Open source plasmids: just add bacteria and reproduce at will


John Schloendorn is distributing "open source" plasmids, giving away proteins that normally cost biotech startups thousands of dollars per milligram, ready to be inserted into bacteria and reproduced at will, without any royalties.

As Schloendorn writes in O'Reilly's new biotech journal Biocoder, the move is a response to the extremely high cost of operating in biotech today, where materials that cost effectively nothing to reproduce are stratospherically priced and locked in with license agreements that prohibit researchers from resupplying themselves.

The protections of the closed-source biologics vending industry are actually thin as paper and brittle as glass. For most of this stuff, they have no patents, no copyright, no government regulations, hardly a lobby to speak of, and no monopolies of any kind. They manage to lock biotechnology away from new entrants and to keep the cost of doing science in the stratosphere for establishment professionals, solely through the physical possession of the source DNA and by imposing contractual restrictions on those willing to sign them.

What if there was an alternative? What if there was a source of DNA, tested and certified for the production of high-value biological reagents, that does not impose any restrictions on how the DNA gets used? If this alternative was available, the existing closed-source system would become obsolete overnight. Different reagent production companies could snap up these DNA constructs and start competing on efficiency of gene expression and reagent production, rather than on efficiency in keeping secrets. The prices of biological reagents would collapse, and the quality would improve, as these characteristics take the place of corporate secrets as the main criteria for competitive success. The power of free-market capitalism (meaning the nonsecretive, noncrony kind) would finally be unleashed to tear down the barriers to biotechnology-based scientific wealth, as it has done with so many barriers before it

Open Source Biotech Consumables [John Schloendorn/Biocoder]

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  1. Molecular biology researcher here with experience in protein purification:

    This is a great idea, but it's important to note that going from bacteria overexpressing a protein product is a far step from ending up with a purified protein product. Keeping enzymes in their correct conformation throughout the purification process is difficult, and the machinery and experience needed to go through the purification protocol is not inconsiderable (depends greatly on method of purification - GST/His tag, size separation).

  2. omems says:

    This is great!
    Addgene.org has long had cheap vectors, but they only ship to verified academic/non-profit institutions. BioBricks and their Foundation have attempted to get genetic parts into the hands of non-scientists, but I think they too use Universities as the gatekeepers, so I, as a scientist, welcome a new program to disseminate the knowledge.

    On other hand, for pros, time is often as much a limiting factor as money. Sure, you can make your own Taq, but unless you have undergrads to exploit help, it's a hassle make, purify and validate on your own. That said, I'm always looking for a way to stick it to Fisher Scientific, who is among the worst offenders in over-charging for reagents.

    I hope this takes off.

  3. Can you please elaborate? Many pieces of equipment can be designed and built for pennies on a dollar, and a list of requirements can be pretty helpful for such design process.

  4. Sure thing. To preface, this is coming from my experience working in an academic lab. I don't see why the preparation of protein in a biotech setting would really be different, but it might be. All I can say is that, assuming that lab practices for getting clean protein purification are standard, this is a short (and likely incomplete) list of the stuff you'll need:

    • Specialized competent cells for the overexpression of protein (we used BL21's from invitrogen). I haven't gotten a chance to look over the protocol, but usually you induce overexpression of protein with IPTG. You can also buy more expensive autoinduction media that begins induction of overespression based on quorum molecule concentrations, I believe). If you want to optimize growth, a way to measure the density of the bacteria you're growing (spectrophotometer) is important.
    • All of the equipment required to transform bacteria (water bath, incubator, LB ampicillin plates, access to an autoclave)
    • A bacterial culture shaker to grow bacteria (including other components such as large glassware flasks - ones with baffles are the best to optimize bacterial cell growth)
    • A floor centrifuge to spin down the cells and lysate after growth and lysis
    • A protein purification column - size can vary
    • GST/his beads (or other antibody beads as necessary - again, not sure about what the protocol calls for in terms of the tag on the recombinant protein). These are generally where you get pretty expensive, but they can be re-used a few times.
    • A peristaltic pump to load fluid onto your column
    • metalware and a set up to hold your column and all of the associated tubing
    • To get ideal purification, a gradient tower to allow a gradient of eluent to run through the column
    • all of the buffers and chemicals that make up those buffers to load, wash, and elute the protein without denaturing it
    • A fractionater set up to distribute your eluate as it comes off of the tube
    • a set up for SDS-PAGE to analyze the fractions in which your desired protein is purest and at its highest concentration
    • Specialized tubes of an appropriate filter size to concentrate your desired fractions into working volumes.
    • storage buffer for your concentrated, purified protein.
  5. wanders off to read protocols...
    Lactobacillus is a really nice idea. From a quick glance, it's definitely worth further investigation. And you can keep it in your fridge without running the risk of poisoning the rest of the household.

    I went the other way from electronics to bioscience. There's far more of an overlap than many people think and some of the skills came in very handy when wrangling recalcitrant lab equipment and troubleshooting experiments. Good times. smile

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