{{I guess you're right after all. Momenta only underperformed the Naz, XBI and NBI by 2%, 12% and 20% over the last year to date. If recent means the last year Momenta only underperformed the group by 28%, 42% and 55%}}

Right let's pick a specific date and make a comparison as if that matters. I can pick many dates where people buying MNTA are doing quite well, but that would be irrelevant too so stop with such non-sense. It isn't about comparisons to an index anyway, it is how each stock you own is doing that matters. So MNTA hasn't performed as well as I would have liked, so what as that happens. I sure as hell aren't going to beat myself up over up it, but you and jmkobers just can't seem to stop, or stop to deleting my posts when I counter you. It is quite pathetic. MNTA also represents only a small part of my portfolio.


The facts are also that MNTA hasn't done as badly as many other stocks, and has built a nice cash supply to carry it through the next few years even though just about everything has gone wrong for it. I also asked you and jmkobers just what you do like, but all I get for my trouble is crickets or deleted posts. That is also quite pathetic. How about telling us what yo do like rather than continually attacking MNTA, or me?

""MNTA has certainly not been a great or good investment in the recent past, but it hasn't been a bad one either""

{{Vin, How can you say that? If you compare Mnta to the Bio index's its sad to say the least. }}

How can I say it? I used a computer keyboard. It depends when you got in and at what price. MNTA still has a lot of cash and a lot or prospects, so it isn't like MNTA is cash starved and will need to dilute the company dramatically to last another year.

{{How some longs can crow about the price @ 13 as the market hits all time highs is beyond me. It simply has consistently remained a horrible investment over a long period and shows no indication of bucking this trend.}}

If MNTA hits $14, are you going to repeat the same post with the higher price? MNTA has certainly not been a great or good investment in the recent past, but it hasn't been a bad one either. I would venture that most long term investors aren't doing too bad or are up. I got into MNTA about 2 years ago, and am down 15%. Do I like that performance? Obviously not, but I am not whining about the money lost. You like to portray yourself as some truth-teller out to save us poor unfortunates who in your eyes ignorant sheep lead to ruin. Lighten up, Francis.

I can see John that you will never acknowledge your obvious major errors. You were stating that the anti-PD-1 approach was doomed because it will be so toxic that it will be withdrawn. This is wat you wrote.

{{You're wrong about that. NSCLC patients want what works, and without losing their quality of life. Anti-PD-1 therapy will be approved, and then recalled, and people will die as a result of it's use. Just like Avastin, and we all know Avastin's days are numbered too.

I noticed that no one has presented a rebuttal for my post regarding why Anti-PD-1 therapy is doomed. That's because it's all true and real.
how the anti-PD, }}


{{"Pot calling the kettle black"}}

Don't flatter yourself, you are no kettle but raher just a guy cuahgt up in the msiofnroation of the PPHM board.


{{Quote:
""I can deal with someone who is arrogant and condescending if they are knowledgable, hell some say that about me, but you aren't""

That in its self is an arrogant & condescending statement.}}

Maybe so, but only after you demonstrate your knowledge can you call yourself the kettle in the trivial little saying above. Many disagreed with your predictions of doom and gloom for the anti-PD-1 approach and stated their reasons. You dismissed them and came up with the following argument.


{{Let's assume PD-1 is part of a system of "checks and balances". Now if you remove either of these, what happens?

Answer:
What you would have is T-cells not knowing their "elbow from their a**holes, and at that point they would be in a state of unresponsiveness, or (T-Cell Anergy). Hows that?}}

Peter pointed out the flaw in that argument based on some in vivo and in vitro data. ""Quote:
In this study, we show that loss of PD-1 does not lead to defective induction of CD4+ T cell anergy in vitro and in vivo.


Sure you are going to get some unpleasant side-effects when you mess with the immune system - a small number of patients had severe side effects. But balanced against that are the durable and deep responses in very hard-to-treat and usually terminal disease.""


You came up with this gem of denial after you took credit for being right when your were clearly not.

{{I don't know how to make my point any clearer. Let me try again, If a researcher makes a point to note a condition as either present or not, proves my point, that it was expected to be. Why? because it's a manifested T-cell manipulated outcome. I was expecting to see it too. That's all, and proves my point, regardless of your denial.}}


The first step to learning is to accept when your pet hypotheses are wrong, include the new data showing you were wrong, then form new hypotheses. You have a very long way to go my friend. PLease accept this as some constructive criticism in your attempt to gain some practical knowledge.
I won't be dealing with you in this thread again

{{The counterintuitive part of the statement is the FDA OK'ing a med like Bavi for a Phase 3 trial with 600 very sick cancer patients because it was their judgement Bavi was safe. }}

Nothing contradictory at all. The FDA is allowing Docetaxel alone as one arm. As long as adding Bavi isn't considered as adding risk, it would be like Docetaxel vs Docetaxel at worst if the second drug was merely a placebo.

goodjohnhunting,

I just returned from some R&R in Las Vegas. I read some of the stuff you posted. You need to cut down or stop because you are embarrassing yourself as well as cluttering up the board. I can deal with someone who is arrogant and condescending if they are knowledgable, hell some say that about me, but you aren't. What I mean is that you come across as arrogant and condescending but you aren't knowledgable. Ask questions and make comments, but don't pretend to be some kind of authority.

Checkpoint was on target in 161321 with a brief one word comment on your post in 1611313.

Johnwayne was on target in 161377.

Biomaven hit the nail on the head with his rebuttal in 161390 {{When you predict something and then it doesn't happen, one doesn't normally describe the prediction as "spot on." }}

I could go on but what's the point. As dew said, the FDA is allowing Bavi to move forward as a combination with Docetaxel is more of a judgement that it won't harm patients as compared to Docetaxel alone.

You are crazy trying to predict ONXX price movements using Ouija boards.

{{Wrong. MNTA’s sialylated-IVIG program has nothing to with Alzheimer’s disease and is not connected to any work BAX is doing.}}

Maybe the rainbow Io-Io keeps spouting off about got into his eye and blurred his or her vision.

Sold off 4% of my ONXX today at $96 so I could load up more SNTA at $6.83

poorgradstudent, What is amazing to me is that you were hypercritical when the issue of fraud in science came up, but it appears you aren't being critical enough now. You were accurately complaining about truncating Westerns, and they did that. They only used one primer pair to look at mRNA, which sure isn't very rigorous. I am trying to get at is the precision and accuracy of the analysis of the TOV-112 cell line, but you seem to not be as concerned about rigor as I am. What gives? Is it because you are close to this research area?


{{2. If you're talking about mutations that change the length of the protein, cause re-arrangements between other genes and c-Met (a la bcr-abl) then they may or may not be captured by the methods used in the paper.}}


That is exactly my point about the TOV-112 cell line and the papers you and Iwfal referenced. I am talking about how rigorous they were in their analyses, and it doesn't look like the were rigorous enough.


{{Which is why I replied as I did. To my knowledge the majority of c-Met mutations are missense, and these often impact amino acids at the tyrosine kinase domain. All of these will be captured. I'm not aware of a mutation that truncates the protein in a manner imagined by Vinmantoo, so my position is that the data in the paper are reliable unless someone finds an example that conforms to Vinmantoo's imaginary protein.}}


First of all, the example I cited doesn't represent an imaginary protein. It is a hypothetical one, and one that anyone with an open mind could see how it could be generated via deletion of the most terminal part of the mRNA, either by genomic deletion or splicing error. Just because you aren't aware of something, doesn't mean it can't happen, and it sure as hell doesn't mean that one isn't present in the TOV-112 cell line. That is the issue here, what is happening in the TOV-112 cell line, not a broad measure of all tumors. All I am asking for some rigorous methodology to be used to remove any doubt.


{{Final point, the new paper I linked in the previous post makes it rather clear that this cell line does not express the protein. They generated another antibody that also came up blank in the TOV-112D*.}}


All I am asking is for rigorous proof to rule out a situation where the terminal part of the protein beyond the kinase domain (or at most only the very terminal part of it) is deleted, whatever the mechanism. I downloaded the C-MET mRNA and looked for where the SINGLE primer pair the authors used in both manuscripts was located. The anti-sense primer is located at the c-terminal in 330bp of the 4172 bp mRNA, meaning it would miss a truncated c-MET that was missing only about the last 110 aa of the ORF. Now this is after most of the listed kinase domain. I don't know enough about how much of the kinase domain is sufficient for unregulated activity, but is certainly raises the possibility of such an event. As far as antibodies, I looked but didn't see where it stated which epitope they used for the second antibody. Now would you be so kind as to tell me EXACTLY what part of the protein was used, point me to where it can be found or post the relevant section here. Repeatedly saying supplemental data isn't sufficient nor is it very informative. Thank you

{{That's fine. But the questions you ask and your other concerns are answered in the supplemental data to the paper, along with the related literature on this cell line and on c-Met. }}

I looked at both papers, the one Iwfal cited and the one you cited. I didn't see anything in supplemental data to exclude what Iwfal stated, or what I postulated. Rather than making a general dismissal, why don't you cite the specific part of supplemental data where the author's claims can be unambiguously shown.


{{Further, activating c-Met mutations are, by and large, missense mutations or amplifications.}}


That may well be true, but we aren't looking at by and large, Iwfal asked about the specific cell line TOV-112D, not the general mutations found in tumors.



{{ I've read of one example of an exon encoding a juxtamembrane region being skipped. None of those would be impacted by your concerns, even if relevant. As for c-terminal truncations, i'm not sure how numerous those examples are since that would truncate the kinase domain and it would not be an activating mutation.}}


I was postulating very c-terminal deletion that would eliminate the short terminal part of MET shown in Fig 1A as the CT domain, which is c-terminal to the kinase domain. If this region was also used in the SINGLE primer PCR used to detect the mRNA, then one wouldn't detect either the truncated C-MET protein or the mRNA. It doesn't matter if they made poly-clonal antibodies if they used that short region, it would still miss the putative deletion. If they used the full length C-MET protein to make polyclonal antibodies, and other parts of the protein had prominent epitopes which cross-reacted to the sera, then this wouldn't be an issue. So, did they use the entire protein to make antibodies, or was it a small c-terminal part? If they did a Northern blot rather than PCR using a SINLGE primer pair, it wouldn't be an issue either, but they didn't do a Northern Blot.



{{So is there a super-secret c-Met mutant that isn't captured by the RT-PCR or IP? Possible, but I'd ask
you to name it.}}


I already explained how it was possible to miss the protein by Western blot AND the mRNA by PCR using a single primer. If you have other papers which more precisely characterize the TOV-112D tumor cell line, then do so rather come back with than some snide comment. Quite frankly, I am surprised at your comments. You need a better attitude if you ever want to go from being a poorgradstudent to a poorpostdoc.

iwfal,

Good eye, and I agree with your assessment. Sorry poorgradstudent but I disagree with you. In the paper Iwfal cited, they don't even tell us which primers they used for detecting c-MET RNA. The 2nd paper, the one poorgradstudent cited, did list the primers for assessing c-MET RNA but they only used a single primer pair, which is very sloppy. If one of those regions was deleted in the genome, or mis-spliced so absent, so they could have easily missed identifying the mRNA of a truncated gene. The paper iwfal sited is vague about the anti-MET antibodies, but figure 1A shows it as CT which I assume is the the C-terminal domain of c-MET and the blots in figs 1E & 6A indicate this as well. If that C-terminal domain was missing in TOV cells, and one of the primers was from that region, you could miss both the RNA and protein.

{{GTCB/MNTA long still not getting it. At what point do you cut bait and move on?}}

Neither of us are long GTCB as it essentially went bankrupt and took us both to the cleaners. It is absurd to connect GTCB and MNTA as if they were the same. We both got something from our GTCB losses. You lost the ability to think calmly and rationally so now keep spouting that the sky is falling because things are taking longer than they could have and MNTA had some legal setbacks. I learned not to underestimate the importance of cash reserves and cash burn, the market for approved products and products pending.
You view each company as the next GTCB whereas I view each company I invest in as independent entities. GTCB had almost no cash on hand and refused to cut back expenses, and was at square one even after getting FDA approval as they had no market for rATIII. MNTA has a large reserve of cash, are getting revenues from their approved Enoxaparin, there is a chance they can still win their lawsuit against Amphastar, are awaiting the FDA decision on a billion dollar drug and can get significant milestones from Baxter in 2014. That sounds like a solid base to me, and worth the risk.


{{Is the market still being "inefficient"?

Really?}}

I sure as hell don't care what the market says. If sold, I would have sold my ONXX when it was in the low $20s, instead of buying more and enjoying its price at over $90 now. I would have sold SNTA when it dropped to under $4 because idiots couldn't understand how the initial data from the phase II NSCLC trial didn't show significant OS improvement because it was an early look at only a small number of patients. Instead I bought more and SNTA sits at around $10. Please stop telling me about the market and how it is right. It is a collection of people who panic or rush in with little knowledge, and are easily manipulated.


{{Another banner day/month/year for MNTA.}}

I don't care. I am looking towards 2014. I did sell 1/3 of my shares after the MNTA lost their last legal battle so feel very comfortable holding the remainder. This seems to trouble you greatly. Hey, why not tell us what you do own and why rather that attack me for holding some of my MNTA.

{{MNTA: TA 5/2/2013 Long term trend still down, down, down. Headed below $10.}}

Good news. The return of tekcor and his ouija board methods of "analyzing" stock means MNTA will soon rebound.

I also don't think Dew was joking about breakthrough designations, but rather his joking comment was a bit of a mea cupla. However, I do understand where Dew was coming from with his crack about breakthrough designations. I also figured it would be reserved for really spectacular early results, and for novel therapeutic treatments.

{There are many well educated biotech value posters on this board.... and how many will freely admit that the "standard of care" SOC for lung cancer: NSCLC is worth at the minimum $4 Billion in pps}

Yes, too bad that PPHM doesn't know how to run an NSCLC trial so that we could assess their monoclonal Ab. Fortunately for NSCLC cancer sufferers, updated data from SNTA and their Galaxy 1 trial using Ganetespib + Docetaxel will soon be available.

{{Palin was commenting on US funding for science being done in France - not as the ever objective Madcow portrayed Palin's comment.}}

Palin is an imbecile and that blurb makes it clear. She was decrying the funding of research on fruit flies. Whether it was done in France is irrelevant as many collaborations are with labs in different countries. The France angle was just the typical xenophobic non-sense that spews forth form that ignorant simpleton Palin.


{{Peer-review for grant funding in the scientific fields I've been involved in is greatly flawed. The "I'll scratch your back and you scratch mine" happens frequently.}}

I am sorry you have had bad experiences, and no system is perfect. I am proud of the decisions that I have made and I didn't let any quid pro quo be involved. If you did then the shame is on you, as well as others who did it, and the shame is well-deserved.



{{I've had federal program managers tell me that decisions on programs to be cut have been made before program reviews for that purpose occurred.}}

There is a big difference between cutting overall funding or in a specific area, as opposed to havgin some pre-deicsn about who gets funding, which is total BS.



{{I've also listened to a couple of professors bragging about how much DOE money they were going to get for their new research institute even though the reviews hadn't been conducted because certain Californian politicians had assured them that the money would be forth-coming.}}


So, you are damning the peer review system such as what happens at the NIH or NCI because you know a few professors bragging about some politically driven funding for California that bypasses peer-reivew. That is absurd. If you are complaining about a state program distributing money without independent peer-review, then yes that is a problem. In fact, that is exactly why I am upset about what some Texas politician, and the imbecile Palin are and were, respectively, talking about doing.


{{Of course, in principle peer-review is a great thing; however, as it is frequently practiced it is often corrupt. A PhD and an understanding of science does not assure ethical behavior.}}

Ah, finally something that I agree with, but it is completely besides the point. The issue is that a system with input by politicians would be far worse than the imperfect peer-review system we have now.

{{Senate bill proposes stripping peer-review from science funding }}

Since some politicians want to strip scientific peer-review from research funding decisions, it might be worth it to look back on what that might lead to when people with little to no scientific training or knowledge help decide. Here is the "learned" Sarah Palin chiming in about science funding in the 2008 presidential campaign.

{{For PPHM it could be good news. If PPHM sets a new SOC for, say, Bavi 2nd ln NSCLC that does indeed improve by 60% (and in practice we know it's 100+%) then the next one will have to come with serious papers to beat that! }}

I do enjoy a morning laugh. Thanks

{{A poster named bearofbleecker on the ONXX yahoo board has been looking into when Kyprolis is being used, and it bodes well for better sales than many are predicting.}}

Here is the web link from the Myeloma Beacon web site that bearofbleeker was talking about in his look into Kyprolis. There are also articles about Revlimid and other MM treatments available there.

http://www.myelomabeacon.com/

Below are two articles from that link.

http://www.myelomabeacon.com/news/2013/04/09/kyprolis-revlimid-dexamethasone-high-risk-smoldering-myeloma-imw-2013/

http://www.myelomabeacon.com/news/2013/04/17/kyprolis-carfilzomib-revlimid-lenalidomide-dexamethasone-elderly-newly-diagnosed-multiple-myeloma-imw-2013/

{{...you were always a defender of automatic [10b5-1 insider] sales?}}

Dew, jbog or anyone else, so how exactly are programmed sales triggered? Is it just at a specific time, at a specific price, or only after both a specific time has elapsed and a specific target price has been achieved?

I was going to lighten up my ONXX, but change my mind. A poster named bearofbleecker on the ONXX yahoo board has been looking into when Kyprolis is being used, and it bodes well for better sales than many are predicting. Unless the stock price surges again, I will hold on until at least the next earnings report.

I would expect that insider selling is a common after a major move up like ONXX had in the past year.

{{In contrast, tivantinib inhibited cell viability with similar potency in both c-MET-addicted and nonaddicted cells. These results suggest that tivantinib exhibits its antitumor activity in a manner independent of c-MET status. }}

If ARQL197 was equally effective regardless of MET status, they why does it appear that low MET patients have an HR higher than 1 whereas high MET patients have an HR much less than 1? This might be yet another case where cell-lines show a different effect than in vivo human data.

GALT, formerly called PRW and PRWP, is one of the worst companies I have run across. They routinely issue BS press releases wildly exaggerating what little data they have, they pay for people to write fluff pieces touting the company line but disguise it as independent research.

OT: {{Just to be clear, I'm not suggesting that the 50% value is fraud. I'm speaking only of reproducibility; that can be due to fraud, ignorance, or the fuzziness that clark refers to.}}

poorgradstudent, I understand what you were inferring a bit more. I am sorry if I misinterpreted what you were saying. I think both you and Clark are missing perhaps the biggest issues, inherent genetic variability in model organisms and certainly in cancer cell lines from lab to lab. The pressure that people will be under differs depending on how hot and competitive a field is, and that must be factored in. The tools available to confirm findings, or to support a conclusion aren't the same for every organism either. Put them all together and one has to come to the conclusion that reproducibility will be far easier in some organism, and in some areas of study than in others.


From the limited information jq1234 provided in his links, it is difficult to understand why a failure to reproduce results is arsing in some companies. If it is work based on cancer cell lines, then the companies needs to check cell lines obtained from the labs which published the studies, as well as test other lines that are supposed to be the same. If some work and others don't, they can then sequence the various lines, and use comparative genomic hybridization to see if any differences co-relate with the reproducibility or failure thereof. They have the chance to learn how genetic variation might alter results, which has real world importance. If they throw up their hands and whine rather investigating, then they are pretty foolish, short-sighted and maybe lazy in my view.

One point about manuscripts is that I view the authors conclusions and models as the least important parts of papers. I focus on the data and what is missing from the data. Someone in the lab recently presented a manuscript for journal club, and while there were some interesting experiments and ideas, we all thought the conclusions weren't supported very well by the data. They even misrepresented something I had published 10 years ago by saying my paper showed Sumoylation of a protein peaks in S phase when I found it did so around anaphase. Their own data showed (anaphase peak) the same but they were fixated on S phase and said it peaked in S phase. Pretty bad analysis and bad reviewing. Still, there we some value to he paper, even though they used a sledge-hammer approach. They also put something in the supplemental data but they clearly didn't understand the significance. I thought it was interesting and was consistent with some phenomenon we have been getting hints about.

{{To be honest I am surprised that anyone reading this board regularly would think some particular area was somehow much cleaner than other areas (see JQ's list).}}

I answered this in the other post I just made.


{{And I would further add the concept that if researchers in one particular area think they are immune it may be a good indicator that they are not - skepticism is a powerful tool.}}

I never said any area was immune, and one would have to be an idiot and a fool to think so. I am the king of skeptics. Certain research areas are far more prone to variation and certain key assays have a low signal to noise ratio.

I am also fully aware that there are pressures and egos that one most deal with and control. The way I approach reading a published manuscript, and the way I teach students to do it, is that you assume it is a complete POS. Look at the data carefully and see how conclusive it is, does it have the right controls, and what if any key controls are missing. Equally important is to figure out what experiments are missing. I also tell students not to read the authors conclusions as they aren't relevant. I also make it clear to technicians and students that I don't care what the data says, I just want them to be as sure as possible of what they are reporting. When I get results that fit my models, then I get worried.

I read the book by Richard Feynman. There was a quote that always stuck with me. He said something along the lines, "You have to be careful as you are the easiest one to fool".

iwfal, {{The problem is a human one and is, IMO, ubiquitous whenever there is opportunity - which is whenever there is fuzz (aka noise) in the system that allows people to see what they want to see. (and note that some areas inherently have more noise than others - but I would suggest none are noise-free.)}}

I fully agree. However, that isn't the issue at all to my point. The articles JQ1234 were involved in cancer research but I got the impression that he or they were extrapolating the 50% "failure" to reproduce results to all areas of science, and that is completely wrong. In one of the articles jq1234 posted, there was a quote from a supposed researcher who said he or she die the experiment 5 or 6 times and got the answer he or she published once. That IS fraud and the company should have reported it to the journal, to the lab head, and told them in no uncertain terms that if this was key evidence for the paper, the paper must be retracted. At the very least, that data must be retracted and a detailed review made on all the other primary data in the lab notebooks to see if the rest of the paper holds true.

The whole tenor of the articles and commentary are towards the idea that there is systemic fraud rampant in all of science, and I don't buy it. The issue of signal to noise is essential, but the inherent genetic variability in a model systems, or cell lines can make one lab get the "right" answer and another lab get the wrong one. For example, a former colleague friend of mine was working on transposable elements and how they are regulated during mouse meiosis. He got a clear and powerful effect in his lab strain background when he did siRNA. He decided to check out two other mouse strain backgrounds, and one didn't show any effect at all and the other was intermediate. If he had only worked on the initial background where there was a fully penetrant and robust effect, would that make him wrong or the research wrong in subsequent labs or even his own used the other background and saw intermediate effects, or no effect at all? Of course not. It shows that there are genetic modifiers that can provide redundant regulation. He is trying to map the modifiers to better understand how they effect the phenotype.

I think this is more of what is going on with cancer research and model organisms that the biotech reports were about. There was a study on one cancer cell line, MCF7, and it involved collecting MCF7 lines from labs around the world. There was an astonishing amount of variation in what was called MCF7, so much so that it would likely affect results. Sure is it is of great concern and needs to be dealt with or at least acknowledged. There were even lines that were HeLa cells not mouse cells. The latter is shoddy science and in the age of PCR and genomic sequencing, it is a disgrace and unacceptable. There might well need to be standard tests that must be applied to cancer cell lines to ensure they are "true" MCF7 cells, or some variation thereof, and of course not restricted to this particular line.

Many of the issues are absent or minimized for other model systems where there is more genetic uniformity. Even in budding yeast, issues of different background can crop up and give different results. A gene deletion in one haploid background can be lethal but not make cells very sick in another. It isn't fraud or bad science, but genetic variation reading its head, but this provides provides opportunities for additional insights.

{{OT: I guess I wasn't asking for a list of what you do. It's a matter of what ALL researchers do. So I find most of your response to be besides the point.}}

No it isn't besides the point, it is exactly the point. You made a blanket charge that 50% of academic research is wring and that is BS.

{{Nor do I find this a pharma versus academic science thing. I'm just worried about what I contribute to, and that's the academic side. I think we owe it to ourselves as a community to do the most reliable / reproducible science possible, and let history sort out what was important and what was incremental. }}

Yes we owe it to ourselves, to those who follow us and to taxpayers who fund our research to provide the best,most accurate information we can, and to point out where others fall short of that standard. I do that when I review papers and when I attend seminars.


{{Also, I do not agree with this concept that airing basic science's dirty laundry somehow helps those who are against it.}}

I am fine, no I applaud and encourage airing "dirty laundry". I am not fine with throwing dirt on all aspects of scientific research because some specific areas has issues of reproducibility due either the complexity or inherent variability of the system, or the methods being utilized.


You posted the following

{{Those are just two simple examples, and I'm even omitting the plethora of proteomic and transcript analyses done without appropriate controls and without regard for the fundamentals behind the methods.}}

Even with the best controls and understanding of the fundamentals there is an inherent error in such broad genomic studies, and so what. I heard a statistic that only about 10% of the synthetic sick or lethal interaction coming of out the yeast deletion collection are valid or stand up to scrutiny. So what. The hits give suggestions of what might be occurring or might be important but others need to investigate in more detail. People follow up using genomic or proteomic screens using other proteins in the same complex or in the same pathway. It becomes much clearer which are true hits and which are spurious background. If you don't think the inaccurate charge that 50% of current published papers can't be reproduced will be used to cut or demean basic research, then you are pretty naive.

poorgradstudent, I like you and value your comments, but you are way off base here. You do a dis-service to the board, and to academic scientific researchers with your comments.


{{I don't think it is a major over-estimate.

I'm saying you could look through 100 papers and find simple flaws in at least half of them that make the conclusions untenable.}}


I think you are greatly over-estimating the kinds of errors that are made and the impact they have. It is also a function of the project and the organism specific as different tools are utilized and different analyses have very different levels of complexity.

It appears to me in this thread that some people are placing researchers in industry on a pedestal of virtue, and acting as if they don't make errors, or aren't driven by pressures to find results that are significant. That is completely false. I worked in both and know it for a fact. You might want to say there are errors in both technique and in understanding techniques academic research and pharmaceutical in house research that share many of the same flaws you list below.


{{For example: 1) Check the sheer number of Western blots that show small windows for the signal, and you can see that they've cut out the "nonspecific" signals. Well, if you speak with many of these people, the only reason the signal they chose is "specific" is because it is near the right size. That's demonstrable BS and goes on all over the place. Given the prevalence of this technique and people's refusal to validate the antibodies they use, that's a giant source of error that would invalidate many studies.}}


The trimming of blots to show only the band size range of interest is far too common, and yes, fraught with issues. I think with the advent of supplemental data, one could place the whole blot there for perusal. But even that is problematic as where do you put the line. We always run smaller proteins off the gel to get resolution for the size range we expect our proteins to run, or may not have resolving power for very large proteins.

Now I work mostly in the budding yeast Saccharomyes cerevisiae. I and others epitope tag proteins so what you are talking about isn't relevant. We use different sized tags to shift the mobility based the different tag sizes to make it unambiguous that we are looking at the correct protein. Despite the power and ease of epitope tagging, I made antibodies to different yeast proteins and used differentially tagged proteins as my reference standard. I also pre-screened my rabbits to select those which lack antibodies which cross reacted to bands anywhere near where my proteins run. I made these reagents because of issues have been cropping up with some tags in different mutant strain backgrounds, as well as in cis, when as generate new mutants of my proteins of interest and tried to tag them. I have sent these reagents out to many labs, and provide advice and caveats they need to be concerned with including Ab concentrations for blots and immuno-fluorescence.


I agree that antibody validation is crucial, but again you resort to a bit of hyperbole. Even in mammalian cell studies, the advent of siRNA enables one to show that the band in the small zone you mentioned above is diminished after siRNA knock-down. You see scientists use this technique to validate their Abs in many or even most papers, especially for the critical proteins central to their hypothesis. Mammalian researchers also employ tagged proteins transfected into cells differentiate their transfected mutant proteins from endogenous proteins as the Abs recognize both forms, the putative endogenous WT and the retarded mobility tagged protein.

I am not sure where you were trained but the errors and flaws would never be accepted in my lab, in the labs where I have joint meetings, or institutions I have been as these are often exposed in internal seminars and meetings. I am also harsh in the papers I review to weed out and correct potential flaws prior to acceptance for publication. Do errors still get made and inaccurate interpretations get published? Sure but to call 50% of all published work wrong or highly flawed is absurd.

I actually resent your broad characterization of fraud and or gross incompetence as it is very misleading and unfair. You also provide fodder for the imbecile conspiracy theorists and anti-science luddites who want to cut science funding further, which would only serve to exacerbate problems.

The 50% comment is a likely a major over-estimate. Are you saying the 50% figure in a particular small area, or as a general view. It also depends on what you mean by not being able to be reproduced.

I own some EXEL but its close to a $1 billion market cap doesn't make it a screaming buy in my book. I may add more but I don't feel any urgency.

Thanks Dew. I can see the point about controlling who gets access to the data, but there should at least be some resource where the data is compiled. It might help save drug companies from damaging themselves via a single minded tunnel vision. One might only let the FDA have access to it for the purposes of including it in approval decisions, and for follow up phase IV assessments.

There should at least be a very public and easily accessible database for each drug where doctors can list issues that arise when patients are receiving drugs. The same should be true with each clinical trial.

Peter, {{But I do agree Venter is a great self-promoter. (But I also believe that ultimately synthetic biology will prove to be important).}}


I would bet that Ventor himself would acknowledge that he is a shameless self-promoter. I just don't get the synthetic biology hype. We sure as hell don't know enough about all the feedback controls and redundant mechanisms in cells which make them robust and function efficiently. Just put in what you want into model organisms that are suited to the processes/products you want to make or the environments in which you want them to grow.

{{I personally don't consider phages or viruses to be truly alive - I want something that is not purely parasitic on another living organism. }}

I can't disagree with that, I was just expanding the parameters by which one could call life.

{{According to something I read a few years ago (can’t recall the source), 25% (!) of the US populace believed this canard in a formal survey by a reputable firm.}}

I wouldn't be surprised if it were a higher percentage.


{{I wonder what these conspiracy types think drug/biotech executives do when a family member has cancer.}}

Excellent point Dew. I would like to hear the conspiracy theorists answer to that one!

""I'd guess we're maybe 5% of the way there. Venter has created synthetic bacteria with a completely artificial genome, but of course he relied on an existing bacterial cell to make that work. Other scientists have created artificial self-replicating RNA structures, but those are a very long way from life as we know it. ""

I consider Ventor one of the great self-promoters and distorter of "potential" as part of his self-promotion. Taking a bacteria, and putting the same genome made in vitro and re-inserting it back into the same bacterial species is a nice technical feat, but it isn't any kind of major advance and I don't think it is worth much in terms of what we can build.

As far as creating life in the lab, it depends on your definition of life. One could argue that synthesizing phages or virus in the lab and placing them in their natural hosts is creating life in a way.

{{"a cure for cancer/magic carburetor would easily be worth $100 billion or more - do you really think drug/oil companies would knowingly turn down that opportunity?" }}

Such a hypothetical cancer cure would be worth far more than $100 billion, as would the magical carburetor.

The reach of conspiracy theorists and their non-sensical comments that there is cancer cure out here but being suppressed is very wide-spread. A friend of mine recently repeated this BS after watching some TV "investigative" news show. I gently set him straight. I am with jq1234, the more I learn, the more amazed I am at how diverse and flexible cancer cells are.

As long as we are on the being amazed at conspiracy theorists and skepticism, one of my friends made a comment about how he finds evolution is hard to believe and fell back on the "intelligent" design canard as making more sense. The guy is smart and a college graduate who used to to work with the SEC. I gently tried to set him straight, including that it was absurd to call "intelligent" design a theory as it is a not so veiled form of creationism.

John, ""I don't think, hypothetically, that bavi's "proposed MOA/approach"* is behind the times. ""

Well that places you in a minority regarding anti-cancer MAbs for the most part. Yes one might make some exceptions for those few MAbs which directly modulate T-cell. That sure as hell isn't what Bavi is thought to do.


"very legitimate and validated approaches of checkpoint inhibition"

Just what does checkpoints and their inhibition have to do with Bavi? Drugs which damage DNA or alter microtubule dynamics exert their anti-cancer effects in a large part by taking advantage of defective checkpoints that may be found in tumorigenic cells in many cases. Since when is Bavi involved in abrogating checkpoints?

cjdaddy,

It looks like Patrick was once positive on PPM and then when data came in he turned very negative. Attacking someone as supposedly being against cancer victims because they don't like the prospect of a particular company is very despicable. You should be ashamed of yourself. My limited experience with PPHM shareholders makes me think it was very likely that Patrick was subjected to a series of nasty and uncalled for personal attacks, like yours, when he change his mind about Bavi.

Patrick didn't use the most sensitive language in expressing his views about Bavi's prospects. I suggest you look at it from a different point of view, which I doubt you can since you are obviously very emotionally and financially invested in PPHM. If Bavi is going to fail, the money spent on it and PPHM is wasted money that would be better used to fund other companies working on different anti-cancer treatments. Time will tell if that is the case. In any event, Bavi is now a bit behind the times as armed MAbs such as T-DM1 form IMGN are the way to go.