I worked for an organization called the Phoenix Program. A required report called the HES report, which basically stated what regions were controlled by the good guys vs the bad guys, had to be periodically submitted up the chain of command starting from the grunts on the ground. Regardless of what you envisioned, these reports were factual when generated and not career destroying — at least to me , but as I found out later, were systematically inflated in favor of the good guys as they moved up through the chain of command.
By the time they reached the Commanding General Gen. Abrams by that time , these reports were totally distorted. Abrams was relying on bad data in order to make decisions and recommendations. I am wondering if the same case could not be made about the decision made by GSK to make this purchase….
I had a friend who worked at Sirtris for a year and left before a GSK bought the company. A friend had to deal with outsourced workers in China for … Do you think that Sirtris created other assets with those workers in China? I think the chemistry leaders at Sirtris were telling the Chinese contractors exactly what to make, so they would likely not have generated additional assets. Kind of like religion.
Did I mention religion? And then the very common working of the mind, coupled with large egos, makes it very difficult for scientists, to derail ingrained beliefs. Examples of this sort of belief system include the broadly held view that low fat diets are healthy despite studies which show no benefit.
People know it to be true because they know it to be true through social belief systems Dr. When our leaders know something works, and is the fountain of youth after all, then scientists pointing out details like assay artifacts, studies which fail to confirm, existing data which unravel the logic, well, these concerns are from the chorus of dissenting voices that that lack the vision of the true believers.
The data are not heard because the messenger is deemed to not have the big pisture. Kind of like the Gnostic movement in early Christianity, to ring the religion bell again. I have seen this several times. In fact, these experiences lead me to reread the fables, which I find more valuable for corporate life than religion.
Though, the power to smite down would come in handy. I was at GSK at the time of the Sirtris purchase, and another complicating factor was that GSK was in the middle of layoffs at the time it went through. As far as unions, after working in pharma for 15 years, I ended up in the federal government after my last layoff. Some people think that the fear of losing your job at any moment makes you work harder, but it just made me less able to focus. And the people I work with in the government are equally dedicated and hard working to those that I worked with in pharma.
However, I imagine that by now most if not all of those people are elsewhere. Some thought combinatorial chemistry and natural products chemistry were the same thing really wrong. Some saw a huge amount of work constantly re-finding the same molecules also kinda correct. Most saw the other companies doing it and so they did too best answer.
There were a lot of reasons that all pharma should have kept a small group around doing natural products chemistry. I had almost no contact with line officers in my two years at Fitzsimons — while all docs were officers, there were few soldier type officers on the post. Your comment also explains why LBJ acted the way he did. I was never sure if he was kidding or not. I just look at the ends and not the means. And unless Sitris fudged the data, SRT was shown to be safe and effective at 2.
I am just a bench scientist and not intimately familiar with regulation and legal issues of drug development. Several are in progress and one PhaseII is recruitng. Once again, I might be mistaken but Phase I purpose one of several is to determine the maximum tolerated dose. That means that some people in the higher dosage cohort must have experienced some dose limiting toxicity hopefully not long lasting and not very severe.
Now, I understand that people sigh the concent form and are paid some pitifull sum of money. Yet, it is all done on the premise of the good faith and genuine attempt to develop a new medication. But, as it becomes painfully clear, GSK knew it is all fake. Several papers have been published on the subject, and not just recent Pfizer and Amgen but also couple of academia papers exposing the dodgy assay well before the Sirtuis purchase.
Still, GSK went ahead despite the objections from their own scientists. That means GSK, either without properly testing clinical candidates according to the procedures of allarmingly contradictinng research studies or filfully ignoring the data, deliberately cause people suffering without any clout of developing the genuine drug.
It all smells of a plain criminal act on the part of GSK management to me. Nigel is absolutely right. At the end of the day it is the physiology that matters and resveratrol increases lifespan in every animal tested while clearly benefiting in nearly all animal models of disease. The compounds were already in the clinic when the purchase went through. It is amazing some of the shit you see in phase I. Hell, even the pos elesclomol made in to phase III before people figured out it was killing patients.
Wow, I was unfamiliar with elesclomol: a bis- thiocarbonyl hydrazine amide monstrosity?!?! GSK was likely not the only potential buyer to whom Sirtris hawked their compounds so I would imagine there were other diligence teams who knew exactly what Sirtris had.
Apparently in those organizations the recommendations were actually followed. The eventual outcome looks to be a loss for GSK. Nigel 34, Anonymous Absolutely, whether it works in vivo is the critical question. But does it? I remember when I heard Sinclair talk there were a number of lines of evidence, all making a beautifully coherent story. Have these results been reproduced by others? Pfizer tried in mouse, and got nothing.
Last night, I had a few beers and looked up the structure of elesclomol. I had to ask myself — how many beers would it take to convince a leadership team to put that compound into development? After all, Metformin is about as ugly as they come…. I think you would have a difficulty developing something like this as a arthritis or Parkinson medication because of the safety, but then again, many popular soda brands contain brominated vegetable oil and a polychlorinated carbohydrate Splenda as a flavoring agents.
Moncef could not resist Sirtris because it fits his vision of reality and what he sold the board to get his job — the purchase was self-affirming. He also has no small molecule DD experience immunologist — vaccine business — business development and his attitude toward chemists is contemptuous at best. Internal innovation takes courage, persevervance and belief in people. It also takes stability. No board wants to hear that drug discovery is just HARD and it takes time — longer than any manager, good or bad gets to stick around.
There is a thin line between being a visionary and being delusional — I think following the data is the only way to stay on the right side of the line in drug discovery. Betting on scenerio A3a unless nothing materializes by spring. Same experience. Made my recommendation to the uppers, and have never been asked to evaluate again.
After all, if you make some big acquisition, it will probably mean decreasing their budgets, their responsibilities, and perhaps, their jobs. And it is to a large extent the failure of internal drug development that has made such acquisitions attractive. Now, that being said, making hard decisions well is why they get the big bucks. Nat Rev Drug Discov , 8 12 , There is a flaw in the system when the people who set the long-term strategy have a half-lfe much less than that of a single project.
How does an organization learn to do better? And what a gem that was! Maybe Moncef and Patrick have invested heavily in Ares Management which owns GNC or, perhaps, they think that medicinal chemists are superfluous and everything can just be bought at the GNC.
And, I seem to recall some recent reports of their competitors compounds currently going into phase III that had eliminated said virus in infected patients. I hope Moncef and Patrick have a plan on how to market their drug, which is apparently still in the preclinical stage, to patients who have already been cured.
I wonder if their bonuses were bigger than the A. The first removal of the then SK NP group was in when the antibiotic groups were fired, followed later by removal of the antitumor group that still did a little NP work. I should know the dates quite ell, as I was part of the crew. Amusingly sarcasm SKF almost purchased Glaxo in the very early s as the H2 antagonists were just coming on line and Glaxo had a competitor but was on its beam ends at that time.
Often wonder how things would have transpired in later years. It seems to me that the timeline proves that this was fraud by Sirtris. It is inconceivable that Sirtris scientists were not highly aware of the JBC papers…after all, resveratrol was their clinical candidate.
So they must have tried other assays and discovered that their new compounds were also false positives. Good, now this discussion makes the Nat. Hi, Derek. Please forgive the belated comment, but I am wondering if, in light of the recent J. Even based on a quick skim, the article is impressive, which should be expected with Ross, an excellent enzymologist, leading the charge. Utako Yukihiro Illustrator.
Get A Copy. Paperback , pages. More Details Original Title. Makai Ouji: Devils and Realist 3. Other Editions 7. Friend Reviews. To see what your friends thought of this book, please sign up. Lists with This Book. This book is not yet featured on Listopia. Community Reviews. Showing Average rating 4. Rating details. Sort order.
What can I say? I love this series very much. View 1 comment. I love this series, it's so much fun! The art is, as always, very defined and gorgeous. Also, the plot is getting more and more exciting, I practically read the whole volume in one breath. To be honest, though, I'd like to remove half a star because all the confusion and the introduction of new characters even reached the point of actually annoying me.
However, I am not quite certain whether this is meant to be, or not, therefore I hope a lot of questions will be solved in the next two or three I love this series, it's so much fun! However, I am not quite certain whether this is meant to be, or not, therefore I hope a lot of questions will be solved in the next two or three volumes.
Nevertheless, I have to admit that I really like Camio, one of the new characters, hopefully we'll get to know him better. The "news" about Kevin are also quite intriguing. I remember laughing out loud when reading that part. Poor William! Apr 28, Dorcas rated it liked it. The story is a little too all over the place and the introduction of a new character nearly every chapter makes it even more unfocused or confusing for the reader.
There's some really interesting historical and religious mysticism incorporated here. This one covers the Mycroft Swallow's father episode and the Camio episode. Needs more Isaac though. He's the cutest. Aug 02, Amanda Setasha Hall rated it really liked it Shelves: manga , zzz , yyy-donated. The story is fantastic, but the art was seriously lacking for a good portion of this volume. It was pretty disappointing.
It definitely picked back up towards the end. I'm not sure what happened in the middle there art wise. I like this series and this book was as good as the first two. I think that Beelzebub is an interesting character.
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Nobody would have thought violence would go down. Family members say Oxendine loved all three of his sons. They say he was a family man with a big heart, a young man on bright mission. Those who knew Oxendine say he was a star.
Burns is charged with murder and second-degree assault. The young father of three was killed yesterday while shooting a music video near City Center. Skip to content. All Blue. Community Calendar. Contact Us. Submit a News Tip. Advertising Information. Jobs at WKYT. Vaccine Team.
Link 2 Hope. Connect with Kentucky CancerLink. Submit Photos and Videos. Latest Newscasts. Closings and Delays. Dismiss Closings Alerts Bar. The legislature resumes its session next week, and the historical racing issue could become a contentious one for Republicans who dominate the House and Senate.
Democratic Gov. Last year, in a huge setback for the racing industry, the Supreme Court ruled that at least some forms of historical race wagering do not meet the standard for pari-mutuel wagering. Racing interests asked the high court to reconsider.
The court said last week it would not rehear the case. The ruling stems from a long-running dispute between racing interests and The Family Foundation, a conservative group that opposes expanded gambling. The foundation has long argued that historical horse racing machines do not meet pari-mutuel wagering standards under Kentucky law. Attorneys for racing interests have insisted that historical horse racing is a valid form of wagering.
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