Drug discovery in academia and NIH, a new type of U01

First off, WOW!!, this has easily been the busiest day ever on juniorprof. Many, many, thanks to Abelpharmboy, Zuska, Melissa McEwan and Almost Diamonds for linking here and sharing your support for the campaign and also to DM for all the support over on twitter for the #painresearchmatters campaign. I am humbled by all of your support and encouragement. Keep the tweets pouring in on twitter with the hashtag #painresearchmatters!

Now, onto our regularly scheduled program: Drug discovery in academia. To some of you this may seem like a strange thing to post about since the common perception is that there is no drug discovery (at least no REAL drug discovery) in academia. I have to admit, I tend to agree that drug discovery in academia is limited and oftentimes lacks the type of rigor that is really needed to develop a drug. For an extensive series of posts on industry vs. academic drug discovery head on over to Derek Lowe’s place. He has all his posts on the topic nicely categorized and they are a very interesting read. One of my all time favorites is this one where he points out that while the compound may be useful as an in vitro tool, it is likely less than useful as a scaffold for further drug development for very obvious reasons. This brings us to the bane of drug discovery: absorption, distribution, metabolism and excretion (ADME). This is something that industry does very well. After all, if you want to make a drug that enters the brain it damn sure better cross the blood brain barrier. ADME in academia, well, let’s just say, not so much. The reasons for this are likely pretty simple: its an important area of drug development but not the most exciting, by any stretch of the imagination (sorry you ADME specialists), and it often requires all sorts of rather expensive testing in model organisms that aren’t used often in academic labs. Its also highly compound-specific and this makes grant writing very hard (or so I hear).

On the other hand, there are very good reasons to do more drug discovery in academia. First, most of the disease models employed for drug development are created in academic labs. Ditto on the development of drug targets for diseases. Its also true that many, if not most, of the endogenous activators of receptors and enzymes have been discovered through the efforts of NIH-funded research. These endogenous ligands are usually the platforms on which additional drug scaffolds are made and academic pharmacologists are pretty darn good at generating structure activity relationships (SAR) for drug-receptor interactions. So what’s the hold-up? In my view its the nature of the academic beast. The medicinal chemists and in vivo and in vitro pharmacologists that are needed to bring a drug discovery effort to fruition just don’t have the opportunities to come together in an academic setting like they do in pharma industry. Pharma industry is built for this sort of thing. NIH grants are not. All of this adds up to major impediments to drug discovery in academia while the potential benefit is huge. Drugs developed through academic efforts have the potential to be much cheaper, target diseases were there is little, if any, potential profit margin (orphan drug programs aside) and would be a huge boon for NIH. Imagine how much easier justifying big increases in NIH funding would be if NIH funded labs were doing work that was leading directly (in the most literal sense of the word) to new therapies. I think this would be huge.

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#painresearchmatters campaign

Yes, I’m on twitter and I’m now posting in Twitterspeak. That’s the hashtag for a little campaign I am starting on twitter to highlight the importance of pain research. The idea is simple, tell the twitter world why you support pain research or why pain research matters to you and use the hashtag #painresearchmatters. I’ll be posting facts about pain and links to interesting papers on pain throughout the coming weeks. I hope you will join me.

This week has not been a good one for pain researchers. Some of our own have come under attack by a publication that is misrepresenting both the purpose and interpretation of their work. This has led to numerous stories around the web resulting in a real firestorm at McGill that has serious potential to spread. I won’t be linking to any of these stories because none of them even bother to describe the purpose of the experiments. If you want to see the story behind the recent fury, read the paper.

It has long been my opinion that us pain researchers do a pretty poor job of educating the public about what we do and why. This is one of the reasons I started the blog. If you’re new here and you want to take a look at some of what I have written about pain and pain research here are some links to start with:

1) What is hyperalgesia and what is allodynia
2) Why does pain become chronic
3) What is central sensitization
4) Why are new classes of analgesics needed
5) Can chronic pain be reversed
If you want to read more, here is an article I co-authored in the popular press. No access? Email me and I’ll send you a PDF.
A wealth of information can also be found at the IASP website

Here are some facts about pain that illustrate why pain research is so important. These are just a taste of what I will be posting on twitter
1) The World Health Organization considers relief from pain to be a universal human right
2) Migraine headache is the most common neurological disorder in the world
3) More people seek medical attention for pain than for any other reason
4) Nearly 50% of people who seek medical treatment for pain report that they do not achieve pain relief with treatment
5) Chronic pain conditions disproportionately affect women

Now that I’ve given you some basic information its time to tell you why pain research is so important to me.

Principal Investigators Association can…

Well, I won’t be as explicit as CPP but that’s about how I feel about them right now. I got an email from them the other day (well, I get an email from them every single day but this one was special) asking me to comment on whether a mouse pain study at McGill was compliant with IACUC rules. That caught my attention just a little bit since I was a pain researcher at McGill for 3 years. I headed on over to the page and was more than a little surprised at what I saw.

I suppose that the purpose of such posts on their site is to help sell their products, whatever those are, and they think their products are going to be helpful to PIs such as myself. Safe to say that I wasn’t interested before and I’m certainly not interested now. The post is about whether the development of the mouse grimace scale, a method to measure affective components of pain in mice, was compliant with McGill’s Animal Care and Use Committee (ACUC) rules. I’m not sure exactly what they’re arguing but it appears to be a pretty one-sided affair and the comments are fairly vitriolic with some threats leveled against the McGill researchers. Great way to sell products to basic scientists doing animal research…

The thing that really gets me about the whole thing (aside from the fact that they are putting my friends and colleagues in danger) is that they completely ignore the scientific findings of the report and the rationale for doing the study in the first place. All of this is straightforward if you take even a glance at the paper.

The past 12+ months and what to expect at the revived Juniorprof

Just over a year ago I abandoned this little blog for 2 main reasons: 1) I was (and still am) incredibly busy trying to get the lab established and bringing in funding and 2) I ran out of things to say. I considered coming back to blogging on many occasions but never really felt like a had a complete grasp on what I wanted to accomplish here. I’m not sure that I do now but I have a much better idea than I had before so here goes…

First, the past year. The first year and a half of my TT position was a real struggle. Setting up the lab was a blast, bringing in exciting and smart trainees was and continues to be one of the great pleasures of my scientific life and getting started on our independent projects was a thrill but writing grants (which I also enjoy) was an utter disaster. I had 8 grants go out and none of them even got a score. Looking back, some of them were truly bad. Some of them were actually pretty good but probably not the right mechanisms for someone like me. The big break came when I applied for a Rita Allen Foundation grant and got it. The Rita Allen Foundation went into an agreement with the American Pain Society to start a Scholars in Pain program (perhaps a rather unfortunate name for a great program) and myself and another researcher at Pitt were the first official recipients of the award. I say official because they actually started the program the year before (but not in name) with an award to a pain researcher at UNC (he may actually prefer sensory systems to pain researcher because his exciting work is a bit broader than pain). Within days, literally, of getting the money for the Rita Allen Foundation award I learned that my R01 from NINDS was going to be funded. While we spent an enormous amount of time getting preliminary data for and writing that R01 (which was triaged the first time), I really believe that the endorsement of the our work from the Rita Allen Foundation played a major role in helping us get the R01. I’d been told many times that getting that first award (whatever it is) is the key to starting to get the funding rolling in. In my case this appears to be true. Since the Rita Allen Foundation award, the R01 came through and the dreaded unscored has gone away. Hence, we’ve got several other grants that I think we are getting close to getting funded and it looks like the lab of juniorprof is going to survive the transition from startup funds to a full fledged NIH supported lab.

Another important feature of the past year was getting the little things done to have my tenure packet where it needs to be to move forward. This meant joining the appropriate committees, doing a ton of reviewing to prove my worth for editorial board positions and saying yes when NIH came knocking to do the study section thing. The study section thing happened in a somewhat interesting way. The day that I got my score for my R01 (which was clearly in the fundable range) I got an email from an SRO to participate ad hoc on a study section panel. I later found out that this opportunity came as a referral from another colleague here at UA so its not like the SRO was trolling for new people with fundable scores but nevertheless I got a kick out of the timing. Since then, I’ve been on as an ad hoc for every cycle. ITs true what they say, you learn more about grant writing from being on study section than any other experience can offer. It really is a shame that they cannot get more junior people into this earlier because it would be a huge opportunity to help people like me get their career going.

Finally, teaching. My teaching load expanded significantly and somewhat unexpectedly. First off, a prof who had run our molecular pharmacology course decided to go part time and this meant that she would not be teaching her course anymore. I became course director and had to scramble to put together the course in short order. This took an enormous amount of time (time I frankly didn’t have) but we got it done and the course is now established (more or less) although it remains somewhat a work in progress (which course doesn’t?). I also took on larger role in teaching med students. Time wise, the commitment is minimal because I am leading group learning sessions (case based instruction) but I am doing it for almost the entire academic year so its a big job in terms of having to get ready for one of these nearly every week for 9 months. On the other hand, I enjoy going into more depth with the students on pharmacology and they seem to appreciate that. Moreover, it has allowed me to recruit several outstanding med students into the lab for either summer research programs or research distinction track training. Overall, all good, but all of things make for a very busy juniorprof!

So, what’s going to happen around here? First off, you may have noticed I am now pretty open about who I am (I’m pretty sure everyone knew before anyways, I think I dropped enough hints that the curious could figure it out in about 10 seconds). If you want to learn more about my lab etc., just go to the about page for all the links. The reason for this is simple. Back when I was actively blogging before I always wanted to talk about our research and especially to try to explain the stories behind how the work came to be and what I think it means in more general terms (translating our obtuse scientific language into layman terms, basically). I didn’t do this for two reasons: 1) we hadn’t really published anything from the lab yet and 2) as an unestablished investigator I felt somewhat vulnerable in doing this. Well, no more. We have a flurry of papers that are either just out or will be coming out (hopefully) very soon and I am going to blog about them here. When I talk to grad students about our research the most common questions I encounter are how did you get that idea and what do you think that means for future therapeutic opportunities. This is what I plan to talk about here. There’s also some self-promotion motivation but why would I put in the crazy hours I put in if I didn’t think the work was meaningfull? I’m pretty excited to get started on this and I hope that giving a bit of the back story behind the work will demystify the process a bit for aspiring scientists and non-specialists interested in pain research and the future of pain therapeutics.

The other thing I want to do here is talk about my class (overview and syllabus). If you take a look at the structure of the class you’ll notice that it is essentially a survey of recent lit that I find interesting. The idea is to expose the students to new concepts and areas of pharmacology and to push them to do independent learning. Most of our students are interested in pursuing Big Pharma jobs after graduation and I think that this is a valuable exercise for them to help them approach the literature in a more constructive way and to help them become better independent learners. So, what I plan to do is to continue the discussion of the papers we do in class here. I’m not sure if the students will go for it but its worth a shot. Maybe the blogosphere will become part of the class… that would be cool!

Finally, I’m going to get back to blogging about pain research in general. My post on hyperalgesia and allodynia has drawn more traffic than anything else I have ever written and is one of the first entries on google if you search for either one of those terms. There are thousands of people out there suffering from chronic pain conditions and I think that resources such as this can be very helpful. I honestly believe that understanding why pain becomes chronic is one of the great challenges in biomedical sciences today and therapeutics that come out of this type of research have a good chance of having an enormous impact on society. I’m looking forward to talking about this theme more in the coming months.

Yeah, I’m back and might actually stay for awhile

Sorry for the prolonged absence (if anyone cares). There wasn’t any big reason to stop blogging for 8 months. Yeah, I was busy, and yeah, probably too busy to blog but I really felt like I didn’t have anything else very interesting to say at the time. In the intervening 8 months lots has happened (more on that later) and I now feel like I’m ready to talk about it. I also have some idea about what I’d like to do with this place moving ahead. An astute reader may have already noticed some major changes here that might give some hints on my intentions moving ahead (aside from the appearance of two new posts).

I’m pretty excited to get this thing started up again and hope some of you who used to read and comment will return. More importantly, to those of you who asked questions about pain conditions that went unanswered, I will try to get to those over the next days/weeks. Hopefully its not too late to provide some input.

Michael Ehlers to head Neuroscience discovery at Pfizer

This surprised the hell out of me. I have long been a big fan of Dr Ehlers’ work. As far as I’m concerned he has done as much as anyone to advance our understanding of the dynamics of dendritic spine plasticity and his work on golgi outposts has had a huge impact on how I think about scientific problems my lab approaches. I’ve met him a couple of times when he has given talks and let me tell you, dude can give a talk! Its an almost surreal experience too because he looks like he’s about 17 years old (don’t believe me, check the link above). He’s been a Hughes investigator for years and recently got an endowed position in neurobiology at Duke… pretty sweet spot to continue a nice academic career if you ask me.

Well that’s not going to happen. He’s moving to Pfizer to take a position as CSO of Neuroscience starting in August. The interview in Nature this week is quite interesting on many levels and I’d like to discuss some of them here in the context of what I’ve learned about industry drug discovery over the past years (basically since becoming a PI).