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Happy Fourth of July and other stuff

dave-dicello_750There are no bad views in Pittsburgh on the Fourth of July. Some are better than others but you really can’t miss a good fireworks display. Best Spots are probably the Dravosburg and West Mifflin area,  Grandview, and a couple streets down from me. And there’s always Kennywood.

Happy Fourth!

Other stuff:

I’ve read in different places that Barack Obama may decide to become a venture capitalist after he leaves the White House, feeding on the corpses of geeks who ran out of early discovery money before they could develop their drugs into blockbusters.

Check out my post from 2011 on Their Plans for Us to get a better sense of what I’m talking about. And yes, the ACS representative really did say that those of us who were unemployed should borrow from “friends, family and fools” in order to work our asses off in our own start up for years before some venture capitalist came along to bail us out.

I’m reminded of the altruism, fairness study of monkeys who don’t think the game is fair if they get less than 30% of the fruit. But it’s OK if vulture capitalists cash in big on the backs of hard working researchers who should be grateful they get 1% back on their blockbuster patents they are forced to sell.

Well, he’ll be trying to fund cancer and orphan disease biological treatments and who can argue with that? If you have cancer or some metabolic disease, this is pretty sweet. But as I have said before, this kind of research has two major characteristics: 1.) It’s a business model that really does feed on the weak. A person with a life threatening disease will not complain about side effects, isn’t likely to sue you if you extend their lives and will pay whatever it takes to get better. Biologicals don’t have the same patent hurdles as many small molecule drugs and for cancer and life threatening orphan diseases they are “fast tracked”. In other words, the FDA will look the other way on many safety profiles. The potential profits are enormous. 2.) Other diseases will be deprioritized. Got heart disease, schizophrenia, or a life threatening bacterial infection? Too f&*(ing bad. Those small molecule therapies don’t get fast tracked, are subject to a lot of patients suing over side effects, are too difficult and expensive to research because of the blood-brain barrier or aren’t taken for long enough periods of time for the dough to roll in.

That’s the harsh reality. Vulture capitalism in new biological therapies is all about maximizing shareholder value while minimizing research at the cost of innovation in other areas. It puts researchers at risk because unless they are early geniuses or incredibly lucky, they will be job hopping from one shaky startup to another and it deprives harder science of the long term funding it needs to make progress.

But don’t take my word for it, listen to Chris Viehbacher, former CEO of a large pharmaceutical who is now into venture capitalism:

In Viehbacher’s view, Big Pharma is still trying to act in the way the old movie studios once operated in Hollywood, with everyone from the stars to writers and stunt men all roped into one big group. Today, he says, movie studios move from project to project, and virtually everyone is a freelancer. In biopharma, he adds, value is found in specializing, and “fixed costs are your enemy.”

Fixed costs are other words for “people who have spent most of their adult lives in a lab getting PhDs in very hard subjects”. These people require life sustaining things like food, water, shelter and money to pay off their student loans. Those things are baaaaad. They’re your enemy.Well, we’ll have none of that. But thanks to Chris Viehbacher, we have the entire working person’s grievance summed up in one paragraph.

By the way, Chris, specializing is important but even specialists have to work in project teams to do real discovery research. A star specialist is only effective if he or she can work in a team of people who put away their egos to focus on their goals. Pharma research has very, very few Mark Zuckerbergs (thank God). In fact, Mark Zuckerberg types who study molecular biology are just as likely to go work on Wall Street as a start up lab because they know where the money is when they have to make a living, didja ever think about that, Chris? But I digress.

and Chris also said…

“It is cheaper. But research and development is either a huge waste of money or too, too valuable. It’s not really anything in between. You don’t really do things because it’s cheaper. The reality is the best people who have great ideas in science don’t want to work for a big company. They want to create their own company. So, in other words, if you want to work with the best people, you’re going to have go outside your own company and work with those people … And, you want to work with them, why do they want to work with you? The reality over the last 10 years is, (a small biotech) wouldn’t get caught dead working with one of these big cumbersome pharma companies. Once you have a funding gap, suddenly there’s a much greater willingness of earlier-stage companies to work with Big Pharma. We’re looking earlier and people who are early need help.

It would take many posts to unpack what Chris is really saying in this paragraph. Let’s just say that to those of us who used to do this kind of research, this is transparent BS pitched to future investors and says more about the only thing that Chris and his droogs feel is a measure of success and value in life. This is from a man who likely never stepped foot in the labs he ran. Discovery sometimes takes a long time, patience and continuity. That’s how we do science. Everything else is either a get-rich-quick scheme or low hanging fruit built on the backs of others- who worked in those big corporate labs for years and years doing the heavy lifting in research.

But it’s the image of Viehbacher and his investors waiting around for early stage companies to have a funding gap, where presumably they can’t pay their top stars anymore, that really fuels my contempt for these predators. “Nice lead compound you got there. Be a shame if something *happened* to it.” This is venturing into Martin Shkreli territory.

And Barack Obama wants to be one of them?

Some presidents build libraries, some presidents build multinational charitable foundations, some presidents look for FDA loopholes, researchers on the edge of bankruptcy and desperately sick people to make a killing in the market.

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

Antecdotal evidence of *something*:

I walked to the bus stop the other day on the way home from work. The buses must have been piled up in traffic upstream because the sidewalk was crowded with about 100 people. That’s an estimate, probably a good one. I didn’t want to block the sidewalk so I stood where I could. It turns out it was in a line that was quickly forming in front of another line of people backed up against the side of a building. All of the sudden, there was a voice behind me, “Is there a good reason you stood in front of me??”. I turned around to see a tall African American man behind me. He looked casually dressed, like he just came from a Pirates game. I looked like I just came from my air conditioned office floor in a tech company with my company lanyard hanging from my neck. I just said “No” and turned away just as the bus pulled up.

It’s just the buses held up in traffic and crowded bus stops with no place to stand. Sometimes, a cigar is just a cigar, not a socio-political statement. Anyway, there was no way I could stand behind him because there was a f^*&ing building there and then, people standing in front of me. So, you know, we’re all in this whole bus thing together.

Then I got on the bus and stumbled on the foot of a white woman who was taking up way too much space (she wasn’t obese) on the side bench seating including sticking her legs out into the aisle. “Excuse me”, I muttered as I quickly took my seat down the aisle and across from her. She too was a casually dressed, graying blonde who looked her age. She gave me the stink eye for several blocks before she got off in mid town.

WTF?? I suddenly felt like the target for Trump supporters AND anti-Bernie people who wanted to pick a fight.

This is going to be an ugly summer.

I ran into a bunch of POC tweeters yesterday who just assumed I was a Bernie supporter because I didn’t think the turn to the left in the Democratic platform was a slap to Obama. The internet is a rough place and I’m used to it, but the level of anger and assumptions, including that I had deliberately used a “sepia toned” photo of myself for some nefarious purpose was hillariously over the top.

Look, POC, calm your g&* damned tits for crying out loud. It was eight years ago that Donna Brazile and Paul Begala fought it out on national TV over the Democratic party ditching its “old coalition” for “eggheads and African Americans”. (They both missed the point, IMHO) This year, thanks to an angry electorate and a definite shift in voter sentiment against getting the shitty end of the economic stick in the past eight years with no bankers going to jail and years of absolutely the worst job market since the Great Depression, the Democratic party seems to slowly be turning back to its roots and in the direction of the left.

Those of you who *think* this turn is a slap to Obama should seriously ask yourselves why the party struggling to embrace its identity with working people and more liberal values looks like it is disrespecting Obama.

I’m not saying your perception is wrong. I’m saying the reason is not what you think it is.

I’ll leave it at that. You’re smart enough to figure it out. It’s got nothing to do with racism.

 

 

 

#antibiotics : somebody should do something

I’m blogging from my iPhone while I wait for my car to be inspected. Expect imperfection, although, some of you may not notice a difference.

To those of you on the left who are finally paying attention to pharma research, head on over to In the Pipeline. Derek Lowe has another story that illustrates the state of R&D research in the era of shareholder value and its potential impact on the rest of us.

This recent event is about Merck acquiring antibiotic research company Cubist. Cubist in-licensed much of its pipeline and had a small early discovery research team of 120 people. It has now been announced that those 120 researchers have been laid off.

I guess you could say, well, Cubist in-licensed much of their stuff anyway. But those 120 people presumably have many accumulated years of experience from working on antibiotic research and that experience will largely be lost because companies are not really investing in antibiotic research. Where are they going to go?

Some of them are going to get a nice payout from Merck but even if they pool their resources, it’s not going to be enough to make a dent in the hole of antibiotic research. It will mean starting from scratch-again- for many of them. Or casting around for another hard to keep job in one of the most expensive housing markets in thtalee country.

In the meantime, there goes some badly needed talent to combat multi drug resistant bacteria.

If only there was an institution big enough to fund research in the public interest…

 

 

My frustration with Krugman

The problem is he is only one of a very few prominent liberals with access to a microphone. Today, he wrote some things I can personally relate to in his piece Twin Peaks Planet:

Furthermore, the travails of workers in rich countries are, in important ways, the flip side of the gains above and below them. Competition from emerging-economy exports has surely been a factor depressing wages in wealthier nations, although probably not the dominant force. More important, soaring incomes at the top were achieved, in large part, by squeezing those below: by cutting wages, slashing benefits, crushing unions, and diverting a rising share of national resources to financial wheeling and dealing.

Perhaps more important still, the wealthy exert a vastly disproportionate effect on policy. And elite priorities — obsessive concern with budget deficits, with the supposed need to slash social programs — have done a lot to deepen the valley of despond.

Unfortunately, there is an older generation of Americans who think there is nothing that can be done to stop this trend. They have been convinced by popular media that corruption is inevitable. These are the same older Americans who are benefitting from the Social Security that was  hard won after the last catastrophic depression. They were children back then. They benefitted from the post war economic expansion that proved beyond a shadow of a doubt that conditions for working class Americans do not have to be one step away from destitution. It is not the natural order.  But these older Americans fail to make the connection time after time. They have been taught to disbelieve their own past prosperity and the conditions that were necessary to keep the predators at bay.

I blame TV.

But I also have to blame Krugman for some serious rationalization of very bad policy in the last 6 years. He states:

So who speaks for those left behind in this twin-peaked world? You might have expected conventional parties of the left to take a populist stance on behalf of their domestic working classes. But mostly what you get instead — from leaders ranging from François Hollande of France to Ed Milliband of Britain to, yes, President Obama — is awkward mumbling. (Mr. Obama has, in fact, done a lot to help working Americans, but he’s remarkably bad at making his own case.)

Obama hasn’t been bad at making his own case. He hasn’t got a case to make.

I’ve been harping on research for awhile now and people have pointed out to me that my industry has not been the only one to suffer during this downturn and I get that. But it is a perfect example of how this country has allowed our leadership in science erode away and that science has provided benefits globally over the past century. I have watched as this administration and Congress has done absolutely nothing to stop the demolition of the American research industry and that is going to come back to bite this country.

Well, I’m beating a dead horse here but I’ve become convinced that our president, Senators and Representatives have been getting some very bad advice from lobbyists and other industry representatives who deceive them into believing that globalization of a very complex industry was beneficial and inevitable. They are going to regret it before long. We can’t get jobs, can’t make a living and can’t contribute to the welfare of this country anymore. You’d think that would be of interest to this White House but there has been very little interest in creating policy to address this problem. And if the best educated in this country can’t get the attention of the most powerful people in the world, then what hope do the rest of the struggling Americans have for having their concerns addressed?

It doesn’t help when Krugman insists that Obama has done great things but he’s too modest to talk about them. Maybe he’s not talking about them because Americans are finally seeing through the PR machine about “green shoots”, Lilly Ledbetter and Obamacare. We’re all asking ourselves, how stupid do they think we are? Anyone not living off their investments in this country is trapped. It’s a real life Ballad of the MTA with no way to exit the train because we’re always a nickel short and the meter keeps running.

One thing Krugman does have right though is the specter of a return to an ugly malignant narcissism that is creeping into our public discourse. The rise of nationalism and the tendency to kick disadvantaged groups when they’re already down is a bad, bad sign.

Once again, I blame TV.

Another thing that irks me

Vox has a new post about Frances Collins remark that if the NIH had better funding, we would have an ebola vaccine by now.  Vox says this isn’t true.  I think this was addressed briefly during the hearing.  The NIH went for years looking for a partner for vaccine research in the private sector and couldn’t find one.  Finally, they got GSK and another company interested in development.

Here’s what Vox doesn’t understand about drug discovery research and I have seen this repeated time and time again until it has become ingrained and hard to dislodge:

The NIH is not the only player necessary to take vaccines to market. The agency’s role in pharmaceutical development is usually basic research, giving scientists grants to look at how diseases function and what can stop them.

When it’s time to use that science to build a vaccine, that’s where drug companies typically come in, paying for the trials and manufacturing. We don’t know whether, in a world where the NIH had more funding, a pharmaceutical company would have stepped forward to do this. There’s decent reason to believe there wouldn’t have been; a vaccine to treat Ebola, an infrequent disease that hits low-income areas of the world, is hardly a blockbuster.

This is the conventional wisdom but it is incorrect.  The NIH does provide valuable basic research but the key word here is basic.  It’s not like the NIH develops a vaccine that just needs to be “built” by private industry.  It’s the same thing with drugs for cancer or any other illness.  The NIH provides very basic starting points.  After that, private industry has to pour massive amounts of money into research to fill out the details to get it to the point where it can be built.

What Vox and others do not understand is that private industry research is Real RESEARCH.

Now, if Vox wants the NIH to do the same kind of research that private industry is doing, starting with basic nuggets performed in NIH sponsored labs and publishing work that frequently can not be reproduced in private industry labs (I have been there, Ezra Klein), then it will need a lot more funding.

And this may be necessary anyway because private industry has decided that Real RESEARCH is way too risky and it would prefer not to do it anymore. (Hence the hundreds of thousands of layoffs that we refer to as Pharmageddon)  So, if we want a vaccine for anything, it may eventually have to come from the NIH.  That is what Collins is referring to.  NIH can only go so far without a private partnership.  If the partnership isn’t there and funding is cut, guess  what?  No vaccine.

This has been another episode of a former drug discovery researcher fruitlessly trying to correct the record.

Freaky Weird Prescience (Ebola Post)

Well, it’s not looking good on the ebola front.  We still don’t know why the nurse in Dallas has ebola despite all of her precautions but I’m still not panicking.  My relatives in Houston are probably safe, though what did they say during the Black Death?  Run fast, go far, stay long?  Ok, that’s not really funny and is only encouraging a kind of hysteria that isn’t helpful.  Two ebola patients in Texas does not an epidemic make.  Then again, it’s Texas.

Nevertheless, there is a some speculation that the virus has become more virulent.  Peter Jahrling of the National Institute of Allergy and Infectious Diseases says this may be due to the increased viral load in infected individuals:

You’re seeing all these patients getting infected, so people think there must be aerosol spread. Certainly, it’s very clear that people who are in close contact with patients are getting a very high incidence of disease and not all of that can be explained by preparation of bodies for burial and all the standard stuff. But if you are to assume that the differences in virus load detected in the blood are reflected by differences in virus load spread by body secretions, then maybe it’s a simple quantitative difference. There’s just more virus.

Jahrling says that HIV was actually a hotter disease, primarily because carriers weren’t obvious and were able to spread the disease easily.  It also helped that HIV attacks cells in the immune system, which prevents a vigorous response.  But it’s a little hard to make this argument when comparing it to ebola.  HIV is a long, slow death and we now have drug cocktails to treat it.  Ebola is quick, excruciating, bloody and the lethality is alarming, especially because the treatment options are so few.

Which brings me to the next bit of bad news.  Frances Collins of the NIH says we might have had a vaccine for ebola except our politicians, with anti-governmental fervor, cut funding to those very institutions that might have helped to develop one.  I’d heard from researchers I met in Cambridge who had recently been to the CDC that morale was pretty low and disorganization was high.  Then, I lived through the summer of sequester when university research groups lost a sizable chunk of their funding as grants became more and more unattainable.  Layoffs quickly ensued.

One of the reasons I have been reluctant to pursue a job in research is because the money isn’t there anymore and I’m really sick of layoffs.  And let me make it clear that while scientists like to get paid fairly for the work they do, they don’t work for the money, for the most part.  They just like the work.  It can be frustrating and maddening and discoveries take a long time.  But it is also intensely rewarding in a way that money isn’t.  That’s not to say that we don’t have our own caloric requirements and shelter needs.  Also, no one likes to be exploited.  But bankers and Jack Welch types don’t understand the nature of science or the vast majority of people who do it for what is turning out to be a vanishing living.  But I digress.

The problem is that the patent cliff spooked pharma shareholders and they abandoned American research in search of get-rich-quick schemes and foreign research that isn’t ready for prime time.  At the same time, rabidly anti-government Republicans, abetted by complacent Democrats, have been slashing research budgets.

This is not the same America that we had in the post World War II days.  This is an infrastructure that is rapidly being gutted.  If you have any doubt of how bad things are, consider that Mapp Pharmaceuticals is virtually the only company on the planet with a possible treatment for ebola (we won’t know how the GSK vaccine is doing for awhile yet) and it is a small company in San Diego facing a logistical nightmare.  How does it grow the monoclonal antibodies and purify them on a scale to meet the urgent need of thousands of patients around the world?  Where is the CDC/NIH/Private Industry SWAT team that can get this off the ground?  We are asking this company to do the impossible on a massive scale in such a way that would attract every class action lawyer in the country if there wasn’t a health care emergency.

But it’s even worse than that.  As Collins says, ebola is only the tip of the iceberg.  The vast majority of us will not die of ebola.  We’re going to suffer from other maladies that no one is studying right now.   The funding is low on antibiotics, certain central nervous system disorders, heart disease, etc.  Companies just stopped working on these diseases because the research was expensive and shareholders didn’t think the profits were high enough.

All of this is happening when there is a revolution in biology.  The most ironic aspect of this problem is that thousands of trained researchers have been sidelined right at the same time that there is more than enough work to keep every one of them extremely busy for the rest of their lives.  There’s a profound disconnect between the people who are experienced enough to do the work and the funding mechanisms, either private or public, that will allow it to get done.

I see a lot of fuming on the ebola twitter feed about how scientists should just step up and get it done.  We’re all going to be saved by scientists.  How this is going to happen without funding is anybody’s guess.  It takes money to buy the equipment and reagents and research the papers and feed these scientists who everyone seems to think are going to be self-sacrificing for the betterment of mankind and to save their asses from some exotic African disease.  But as soon as the crisis is over, will we go back to chain sawing through the NIH budget?

From what I can see, neither private industry or our political leaders are taking the threat seriously.  So, I stand by my earlier prediction.  It’s going to take a plague to focus the nation’s attention on our crumbling research infrastructure.  It might as well be ebola.

 

The world ends not with a bang but a PowerPoint presentation

My laptop is still out for repairs. I am preparing for a blow to my bank account. Tips gratefully accepted.

In the meantime, I had one credit left at audible so I downloaded the latest book on the coming zombi apocalypse, The Girl With All The Gifts. I don’t think I’m giving too much away by telling you it’s about zombies. Where would summer be without a zombie beach read?

I won’t get too much into the plot, because I can’t without totally spoiling it for you, but I did find the historical narrative on the apocalypse struck pretty close to what I imagine the truth will be.

The narrator says that after the initial phase of the infection, there was a brief calm and window of opportunity to do some emergency research. But while the pathogen was temporarily quiet, looking for new victims, “global capitalism” was still on a feeding frenzy, tearing the world apart as quickly as it could. Of all the elements of this book, I found this the most believable, I can almost see the suits on Wall Street trying to find a way to corner the market on respirators and disinfectants.

But what was really funny, but not belly laugh funny, unless you’ve been on the receiving end of the MBA masters of the universe bean counting strategy when it comes to research, was the plan that the capitalists, and governments at their mercy, put in place to take advantage of that brief lull to conduct some in the field R&D. They found two articulated buses used by the national science museums and retrofitted them with labs and bunks. Each bus would accommodate 6 scientists each, to be comprised of a mix of biologists and organic chemists. That’s two buses of twelve scientists total to save the world.

One can easily imagine the presentation of this plan and the slick PowerPoint slides to accompany it. On one slide would be the pretty picture of the buses, the next a floor plan where the air locks, microscopes and hoods would be. Then a breakdown of the costs on the next slide:

“The shareholders are prepared to commit $10 million to retrofit the buses, 12 FTE’s for the research. Salaries are competitive with academic research for post-docs at $37,000/year but this is unimportant. If they return, and their experiments are reproducible, we anticipate further renumeration to come from prizes so our costs there are minimal. In essence, this is a self-funding grant. It goes without saying that we will hold any patents and government will fast track approval. Any questions?”

Anyway, the timeframe of the book is years later and the survivors find the buses. No sign of the teams though. It turns out that the pathogen didn’t give them much of a break in the action and those 12 people were just pampered slackers who futzed around with the shareholders’ expensive equipment. Totally unproductive. The MBA’s should have just cut them out all together. What a fricking waste of money.

5 sponges. Highly recommended.

The Desolations of Smaugs

Gotta make this quick so I can bop down to the farmers’ market in East Liberty.

Here are two posts that belong together.  The first is about the crazy amount of money that the wealthy are just sitting on and not investing.  In The World’s Richest People are Sitting on Gigantic Piles of Cash that aren’t Earning them Anything, we get confirmation of what we have suspected for some time, that is, rich people are hoarding money.  But the reason they are hoarding makes no damn sense.  Apparently, the wealthy are waiting for a market correction before they dive back in to investing and since that doesn’t look like it’s going to happen anytime soon, they’re going to sit on the cash.  Now, I can understand that feeling if you’re a poor schlub like me, hoarding the miserable little bit of IRA you have left after several years of employment insecurity.  It makes less sense if you’re a plutocrat with more money than god.

Hmmm, maybe we should be wondering why the wealthy think there is going to be a pullback.

The second is about the consequences of hoarding all that money.  When the shareholders demand more money and less investment, companies tend to shutter their facilities.  Recently, Hoffman-LaRoche in Nutley, NJ closed it’s doors and is preparing to dismantle the site.  When I was a young chemist a long, long time ago, I visited the Nutley campus.  Like many research facilities, it was more like a small town with a gatehouse and a shuttle that delivered the visitor to her destination.  Now that Roche has decided to stop doing research in the US because shareholder value (and Americans are notoriously easy to lay off since they have virtually no labor protections whatsoever), the Nutley facility is about to undergo a radical transformation.  If it is anything like my facility where the rent the company was demanding from small startups was prohibitively high, they probably won’t get many takers.

In other words, if some of the scientists they laid off decided to get together and try to operate one of the buildings as a small incubator, they wouldn’t be able to afford it.  And these days, vulture capitalists want a lot of the research done up front so they don’t actually have to risk any money at all.  That makes research on small scale even more difficult to finance.  Rent, reagents and researchers are expensive.  So, if Roche can’t get any takers to rent its empty labs, it may go the route of some of the other companies in similar circumstances and demolish perfectly serviceable, and in some cases, brand new research buildings, rather than keep them on the books.

Lovely.

One final thing, Hillary Clinton gave an interview to Terry Gross, former Obama fangirl extraordinaire, the other day.  It got a little testy about half way through when Gross started pushing her on same-sex marriage.  Hillary talks primarily about her four years as SOS and seems to think that Edward Snowden had other options to spill the beans.  I’d have to differ with her there though.  Snowden had superuser privileges.  Anything he revealed while he was still in the US would trace right back to him very quickly.  You don’t give su privileges to many people, or at least I don’t think the NSA and its contractors would.  I could be wrong about that.  It seems a little sloppy to allow one person to download massive amounts of information and have no one notice.

Given the reaction of the Obama administration to leakers, I think Snowden did the only thing he could have done and I’m not unhappy that he did it.  I meet people everyday who are pretty non-political who are keenly aware of what Snowden revealed and they are not happy to know that the government has so much information on them.  Until Snowden, the conversation about spying on Americans was tepid at best.  Hillary should know by now that timing is everything.  Snowden forced door open and let the sunshine in a lot more quickly than some politicians might have found convenient but he sure did get their attention, didn’t he?  No putting the genie back in the bottle now or slowing that genie down now.

Ok, enough with the foreign policy stuff.  What about domestic issues?  I want to hear about that now.  No time like the present.  Let’s not put it off any longer.