In which I differ with Derek Lowe over NIH funding

Typical private industry lab circa 2014

Derek Lowe, blogmaster over at In the Pipeline, took issue with NIH Director Frances Collins contention that if the NIH budget hadn’t been cut in the past decade, we might have had an ebola vaccine by now.  I remarked on the Vox article about this very same topic last week.  However, I’m siding with Collins on this topic.  True, he might be using the very scary disease of ebola to make his point but it is a valid one.

To get an idea of what the NIH has been up against, I recommend that readers review the congressional testimony on the ebola outbreak from last week.  I believe it was Anthony Fauci who laid out the problem.  It goes like this:

1. The NIH identified the need for an ebola vaccine about a decade ago.
2. (This is the crucial part) The NIH is engaged in basic research.  We are talking very, very basic research.  Like, identifying the genes and sequences and making them available to other researchers, or studying how the virus works and propagates, or figuring out which enzymes chop up the viral proteins, or how the viral proteins are exposed to the rest of the body.  That’s the kind of research the NIH does.  And sometimes, the research is so preliminary that there are mistakes that get published that industrial labs have to figure out when they try to replicate the results in the lab.  Not a criticism.  It happens.  You only have so much money to do the research and sometimes, it’s not enough to double check your results.  I get it.  But it does make it harder for your private industry partners to figure out what’s going on and sometimes means that projects need to take detours to unpack mechanisms and rerun assays and such.  In other words, REAL RESEARCH.  That’s just the way science works, much to the finance industry’s chagrin.
3. So, the NIH tried to get a private industry partner to help finish the research on the vaccine and develop it.
4. But during the same decade, private industry was going through a chaotic destructive process brought on by the “patent cliff”.  That is, the blockbuster drugs that fueled industry research suddenly went off patent.  In response, the shareholders who were not about to take a haircut just so some lab rats could continue to do research for them, decided to take the money and run.  That precipitated Pharmageddon, where I and my colleagues got tossed out of corporate labs by the hundreds of thousands.
5. The NIH couldn’t find a private industry partner until the last couple of years when Glaxo Smith Kline (GSK) decided it would take a risk and start working on one.
6. In the meantime, in the last couple of years, the Republicans have lost their freaking minds over the budget and would rather let every government institution rot in hell before they would approve any funding.  This is about the same time we wrote a blank check to AIG, and other lords of the finance industry (see Neil Barofsky’s book).  Then the Democrats came up with this great idea of a sequester, you know, to call the Republicans bluff.  And the raving mob that calls itself the Republican party took the deal and slashed NIH funding by 20%.  The Democratic leadership that came up with the boneheaded, backfiring sequester idea should be kept away from sharp objects for their own safety.
7. So, to recap: NIH needed a vaccine but couldn’t find a private partner for nearly a decade.  Private industry contracted at a time when additional research and development is crucial.  Regular NIH funding is not sufficient for it to develop a vaccine on its own.

This would probably be a good time to insert some Paul Krugmanesque graph that shows the equilibrium between private and public investment in scientific research.  This one should show that when private industry stopped funding research, the corresponding expected increase in public spending was notably absent.

Derek has a libertarian streak and works for one of the last small molecule drug discovery companies in Cambridge.  That’s not necessarily a bad thing but it does skew his perspective just a tad.  Not only that but Derek is operating in the old world order when we tested every therapeutic treatment to death.  That’s clearly not happening with the ebola treatments.  Those suckers have been fast tracked like nobody’s business.  We are treating ZMapp like it’s a cure for ebola when it’s nothing of the sort.  It’s just that it’s the only thing we’ve got.  ZMapp is so early in development that back in the old days of real drug discovery, it might have been killed in a project portfolio review before it ever made it to development.  And the vaccines?  Well, normally, they’d go through many stages of development and testing for safety, efficacy, and side effects with an expanding number of trial recipients at each stage before it was approved by the FDA.  Forget that.  In this epidemic in West Africa, with number of exposures increasing exponentially, no one has time for these niceties (though I can just see some lefties screaming about how we killed West Africans with an untested vaccine that triggered a cytokine storm or autoimmune disease.  Wait for it.  You know it’s going to happen.  There will probably be a movie about it featuring some ruggedly handsome Liam Neesom type and a earnestly beautiful lady scientist detective out to uncover the awful truth of corporate exploitation of poor third world citizens.).

The real world is not so simple but there definitely is money at the bottom of this mess.

I’ve worked on both sides of the problems in both industry and in academia, if only briefly.  But I got a good look at what it’s like to do research on NIH grant money and it’s not pretty.  Most of a principal investigator’s time is spent preparing grant applications.  It’s very bureaucratic and, I suspect, very political.  If there isn’t a retrospective analysis on the amount of grant money that goes to the Ivies that leave the rest of the academic labs starving for funds, there really should be.  Not every breakthrough has to happen at Harvard.  The polio vaccine, for example, was developed in Pittsburgh.  Oh, yeah, how many of you knew that Jonas Salk worked for the University of Pittsburgh? True story.

And yet, it was about a year ago that I got a call in my office at Pitt from a researcher in the immunology group who had just lost her job because of the sequester.  It was last year at about this time that we had to cut back sharply on ordering chemicals and lab supplies for my lab because grants were on hold, also due to the sequester.  Even today, I see positions at Pitt for the kind of work that I used to do but the hours are part time.  Really??  You expect scientists to do protein production, extraction and crystallization experiments on a part time basis?  That’s the craziest thing I have ever seen.  You can’t just interrupt an experiment half way through the week because you’ve run out of hours.  That makes me think that the people posting the positions aren’t serious about how many hours they expect the researcher to be available.  It’s deceptive and weird and unrealistic.  But that’s life on soft money.  Here today, gone the next.  Yet the cells still need to be fed, lysed, protein collected, spun, purified, etc, etc, etc.

Friends, Americans, countrypersons, this is no way to run a research infrastructure.  Ok, sure, it’s the way to run a research infrastructure if you don’t want to do it like Americans used to do it.  If you are content to run a research infrastructure like Bolivians do it, fine, do it this way.  But don’t complain later that nothing of significance happened on the science front from 2008 onward.  Don’t complain that the NIH is not telling the truth about funding.  It can’t be all things to all people without a steady funding mechanism that isn’t going to be subject to violent shocks brought on by crazy people who get elected to Congress.

Here’s the bottom line.  If liberals expect the NIH to do all of the things that they *think* it already does, it needs more funding.  It needs waaaaaaaay more funding than it already has.  It needs as much funding as private industry used to pump into its own research coffers but no longer does.  It needs billions and billions more.  It has to become what private industry used to be but no longer wants to be.

And if Republicans are committed to free enterprise at all costs, it’s going to have to get tough with private industry drug discovery and force it to take on research that it sees as unprofitable.  It needs to have a serious talk with the bonus class and shareholders about greed at the expense of public health.  Isn’t that what the GOP is all about?  Morality?

That’s just the honest truth.  The NIH is not private industry.  If we want the NIH to replace private industry, which has abandoned certain, critical research areas because it can’t make the kind of profits that shareholders demand nowadays, we need to put more money into the NIH and fund researchers properly and seriously.  That is the point that Frances Collins has been trying to make.

Liberals have a complete misunderstanding of what the NIH does or is capable of doing.  Libertarians have an inflated view of what private industry can do, sometimes because they are living in one of the last holdouts of productive private industry drug discovery (that could end at any time, so don’t get too comfy, Derek).  But once you have lived in both worlds, you can see what a shambles the whole system is.  It’s unsettling and alarming.

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.

 

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.”