What is granted can so easily be taken away, like coaches that turn into pumpkins at midnight.  Sometimes, I think I might have been better off if I’d taken my academic advisor’s advice and studied law.  Then I think I’d rather eat glass than study torts.

So, science, yeah.  You can barely make a living at it anymore and yet can’t quit the habit. The best I can do at this point is try not to frighten the new, untested, warriors in training that there be dragons out there and to pass on what a wizard once told me, “Don’t let anybody steal your bliss.”

 

Calling all medicinal chemists, time to contact Virtually Speaking

I was mulching my flower beds, listening to the latest Virtually Speaking with Dean Baker and Jay Ackroyd when I heard the same moronic bullshit about how drugs are REALLY all discovered in academic labs using government money and the drug companies just put the finishing touches on them, develop them and charge a small fortune.

I’ll give you the fortune bit, for sure.  There’s no doubt that the marketers and finance guys are charging what the market will bear and then some.  They’re greedy, ruthless and cruel.  The whole drug industry has pivoted to serve the owners and the owners want money.  That affects what gets researched, promoted and sold and at what cost.

BUT

There is absolutely no truth to the idea that academia passes on almost fully formed drugs to industry where we researchers add our special sauce flourishes and then cash in big.

I repeat.

There is absolutely no truth to the idea that academia passes on almost fully formed drugs to industry where we researchers add our special sauce flourishes and then cash in big.

If Dean Baker and Jay Ackroyd and Yves Smith want to propagate this myth, they can knock themselves out.  But it’s no more true that the idea that Bill and Hillary Clinton did something nefarious with a land deal in the Ozarks.

Maybe it’s what they want to be true, maybe it fits their worldview, maybe it’s wishful thinking but it not true.  And I should know because I’ve worked in both industrial and academic settings and I actually DO the kind of drug discovery that Jay and Dean talk about so confidently but have no clue about.

The truth is that academia rarely submits a fully realized drug entity to industry for development.  What it submits is frequently just an idea.  Sometimes, that is just a target (a protein, receptor, gene, etc) and sometimes, it consists of some very basic building blocks.  Those building blocks will not resemble the final drug product until industrial medicinal chemists spend years and years rescaffolding it, making new appendages for it, and developing whole libraries of potential drug compounds that may not resemble the initial compound in the least when they are finished.

So, yes, the NIH funds a lot of research but, no, that research does not result in anywhere near effective or consumable drugs until industrial chemists get their hands on it and bend it to their wills.  By the way, those industrial chemists used to be academic chemists.  It’s not supposed to be an adversarial relationship.

Anyway, for all you pharma researchers out there who are pissed off by the “everybody knows” truthiness and yet more dissing of your shrinking profession and want to set the record straight, let Jay Ackroyd at Virtually Speaking know.  God only knows why Jay won’t simply invite someone like Derek Lowe on his show to tell it like it really is.  It’s almost like they don’t want to hear the truth, that somehow by sticking their fingers in their ears and singing “la-la-la, I can’t HEAR you”, that that’s going to make the poor graduate students working for peanuts into unsung heroes and pump lots of righteous indignation into the put upon American people.  Well, those graduate students ARE unsung heroes, but so are many of my former industrial colleagues in medicinal chemistry and drug design who have slaved tirelessly for years wrestling some academic’s decidedly un-druglike molecule into a real drug that can be developed.

I’m really insulted by this poor performance by Ackroyd and Baker.  The left deserves people who are not lazy and who will actually go out of their way to get to the truth.  Otherwise, the drug industry will continue to fail, drugs will continue to skyrocket in price and no one will be able to do anything about it because they’ll all be off chasing wild geese or red herrings or whatever it is you call it that is just a waste of time and energy.

Jay and Dean aren’t even seeing through a glass darkly at this point.  If they would only come and actually, you know, talk to us, we could tell them what’s really going on so they could talk more intelligently about a subject they clearly know nothing about at the present time.  I’m not sure what is holding them back.  Is it the absurd notion that those of us who work(ed) for industry  are as greedy, ruthless and conservative as the guys who laid us all off?  Even if that were true, (it’s not, not by a long shot) is that a good reason for ignoring what we have to say?

You can’t fix a problem if you are totally ignorant.

Here’s Jay’s links if you want to set the record straight.

Jay on Facebook

Jay on Twitter

VS Guests on Twitter

VS in Second Life

VS Ning

VS on BlogTalkRadio

VS on Facebook

VS on Itunes

And here is Dean Baker’s twitter feed.

 

 

 

 

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…

Debunking the myth that the NIH discovers drugs and industry just exploits it

Derek Lowe describes how the drug discovery process really works and why critics who perpetuate the myth that the NIH discovers targets and drugs before the pharma industry ruthlessly exploits the taxpayer don’t know what the hell they’re talking about.  Here’s a snippet but if you’re interested in this kind of thing because you don’t know much about it, you should read the whole post:

 I think I’ve hit on at least one fundamental misconception that these people have. All of them seem to think that the key step in drug discovery is target ID – once you’ve got a molecular target, you’re pretty much home free, and all that was done by NIH money, etc., etc. It seems that these people have a very odd idea about high-throughput screening: they seem to think that we screen our vast collections of molecules and out pops a drug.

Of course, out is what a drug does not pop, if you follow my meaning. What pops out are hits, some of which are not what they say on the label any more. And some of the remaining ones just don’t reproduce when you run the same experiment again. And even some of the ones that do reproduce are showing up as hits not because they’re affecting your target, but because they’re hosing up your assay by some other means. Once you’ve cleared all that underbrush out, you can start to talk about leads.

Those lead molecules are not created equal, either. Some of them are more potent than others, but the more potent ones might be much higher molecular weights (and thus not as ligand efficient). Or they might be compounds from another project and already known to hit a target that you don’t want to hit. Once you pick out the ones that you actually want to do some chemistry on, you may find, as you start to test new molecules in the series, that some of them have more tractable structure-activity relationships than others. There are singletons out there, or near-singletons: compounds that have some activity as they stand, but for which every change in structure represents a step down. The only way to find that out is to test analogs. You might have some more in your files, or you might be able to buy some from the catalogs. But in many cases, you’ll have to make them yourself, and a significant number of those compounds you make will be dead ends. You need to know which ones, though, so that’s valuable information.

That’s just the start of the problem as Derek goes on to point out.  This is usually where the drug designers get involved, sifting through the information that comes from the screens, clustering the compounds that show activity, doing searches on in-house and commercial databases, finding the common features of the hits to determine if there’s a reason why they’re active, and proposing modifications to those lead series (that the chemists will ignore).  You do this on enough projects and you become a very good pattern spotter without really trying.  But that was only a small part of my job.  Most of the projects I’ve been involved in go on for years.  It’s a very iterative process and sometimes, the project takes off on tangents  It’s like untying a giant knot with lots of little subknots that sometimes need to be solved first.

The bottom line is that as valuable as the NIH contribution is, it’s usually the 1% inspiration that leads to the drug industry’s 99% perspiration.

Politicians should spend a little time interviewing the drug discovery people.  I don’t mean the executives or the lobbyists.  I mean the people who actually do the work.  It appears that there is a lot of mythology to dispel still.  And without a more complete concept of how drug discovery works, it’s difficult to craft policies to make pharma research work for patients, government and businesses.

If I might make a suggestion to Derek, visual aids might be useful.  Just dig a couple of slides from your latest pre-project team meeting and modify the names of the targets.  People will not really grasp what is involved until they see it.

Friday: Well, this is interesting- NIH request for information on the future of biomedical research

From Jared Berstein's blog. If you havent' found a job after 6 months, your chances of getting are slim.

A few months back when I was still working, the American Chemical Society held a webinar with some people from the Bureau of Labor Statistics where they proceeded to tell us that unemployment was really, really low for chemists.  The disconnect was astonishing until we realized that the BLS hadn’t collected data since before the Lesser Depression began.  The pharmaceutical industry has laid off something like 300,000 people since 2007 and this time, the sales division did not take the biggest hits. In my own immediate family/friends, not one of us has a full time job with benefits for the first time in our working lives.  We are all either un or under employed without health benefits and are barely managing to scrape by with paying our rents and mortgages after the industry lured us out to the most expensive part of the country to live and then stranded us here.  And we are not high school dropouts.  We all have degrees, some of them PhDs from prestigious universities, in physical or natural sciences and our performance evaluations were good.  Some of us even got performance awards (for the second year in a row!) a month before we got our pink slips.

Well, it seems like the NIH is trying to get some new data.  As Derek Lowe reports on In the Pipeline:

A reader passes along this request for comment by the NIH. The “Advisory Committee to the NIH Director Working Group on the Future Biomedical Research Workforce” is asking for thoughts on issues such as the length of time it takes to get a PhD, the balance between non-US and US workers, length of post-doctoral training, the prospects for employment after such is completed, general issues relating to whether people choose biomedical research as a career at all, and so on.

If you are in the industry, let me rephrase that, if you once had hopes to work in the industry but have had those hopes brutally dashed after you spent years slaving away over a hotplate, you may want to contribute your constructive input.  You have until October 7, 2011 to do it.  Go to this form.  Try not to get tears and snot on the keyboard while you’re filling it out.

From the  NIH website on this RFI, here’s some of the information they are interested in:

Purpose

This Notice is a time-sensitive Request for Information (RFI) requesting input into the deliberations of the Advisory Committee to the NIH Director Working Group on the Future Biomedical Research Workforce.

Background

The Advisory Committee to the NIH Director (ACD) has established a working group to examine the future of the biomedical research workforce in the United States (seehttp://acd.od.nih.gov/bwf.asp for charter and roster).  The group will gather information from various sources including the extramural community, and will develop a model for a sustainable, diverse, and productive U.S. biomedical research workforce using appropriate expertise from NIH and external sources. The model will help inform decisions about how to train the optimal number of people for the appropriate types of positions that will advance science and promote health. The working group will recommend actions to the ACD and to the NIH Director.

In its initial deliberations, the working group identified the following issues as important to consider when developing a model of the future biomedical research workforce:

  • The balance between supply, including the number of domestic and foreign trained PhDs and post-docs, and demand, i.e. post-training career opportunities.
  • Characteristics of PhD training in biomedical research, including issues such as
  • The length of the PhD training period.
  • Recommendations for changes to the PhD curriculum.
  • Training for multiple career paths (including bench and non-bench science).
  • Characteristics of clinician-research training including issues such as
  • The balance between MDs and MD/PhDs
  • Career development of clinician-researchers.
  • Recommendations for changes to the curricula for training clinician-researchers.
  • Length of Post-doctoral training.
  • The ratio of PhD students and postdoctoral fellows on training grants to those supported by research grants.
  • Possibilities for professional/staff scientist positions and the level of training required for such positions (e.g. PhD or MSc degrees).
  • Issues related to the attractiveness of biomedical research careers (e.g. salary, working conditions, availability of research funding)
  • The effect of changes in NIH policies on investigators, grantee institutions and the broader research enterprise.

I’d like to thank whoever is responsible for getting this together for actually taking an interest in the issue, even if it is years too late to save our careers or the underlying infrastructure that all Americans are counting on to produce the results we have taken for granted in modern times.  If I were to hazard a guess, I’d say that the number of PhDs produced is irrelevant if no one wants to hire you.  Regardless of your degree level, studying the sciences is not for the faint of heart.  It takes dedication to master some difficult material, perseverance to learn new information and years and years of practice before you’re any good.  You can get your 10,000 hours in graduate school or on the job.  Some non-PhD scientists are extremely capable and some PhDs come to industry with lots of attitude but no practical skills.  But whatever the degree level and regardless of where we are located in the world, there just aren’t a whole lot of us who have the skills to do research at this level.  We need to be compensated accordingly.  At some point, research becomes an art.  It’s not something that can be broken down into assembly line, just-in-time parts.  It operates best when there is “frictionless” collaboration, when the physical barriers that separate groups are minimal and leadership is partitioned away from the bean counters.

JMHO.

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.

Hillary’s Plan to Revive Research Starts with Breast Cancer

BRCA1 Breast Cancer Susceptability Protein

Hey all you geeks out there. Remember the NIH? Yeah, that’s the place a lot of you camped out at for a few years doing post-doc work solving crystals and running assays and groovy $&*( like that. Bush et al didn’t really believe in research though because, you know, most of that stuff relies on evolution and we all know the world is only 6000 years old. So, our research institutions have been sorely neglected.

Well, Hillary is going to revive the ailing United States scientific research community, starting with a $300 million infusion to the NIH for breast cancer research. Friends, can stem cell research be far behind? Wow! I am so looking forward to that. Just think of the progress we will make in the biotech fields when we can use stem cells to run better more accurate assays and grow human tissues instead of less than adequate facsimiles. Maybe we can catch up on 8 years of being dragged back into the 19th century.

* The image above is of BRCA1 (Breast Cancer Susceptability Protein) that can be retrieved from the publically available repository at the Brookhaven Protein Data Bank.

Update: Commenter Marco thinks that Obama will shortly release his own copycat policy.  I predict it will be $500 million for research into erectile dysfunction.

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