This April, Oxford flew many of
its key users to London for its annual
event, a kind of biological developers’
conference. At the conference, chief
technology officer Clive Brown took the
stage to alternately boast about and
apologize for a parade of half-finished
ideas for making the MinION better and
creating future products.
Starting with what Brown now
calls the “notorious” and premature
announcement of the MinION itself
back in 2012 (it didn’t appear for
another year and a half), Oxford has
frequently made big promises and then
missed deadlines. Twice since 2016 it
dodged patent infringement lawsuits
brought by Illumina and another competitor, Pacific Biosciences, by changing key aspects of the MinION. In both
cases, the updates ended up making
the device better, not worse.
“There seems to be a halo around
this company,” says its patent lawyer,
MinION can do some unusual tricks.
One is to read out extraordinarily long
stretches of consecutive DNA letters.
Illumina’s instruments read DNA in
short fragments of 150 letters. With a
MinION, readouts of 10,000 letters are
common. Its record: 882,000 DNA letters in a row.
Being able to read long sequences
of letters eases the job of digitally
reassembling a genome from its parts:
imagine a puzzle with thousands of
pieces to fit together rather than millions. That’s a crucial factor when
exploring an organism’s genome for
the first time. It also makes it simpler to
study patients’ DNA for certain disorders and cancers caused when genes
get duplicated or deleted— what scientists call “structural variation,” as
opposed to mutations that affect single letters.
While MinION is mostly suitable for analyzing bacteria and viruses, it’s a second
device Oxford is developing, the Promethion, that Brown believes will be Oxford’s
“Illumina killer,” because it will be suitable for sequencing humans and other organisms with large genomes. A printer-size instrument that can route DNA through
tens of thousands of pores at once, the Promethion will read a trillion DNA letters
in a few hours, Brown claims—similar to Illumina’s high-end $1 million sequencing
instrument, called the HiSeq X—but won’t cost nearly as much to buy.
Like many of Oxford’s ideas, Promethion is a work in progress. And it’s already
well behind schedule. Oxford now plans to start selling it later this year. “Just sit
tight,” Brown told scientists at Oxford’s meeting. “The raw horsepower is enough
to put you ahead.”
One team in possession of an early model is ZF-Screens, a company in the
Netherlands, where scientists hope to decode the genome of the country’s
national flower, the tulip. Knowing this commercially valuable flower’s genetic
details could speed up the creation of new varieties, which can take as long as
30 years because the tulip’s maturation time is so long. But the plant’s genome
is huge—about 10 times the size of a human’s—and so highly repetitive that
it can’t easily be decoded using existing sequencing methods. Team member
Hans Jansen says he has tested the Promethion and “it kind of works and kind
of doesn’t work.” The software to capture data is poorly worked out, and the first
batch of pore cells arrived broken.
But Jansen plans to stick with it. That’s because he thinks the longer DNA read-
outs may be the only way to conquer the tulip’s labyrinthine genome. “We need
this technology,” he says. A D A