Spanish Prisoner, ZX-81 or Turbo Pascal?

In  the movie The Spanish Prisoner, a brilliant inventor possesses a paranoia that "The Process" he has invented will be stolen by deceitful competitors, and everyone speaks with a highly distinctive cadence. The entire movie is suffused with deceit, starting with the title which is a notorious con scheme akin to the modern Nigerian scam. I spent last evening in some of the space in which the movie was filmed listening to a scientist in that mold (& distinctive speech) describe a process his group has invented (indeed, by lucky chance I helped him find the venue). But many remain unconvinced that Clive Brown and Oxford Nanopore are not themselves the puller of ocular wool.

Lex Nederbragt has a good post on the hubbub which likens the MinION sequencing platform to a washing machine.  If a company claimed to have a radical new washing machine which used its own radical new detergent, would you lay out $1K to try it out?  Sure, the deposit is refundable -- just like the deposits made on behalf of the widows of deceased dictators who contact you via email.  That is the über cynical view; that while I and others loaded liquid into a device and saw squiggles appear on a laptop screen, the fact that Oxford Nanopore still hasn't released actual sequences nor error rates -- and that we took none home last night -- means we might have run the most over-engineered buffer detection system ever built. Perhaps the MinION flowcell lookalike USB memory sticks we got will be the only useful tools to come out of Oxford Nanopore.

To me, the chance to wager a bit of time and not a whole lot of money (in the scheme of things!) to try out a potential ground-breaker is a no-brainer.  Whereas other companies, notably Ion Torrent, have talked about rethinking the way product launches are run, Oxford is really doing it, allowing a diverse group of scientists who are not the usual suspects to beta test their instrument. If it really is vapor, we'll find out soon.  Some product launches go well; some are awful.

I'm reminded of some earlier experiences with trying out the bleeding edge.  In the mid-70s, my brother and father assembled a single board computer kit called the DATAC-1000; my contribution to assembly was limited to sorting resistors by their color codes.  Similar to the KIM-1, DATAC never really took off, particularly when a computer was launched with the same microprocessor but built-in video by two guys named Steve.  A few years later, Sinclair Research launched a new computer, the ZX-81, in the U.S. with two purchasing options.  One was to buy it fully assembled, the other to get it as a kit for 2/3 the price.  Dad saw this as a great opportunity for his youngest offspring, so this time I did all the assembly and soldering.   Moore's Law plots have become cliche, but I could see it with my own eyes: whereas the DATAC had a herd of over 16 memory chips and supported neither video nor anything higher than machine language, the Sinclair had the same memory in a single chip and 4 integrated circuits total, yet had both video and BASIC.  My output with that machine never got close to my ambitions; the membrane keyboard was a hassle, the cassette tape program storage a pain and the graphics limited, but just building it was well worth the money.

A few years later, a keyboard showed up under our Christmas tree, to be soon followed with the second IBM PC clone on the market. Dad had invested in an add-on board with an older microprocessor in order to support a Pascal compiler that was available; that compiler turned out to be slow and painful.  So when ads appeared claiming a $30 Pascal compiler that included an editor and which was faster than anything out there, our attitude was that this was clearly a con job.  Better, faster & cheaper? Yeah, right.  But, $30 wasn't within Dad's mad money limits, so he decided to buy it.  Shockingly, Turbo Pascal was everything it was advertised to be and became my preferred programming language for a number of years, and indeed what I wrote my first few bioinformatics programs.

Is Oxford Nanopore's MinION a con? A silly sideshow? A clever but ultimately not terribly useful toy?  Or a revolution in sequencing?  The only way to find out is to invest some time and money, and  with the lucre part being so low, that just means a bit of time. And perhaps Clive Brown is correct, and no matter what data ONT released nobody would trust it anyway? After all, I work in crazy GC space, which most sequencer comparisons have ignored.  Clive claims the device can tease out all sorts of DNA damage ("it's the first sequencer to read the strand you give it" and even abasic sites; if you are in that field, the most some data would do is convince you to run your own tests.  I won't claim to not be a bit frustrated with the lackof information on throughput or quality (among the rare hard details is their transposon-based single-tube library scheme, as detailed nicely by Yaniv Erlich), but would I rather have a lot of claims but no access for months and months?  No doubt about it, Oxford is sticking its neck way out, and should they provedelusional about their performance it will be disastrous to their reputation.

So stay tuned.  A small army of genomicists expect to get devices late this year. Oxford has also indicated that an API to instrument will be made available. Oxford is way behind their original schedule, and so few will cut them slack if they miss their new public promises.