Thursday, March 29, 2007

454? How Roche!

Today's GenomeWeb bears the news that Roche Diagnostics is buying out 454 Life Sciences. Since Roche was previously the sole distributor of 454's sequencers and Curagen had announced their desire to sell the subsidiary, this is hardly a shocking development. But it is the third next generation sequencing company to be bought by an established player -- ABI slurped up Agencourt Personal Genomics and Illumina recently bought Solexa. So far, Affymetrix and Agilent have stayed out -- as has Nimblegen. There are plenty of other startup next generation sequencing shops out there, and certainly other candidates for acquirers. Roche, of course, got the clear current front runner, though it may be that the next wave of sequencer launches will close the gap quickly.

Whether these acquisitions are good for next generation sequencer development is an open question. On the one hand, these larger organizations bring deep pockets and substantial marketing expertise. But, there are plenty of pitfalls. For both ABI and Illumina, the new machines compete with their old machines -- smart companies see this as inevitable, but many companies completely botch the job due to internal conflicts (as amply documented by Clayton Christiansen in his books). It isn't encouraging that the Agencourt Personal Genomics technology is impossible to find on the ABI website.

It will also be interesting to see how long the 454 moniker lasts -- one hates to see pioneers go, but on the other hand I find naming a subsidiary after the accounting code tres gauche.

An interesting note in the GW item is that Roche was previously prohibited from marketing regulated diagnostics built on the 454 platform. Roche has previously tried to launch some molecular diagnostics -- the D word is after all in their name -- so this is a clear fit. On the other hand, a run on the 454 is reputed to be serious money, so they'll need to either find a very high value application (in a field notorious for antiquated, miserly reimbursement rules) or figure out a way to run lots of tests simultaneously. Given the rather long read lengths of the 454, one approach to the latter would be to use sequence tags near the beginning of the read to identify the original samples.

Another GW item describes some roundtable discussion at a recent meeting on next generation sequencing. The price for a genome in 2010 is still a big question, but a lot of bets are apparently in the $10K-$25K range. Some of the leaders in the field are taking a realistic view of the utility of such sequencers at such a price tag -- if you can scan the most informative SNPs for $1K, then why sequence? I'm guessing that other than a few pioneers (J.Craig is apparently resequencing his genome), there won't be a lot at those prices. On the other hand, cancer genomics is a natural fit, as each genome is different (indeed, each sample probably has many distinguishable genomes) and understanding all the fine molecular details will be valuable. SNP chips can estimate copy numbers, but not tell you how those pieces are stitched together nor find all the interesting mutations.

Even with the price at $1K, sequencing will certainly not be 'too cheap to meter'. Notions of sequencing a big chunk of the human population have appeal, but do we really want to blow another few billion dollars on human sequencing? On the other hand, as I've suggested before, other mammalian genomes may provide a lot of interesting biology for the buck (or bark). What are the most interesting unbagged genomes out there -- that sounds like the topic for another day's post...

6 comments:

Sandra Porter said...

Hi Keith,

I think you mean "short"reads. I think the average read length from 454 technology is less than 500 bases.

Anonymous said...

if you Google Applied Biosystems and Solid you will find their Agencourt sequencer

Keith Robison said...

I wasn't clear there, was I -- I meant long for next generation technologies (most af the rest are in the 20-50 nt range) -- but yes, 454 reads are very short compared to good Sanger capillary data.

Thanks for pointing this out

Keith Robison said...

Thanks for the tip on the solid.applied-biosystems.com website -- they do have a slick one there. But, I think my point still has some validity -- some obvious keywords find it ("next generation sequencing applied biosystems") but others ("ligation-mediated sequencing applied biosystems") don't. It's even hard to find the right keywords (I haven't yet) to get to the SOLID site from the main ABI site (even "solid" as a search term doesn't work).

Ned said...

I am surprised at the rather low price tag (~140 M). Any guesses why Curagen sold 454 so cheaply?

Keith Robison said...

The 454 sale does seem cheap, particularly when benchmarked against $600M Illumina paid for Solexa. My own guess is that it was a combination of Curagen being desperate for cash (to fund clinical activities) and Roche having them over a barrel -- since Roche already had the key distribution rights, the rest of the pie wouldn't be tempting for anyone else.