Friday, October 8, 2010

On the importance of sequenced model organisms, & a crude taxonomy of their users

I've carved out some time recently to meet and interact with more of those people, like myself, who identify with the nascent DIYbio community. It's been a genuine pleasure. Some of this networking has happened at summer conferences, such as H+ Summit held at Harvard and Open Science Summit at Berkeley, as well as at smaller, less formal events, including one held earlier last week at a downtown Manhattan design studio used by an intriguing project in Columbia's architecture program. But as with most hackerish subcultures, my richest interactions have happened between face-to-face meetings, mostly on the diybio GoogleGroup mailing list.

I've had to struggle with a few things, and do a bit of Blind Man and Elephant feeling around, but I'm starting to develop a model of the beast in my head, one probably partially right and likely largely wrong, since the beast seems to be growing on a bauplan not comporting with a developmental model I, or anyone else, fully understands. So far, I've provisionally identified four rough categories of aspiring DIYbio biologist:
  1. The Educator
  2. The Hobbyist
  3. The Entrepreneur
  4. The Independent Investigator
The Educator's interests seem to lie in outreach, addressing the shortfalls and broken-ness of an embarrassing government public education system. He supplies passion, expertise, and - sometimes - equipment to cash-strapped science departments. His challenges are manifold, but his cohort's solutions are remarkable, such as a proposal to supply schools with PCR thermal cyclers at a low enough price point to make economic sense for a teaching module lasting a couple of weeks: a cheap, reliable, plain-Jane $200 cycler. Proposed devices may look like prototypes, but they're vastly preferable - and more easily justified - to the average run of knackered $800 commercial units sold by indifferent hardware clearance houses on eBay. And there are simply some approaches to teaching best seeded by outside ingenuity.

The Hobbyist is, of course, the consummate do-it-yourself'er: she's the DIY purist, and her motives are much more easily evident. She wants to tinker with everything at every step of the way, preferring all her own metal bending, DNA electrophoresis gel compounding (plain Jello gelatin is not to be laughed off, folks), and like one of those fabulous self-taught cooks who prides himself on where to source the best spices in New York City's Astoria or Chinatown, she would rather source her wildtype flies from a neighborhood compost heap and her wingless flies from a pet supply operation, than order them from a standard supply house like Carolina Biological. She is a dedicated life hacker and preferential locavore, and she advances the art and brings to it a delightful panache.

The Entrepreneur has plans, and could benefit in the execution of them by having access to low-cost facilities and equipment for prototyping new processes. He's probably just out of college, or a career changer, or both, and his highest barriers entail access to gear & expendables for proof-of-principle exploration. He wants to try some things out, and he needs low-cost access to a friendly workspace where the owner-operators aren't waiting to pounce on him and lay claim to a piece of a potentially lucrative business model. In fact, he'd really prefer a social setting in which he can collaborate with others, and maybe get noticed by potential angels and other investors. You might want to hire this guy, or at least stalk him from afar and throw money at him at a vulnerable "Eureka!" moment.

The Independent Investigator is a guy with some academic grounding in the field, maybe some additional industry experience in (or on the periphery of) biotech or pharma. He might be between schools on a gap year or two. He might want to work on something his lab's PI doesn't find interesting, or in a facility which doesn't allow "Saturday projects" as as matter of policy. Or, maybe he does work with an enlightened team in fabulous facilities, but fears the conflicts of doing his own thing under the aegis of an NIH grant not scoped for his pet project: who owns the outcome? So he chooses to set up a bench at home, or in a shared space where he might do his thing unencumbered. Because sometimes, even professional chefs prefer to cook at home.

Now, these are rough, subject-to-revision taxa, and exist mainly to help me organize my own thinking on the matter. Like most early attempts at classification, they're rife with observational deficiency and confirmation bias, and I expect my categories to be revised over time as the community and I mature together. I find these roughly useful, though, especially when used in combination, to model the motives and project the needs of individual actors, myself included. The interesting fact is, most of those involved don't fit in one category to the exclusion of others. Many of us harbor the Educator impulse, that desire to share domain expertise with those who might join us. Who doesn't have a bit of the Hobbyist in them too, that drive to build one's own toys? And in this community, the Entrepreneur and Independent Investigator are often aspects of the same agent. This last embodiment feels most kin to me when I meet it at events, and he and she are my intended audience here, though others may also find what I have to say of some use.

For the sake of brevity, I'll refer to my own cohort as "3:4" per the list above. Having first met 3/4s in person, and 1s & 2s later, I'd erroneously assumed the majority of DIYbiologists to have had some formal education and lab background like myself, since these were the people I was meeting at conferences. I think I was wrong, at least if mailing list traffic is any indication of underlying demographics. At least, I don't have good reason to attempt a census of lurkers, because actively interacting participants are likely to be much more interesting than lurkers anyway.

Given the relative scarcity of type 4s like myself, then, I've seen some discussion predominated by 1s and 2s in which the topic of some model organism comes up, but without the usual banter about strains and other identifying information one would expect when talking to a collaborator in another group about a mouse, say, or a fruit fly: "We need a couple of weaned litters of Black 6 delivered to our barrier facility," or "This protocol's DNA extraction requires at least 50 wingless flies to be homogenized first." These organisms are inputs to experiments, and one can assume -from how the critters were sourced - they've had their DNA sequenced or, at the very least, to have been genotyped. For those who don't understand the difference between "sequencing" and "genotyping," by the way, some study is in order. To those working with E. coli, M. musculus, and D. melanogaster: you have the benefit of having fully-characterized, sequenced organisms available to you now. Be glad you were born in these times.

To those of us in the 3:4 crowd: unless you've planning on personally conducting the first reference sequence of the strain of whatever organism you're working with, you're need to use a strain with documented sequence. More often than not, you'll need the particular strain that commercial and academic investigators are using, because assumedly, you're either working on a problem which has its roots in the literature (but which no one's yet tackled) or you want to extend someone else's work yourself. For example, you may think you want to take a crack at the potentially lucrative MPrize yourself, but even if you accomplish its stated objectives and produce a spectacularly long-lived mouse, you are in for a bit of trouble if you started with mice of unknown provenance: how are you going to expect others to replicate your findings and take you seriously? You may be a short-term pop journalistic curiosity at best, but you'll have to start all over again with a known strain.

Now, if you sit squarely in the Type 1 or Type 2 camps, then acquiring your flies and mice in the urban wilds is not only perfectly cool, but could also be fun, and might make for some interesting field trips, as well as great stories to tell. If you're interested in educating yourself or others about Mendelian inheritance, for instance, it could be argued that growing up city flies in large lots and selecting interesting mutants with obvious naked-eye-evident phenotypes, then crossbreeding them, is exactly the way to go about doing it. I would agree, and might even strongly advocate that approach. The last thing one wants to do is tell an aspiring child biologist that in order to work with flies, her only option is to have Daddy order a box of them from The Fly Store. That's a great big Curiosity Hammer swinging its way down hard on her motivation, a tailor-made way to kill the notion that she can do the stuff herself. Not good, not recommended.

But if you're wanting to "do science" and generate data for hypothesis testing, you're going to have to follow a few of the same ground rules of science that obtain regardless of your background or institutional affiliation. OK, so I've ranted a bit about the requirement to work with known model organisms, but I've said Jack about the logistics of actually going about it. The short answer to that one, my friends, is that I don't yet have a full set of answers. I do have some ideas, though: the biological sciences department of your local university is not a bad place to inquire, at least when it comes to finding E. coli and flies. To anyone reading this: have you tried asking someone? I mean, it's hard not to breed flies, given non-demanding room conditions, and they do breed like flies. I've worked in labs where excess flies are available, and often have to be killed. Try asking around. And E. coli? Bring your own LB medium and they might inoculate a culture for you. Good to go. Mice, though, are a very different issue, one I hope to treat of later.

Added bonus: you might just develop a really valuable relationship with a local lab, one whose postdocs might not have enough grad student helpers; if you can earn a track record as a reliable volunteer "outsource experimenter," you're golden. Consider it seriously. I'm surprised to hear nary a mention on the mailing lists of this type of thing, so it's worth mentioning.

Over the next few weeks, I hope to learn more about how the community sources its model organisms, and expect to report my findings when I can make concrete recommendations. Stay tuned.





3 comments:

  1. Great post, really well written and thought-provoking. I'm probably somewhere in the Type 1/3 categories by your classification: I really love Education and Outreach, but my real aim is to try and make a gainful career of Garage Biotech and to help others do the same. And, to that end, I wholly agree that you need to work with a model organism.

    In my experience, university labs are usually pretty friendly and approachable places. Sure, they're required to put "DO NOT ENTER" signs on the lab door (and indeed, don't enter: try knocking on the office doors rather than the labs to put your best respectful-foot-forward), but the people inside are usually delighted to meet someone interested in the art. Getting an organism that is certifiably harmless to everything shouldn't be an issue if you really make it easy and give them a reason to care (which an interest in outreach normally fulfills).

    It *does* help to make friends with these people. Not only may your local lab be a ready source of advice and interesting conversation, but they may help you perfect protocols and even source old equipment in the back. You might be surprised; just knowing that you're out there attempting cheap and effective methods might be enough to pique their interest. If you come back and tell them "I did a miniprep using dishwasher detergent!" (unlikely as that may be), they might be intrigued to learn how. Scientists are a naturally inquisitive lot, after all.

    My recommendations for things to request of the local micro lab: E.coli K12 or "Bacillus subtilis 168" (the type strain used by most). These are fully sequenced and are safe model organisms for Gram-Negative and Gram-Positive bacteria, respectively. There are tons of protocols out there for both that can be easily DIY'd, and they are both pretty easy to work with on any scale, from the streaking-plates-for-fun to full-blown molecular biology work. I particularly like B.subtilis, for lots of DIYbio-y reasons: it's naturally competent, it grows on Potato-Glucose/Sucrose broth/agar (easy as sin to make), it sporulates making long-term-storage a doddle and obviating the worry of "Oh God I Forgot My Cultures" while on holidays, and it's edible (qualifying for "Biosafety 0").

    Of course, if you can't muster the courage to meet and get acquainted with your local lab, or if they prove snotty and unhelpful, you can always get B.subtilis by special order from your local hippy/health store. It mightn't be 168, it might be subspecies "natto" (used to make the dish of the same name), but it's probably one of the key strains and it'll tide you over while you learn before you get the real deal.

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  2. Something you wrote about the publishing of magazines was republished at http://lists.extropy.org/pipermail/extropy-chat/2010-October/060908.html and I thought it was a good read, so I surfed on in here to your weblog. Bye, -Arthur

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  3. Working in Manhattan, i.e. ground zero for potential terrorist activities, it is not practical to just ask a university scientist for some bacterial cultures, no matter how harmless they are. Remember, the only one who was finally beaten into pleading guilty in the Steve Kurtz case was the poor academic who supplied him with his strains. They got him on violating the materials transfer agreement that ATCC makes you sign. Granted, the story is not finished yet, but the New York DIYbio group is obtaining their strains directly from the sellers, keeping them in-house, and being as public as possible about their work, even hobnobbing with their local FBI Weapons of Mass Destruction Coordinator (I kid you not- that's his title) to prevent future "misunderstandings".

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