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    • Why Would Iran Attack Tankers?
      Well, if it did. Let me tell a story, possibly apocryphal. Back in the 70s the Russian (USSR) ambassador supposedly had a talk with the Pakistaini leader of the day. This is what he is reputed to have said. ” I do not know who will be in charge in Moscow in ten, twenty or […]
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Stupid Drug Discovery Advice, $2 Billion dollar prizes and Antibiotics.

The NYTimes posted a column from Ezekiel Emmanuel, Vice Provost at the University of Pennsylvania, on the subject of antibiotic resistance and how to encourage more companies to develop antibiotics. He wants to reward the successful researchers with a $2B prize. BUT, he says: “no payment for research that fizzles. Researchers win only with an approved product.” Oh, and he says that the bragging rights would be great! Yes! That would make the starvation diet so much more meaningful. Funny, we don’t expect any other employed person to live on nothing for close to a decade on something that might not pan out or may need to be sold to a big company to keep our little startup from declaring bankruptcy.

He’s identified the problem. Companies don’t want to invest a ton of money in a treatment that’s only going to be used for a short period of time. By the way, that’s the new business model. Back in the olden days when I first started working in pharma, we had all kinds of therapeutic areas to choose from. But during the mergers and acquisition years during the 90’s to the mid Naughties, those therapeutic areas had to be eliminated to make room for shareholder value. Ok, I don’t want to get into this too deeply because it’s territory I’ve covered before but I might touch on it towards the end.

As I’ve discussed before, the antibiotic shortage problem was bound to come up. Bacteria mutate. It’s what they do. They are masters of natural selection, if you believe in evolution. If you don’t, an infection might just be one of those mysterious things that happen to people who do not pray enough. See, there’s another topic I don’t want to get into right now.

Here’s the problem: as Derek Lowe at In the Pipeline has pointed out, the molecule space around the typical antibiotic therapy has been exhausted. There are other targets than beta lactamases but they are not low hanging fruit anymore. There are new mechanisms that we have to learn, like quorum sensing for example.

When a new target is identified, it takes many years for that project to reach any semblance of what Silicon Valley industries would call fruition. In fact, the most promising project I was ever on started back in 2006. I don’t know what its status is at this point. It was promising enough that I think there was a drug there. But I’m betting it is still in the early phases of clinical development even now. That’s almost 10 years later.

This is the problem that a $2B prize does not solve. You can’t incentivize research like this. The reason is that the money has to be spent up front. That is the problem that almost all R&D, both academic and industrial, is grappling with right now. The scientists have to be hired and paid, the reagents have to be ordered and paid, the equipment has to be bought and maintained, and the people funding all of this have to have the patience of saints while the scientists churn through iteration of iteration of assays, high throughput screening, medicinal chemistry and drug design, pharmacology, ADME/T optimization and scale up. It takes a long time and it’s expensive. What will the R&D staff live on in the meantime? What are they supposed to use to get their work done? It’s like marooning a bunch of scientists on a desert island and telling them to come up with a drug using sand and chewing gum. Or hitting their “friends, families and fools” up for early funding as the American Chemical Society encouraged us to do when we first got laid off.

There are ways to reduce costs. For example, don’t make everyone live in Cambridge, MA or San Francisco. That right there would save the funding agent a bunch o’cash. Move people back to the mid-west from whence they came 25 years ago. You know, those places like Kalamazoo and Cinncinatti or even Pittsburgh. It’s cheap to live here and there is such a thing called the internet. We might even use web meetings to interact with each other. Wow, I believe I even used to do that with my colleagues in France and Germany once upon a time about 5 years ago! Let’s face it, there is not a big melting pot of exchange going on in Cambridge when everyone has signed confidentiality agreements. The only reasons to relocate there is 1.) it allows the MBAs who were once bio majors but sold out for the big bucks to live vicariously and 2.) I have absolutely no idea. No one I know actually wants to relocate to Cambridge. But I’m getting off topic.

My point is that the investment has to be made up front. It doesn’t do much good if it comes afterwards, especially if there are side effects and litigation that need to be covered. This is the case with all drugs. To get the drug discovery mechanism rolling, the fuel has to come early in the process and be committed to seeing the process through. That’s what we don’t have anymore. Once the drug is discovered and marketed, the profits can be reinvested in the next drug. That’s what used to happen.

Note that in this scenario, it is the R&D professionals who are important, not marketing, finance or shareholders. The researchers aren’t in it for the big bucks. You will have to take my word for this. Almost no one I ever worked with went into chemistry or biology with the intention of becoming an entrepreneur or cashing in big on their first blockbuster. Pushing us to become what we are not may be hampering the drug discovery process. Do you want someone in the lab making discoveries or do you want that person negotiating with contractors and venture capitalists? You can’t have both. There may be a few people who have the energy for both but they are exceedingly rare or exceptionally lucky.

And here is where I revisit the cause for why antibiotics, and other therapeutic areas like CNS, Cardiovascular and reproductive health, have been abandoned. It was the frenzy to merge that caused this to happen. All of those mid-size labs were joined and then a purging went on when the executive bonus class and shareholders took their cut. They created “efficiencies” by cutting out R&D and imposing cost cutting measures on research. They made research departments compete with outside vendors for services. They destroyed the collaboration between departments and exacerbated the complexity of the problem to be solved. They looked at their post-merger portfolios and said, “Antibiotics are not chronic therapies. We can’t make money on those. Let’s cut them.”. That’s what happened, Mr. Vice Provost.

And THEN, to top it all off, the mergers and acquisitors decided that academic researchers were so much less expensive. Why not scrap the R&D group altogether and let grad students do it?? Not that I have a problem with grad students but realistically, you have to do industrial research and follow a project from start to finish (if that’s possible without being interrupted by a merger or layoff) before you actually “get it”. Solving a drug discovery problem is one of the most difficult problems in science. Pretending it can be done on the cheap or rewarded afterwards when the vulture capitalists are going to demand their cut is not really understanding the nature of the problem.

A $2B prize is not a solution. It is the definition of success from a country that thinks the only reward is money. THAT is the bigger problem that we have not solved and the reason why new antibiotics are in short supply.

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A Pleasure in Work

The late John Huston once said, “Choose your career as you would choose your spouse- for love and money.”

The money part has been dogging us for a couple of decades.  We’re so worried all of the time over whether we can pay the bills that we tend to forget about the love of work.  Your job is a place where you spend 1/3 or more of your day.  You should enjoy it, look forward to going to work in the morning, be excited about solving new problems, deliver service to your customers to make their lives a little better, put quality into craftsmanship.

I consider myself very lucky to have a job I love.  Recently, it has gotten much more interesting and I look forward to going to work each day to collaborate.  This is a serendipitous revelation for me and makes me realize that learning new things can keep your mind flexible and young. For people like me who have wanted to do science since they were children, to have a place to go to discover the wonder and delight of nature is a thing divinely to be thankful for.

So, I was deeply saddened to see the following labor statistics:

Pharma Layoffs per Month, 2010

Month Layoffs
January 8,170
February 17,687
March 308
April 1,049
May 6,943
June 830
July 2,023
August 255
September 6,069
TOTAL 43,334

Even more disturbing is what the layoff picture in R&D looks like over the past two years:

Industry 2010 2009
Government/Non-Profit 123,469 109,433
Pharmaceutical 43,334 52,683
Retail 31,246 88,352
Computer 22,609 61,578
Telecommunications 22,609 53,145

Source: Challenger, Gray and Christmas

Regardless of how you may feel about Big Pharma, the loss of almost 100,000 jobs in the past year should set off alarm bells.  Although a number of the layoffs have been related to reduction in pharmaceutical sales staff, an increasing number have been to scientific staff, specifically medicinal chemists, whose jobs are going to China and India, possibly permanently.   Other layoffs in R&D are a consequence of mergers and acquisitions where salaries of scientists, frequently located in very high cost of living states, are considered a drag on the bottom line at a time when patents are expiring and new drugs can’t be approved by the FDA.

That’s thousands of well trained, dedicated scientists whose knowledge base is gone from the American workplace landscape.  It is destruction of American scientific infrastructure on an unprecedented scale.  But more than that, it is the loss of eager minds with almost childlike enthusiasm for science that will doom us as the greatest nation on earth.  In order to keep discovering new breakthroughs in physics, biology, chemistry and medicine, we need a place to go and the means to keep a roof over our heads.  Even scientists have base level caloric requirements and families and children.

I hope that lawmakers  and businessmen wake up before it’s too late.  There’s more to life than making obscene gobs of money.

To close out this post, here’s a video of crystallographers from the University of Michigan riding tricycles around the Advance Photon Source Syncrotron at the Argonne National Labs.  May we all stay forever young, as learners, employees and American citizens.