[Geneus]

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

That would be Merck...not Roche.

[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

[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.

[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.

[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?

[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.

[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).

[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.

[steinmann]

Don't get hung up on semiconductors versus optics - it's all post light marketing. Flourogenic sequencing is more sensitive than either 454 or Ion method http://www.nature.com/nmeth/journal/...meth.1629.html. And both Helicos and PacBio show that you can sequencing single molecules with optics.

I am confused. Helicos and PacBio are the perfect examples to support my point. Why do you think that Helicos is dead and PacBio slowly dying? Yes, flurogenic sequencing of single molecules is pretty damn cool, but error rates are way too high and the machines are the most expensive and unreliable ones on the market.

[krobison]

I wish folks would stop about the 100$ genome, 100$ of garbage in is garbage out... I hate to be so blunt but please give me a direct clear clinical setting where a WGS system saves lives as opposed to clean water, running shoes and measuring one's girth over time... The cost of implimenting a new technology in a health system is tremendous and requires an enourmous social pull... The common patient has been told that sequencing would save his life for the last 15 years... Roche knows this and it's buying price is the expression of this, I woulnd't be suprise if Flatley knows also... If I hear another ridiculous marketing hype about the revolution of the cancer single bullet, I'm gonna faint. I'm sure a few folks made some nice sells today, cause it's all about your options, not your condition.

As much as we might wish otherwise, large health systems are not always focused on saving lives. Reducing the cost of delivering the current level of care is another. Choosing the right chemotherapy drug can save costs both in terms of saving on expensive drugs and avoiding expensive side effects. Identifying cases of rare disorders is far more efficient than flailing away with bad diagnoses, and is more humane.

For various reasons good and bad, large health systems also have little if any ability to alter some of these things. Forcing healthy choices (even when it is agreed what they are!) is not trivial in a democracy; look at the spectacular lack of success with Prohibition. So health systems go for what they can.

Sequencing in the clinic is happening NOW! Large U.S. medical centers are making it routine for cancer care, and that will percolate into the rest of the system. Now, most of that is amplicon sequencing, but it is still sequencing on a broad scale.

[Elcannibal]

I wish folks would stop about the 100$ genome, 100$ of garbage in is garbage out... I hate to be so blunt but please give me a direct clear clinical setting where a WGS system saves lives as opposed to clean water, running shoes and measuring one's girth over time... The cost of implimenting a new technology in a health system is tremendous and requires an enourmous social pull... The common patient has been told that sequencing would save his life for the last 15 years... Roche knows this and it's buying price is the expression of this, I woulnd't be suprise if Flatley knows also... If I hear another ridiculous marketing hype about the revolution of the cancer single bullet, I'm gonna faint. I'm sure a few folks made some nice sells today, cause it's all about your options, not your condition.

[GW_OK]

Say Roche is successful, what do things look like 1 year from now?

Human sacrifice, dogs and cats living together, mass hysteria...

Seriously though, Roche promises PE1000 in the next quarter, but won't be released until several years later when 90% of the market has already switched to Oxford Nanopore...

[pmiguel]

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".

Yeah, maybe so. If they purchase Illumina, suddenly all that IP is theirs to exploit. Reversible terminators, Bridge PCR -- no problem.

Say Roche is successful, what do things look like 1 year from now?

--
Phillip

[ECO]

The irritating thing about this is that Roche could pour enough money into 454 development to make it competitive with Illumina. They apparently have not thought it worthwhile.

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".

[ETHANol]

For research the $1000 genome is great. For clinical applications, you need to be looking at the $100 genome or maybe even the $10 genome if you have a public health service and are a trillion dollars in debt (like the UK is).

That's what people said about the $100,000 a year drug. The cost of sequencing is not what is keeping sequencing out of the clinic at this point. And it's probably not even the cost of data analysis. It's mostly that we just don't have much of a reason to be sequencing people's genomes at this point.