[JPC]

I'm not sure I agree with this...Roche has probably realized what most people have...that emulsion and beads will never compete with clustering in the mythical "clinic".

Life Tech also seem to agree with this, the summer upgrade on the 5500 will drop emPCR and read top and bottom of the chip.....no doubt litigation and counter litigation will follow.

[GenoMax]

WSJ is reporting today the bid is definitely targeting the healthcare potential (as I had suspected yesterday). They are also saying that majority of illumina investors do not want to tender their shares unless Roche's offer tops $70 per share (price many of top investors apparently paid before the price slide late last year).

[Elcannibal]

Keith, there is a large difference between what is currently pushed in the news, grants and university press releases. What we both imagine, is basically a take over of what is being done on cap sequencers, sure Mayo does that exome/multi amplicon thing for prostate cancer for probably a few grand (they probably don't even care about cost at this point).


No one has done a true blind clinical study or even calculated the clinical benefits of this. I have yet to see a full cost analysis of a blind clinical study... So sure, I appreciate that, but it is a far cry from creating a 501K box, get approval on both kit and machine, manufacture under ISO 13485 and have 21CFR11 software for WG Analysis... Sure the buffer and the enzyme could cost zero... but that is a weird reversed razor and blade system that I suspect manufacturers will not enter into because genomes demand will simply be over estimated...

I could not agree more with Emily Walsh who released 'Angry at the Genome' this week

"My fear is that for most complex diseases there are not enough patients on earth (in extant generations) to differentiate fully between individuals who will develop disease and those who will not. In fact, current research suggests that we’ve now sampled enough of the complex genetic-disease patient population to be able to definitively rule out the possibility for many diseases. Moreover, the data suggests that while we may be able to eventually describe all the alleles that confer risk to disease, we will never be able to pinpoint for most patients, even related patients, the precise set of variants that gave them their disease. Or to quote a Boston sage: “we will never be able to differentiate casual from causal” at the level of the patient."

To further establish the complexity of WGS in a diagnostic field, one only needs to look at the most profitable sequencing business of all, one that is standardize and... to a certain extent... is a matter of life and death... Forensic sequencing still depends almost exclusively on capillary sequencing and almost no NGS inroads have been made. Purely for complex regulation and technical issues.

There is a dubious message out there that comparing a static cancer cell with a normal cell will enable a doctor to look up a magic medication on an Ipad that will save lives. Yeah maybe... but l will remain skeptic, after all, as we can see, the amounts involved, the CEO's call to investors and the patent lawyers would all agree with 'the revolution'.

This is mostly why I think Roche is probably the best player in this game, Illumina, because of the front end, one of the best target. I think ILMN will play 'hard to get' and Roche, as seen in the past will not give another dollar. This bubble will not be endless. Just go back in time, I can certainly remember when my CRA stocks were at 172 before they fell to 8... As of yesterday, a new bubble is in the works, some people will go full throttle, others will warn. Some will just look at it from a simplistic "by gosh, 100$ for a genome !''.

Apologies for my rant, I just think it is not expressed often enough on this board. I have and will remain an advocate of molecular technologies.

[rskr]

One thing for sure, is that 454 is not competitive. Maybe there would be some other way to interpret the take over, but if 454 were competitive with Illumina, then why would they need Illumina?

[krobison]

Keith, there is a large difference between what is currently pushed in the news, grants and university press releases. What we both imagine, is basically a take over of what is being done on cap sequencers, sure Mayo does that exome/multi amplicon thing for prostate cancer for probably a few grand (they probably don't even care about cost at this point).

To give two local examples, Massachusetts General Hospital now scans every oncology patient for a few hundred mutations using SNaPShoT; this will probably be replaced by amplicon NGS in the near future. Dana Farber / Brigham & Women's has a Sequenom assay for close to 1000 mutations; this will be used routinely there. It also is in line to be replaced with an NGS assay.

No one has done a true blind clinical study or even calculated the clinical benefits of this. I have yet to see a full cost analysis of a blind clinical study... So sure, I appreciate that, but it is a far cry from creating a 501K box, get approval on both kit and machine, manufacture under ISO 13485 and have 21CFR11 software for WG Analysis... Sure the buffer and the enzyme could cost zero... but that is a weird reversed razor and blade system that I suspect manufacturers will not enter into because genomes demand will simply be over estimated...

I could not agree more with Emily Walsh who released 'Angry at the Genome' this week

"My fear is that for most complex diseases there are not enough patients on earth (in extant generations) to differentiate fully between individuals who will develop disease and those who will not. In fact, current research suggests that we’ve now sampled enough of the complex genetic-disease patient population to be able to definitively rule out the possibility for many diseases. Moreover, the data suggests that while we may be able to eventually describe all the alleles that confer risk to disease, we will never be able to pinpoint for most patients, even related patients, the precise set of variants that gave them their disease. Or to quote a Boston sage: “we will never be able to differentiate casual from causal” at the level of the patient."

To further establish the complexity of WGS in a diagnostic field, one only needs to look at the most profitable sequencing business of all, one that is standardize and... to a certain extent... is a matter of life and death... Forensic sequencing still depends almost exclusively on capillary sequencing and almost no NGS inroads have been made. Purely for complex regulation and technical issues.

Clearly these are real issues; but if we hold the same lens to a lot of successful medical practice it will fail miserably.

There is a dubious message out there that comparing a static cancer cell with a normal cell will enable a doctor to look up a magic medication on an Ipad that will save lives. Yeah maybe... but l will remain skeptic, after all, as we can see, the amounts involved, the CEO's call to investors and the patent lawyers would all agree with 'the revolution'.

Yes, this is the message in the press, which has gotten it badly wrong. But saying it is junk is just as ridiculous. There are now multiple trials showing that targeting therapies can extend life in cancer. Yes, cures are rare and this is mostly due to tumors mutating and the current drugs being essentially tumoristatic. Yes, correlation between tumor genotype and response is not perfect. But there are now many mutations which this works for & yes, this has been demonstrated in multiple large multicenter trials.

[ECO]

Life Tech also seem to agree with this, the summer upgrade on the 5500 will drop emPCR and read top and bottom of the chip.....no doubt litigation and counter litigation will follow.

Source? This is definitely worthy of a new thread if true.

[pmiguel]

Source? This is definitely worthy of a new thread if true.

There already is a thread.

Or the direct link to the ABI webinar is here.

I tend to be cynical. But, especially if Roche takes Illumina over, it is not impossible that the SOLiD could be back in the game with Wildfire on the 5500W instruments.

--
Phillip

[Geneus]

I favor the later based on the rosetta inpharmatics, 454 and Nimblegen experiences.

That would be Merck...not Roche.

[ECO]

There already is a thread.

Or the direct link to the ABI webinar is here.

I tend to be cynical.

Thanks. Can't believe I missed this.

Not to knock LIFE at all, but my hunch is the fact that Joe Beecham (future gen R&D leader) is presenting this in January means it's not going to be productized and launched in summer. I could be wrong though, it happens.

[pmiguel]

One thing for sure, is that 454 is not competitive. Maybe there would be some other way to interpret the take over, but if 454 were competitive with Illumina, then why would they need Illumina?

All I am saying is, if Roche had put an amount of money/resources into continued development of the 454 platform to what they are poised to spend on acquiring Illumina, they could have a competitive instrument now. Post Titanium they lost focus. I think they diverted resources to the development of the 454Jr at that critical juncture.

But maybe the sequencing market is too diverse and would benefit from some coalescence.

--
Phillip

[GW_OK]

All I am saying is, if Roche had put an amount of money/resources into continued development of the 454 platform to what they are poised to spend on acquiring Illumina, they could have a competitive instrument now. Post Titanium they lost focus. I think they diverted resources to the development of the 454Jr at that critical juncture.

+1 to that.
When the roche deal was first announced there was mention in several articles about roche "failing to keep" or "forcing out" jonathan rothberg. I think that was another huge mistake on their part.

[steinmann]

All I am saying is, if Roche had put an amount of money/resources into continued development of the 454 platform to what they are poised to spend on acquiring Illumina, they could have a competitive instrument now. Post Titanium they lost focus. I think they diverted resources to the development of the 454Jr at that critical juncture.

Isnt that like saying: "If Sony had invested more money in the development of the Walkman, Apple would not have been able to take over the market with the Ipod." ?

Maybe they just saw that the technology was going to become obsolete no matter what and decided it would not be worthwhile to further invest in it.

[pmiguel]

Isnt that like saying: "If Sony had invested more money in the development of the Walkman, Apple would not have been able to take over the market with the Ipod." ?

No. That is my point. Roche was not at that big of a disadvantage.

--
Phillip

[Elcannibal]

This even happens intra-muros, when large companies benefit mostly from cutting back. I would be very surprised if Life follows through on the 5500 plans. Decision makers have already looked at the 5500 return on investment, don't expect a youtube commercial on that one... All sailors to the Proton galley...

[steinmann]

No. That is my point. Roche was not at that big of a disadvantage.

--
Phillip

So how do you think it could have been done? Seems impossible to me without fundamentally changing the technology. How could you possibly increase throughput 10 or 100x without resorting to something like Rothberg ended up doing?