Back off, man. I’m an independent scientist

April 26, 2013

I emigrated to the Bay Area as an independent scientist three weeks ago. Since then I’ve been planning the revival of Perlstein Lab, which is in post-academic hibernation. After several months of soul searching, PubMed sleuthing and Twitter colloquy, I’ve decided to pursue rare disease drug discovery using the evolutionary pharmacology approach I validated during my Princeton fellowship.

 

There are over 7,000 rare diseases, which are almost all caused by having two mutant copies of a single gene. En toto rare diseases affect 10% of the population, so 250-300 million people worldwide. Remarkably, many rare disease-causing genes are conserved in all eukaryotes. Using copiously studied genetic model organisms — yeast, worms, flies and zebrafish — for rare disease drug discovery may have its greatest impact on brain diseases, whose underlying mechanisms are still poorly understood. For example, a tsunami of neurodegeneration is massing over the demographic horizon, and we desperately need genetic illumination. And the cherry on top of the sundae of conservation is that common diseases can be modeled by rare diseases.

 

Besides scientific curiosity and idealism, there are practical reasons to choose rare disease drug discovery. For one, there’s expedited FDA review under the Orphan Drug Act, and a more recent “breakthrough” track, which decrease the time to translate discoveries from the bench to bottles in the pharmacy. Related to clinical trials, the drug repurposing fad — finding new indications for old drugs — dovetails nicely with rare disease drug discovery because the FDA pharmacopeia has plenty of surprises up its sleeve that can skip safety trials (Phase 1) and go straight to efficacy trials (Phase 2 and 3).

 

The big questions are how to fund and staff this rare disease drug discovery enterprise, and of course where to house it all. I am, after all, an experimentalist. And being a recent transplant, I also happen to be looking for a place to live, so I’ll focus on the search for lab space here, and save funding and staffing for future posts. One of the many professional reasons to relocate the Bay Area is the opportunity to access unconventional lab space outside Academia and Pharma. It looks like I have two ready-to-go options: 1) lease a bench from a life science startup incubator, or 2) join a community lab, sometimes called a biohacker space. There are also more creative options, like carving out a niche in a local academic lab, but the regulatory and administrative hurdles would be non-trivial even if I were to find a magnanimous host.

 

As of last count, my new home boasts seven sites where lab space can be leased on a monthly basis. Five of these sites are life science startup incubators in the QB3 network, which promotes and advances translational research from the Bay Area UC schools. However, as I mentioned above, there is also a bottom-up alternative sprouting up around the Bay Area, as well as in other cities. Biohacker spaces like BioCurious in Sunnyvale and GenSpace in Brooklyn level the playing field with tech startups and hackathons without compromising safety or reproducibility, and even allow independent scientists to commercialize their results. I’ve been introduced to members of the BioCurious team and I plan to drop in soon.

 

So, it’s between biotech incubator vs biohacker space. Or is it? A question I keep asking myself for the near-term is: do I need one central lab space, or can I manage projects that are distributed across research sites with unique communal resources? Evidence that the distributed model works is the Crowd4Discovery project, which is currently underway in the Sulzer Lab in New York City while I manage the project remotely. Of course one could also leverage websites like Science Exchange or Assay Depot to source experiments from third-party providers, the way Atul Butte of Stanford Med and others have been doing to great effect.

 

In these situations, I do what I’ve always done: strategic cold emailing. I scoured the QB3 site for contact@XYZstartup email addresses and blasted out 20 messages; almost half replied within 72 hours. From the subsequent Skype/phone chats and in-person meetings, I gleaned the distribution of startups at QB3: a good mix of companies founded by serial entrepreneurs as well as n00bs. Many of the representatives I spoke to had actually graduated from QB3, which as the name incubator implies only nurtures companies with 5 people or less, after which point they’re ready to leave the nest (or plummet perilously to the ground).

 

I also got a tour of the East Bay Innovation Center, which is the newest of the QB3 incubator sites. Turns out this space is sublet from an independent commercial entity, as is another QB3 incubator site. Some equipment is communal, like the fridges and freezers and the occasional incubator or shaker. Several of the QB3 folks I chatted with affirmed the positive community ethos. The catch is QB3 costs $900 per bench per month. For some sense of scale, my old lab at Princeton was comprised of 9 benches as defined by QB3, so it would cost $81,000/year to recapitulate a comparable footprint. For the uninitiated, here’s what a typical bench in a basic biomedical research lab looks like:

 

lab bench

 

Lots to think about. If anyone has any other suggestions about where and how to reconstitute Perlstein Lab, I’m all ears. Per usual, the comment thread is open.

 

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  • sonic

    Good Luck! Looking forward to hear how things progress.

  • http://twitter.com/enature enature

    It all boils down to genuine results. If you get them you are a hero, if you don’t you are a 0. Or so they will say. Biomedical research funding is in many aspects pathological. Making it on your own will take real courage. Wish you sincerely success!

  • http://twitter.com/hbergeronx matt harbowy

    There are at least two other spaces under development, planned to be better equipped and much less expensive than QB3. Follow me on twitter at @hbergeronx

  • http://twitter.com/Antonio_Kon Antonio

    Good luck! Sounds exciting…scary as hell but exciting!
    What sort of equipment do you get other than just a bench in these lab spaces? Do they look after waste disposal and other costs (significant costs actually…my uni is planning on opening it’s own furnace for med waste to save money)?
    Have you thought of how you might create some IP from your work, I mean something someone would possibly fund? Research without proper support or collaboration is tough, and those will only come if there are the right incentives around.

  • Andrea

    I just invited you to Venture Lab. It’s a class, it’s a good free networking tool all rolled into one!

  • Kyle Brown

    Part of the challenge is presenting a view of the size of the patient population and their pheotypes. Patient registries are a good place to start … quantify and qualify the patient population. patientcrossroads.com

  • Miriam Boer

    Hey, I’m doing something similar; bootstrapping my biotech startup, which I started straight out of grad school. I’m renting space in a teaching hospital’s core facility, which is a pretty sweet deal bc I get access to all the shared equipment (culture hoods, centrifuges, pipettors, plate readers, microscopes, freezers, etc.), the university subscriptions to journals, I’m not working in a vacuum, and I get a clinical perspective from the folks around me. Additional cost beyond the $1k is for disposables and my own personal supplies (pipettes, plates, cell lines, gloves, etc.) In my search for lab space, I came across Janssen Labs: http://www.fiercebiotech.com/press-releases/janssen-research-development-llc-opens-janssen-labs-san-diego Yeah, you’re going to pay $1k a month for a bench, but that includes shared equipment. It’s definitely possible, and you’re not the only one.

    • Ethan O. Perlstein

      Thanks for the comment, Miriam!

      I actually don’t necessarily want to bootstrap. My indie science funding model will rely on some combination of crowdfunding, venture philanthropy (crowdfunding + expert filtration), and patronage. I can imagine fee-for-service experiments in the medium to long term, but I want to get off the ground quickly focusing on discovery science without having too much drag.

      • Miriam Boer

        Ahh, I misspoke. I meant the startup model I’m developing can keep costs in the tens of thousands of dollars (bootstrap territory) for someone just starting out as opposed to hundreds of thousands of dollars (serious investment territory). My funding is all private investment, done as a sort of science philanthropy/encouraging a local startup scene and culture with the somewhat remote possibility of it paying off in financial terms down the road. (It’s biotech, so come on… higher expectations are unrealistic.) But what it does is make that initial external investment more attractive while allowing the owner(s) to keep a lot of equity. It gives a researcher the same incentive that low overhead computer-based startups have, namely to keep equity, and private investors write it off as a loss in those first years (ah, tax incentives…).

        As far as crowd-sourcing and patronage as a means of investment go, I’m really interested to see how you fare. I had essentially zero network coming out of grad school, and the way I got anyone’s attention was by pointing out a massive market and unmet need for what I’m doing and that what I’m trying is just developing as a field of study. So, there was sort of a novelty factor and potentially large market to encourage investment. Granted, you probably know a lot more people, you have some very pretty credentials, and so you may have an easier time of it. But no matter how the funding comes, more of us need to do this. Academia is kind of a shit show these days. I really hope it works out for you!

        • Ethan O. Perlstein

          Thanks for clarifying, Miriam. I admire your fortitude! What I hear from friends in academia is that they’d never try something so risky as a startup or an indie science path. Academia has to go from shit show to diarrhea fest, I guess, before people start flocking for the exits without abandoning science itself.

  • R Evans

    You’re doing everything I want to do at some point, and would be doing if it wasn’t for $50k college loan / credit card debt and a $40k/yr income. Rock on! The more that people like you advance the potential for independent scientists at your level the more likely opportunities will trickle down to my level. I started a LinkedIn profile a couple months ago, and am currently linked to no one. Mind if I link to you?

    —————
    Why treat what you can cure? Yes, I understand why: because it’s short-term more efficient, and because that’s where the easy and abundant money is (comparatively). And because some diseases need treatments in addition to cures to undo the existing damage.

    My idea is to engineer hetero-tetrameric serine recombinases with sequence specific catalytic domains and interacting head-groups that would ensure precise arrangement and a strong preference to unidirectional activity for direct genomic editing.

    This would be relatively simple for most of the repeat expansion diseases – at least most of those that don’t suffer from methylated repeat induced chromatin compacting – because you don’t even need to introduce exogenous DNA. All you need to do is excise the extra repeats.

    It’d be a little more of a task for those diseases caused largely by missense, nonsense, etc… mutations, especially given the possibility of random insertion of the correcting DNA due to NHEJ and the like. But it would still be doable.

    Genetically edit the germ line and you could reduce the incidence of most of these diseases to the one-in-a-million / one-in-a-billion spontaneous mutation.

    —————
    “There are also more creative options, like carving out a niche in a local academic lab, but the regulatory and administrative hurdles would be non-trivial even if I were to find a magnanimous host.”

    No kidding! The reply I got when asking someone about this was: “I appreciate your idea, but what you are asking is not possible. You need to be a faculty member to be eligible to apply to CHDI because sponsored research has to sign off on any extramural funding application.”

    Robert Evans
    pulnimar

  • R Evans

    “The catch is QB3 costs $900 per bench per month. For some sense of scale, my old lab at Princeton was comprised of 9 benches as defined by QB3, so it would cost $81,000/year to recapitulate a comparable footprint.”

    There are more than 10 months in a year.

  • richardgordon

    In the 1800’s the production of excess scientists (who then became high school teachers) went in 30 year cycles. See:

    Nyhart, L.K. (1995). Biology Takes Form: Animal Morphology and the German Universities, 1800-1900. Chicago, University of Chicago Press.

    This could probably be modelled by a differential delay equation. So the Ponsey scheme of training more scientists than academia can hold has gone on for quite a while.

    I understand that you are near the beginning of your career, but there are a few of us who slipped through the system as independent scientists with tenure, doing what we felt was most important, albeit with little in grant funding from our dysfunctional colleagues. And then there is another group put out to pasture: the retired academic scientist who continues to answer to the calling, despite lack of funding and institutional support. Time to organize? After all, there is no union of scientists, let alone a union of independent scientists.

    In your interview, you briefly mentioned the grant system as no longer functioning. Nevertheless, you might want to tilt at that windmill and occasionally file a grant application, even though you won’t qualify, since you are outside the academic closed shop that is in cahoots with government and private grant agencies. You may need a lawyer for this, but if you are going to start a declaration of independence for scientists, might as well scale the walls and get your share of the booty. I recall in the 1960s a policeman who did science in his basement applying for a grant, and got turned down for his independence.

    Thanks for leading the charge.
    Yours, -Dick Gordon DickGordonCan@gmail.com