Dipak Das, who until earlier this year ran a high-profile cardiovascular research center at the University of Connecticut, has recorded a slick looking video defense against allegations that he cooked data and manipulated images in scores of published studies, 12 of which have been retracted to date.
Das, who was hit with a 60,000 pages of allegations stemming from a three-year investigation by the university, spends the bulk of the documentary-style interview — which is available on YouTube — talking about the wonders of resveretrol. But he gets into the misconduct charges at about the 15-minute mark.
A couple things jumped out at us. The first is that, as the narrator intones at about 15:30, Das admits doctoring his Western blots — at the behest of the journals in which he published!
Dr. Das concedes that Western Blot images were altered, but only at the demand of journal editors.
Das goes on to explain how the editors demanded that he and his colleagues “enhance” the images because the backgrounds were too dark or the protein bands were difficult to see. He calls that a “routine process.”
In fact, Das has a point there. Inappropriate manipulation of Western blots does appear to be fairly common, in about one percent of papers, according to work by the Journal of Cell Biology and others. But that doesn’t make it right, as everyone from COPE to the ORI makes clear.
You can watch the whole video here:
Update, 5:20 p.m., 6/18/12: We asked Bill Sardi, managing partner at the resveratrol maker Resveratrol Partners (which does business as Longevinex), whether his company had a hand in the Das video. He answered our question, and then some.
Yes, we put up the money for the taping. We will disclose that in an upcoming release.
Because the university has terminated Dr Das and he has no legal recourse without putting up hundreds of thousands of dollars to fight the attorney general of the state of Connecticut, and because he has not been given due process (present evidence refuting the UCONN allegations), we elected to put up money to air his side of the story. There were no edits to his answers. Whether he delivers a convincing defense is up to online viewers. I don’t personally think Dr. Das’ letters to UCONN were appropriate or convincing, but we are personally aware that Dr. Das has been affected by the stroke he claims to have experienced. So we don’t believe he was in a solid state of mind to address the allegations by the university at that time. He appears to have improved his health. The over-riding issue is why the university is sending letters to journals to expunge 40 years of research conducted at three different institutions by numerous researchers when the evidence to refute UCONN’s allegations no longer exists (records storage is 5 years). Also, UCONN claims it lost the original computer disc with all the evidence on it. The UCONN review board never examined the original western blots but only “representations” of western blots in their 25-page summary which were analyzed by computer software.
We as a company are aghast that the scientific community has elected to condemn Dr. Das based upon hear-say evidence. If a university can “out” a researcher unfairly this time, then all researchers are at risk. The university originally issued false allegations that stated this negated the scientific conclusions that resveratrol averts mortal heart attacks in lab animals when the western blots only dealt with the mechanisms involved, not the conclusions. Canadian researchers in a published paper begged that resveratrol research for the heart not be brought to a halt over this case and that the science is solid, validated by others. But in 8 years since resveratrol pills have been on the market, cardiology has not launched or even proposed a single human clinical trial involving resveratrol. That the product we make was shown to be about twice as cardioprotective as plain resveratrol is also of significance. If there is doctored science, Longevinex wants no part of it. To this point, we cannot find any significant evidence for fraudulent science. That the UCONN withdrew its website and took it offline after we refuted manyof its false allegations against Dr. Das is a tacit admission UCONN over-stated its claims against Dr. Das. We have talked to Dr. Das’ former students and his attorneys before coming to these conclusions. Your news source (RetractionWatch) and the Hartford Courant were the only outlets to obtain a counter opinion. That is out of over 300 news sources that covered this story worldwide. The allegations were so overwhelming and drew so much public attention, the news agencies never followed their obligation to obtain Dr Das’ side of the story. But there are no corrections now which will right the wrong. The public has been unduly frightened away from resveratrol pills and according to Rush Limbaugh, Dr Das “made it all up.” No retractions will be forthcoming from Mr. Limbaugh, that icon of science.
By the way, at least one commenter has been puzzled by a term Das uses in the video to burnish his resume. He called himself a skouser, and said that title was the
highest decoration a university can give.
We couldn’t find that word anywhere, either, at least as it might pertain to academic honorifics. We’re guessing Das wasn’t referring to this use of the term:
a combination of wraparound skirt and loose-fitting trouser that has become the must-have fashion item for every teenager this side of Finland.
It’s hailed as adaptable, youthful, multi-cultural and all-round All Saint, but does any self-respecting female really want to be seen in something that looks as though she threw it on in the dark?
Also known as “skants” by Americans, or “twofers” – short for two for one – skousers are this year’s hottest seller.
Update, 6:30 p.m. Eastern, 6/18/12: Thanks to @DrBarbara1 and @edyong209 for letting us know that “scouser” is also used to refer to someone from Liverpool.
Update, 6:40 p.m. Eastern, 6/18/12: Emily Willingham found the answer: It’s “SCOUZA,” per this UConn announcement (see last page), as in
Sc.D. and the highest honor [HONORARY SCOUZA] from the University of Debrecen was presented to Dr. Dipak Das during November, 2007.
The term seems to derive from “Honoris Causa.”
This is an interesting example of the psychology of people who carry out scientific fraud. Right from the start, there is a huge emphasis on his fame and power, his multiple degrees, how many times his papers have been quoted and how wonderful he is. There is not a hint of humility or any acceptance that mistakes might have been made. And most importantly there is no integrity – no attempt to stand up definitively for any aspect of the research; instead he uses multiple lines of defence:
‘The journals asked me to do it’
‘I didn’t actually do it – the students and fellows did’
‘Even if the Western blots were fabricated, this doesn’t change the fact that resveratrol protects the heart’
‘And whatever happened I didn’t use federal money to do the research’
Would you buy a car from this man?
Yeah, I immediately thought of Richard Nixon too.
I was thinking less of Tricky Dick than the Nuremberg Defense: ‘I was just following orders.’ At this point should we be laughing or screaming in outrage?
It was the line “would you buy a car from this man?”
Fifty(!) years ago there was a campaign poster with a picture of Nixon, captioned “Would you buy a used car from this man?”
I understood amw’s reference the first time, thanks.
‘I didn’t actually do it – the students and fellows did’
Hahahahahaha. Love it. Grab all glory, deflect all responsibility.
You might not by a car from Dr Das, but his research might end up saving your life. Canadian researchers have independently validated his work showing a unique biological action unlike any other drug where the heart is protected prior to a heart attack by release of adenosine, heme oxygenase and nitric oxide. The researcher may not be important to you, but the science should be. Cardiac preconditioning is following the three stages of any new concept: 1) it’s an impossibility; 2) it is plausible; 3) it is a fantastic discovery and I discovered it myself!
By the way, if not resveratrol, then Dr. Das also showed a molecule found in fresh-crushed garlic does the same. For the purpose of complete disclosure, I have no commercial interest in garlic cloves.
J Agric Food Chem. 2009 Aug 12;57(15):7137-44.
Freshly crushed garlic is a superior cardioprotective agent than processed garlic.
Mukherjee S, Lekli I, Goswami S, Das DK.
Source
Cardiovascular Research Center, University of Connecticut School of Medicine, Farmington, Connecticut 06030-1110, USA.
Retraction in
J Agric Food Chem. 2012 Mar 14;60(10):2766.
Abstract
In this study, we compared the cardioprotective effects of freshly crushed garlic vis-a-vis that of processed garlic. Two groups of rats were gavaged with respective garlic preparations while the control group received vehicle only. After 30 days, all of the rats were sacrificed and isolated the hearts were subjected to 30 min ischemia followed by 2 h of reperfusion. Both of the garlic preparations provided cardioprotection, but superior cardiac performance was noticed for those fed with freshly crushed garlic. Consistent with these results, the freshly crushed garlic group displayed significantly greater phosphorylation of antiapoptotic ERK1/2 proteins, reduced Bax/Bcl-2 ratio, and reduced phosphorylation of proapoptotic p-38MAPK and JNK. Moreover, the survival signaling network consisting of Akt-FoxO1 was increased in the freshly crushed garlic treated hearts. Freshly crushed garlic, but not the processed garlic, showed enhanced redox signaling as evident by increased level of p65 subunit of NFkappaB, Nrf2, and enhanced GLUT 4, PPARalpha, and PPARdelta. The results thus show that although both freshly crushed garlic and processed garlic provide cardioprotection, the former has additional cardioprotective properties presumably due to the presence of H2S.
PMID: 19722587 [PubMed – indexed for MEDLINE] PMCID: PMC2775434 Free PMC Article
so does prof bharat aggrawal -who has discovered so many compounds from spices which can protect you from cancer, diabetes and many other diseases by acting upon certain signal transduction pathways.
I have two questions.
First, do you have a citation for these Canadian researchers who have validated the results? Even a name would be helpful.
And second, did you you just reference a paper that has be retracted?
Umm…what is an “honorary skouser”? At 1:13, Das states that he has “an honorary skouser from two universities”.
“Skouser”: a get out of jail free card.
Infuriating. That is some unbelievable ego on display. Paranoia too. He claims the university manipulated the data. What does the university gain from sabotaging their own researcher?
It would be best for Retraction Watch to not link to the video. It’s just free advertisement for the resveratrol products this quack has been helping to sell.
And as of 5:20pm, it’s been confirmed that it’s just an advertisement for Longevinex.
Longevinex refrained from placing its name next to the Dr Das video because we did not want to commercialize the issue. We did not want to present “brought to you by……. ” But Adam Marcus appropriately inquired whether our company had produced the tape and we indicated that was so.
Lots of paranoia and lots of misleading information making it seem like the images were just lightened or darkened for viewing purposes… Dr. Das completely fails to address falsification and fabrication of data associated with the images which is what he is really in trouble for.
“Urban Dictionary” supports Liverpool def. – http://bit.ly/NLb5R2
He cannot be a Liverpudlian because his English is actually comprehensible.
The following statement from the company is telling and corresponds to one of Das’ own defences:
‘The university originally issued false allegations that stated this negated the scientific conclusions that resveratrol averts mortal heart attacks in lab animals when the western blots only dealt with the mechanisms involved, not the conclusions.’
The idea that you can separate the various elements of a scientific piece of work into ‘mechanisms’ and ‘conclusions’, as if the two are independent, is against the whole process of scientific investigation. Das’ conclusions can’t be trusted because his descriptions of the mechanisms are unreliable – and if the company can’t see that they really shouldn’t be involved in science at all.
‘Mortal heart attacks’, ‘skousers’ and a company called Longevinex – it’s getting more like a badly written science fiction movie all the time. It’s actually reassuring to know that, in the end, the system can spot junk science.
Please, UCONN withdrew that allegation by yanking their website offline.
Here is independent validation of Dr Das work:
Arch Biochem Biophys. 2012 May 23. [Epub ahead of print]
Resveratrol protects adult cardiomyocytes against oxidative stress mediated cell injury.
Movahed A, Yu L, Thandapilly SJ, Louis XL, Netticadan T.
Source
Canadian Centre for Agri-Food Research in Health and Medicine, Winnipeg, Canada R2H 2A6.
Abstract
Recent studies from our laboratory have showed that resveratrol, a polyphenol found predominantly in grapes rendered strong cardioprotection in animal models of heart disease. The cardioprotection which was observed was primarily associated with the ability of resveratrol to reduce oxidative stress in these models. The aim of the current study was to corroborate the role of resveratrol as an inhibitor of oxidative stress and explore the underlying mechanisms of its action in heart disease. For this purpose, we used a cell model of oxidative stress, the hydrogen peroxide (H(2)O(2)) exposed adult rat cardiomyocytes, which was treated with and without resveratrol (30μM); cardiomyocytes which were not exposed to resveratrol served as controls. Cell injury, cell death and oxidative stress measurements as well as the activities of the major endogenous antioxidants superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were carried out in control and H(2)O(2) exposed cardiomyocytes, treated with and without resveratrol. Pharmacological blockade using specific blockers of the antioxidant enzymes were used to confirm their role in mediating resveratrol action in H(2)O(2) exposed cardiomyocytes. The status of H(2)O(2) and antioxidant enzymes in serum samples from spontaneously hypertensive rats (SHR) treated with and without resveratrol (2.5mg/kg body weight) was also examined. Our results showed significant cell injury and death in H(2)O(2) exposed cardiomyocytes which was prevented upon resveratrol treatment. SOD and CAT activities were decreased in H(2)O(2) exposed adult rat cardiomyocytes; treatment with resveratrol significantly prevented this reduction. However, GPx activity was not altered in the H(2)O(2) exposed cardiomyocytes in comparison to controls. Pharmacological blockade of SOD and/or CAT prevented the beneficial effect of resveratrol. In SHR, H(2)O(2) levels were increased, but CAT activity was decreased, while SOD remained unchanged, when compared to WKY rats; resveratrol treatment significantly prevented the increase in H(2)O(2) levels and the decrease in CAT activities in SHR. Based on our results, we conclude that treatment with resveratrol prevents oxidative stress induced cardiomyocyte injury mainly by preserving the activities of critical antioxidant enzymes. This may be a crucial mechanism by which resveratrol confers cardioprotection.
Copyright © 2012 Elsevier Inc. All rights reserved.
PMID: 22633977
Here is a link to Canadian researchers plea that resveratrol research continue: http://www.nrcresearchpress.com/doi/abs/10.1139/y2012-065
Pubmed search produced this paper from T Netticadan where Das DK is the corresponding author. So much so for the independent validation!!
Juric D, Wojciechowski P, Das DK, Netticadan T.Prevention of concentric hypertrophy and diastolic impairment in aortic-banded rats treated with resveratrol. Am J Physiol Heart Circ Physiol. 2007 May;292(5):H2138-43.Cardiovascular Research Center, University of Connecticut School of Medicine, Farmington, CT 06030-1110, USA.
In this 2007 study, all the authors except Dr Das are from Canada, still Dr Das was the corresponding author.
I just browsed for something and found out that Prof Das has an honorary M.D. degree? What does an honorary MD mean?
It means he has been acknowledged for his contribution to the medical community by giving inane recommendations like high vitamin C can cure cancer! Ha!
It seems that one of his friends/co-authors has just retracted a review article: Singh R, George J, Shukla Y. Retraction: Role of senescence and mitotic catastrophe in cancer therapy.Cell Div. 2012 May 15;7(1):15.
Dear, oh dear… What next, the “I am not a fraud” infomercial channel??
If UCONN had conducted proper review and given Dr Das due process, such a videotape would not be necessary. Outside of finding hundreds of thousands of dollars to go to court against the Attorney General of the State of Connecticut, the online videotape is his only public defense. If you choose to believe UCONN over Dr Das, that is your choice. But allow him to defend himself, without ridicule. None of us know Dr Das is guilty, we have only heard he has been declared guilty of scientific fraud. UCONN’s review board which dismissed Dr Das only scrutinized a 25-page summary that did not contain the original western blot images and was withdrawn from online viewing once it was challenged.
But in the video, Das says that he did manipulate images… so whether we believe Das or UConn is immaterial – they are now saying the same thing! And their executive summary included images taken directly from his papers, where it was obvious these were not simply “enhancing the contrast” of western blots. Lanes were replicated from one blot to another, although they claimed to be looking at different proteins. Controls were replicated, although they were for different experimental conditions. And there were obvious cut-and-splices.
Has that document now disappeared? I can’t answer that because I didn’t google it just now. But Das admitted to a reporter that he received the entire 60,000 page document from UConn on a disk. Why doesn’t he post that document online so that everyone can see what UConn has accused him of, and we can decide for ourselves whether the evidence supports Das, or UConn??
That’s a lovely abstract that Mr Sardi has produced, here, but it’s irrelevant because it’s in vitro work and I don’t live in a glass bottle. It certainly is promising but I’d have to tie it to, one, can you get that much resveratrol into your own cardiomyocytes, and two, if you could, would hydrogen peroxide injury be a good prototype for cardiac thrombosis?
I’m sorry about the Liverpool (oh, he’s saying “honoris causa”, yeah) thing, anyway, plus I’m sorry that he had a “stroke” (is that in the medical sense of brain infarct or in the popular sense of any physical collapse–it’s a very old word, you know…) I won’t ask for the MRI scans.
you know, I’m gonna keep it short because I’ve got some Western Blots on the stove, here…yummy.
This is not in vitro work. It is animal model, not lab dish. It is demonstrated in a working animal heart and verified by others and accepted for many years. Cardiologists themselves believe in the phenomenon called cardioprotection or cardiac preconditioning because they use a pressure cuff on the brachial artery prior to invasive cardiac procedures or even on the way to the hospital. You can read about it here:
http://www.cbc.ca/news/health/story/2010/02/26/heart-attack-blood-pressure-cuff.html
and here
http://www.theheart.org/article/942601.do
Dr Das’ work showed preconditioning of the heart can be accomplished molecularly.
OK Bill Sardi, time for a reality check. I’ve taken my in-depth comments about the video from the main Das thread, plus your (comical) responses, and added some additional commentary. This whole affair really is starting to come into its own as a form of entertainment…
1) I called you out on the claim that UConn “posted a website” containing 60,000 pages of allegations, saying it was not so. An abridged version of the report was made available, but the entire 60k document has not been released. You are now telling me I’m wrong? WTF? I will happily back-down on this point if you can actually provide proof – has the 60k document actually been made available in public? Ivan/Adam – have you seen it? Anyone? Can someone please clarify this point – has the 60k document been released to the public? AFAIK, only the summary was ever available on the UConn site, and nobody apart from Das and his legal team has seen the whole thing.
2) I disputed your claim that UConn investigation encompassed ALL of Dak’s research going back 4 decades. Not so. Only 145 counts of image fraud across a few dozen papers. The allegations are highly selective and accurate, and do not question his entire output. I then asked if you were aware that ORI has a statute of limitations of 6 years?
You respond by stating as a fact, that “UCONN is sending letters to journals seeking retraction of all of his papers”. I will merely state, as an editor at journals that published much of Das’s work, that this claim is total BS. Nobody (least of all UConn) is claiming everything he did was fraudulent. Please stop over-stating the magnitude of the case against him. The case has been clearly laid out, and has limits. It never ever encompassed Das’ entire opus.
3) I called out the rambling narrative about students, former students, locked door policies etc., with NO NAMING of anyone involved. At the very least, when refuting such charges, cite credible names for the people you are basing the refutation on. You respond that naming these people would be inappropriate and immaterial. This is again total crap. INCREDIBLE CLAIMS REQUIRE INCREDIBLE EVIDENCE, and this is one of those cases.
4) I refuted your claim that resveratrol is the “only agent under scientific investigation that can prevent sudden cardiac death”. You respond by listing a couple of other drugs which lower CVD risk (statins etc.) Seriously? You are completely oblivious to the multitude of compounds that have been investigated over the years as cardioprotectants, of which resveratrol is just one. See this review by Downey et al. (http://www.ncbi.nlm.nih.gov/pubmed/19506318) for a laundry list. Resveratrol is just a tiny tiny part part of a humongous effort, funded by millions of dollars of NIH money, to find drugs that prevent heart attack. To pretend it is in some way uniquely different, or more efficacious than anything else that’s been tried, is (a) ignorant, (b) arrogant, (c) stupid, (d) misleading – take your pick, a trhu’ d (I vote for all).
5) You asked how did the alleged image manipulations pass peer review? I responded that in some cases they didn’t, as evidenced by a number of retractions, corrigenda and errata, on Das’ previous work before all this stuff surfaced.
I will concede the point here – you do make a valid point (although it’s hardly a novel one to anybody versed in the subject) that journal peer review needs improvement. The problem is when you use this as a segue into…
6) The best one of all… “Scientific journals DEMAND that all western blot images be enhanced before publication”. WTF? They actually demand the opposite – that no manipulation of any kind occurs, and the image should be as close as possible to the original (i.e. un-enhanced).
Your response is funny (both in the ha ha sense, and the weird sense)… “You obviously have not read recent write ups in journals about western blot imaging quality. There is a current topic of discussion.” Err… actually I’ve contributed to the writing of such articles, so I think I know what I’m talking about here. Let’s just say that if you (the drug company shill) and me (the respected scientist on the editorial board of numerous journals) were in a public debate on what exactly journals want and do not want, in terms of image quality, you might want to consider staying in bed on the day of the debate unless you like having your a** handed to you on a plate.
Just for clarification, here are some quotes from the JCB guidelines, which are widely used as a template by other journals… “While it is acceptable practice to adjust the overall brightness and contrast of a whole image, such adjustments should not obscure or eliminate any information present in the original”. I think this is the “enhancement” Das is speaking about in the video. The problem is, that’s not what he did!
Also from JCB…. “Adjusting the intensity of a single band in a blot constitutes a violation of the widely accepted guideline that no specific feature within an image may be enhanced, obscured, moved, removed, or introduced.” This is in-fact exactly what Das did. Do I need to clarify it any more for you? There is a clear and well-defined line between enhancing clarity for readers (e.g. brightening a whole blot), and we’re all agreed that’s NOT was Das did. He crossed the line and selectively enhanced certain features of blots, which goes by the more common name of fraud. Now do you get it?
7) I questions Das’ claim that the University, when asked for the hard disk, said “we lost it”. Really? That’s a pretty serious event, one which you think would be publicized. Has anyone from the University ever gone on the record as saying that the hard disks were lost? You respond that I should “call up Dr Das’ attorneys” OK, maybe I will, but what’s the betting they won’t tell me because it’s private information. Like I said before, INCREDIBLE claims require incredible evidence. You just invoked the god argument… you can claim outrageous things because (supposedly) it’s impossible to ever know the truth. Maybe we should all focus on the knowns (Das committed fraud) rather than speculate on things that cannot ever be confirmed.
8) I questioned Das’ claim at 17 min. that he never used federal research funds for resveratrol research, only the consulting and industry money. Why then, do the papers on resveratrol acknowledge federal funding? Why then, is NIH ORI involved (they only investigate if work was federally funded)? You respond saying most of it was industry and maybe only one was federal. Again, this just does not fit with the truth… virtually ALL of Das’ papers acknowledge the NIH as a source of funding.
Interestingly, your response then includes the following statement… “The NIH ORI has distanced themselves from this university action. I contacted them and received an e-mail saying Dr Das’ work was not under current investigation.” REALLY? I was not aware that ORI was in the habit of announcing that a previously confirmed and ongoing investigation had been dropped, over the ‘phone to anyone who calls in. You do know that ORI is a federal agency right (kinda like the FBI)? You also surely know that mis-quoting a government representative in a public forum can constitute a felony offence right? Of course, if you knew anything about the ORI, you would actually know that it’s NOT EVEN PART OF THE NIH! Your conjugation of the term NIH ORI belies how little you even know about the inner workings of the organization and what it does.
9) I disagreed with Das’ claim regarding the way in which the investigation was handled, and the University’s refusal of an appeal…Das openly states in the video “even NIH said it is wrong”. Really? I recall no statement in any way implying that NIH found fault in the investigation.
You respond “NIH did not say it was wrong, to my understanding. Please provide evidence of this”. No, you don’t seem to get it. DAS SAID THIS IN THE VIDEO!!! I’m the one asking YOU for evidence, not the other way round. Jeebus!
Mr Sardi ends his diatribe with “Your response is evidence of ignorance of the facts involved in this case and an undeserved belittling of Dr. Das’ work.”
Yeah, dream on pill pusher.
Thank you, vhedwig, for those cogent statements as well as the ad hominem comments I was too delicate to throw in (Mr Sardi deserves every one, for calling me an ignoramus.) I certainly don’t have the “skin” that you have in this “game.”
To pile on a bit, I thought I’d go and look at the other stuff but I got a 404 on the “49 page summary” of the U Conn investigation. Dr. Das’ personal letter from June 2010 is certainly damning; he should have shown it to his lawyer first.
Does anyone have a functioning link to the U Conn report summary?
It certainly appears that the media, in its pursuit of juicy headlines, got the entire story backwards and then never followed up. That’s pretty much standard operating procedure.
My question, as a former practicing physician, is why Dr Das wasn’t put on disability leave before all this carp hit the fan. Surely he was showing clear signs of problematic cognition and behavior in the months before? In my personal opinion, he either had a stroke which deformed his personality (it happens a lot) or he was already suffering from a paranoid personality disorder before, as in for the last ten years or more. I vote for the latter, because he looks the part of a chronic paranoid(they’re everywhere, and they’re watching you.)
That includes the delusional part visible in the seventeen minute video that prompted this post.
Puzzled Monkey, I don’t have a functioning link, but I have the report itself. Forty-nine pages, pdf. Is there a way to send it to you?
Reply:
1. It may have been abridged, but news reports said it was the full 60,000 page report. I opened and read some of it, but no way to confirm there were 60,000 pages there, obviously. You calling me on an inconsequential fact.
2. You are not an insider. UCONN is attempting to expunge all of Das’ work by sending letters to editors.
You need to speak with his attorneys if I am not a believable source. I’m not even sure his attorneys know the full scope of UCONN’s actions as they don’t receive these notifications, Dr. Das does.
3. Look, UCONN didn’t identify the name of the student. Should I drag her into this? Again, her name is inconsequential. The former students don’t want to be ridiculed either. Why did UCONN withdraw the claim that Dr Das outed this student? It never happened. She still works at UCONN.
4. You did not refute this. There is a distinct difference between cardioprotectants and cardiac preconditioning, as I previously explained. Cardiac preconditioning is unique and not to be confused with other heart protectants. Das also found that tocotrienols facilitated preconditioning. It is the most desirable form of heart protection.
5. Dr. Das is being taken to task for papers he published over 5 years ago for which there is no records storage. So he can’t defend himself against those allegations. I ask again: what happened to the prior peer review by the journals? Why weren’t all these journals doing their job? Casts a pall on all scientific research, especially medical imaging.
6. The reviewers at U CONN only examined “representations” of western blots, and not the originals which the NIH ORI says must be compared for adequate scrutiny. Then the university said they lost the disc containing the original images. This fact was not made public to my knowledge. Why do you presume guilt before innocence and why do you resort to ridicule? It is not necessary here. This is an important issue.
7. Some of the research conducted outside of Dr Das’ lab was conducted at NIH, so NIH funding is cited, but it did not refer to funding directly to Dr Das’ lab. Alos, it is Dr Das making this claim, not me. Do you think he would get away with such a claim if not true? It is easily fact checked. I looked up one study found at this link ( http://www.nrcresearchpress.com/doi/abs/10.1139/Y10-082 ) and it was not NIH funded.
8. To my knowledge, the NIH ORI is not investigating Dr Das’ work and we wish they would and clear the air on this case.
9. Dr. Das was referring to the methodology of reviewing the western blots when he said the “NIH said it was wrong.” UCONN’s reviewers used a computer analysis of enhanced western blots and had no originals in hand for comparison. What the reviewers saw were “representations” of the western blots, not the actual western blots. The NIH says originals must be used for fair comparison. – B Sardi
Interesting but I don’t see any evidence that Dr. Das has any mental illness or is suffering from delusions. His behaviour is typical of people who commit research fraud and are then found out – they have to discard all their scientific training to defend their fraudulent papers, and then turn themselves into unconvincing amateur lawyers as they mount a multi-level defence saying they did nothing wrong. In doing so they need to blame responsible organisations such as universities for their problems when it is these same institutions that helped them become what they are. Das continually speaks of the research as his and his alone, ‘I am famous for this’, as if the university was irrelevant.
So what he says simulates paranoid delusions, but underneath it’s simply that he can’t publicly admit to the truth.
As for Mr. Sardi’s comments, it is simply not relevant if other researchers have reached similar conclusions to Das in certain cases – it is still research fraud. The effects of research fraud go way beyond the subject itself – imagine all the students and post-docs who have been ‘trained’ under Das now going out into other fields (on the back of their publications in Das’ group) and using the same approaches to science. Such people can create mayhem in universities around the globe.
I would see it the other way – if resveratrol indeed has potential benefits, then Das has been doing the field a disservice by contaminating it with research fraud. But personally I suspect the story has been overblown – there are countless numbers of interesting molecules out there worthy of study (none of them with a self-proclaiming formulation like Longevinex).
I also agree that the field has clearly been lax in terms of reviewing Das’ papers. As an example I looked at his Plos One paper http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3009730/pdf/pone.0015705.pdf . The article reads like a bad advertising brochure, with many phrases that seem alien to the careful process of scientific argument e.g. ‘Resveratrol can alter a variety of genes thereby changing the ‘‘death signal’’ into a ‘‘survival signal’’ [8]. Reference 8 is in fact a review by Das in Biochemisty (Mosc) with no mention of resveratrol. In other words, the work was effectively not reviewed, otherwise such a blatant assertion would have been picked up.
If this drug is so vital to the future of mankind, clean up your act and do some rigorous research, unconnected to private companies. Or else stay in advertising. Don’t mix the two up.
NO, it is relevant that other independent researchers validate Dr Das’ work BECAUSE UCONN is the one that made an issue out of this in the first place, claiming the conclusions of Dr Das’ work were invalid, which is what led Mr. Limbaugh of radio-talk show fame to make the statement “he made it all up.” Let’s say for discussion sake that Dr. Das’ western blots were misleading (however the bar charts that accompanied them provided accurate data!), the western blots only address the mechanisms (gene proteins involved). If you examine the photos of the rodent heart you can graphically see that the area of fibrosis (scarring) was dramatically reduced by preconditioning the heart with resveratrol, and more so with Longevinex. UCONN did not challenge these images. Dr Das was pre-funded for 10 years by NIH. He didn’t need to alter western blot images to maintain or gain NIH grant money as U CONN’s press released alleged. UCONN says it is returning the research funds to NIH. I’d like to see that check.
Again with the misinformation. When will you learn…
UConn never said it was returning the funds. It merely said they were freezing the grana, and turning down awards. There’s a difference between cashing a check, spending the money, then giving the money back late (what you claim), or just handing back the check before cashing it.
You claim that the western blots are bad but the bar graphs that accompany them are OK. I have a proposition for you…. I have a wallet full of money, and I owe you $100. I give you a fake $100 bill, and you spot it and ask for different one. I give you a different $100 bill. Do you put it away without looking at it? Of course not… One instance of fraud creates a requirement for scrutiny on subsequent occasions. The fake western blot is the first intance, and the bar graph that (allegedly) came from similar experiments is the subsequent occurence. If he faked one, he could have faked them all. The entire data set is drawn into question.
What you fail to realize, is that people who fake one kind of data are often found to have faked other kinds too. Thus, your assurance that the photos of the rodent heart are genuine, just does not hold water. Anyone capable of faking a western blot can easily pump BS numbers into Excel spreadsheets and generate bar charts – if anything we should be more worried about this type of fraud because it’s much harder to trace! It’s like saying…. Hey, I just gave you a fake $100 bill, but here’s a real diamond…. It’s even harder to spot the fraud (unless you’re a diamond expert), but somehow you expect people to be more convinced. That’s Bass Ackwards reasoning if I ever heard it.
And FYI, preconditioning is not the most desirable form of cardioprotection, because it requires you to pre-treat someone before they have a heart attack. The at-risk population is just about anyone aged over 55, a very difficult proposition. Far better to treat only those who actually have a heart attack (and that can only be done after they’ve had it, unless you have a time machine). Proposing to treat millions of people prophylactically is a ridiculous, inefficient, and not clinically desirable scenario.
“preconditioning is not the most desirable form of cardioprotection, because it requires you to pre-treat someone before they have a heart attack.”
A treatment many people call “exercise.”
Quote: “Proposing to treat millions of people prophylactically is a ridiculous, inefficient, and not clinically desirable scenario.”
That’s actually what the medical establishment/pharma industry is currently trying to achieve, by prescribing statins for everyone who’s ever had increased cholesterol or off-ratios… And looking at the profits of big pharma made with this class of drugs, I would say they’re doing a pretty good job.
Again, it is not important whether some sections of Das’ work appear valid (or can’t be proven to be fraudulent because of age or lack of evidence). Or if some of the conclusions reached during his fraudulent work are true. The point is that a large body of his work has been investigated by UCONN and found to involve research fraud to a major degree (145 counts of fabrication / falsification).
Accepting what you don’t know is a normal part of scientific investigation, but Das and Longevinex in general are world experts on everything. Let’s remember what Longevinex (through Bill Sardi) themselves have said about their product, see http://www.forbes.com/sites/larryhusten/2012/01/16/resveratrol-and-fraud/
‘Resveratrol is an antidepressant, an anti-inflammatory, an anti-bacterial, anti-fungal, anti-viral, anti-cancer, cholesterol-lowering, liver-cleansing, brain enhancing molecule. If Americans embraced resveratrol pills en masse, many prescription drugs would not be needed. Modern pharmacology and its model of developing a single synthetically-made molecule to treat each and every disease, would become antiquated.’
And it can make you see better as well.
People who commit research fraud believe that if they just keep saying the same thing forcefully enough, people might just believe it enough to buy their story or their product. This is the difference between advertising and science. And this is what UCONN have seen in Das’ work – an abandonment of scientific principles.
In reply to amw June 19, 2012 at 8:36 pm
“People who commit research fraud believe that if they just keep saying the same thing forcefully enough, people might just believe it enough to buy their story or their product. This is the difference between advertising and science.”
Very well put!
A problem is that we have come to believe advertising.
And of course, much of this was covered by RW before:
http://www.retractionwatch.com/2012/01/11/uconn-resveratrol-researcher-dipak-das-fingered-in-sweeping-misconduct-case/
I thank Adam Marcus of Retraction Watch for allowing me to represent a counter story to the false allegations posed by UCONN against Dr. Dipak Das. What is curious here is the belittling and denigration of great science that could save lives. Why are the participants at this blog so anti-pill? We are talking about prevention of mortal heart attacks, something which the best pharmaceutically designed pills have not been able to demonstrate, even aspirin. That antagonists have identified themselves as physicians and journal editors suggests even more professional bias against what appear to be real scientific breakthroughs, and as cheap as a fresh-crushed clove of garlic, for those who are concerned about my commercial interest in dietary supplements. Cardiac preconditioning is a real phenomenon as evidence by long-standing published studies. There are natural molecules that can molecularly mimic this unparalleled cardiac protection, namely resveratrol, tocotrienols and a garlic-derived molecule. Why is there such animosity to this science at this forum? Does no one question the self interest of the doctor side of this story? If the bias expressed here is from health professionals and journal editors, then the unjustified dismissal of Dr Das is at least now explainable.
If you were right and had all this huge weight of evidence to back you up, why would you be so concerned about the fate of one researcher? This is about Das, not about nutritional medicine. You’re the only one equating the two.
May be it is working!!
There is another support for this work :
Bixi Jian, Shaolong Yang, Irshad H Chaudry, and Raghavan Raju 2012 Resveratrol Improves Cardiac Contractility following Trauma-Hemorrhage by Modulating Sirt1 Molecular Medicine 18: 209 – 214.
But your earlier claim that canadian study is independent – difficult to believe.
The Canadian study is not NIH funded, and it is simple to open the paper and read it to determine that. What is so difficult to believe? You can’t even concede a simple fact.
Is your assertion that the Canadian study must be independent based on the fact it is not NIH funded? That how I’m reading your comment above.
the study you quoted earlier in your comments: The corresponding author T Netticadan was Dr. Das’s collaborator. Is a paper from T Netticadan group an independent study? This is hard to believe and I am not convinced that this was an independent study. Period. Please read my comments June 19, 6:41 pm. May be we have different perception of independent studies.
What we have here are volunteer judges, who have disclosed they are doctors, journal editors, etc, who apparently do not know what cardiac preconditioning is and therefore revealed they never read one of Dr Das’ research papers or they would know that. And they have revealed they can’t even take a moment to quickly scan a paper and determine where the funding came from. And they are biased against dietary supplements (I am a “pill pusher” but doctors aren’t). And they sit in judgement of a researcher who has 500 published papers and all of them have ??? papers published, and it appears none of them have ever performed a western blot test. It is fine to be skeptical and not easily fooled. But it is ridiculous to flatly deny Dr Das’ assertions such as lack of due process, loss of an original data disc, holding Dr Das accountable for studies where records no longer exist, etc, etc. These are substantive issues that would exonerate Dr Das from all charges against him. Can they be verified here? This is not a court where evidence is presented. It is a court were opinion is rendered. A kangaroo court judged Dr Das work at UCONN, and amateur judges failed to even fairly review his published papers here in this blog-court. All I can say is– keep talking. You’ve disclosed your biases perfectly. It is all a matter of public record now. The Google archival service will ensure that. – Bill Sardi
You forgot to mention that most accusers/judges here are making their judgements anonymously…
Maybe he just realized that’s neither here nor there.
Guilty as charged… Sebastian.
IMPORTANT:
Just so that everyone understands how little credibility Bill Sardi deserves, he believes that vaccines cause autism. This has been so thoroughly debunked that we can all agree that anything Bill Sardi has to say can not only be disregarded, but also assumed to be probably false.
See for yourself
http://www.lewrockwell.com/sardi/sardi119.html
“Children below the age of 2 years do not have a sufficient blood—brain barrier developed and are subject to chronic brain infections that emanate into symptoms that are called autism. Toddlers should not be subjected to injected viruses. ” — Bill Sardi
“The CNN report “Beneath the Veil,” which graphically displayed atrocities perpetrated by the Taliban on Afghani women, preceded the events of September 11, 2001 that resulted in a U.S. military assault on Afghanistan. The Taliban were being demonized a month prior to the war so public attitudes toward them would be negative. CNN obviously had foreknowledge months prior to 9-11.”
http://www.lewrockwell.com/sardi/sardi104.html
O – M – G.
“When are paleontologists going to stop digging up chimpanzee bones and calling them your ancestors?……To totally confound modern science, miners have unearthed a man-made metal sphere from the Ottosdal Mines in South Africa, whose rock strata is estimated to be 2.8 billion years old. ” – Bill Sardi
http://www.lewrockwell.com/orig/sardi3.html
Is this really the same guy? And he’s claiming THIS BLOG is anti-science?
Congratulations, Bill Sardi. You have succeeded in improving Das’s reputation. Compared to you, he’s Einstein.
I’m really curious whether he’ll be back after being exposed as a 9/11 truther, creationist, and anti-vaccine conspiracy nut. I’m hoping he will be back to defend those positions as ineptly and humorously as the garbage he’s selling.
Dear FailureToReplicant
I will respond to your posting because it is pertinent to the issue at hand regarding resveratrol.
When Charles Darwin visited the Galapagos Islands (twice) for a 2-month period, he didn’t have a Kodak snap camera so he drew eloquently detailed images of bird beaks. Darwin noted the change in the shape of the beaks over this short time.
Darwinian biology postulates that gene mutations over a period of many millions of years can produce advanced forms of life and that humans evolved due to that process from a common ancestor. Crick and Watson who were credited with discovering DNA said this was the mechanism behind Darwinian evolution.
However, what Darwin observed were not gene mutations but rather obviously, epigenetics (adaptation), which is the underlying mechanism involved with resveratrol. This was not Mendelian genetics which emanates in variations every so many generations.
Darwinian evolution is fatalist biology. Gene mutations speak for maybe 2% of all human disease. However we know that a person born in Japan and who moves to Hawaii will not live as long compared to staying in their native country. This is epigenetics, that is, environment (food, lack of food, temperature, radiation) controls the genes.
The idea behind resveratrol is to produce a molecular mimic of a calorie restricted diet which is known to roughly double the lifespan of all living organisms, even mammals. It is a totally anti-Darwinian molecule.
In a rodent study (98% of the rodent genome is homologous to humans), resveratrol and Longevinex were compared to a calorie restricted diet by global gene array over a 12-week period. A CR diet significantly differentiated 198 genes, resveratrol 225 genes, Longevinex 1711 genes. If lab mice are given a CR diet over their lifetime, 831 genes are expressed. Longevinex altered 677 of these genes in the same direction as CR. Here is the published abstract of that study:
Exp Gerontol. 2008 Sep;43(9):859-66. Epub 2008 Jul 9.
Short-term consumption of a resveratrol-containing nutraceutical mixture mimics gene expression of long-term caloric restriction in mouse heart.
Barger JL, Kayo T, Pugh TD, Prolla TA, Weindruch R.
Abstract
An active area of aging research is focused on identifying compounds having the ability to mimic the effects of caloric restriction (CR). From 2 to 5 months of age, we fed male B6C3F(1) mice either a 40% CR diet, a control diet supplemented with a commercially available nutraceutical mixture (NCM) containing resveratrol, quercetin and inositol hexaphosphate, or a diet supplemented with an equivalent dose of chemical-grade resveratrol (RES; 1.25 mg resveratrol kg(-1) day(-1)) from 2 to 5 months of age. Cardiac gene expression profiles were generated for the three groups of treated mice and compared to age-matched control (CO) mice. All three treatments were associated with changes in several cytoskeletal maintenance pathways, suggesting that RES and NCM are able to mimic short-term CR. CR uniquely affected several immune function pathways while RES uniquely affected multiple stress response pathways. Pathway analysis revealed that NCM (but not CR or RES) regulated multiple metabolic pathways that were also changed by long-term CR, including glucose and lipid metabolism, oxidative phosphorylation and chromatin assembly. Examination of key genes and pathways affected by NCM suggests that Foxo1 is a critical upstream mediator of its actions.
PMID: 18657603
The future of biology belongs to epigenetics and small molecules that can control genes. The largest library of small molecules that control genes are known to be polyphenols which occur in nature. They out-perform gene-targeted drugs.
Mr. Sardi, I don’t think Darwin was observing a change in bird beaks during the short period that he was on the islands. He was observing the results of many years of change before he arrived. Do you have a reference for the idea that the change in beak was due to epigenetics?
Bill Sardi, I feel I must correct some grave assumptions on your part, namely that your critics here have not read Das’ papers, do not know what cardiac preconditioning is, and have never done western blots themselves. In my case, you are wrong on all three counts. I have read a significant portion of Das’ opus, I have published upwards of 30 papers on preconditioning myself, and many of those papers included western blots. So, I think I know what I’m talking about here. Allow me to elaborate on why I think you are coming across as someone with a paltry understanding of this very complex field…
Ischemic preconditioning (IPC), in the classical definition as discovered by Chuck Murry in 1986, refers to the phenomenon in which a small period (or many small periods) of ischemia (blockage of blood flow in a coronary artery), followed by reperfusion, can bring about a protected state, so that when a large ischemic event occurs (your so-called “mortal heart attack”), the heart suffers less damage and recovers its function better. It’s called “preconditioning” because the same insult that kills the heart (ischemia) in small doses can pre-condition it. You use the terms preconditioning and cardioprotection as if they are interchangeable – they are not.
Much of the work done in the 25+ years since, has been aimed at figuring out what are the signaling mechanisms of IPC, and trying to design drugs to mimic that signaling – this is more commonly known as “pharmacologic preconditioning” (PPC), even though strictly speaking it is not preconditioning because the stimulus is not the same as the insult. A large number of agents can mimic IPC, to bring about PPC, including opioids, statins, GSK3b inhibitors (lithium), insulin, growth factor receptor ligands, bradykinin, adenosine, to mention just a few. They do this by activating the same signaling pathways (such as protein kinases) that IPC activates. The other half of the field has been aimed at trying to figure out the molecular mechanisms of damage that occur during ischemia, and design drugs to stop that damage. None of those drugs has made it to the clinic. Cariporide (NHE 1 blocker that prevents sodium overload) was a big failure – very promising in animal studies but just didn’t pan out in the clinic. Antioxidants are another example – a big hoopla in the 1980s about the role of free radicals in ischemic injury, but all antioxidant therapies failed in large animal and clinical trials.
With the above framework, let us agree on some definitions… resveratrol is not a preconditioning agent. It may be a cardioprotective agent, with an uncertain molecular mechanism of action. It has been reported to prevent ischemic damage in animal models (rats and mice). No clinical trials (proper ones) or even large animal studies have been performed for resveratrol in heart attack (acute myocardial infarction). It may be an antioxidant (making it by unlikely to succeed in the clinic). It may activate some protective signaling pathways, but the evidence for that is western blots from Das and others (ha!). It is in the public domain – it cannot be patented because it does not represent a unique and novel chemical composition of matter. That’s why the drug companies are not interested – why should they invest millions in performing clinical trials, when at the end of the day their new blockbuster resveratrol wonder drug can be bought at the corner store? It’s a total non-starter from a financial perspective, as are most of the “nutriceuticals” out there. Why do you think Sirtris went to all the trouble of designing molecules that do the same as resvertrol but look chemically different? So they could patent them. Intellectual property is what makes the pharma world go round.
So… problem #1, resveratrol has “issues” as a chemical, from a drug development standpoint.
Another reason is you use terms not common in the scientific literature… e.g. “prevent a mortal heart attack”. I have never seen this term, until I came across you and Das and your Longevinex astroturfing machine. It’s odd, because resveratrol doesn’t actually prevent the heart attack. All it might do is prevent some of the damage due to the heart attack, but it doesn’t actually prevent the heart attack itself. That would require some effect on blood clotting or atherosclerosis, nether of which have been shown to be affected by resveratrol. What’s laughable is that most of Das’ work is performed in Langendorff perfused hearts. In this preparation, the heart is removed from the body and kept alive on a perfusion rig, and the rat is sitting dead in the bottom of the ‘fridge! On this basis (ex-vivo perfused model), you throw around the term “mortal” as if the agent under investigation is going to save the life of the animal involved. Like I said, the animal is dead, it has ceased to be, it has gone to meet its maker, it wouldn’t speak if you put 10,000 volts up its backside, it is an ex rat, wake up ratty, I’ve got a lovely pellet of chow for you (sorry, got carried away there).
So… problem #2, you’re simply not making the case for resveratrol using the correct scientific terminology. That’s a key reason why the medical establishment is not interested in what you have to say. Go back to school and learn to talk the talk before trying to play with the big boys.
In addition, allow me to clarify the problem regarding prophylaxis for heart attack. All of these drugs (both the IPC mimetics and the anti-ischemic damage agents) suffer from a major limitation, which is that most of them have to be added before a heart attack occurs. Clinically speaking, this is a massive problem because it requires you to predict who will have a heart attack, and give them a drug right beforehand. Alternatively you have to prophylactically dose everyone in the at-risk group, which for heart attack means pretty much everyone over age 55. As you corectly point out, this is being tried right now (with moderate success) for the statins, but there’s a huge difference… statins are molecules about which we know a lot. They have a well-defined mechanism of action and they have been the subject of multiple placebo-controlled double-blinded clinical trials (because they are patentable molecules so the drug companies can recover the cost of the trials in sales revenue). This is simply not the case for resveratrol. No drug company is going to sponsor a trial giving resveratrol pills to the over 55’s, then doing follow up tests for 5 years to see if it did anything. That’s what I mean when I say “ridiculous”.
What we should really be focusing on (given that we can’t predict who will have a heart attack) is the delivery of drugs to prevent damage to the heart once a heart-attack has already occurred. This means drugs that can be delivered during percutaneous coronary intervention (PCI), i.e., balloon angioplasty to unclog a blocked coronary artery. Drugs that can be taken by someone in the ambulance on the way to the ER when they have an out-of-hospital MI. As far as I am aware (please correct if I’m wrong), there is absolutely NO evidence that resveratrol does anything when added post-MI. In addition to aspirin, there are some newer molecules in development which do protect when delivered at reperfusion, but it will be a long time before we see them in the clinic.
And… there’s problem #3. It wouldn’t matter if you were shilling garlic, resveratrol, or holy water, it’s all a problem of timing. None of these things are going to work if it requires daily prophylactic dosing of millions (billions) of people.
Hopefully Bill, you will gather from the above that I’m way more qualified than you on this topic (for the record I’m PhD cantab). With no medical training* you are asking the entire medical establishment to throw all its current practices out the window and put everyone aged over 55 on a daily pill, with unknown side effects (actually some pretty nasty ones if you read the literature), in the hope that it will prevent them from having “mortal heart attacks” (a non medical term), all on the basis of no clinical trials, and oh by the way one of the major players in the pre-clinical history of this molecule faked a bunch of data. Oh, and you also just so happen to run a company that sells those pills. JTFC!
*I searched around and can’t find any information on what your qualifications are. No undergrad, no graduate degree, nothing. One website even has you quoted as saying “when asked about my qualifications, I say I am not an expert”. Care to weigh in on what your qual’s are and where you got them from?
Thanks for the extremely well written background info on IPC, ex vivo experimentation, etc. I learned something today!!!
Dear Dr. vhedwig, whoever you are. I must blog with my full name and subject myself to ridicule while you as a noted authority hide behind a pseudonym. But OK, let me proceed.
You say: “No clinical trials (proper ones) or even large animal studies have been performed for resveratrol in heart attack (acute myocardial infarction).” Well, explain to everyone how you would proceed in conducting an ethical trial of an agent that prevents a mortal heart attack? You would give high-risk individuals an inactive placebo pill or a resveratrol pill and stand by and see how many die? That would be unethical, as previously explained here at this website. What you are asking for is evidence that is impossible to produce. As previously explained, only retrospective studies (as performed initially using aspirin) would be practical.
You say: “you are asking the entire medical establishment to throw all its current practices out the window and put everyone aged over 55 on a daily pill, with unknown side effects (actually some pretty nasty ones if you read the literature), in the hope that it will prevent them from having “mortal heart attacks” (a non medical term), all on the basis of no clinical trials.”
No, I am pointing to science, performed by Das and others. You are presuming existing cardioprotective agents to be effective. They are not. Statin drugs don’t prevent mortal heart attacks, they weakly prevent non-mortal events among healthy individuals and high-risk groups. See the work of Harvard Professor John Abramson who reviewed the 10 largest statin drug trials and found no evidence for reduced mortality (see Lancet. 2007 Jan 20;369(9557):168-9. Are lipid-lowering guidelines evidence-based?) The same goes for aspirin, which a report in the Archives of Internal Medicine in Jan ’12 revealed does not prevent mortal heart attacks. ALL OF THE CURRENT PILLS TO PREVENT MORTAL HEART ATTACKS SHOULD BE THROWN AWAY if you consider the published science. If existing therapies work, why even consider resveratrol or any other agent for that matter?
A recently published paper says: “Limitations of the current treatments are clear…. the known effects of these medications show only marginal interactions with some of the major processes known to be responsible for creation of unstable plaques.” The report goes on to describe many of the molecular pathways involving resveratrol in detail. The report also says: “studies show the enormous potential clinical applications of this compound from demonstrations of its complete lack of toxicity in humans even at high doses…” (See Vascular Cell 2012, 4:9)
And the question of whether reveratrol should be prescribed as a main-line drug or supplement for patients at risk for MI, these researchers said: “Although much of the data is based on work carried out in vitro — mostly to determine mechanisms of action– and using animal models, a significant amount of recently reported data from clinical trials now suggests these products (resveratrol) prescribed alone or in combination may prove to be important alternative or additional main-line prescription drugs.” (See Vascular Cell 2012, 4:9)
And yes, others have been begging for human clinical trials of resveratrol pills in cardiology for nearly a decade. Why are there none? Dr Frank Sellke at Brown University says “yet translation to the clinical arena has been unexpectedly slow.” (see Curr Atheroscler Rep. 2011 Dec;13(6):439-46)
And you say resveratrol pills have inherent potential for serious side effects— well over 350 brands of resveratrol pills have been sold in the marketplace for 8 years now and not one death has been reported. There are potential side effects, mostly posed by mega-doses of resveratrol. At high dose concentration resveratrol turns from being an antioxidant (binds copper) into a pro-oxidant (releases copper). Of interest, Longevinex at very high dose (2800 mg human equivalent) was found to be completely non-toxic, unlike plain resveratrol. (See http://www.ncbi.nlm.nih.gov/pubmed/21264071) While Dr Das’ name is on this paper as co-author, the work was done in a laboratory in Europe and he did none of the experiments.
And you say “resveratrol is not a preconditioning agent. It may be a cardioprotective agent, with an uncertain molecular mechanism of action.” The molecular mechanisms have been described in detail.
One such report described the microRNA patterns produced in a rodent model of heart attack. Half of the study was performed by Dr Das where damage to the rodent heart was imaged and presented. The other half was microRNA analysis conducted by NIH researchers. The study concluded that resveratrol, and more so Longevinex, restored a normal microRNA expression pattern following an experimentally induced heart attack. More important here, if the microRNA data produced by NIH researchers was at odds with Dr Das’s data, that would have been revealed. Dr Das’ alleged fraud would have been revealed to all.
Instead, it validated Dr Das’ work, that resveratrol and Longevinex are beneficial in regard to limiting damage caused by a heart attack. The microRNA data showed that microRNA 20-b, involved in control of VEGF, was down-regulated 112.9 fold post MI, resveratrol modestly down-regulated microRNA 20b by 189 fold and Longevinex by 1366-fold. (see PLoS ONE http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3009730/?tool=pubmed )
Bill, if the work was done in a lab in Europe (which would be Hungary), the paper may well need to be retracted for failing to get proper approval for the animal experiments. The paper states that IACC approval was obtained from the University of Connecticut…
Wow what a mess!! I personally stopped reading after the “skouser” comment. This Bill Sardi character should be embarrassed with himself.
More Sardi fun – http://www.churchdebt.com/moneychristians.pdf
“A Biblical Review: How Christians Should Face Imminent Worldwide Economic Calamity”.
How’s that going, Bill?
I had a good laugh out of that one.
I am not one to judge people so quickly without even meeting them, but I just lost all respect for Bill Sardi after reading that one.
Thanks for bringing it to our attention.
Science fair and balanced. Bill report. You decide. Bill Sardi the author of “The Red Wine Pill” and other
scientifically unbiased bestsellers:
http://www.naturalhealthlibrarian.com/
Case closed.
The case is indeed closed: he’s a crackpot.
Thank you, vhedwig. You are a veritable fount of knowledge, plus you can remember Monte Python’s dead parrot sketch!
Shame on you, Bill Sardi. That “imminent worldwide economic calamity” stuff is too far out there. Watch out that I don’t put a psychiatric hex on you for using your writing skills for the purpose of putting over evil ideas.
As to psychiatric “impressions” (not diagnoses) there is plenty of room for disagreement. One man’s paranoid is another’s misunderstood genius. Being the son of a psychologist, I have a tendency to place a diagnostic category on everyone’s hat, including my own (when my mother slammed the car door, it was “passive aggressive” and that really “traumatizes” an eight year old). What put me over the edge on Das was the letter from June 2010 where he complains of a conspiracy against Indians (the Southeast Asian kind.) That thing was a mess.
JudyH, I am still interested to read the UConn summary, so if you could email me your copy to [email protected], I would really appreciate it. Wonder why it’s not online any more.
To add my “literature search” to this fascinating list of Bill Sardi’s work, last night I just happened to pick up a copy of “Woman’s World” for June 12, 2012 (my wife’s copy, if you must know.) There is a two page spread on the wonders of resveratrol which doesn’t mention Das at all, although it does credit three other “antioxidant experts”…I was more interested in the article on the next page, which touts watermelon as being as good as Viagra.
As to the issue of what to take and when, resveratrol, if it was cheap enough, would have a satisfactory risk/benefit profile for everyone to take starting at age forty… but then Lipitor is cheap enough, now, too, and it would PREVENT the problem for which the resveratrol would protect the cardiomyocytes from the effects of, so it’s probably going to have a negative effect on the benefit profile of resveratrol if you take Lipitor too. Personally, I’d rather take Lipitor and hope that the other elements in my “varied” diet would give me some protection if the Lipitor failed…
So the bottom line with drugs, and it’s not really satisfactory, is that unless it’s patentable(ergo potentially profitable), no company will take the trouble to study whether it would be helpful enough to actually use. This is an obvious place for government to step in and do the necessary work–because government is NOT for profit, it is for the welfare of all… This is the key difference between government and business, one that right wing folks really miss out on. Government should not be run like a business, it should be run like a welfare state. If government is making a profit, then it is doing the wrong thing. Yay! (sorry about the political digression, but I think it’s important for scientific types to get involved in these issues at least a little bit.)
I notice Bill Sardi kind of shut up after you-all piled on to him. Probably he realized he was losing the argument. At least he’s not a troll.
Come back Bill. Please. We want to hear more of your wisdom!
To JudyH: I’m an idiot. My address is [email protected]… the other doesn’t exist.
To the rest of youse: don’t email me with your sardonic laughter. I’ve got enough problems finishing the mails I have.
Well, so am I. because I sent it to the other address without thinking that it might be phony. Shame on me. You could have been a UConn secret agent trying to trick me into showing my hand. It’s probably illegal to possess that document. ;-0
Bill Sardi,
What’s your background? You promote Longevinex, but you also believe that humans have existed for over 2 billion years, vaccines cause autism, the media knew about 9/11 before it happened, and that we should all invest our money based on biblical prophecy.
Quite frankly, I’d rather eat broken glass than put something in my body endorsed by someone with your set of beliefs.
To clarify, regarding the questions about the Office of Research Integrity (ORI), where I was a chief scientist and later Associate Director (1989-2006): (1) Right — ORI is NOT part of the National Institutes of Health (since 1992); (2) When someone outside a case asks ORI for information about whether ORI has such a case or someone is a respondent (accused person) under investigation, ORI responds that it cannot either confirm nor deny that there is such a case (ORI has to maintain confidentiality, until there is a public finding by ORI against the person, which is often many months or years after an institutional finding is made); (3) Right — ORI has authority only over cases in which there was funding or application for funds from NIH or other Public Health Serice agencies in the Department of Health and Human Services
Well, I tried to read it…thanks to JudyH… this time, it wasn’t nausea, but compassion fatigue, that set in. The people who did that investigation were nearly overwhelmed by the quantity of “stuff” they had to go through. I don’t know why this document is no longer online, but I suspect it has something to do with Dr. Das’ lawyers threats, as empty as they may be.
My superficial and incomplete analysis:
First, some minor details: the investigating committee was established finally as of January 2009, and was commissioned to study work by Dr. Das and the CRC from 2002 to the end of 2008. It also looked at a few papers and communications from 2009, but not all of them. Due to the volume of material, they were forced to ask for extensions every six months until mid-2010. They tried to talk to everyone who worked at CRC in the labs, but some people did not respond to inquiries, or were uncommunicative. There was an enormous volume of information on computer hard drives that they had to subcontract to IT, and the collation of that data alone took six months. They also took some training in Western blots as well as including on the committee a member with special expertise. After looking at all of it, they concluded that some instances (88 or so) of fabrication and falsification occurred, but in other cases, the resolution of the figures provided was not adequate to determine if any jiggery-pokery had occurred.
The major points: there was a period during 2004-5 in which no-one at the lab (due to departures not replaced) really knew how to do Western blots; this was the time in which the craziness started. There were files on Dr. Das’ personal computer which showed the progression of fabrication or falsification through several intermediate versions, that is there was detailed work which he is recorded as having been the author of, showing how he faked it. While someone else could have created the working files involved in the fakery, they are all on his personal computer, the one in the office to which only he had the key (whether or not he kept it locked up all the time is another question.)
The report makes note of the “assembly line” organization of the lab, in which individual workers were limited to doing only the autopsies or only the data collection or only, etc., making it very easy to do something wrong without anyone else noticing.
Finally, there is a list of papers and communications which the committee felt were definitely stocked with bogus pictures. I will repeat that there were a number of pictures which could not be analyzed due to lack of sufficient resolution; these are listed as suspect but not fake. There were also a number of pictures which the committee felt were good (no problems noted.)
There are two definite conclusions I can make from a superficial reading of the report: one, the committee worked very hard for over two years on a mountain of material and concluded, with very clear evidence, that some of the Western Blots (a lot of them) were faked or fabricated, but some were alright, and some could not be analyzed; and that there was clear evidence that Dr. D Das was personally responsible for the fakery. Two, Dr. Dipak Das was probably very frustrated because they named him as the sole respondent and “sequestered” (confiscated) everything in his office, leaving him with nothing to look at for over two years.
There is no question, however, that Dr. Dipak Das is, on the face of it, responsible for a large amount of image manipulation, quite possibly out of necessity, since there was no-one in his lab with expertise in blotting during a significant time period.
What makes it funny with regard to Mr. Sardi is that only some of the fakery was related to resveratrol; some of the papers related to palm trienols, and some to other “antioxidants.” A lot of other labs have done work on resveratrol, and none of that is under suspicion at present. It would be a good idea for Mr. Sardi to take a look at the literature and see if there is someone else who has done work which might support his Longevinex company’s sales. The general media seems to have jumped to the conclusion that all thirty or forty years of Dr. Das’ work is suspect and that resveratrol is no good; this is obviously wrong.
I see that Mr. Sardi has exited the woodwork for another long and elliptical screed claiming some of the same things we’ve already shot down. I would at this juncture like to warn vhedwig against giving us his email address. Mr. Sardi still hasn’t addressed the issue of why we should take resveratrol (or anything else) to precondition us to tolerate an event which we should really be preventing in the first place. I take issue with his denigration of statins as “weak” since they have clearly reduced mortality in adequately large studies. I don’t believe there are any clinical studies of Longevinex that demonstrate reduced mortality, and that, to me, (as a front line soldier) is the most important thing.
What you say is all conjecture, you have no first-hand knowledge. You have pre-judged and taken the approach Das is guilty, just don’t confuse yourself with the facts. I have repeatedly claimed UCONN withdrew the 60,000 pages of allegations and its 25-page summary when I put many of their fabrications to task.
What is ludicrous here is that cardiac preconditioning with a pill, be it garlic, vitamin E (tocotrienols) or resveratrol, is being dismissed when there is other corroborating research. Why? Why is everyone participating in this blog so anti-preconditioning? Aspirin and statin drugs don’t do this, as previously cited.
The statement “Mr. Sardi still hasn’t addressed the issue of why we should take resveratrol” is factitious. I cited studies where independent researchers showed resveratrol cardiac preconditioning is a real phenomenon.
You might be interested in learning that a brand of resveratrol pill I am affiliated with abolished the first sign of blood vessel disease (loss of flow mediated dilatation) in a small human trial. The study can be found here: http://www.ncbi.nlm.nih.gov/pubmed/22118755 Would this be a good reason to consider taking resveratrol pills?
I cited chapter and verse for my claims, while other bloggers just shoot from the hip with opinion, having never spoken to Dr Das, his attorneys, former students, as I have. And why would I stick my neck out defending Dr Das if he were guilty of scientific misconduct? I am telling you UCONNs review board never read the 60,000 pages of allegations and evidence and only reviewed “representations” of altered western blots, not originals. Then UCONN claims the disc with the originals was lost. So there is no substantive evidence against Dr Das, who was not given due process (allowed to present a defense).
To clarify further, regarding the issue of “sequestration of evidence”, under ORI regulations and university policies, the evidence of possible research misconduct is required to be taken by the Research Integrity Officer when the allegations are forwarded to the respondent (accused person), so that there is no opportunity for anyone to alter, remove or destroy the evidence (western blots, manuscripts in hard copy and on computer files, imaging the whole computer drives including emails and erased files, and all related records). However, the respondent is always allowed to have copies of the evidence, and direct access to the evidence while under supervision of the RIO or counsel for the university, to ensure it remains intact.
The respondent is also given a draft investigation report and allowed to rebut it; the report may be modified after that. The respondent can also submit further rebuttals to the deciding official after the investigation committee has submitted its final report. And the respondent can submit additional rebuttals to ORI after the deciding official has made a final decision and forwarded the report and rebuttals, and evidence on request, to ORI. ORI then decides whether to pursue a federal finding of research misconduct and administraive acdtions (commonly debarment of the respondent for 3 to 10 years, or even lifetime, from applying for or receiving any federal funds).
The nut of the case:
(page 33:)
“Manuscripts with the first instances of egregious duplication and pasting (e.g. the same gel band used in multiple figures to represent different experimental results) began to be submitted during a period in 2005 when there was little if any expertise in the CRC in Western blotting… Thus for a period of approximately one year, there was apparently no one working in the lab with the expertise to prepare western blots.”
These statements from the report stuck with me and provide what seems to be a clear reason why so many faked figures were created: there was no one at the lab to make real Western blots, so Dr. Das decided (in order to keep up the rate of production) to make them up. This was easy for him because no one else at the lab had any involvement in the final analysis of data and preparation for publication. What’s more, the lab tech (who was the last one doing WB’s) who had her salary support discontinued left at this same time (the report says that Dr. Das was “unsatisfied with her efforts.”)
Whether this surmise is true or not can’t really be ascertained without Dr. Das’ cooperation, and that seems highly unlikely. The “bad” papers were published between 2007 and 2009; whether he stopped faking figures after he got lab techs who could do the blots (“later in 2006”) is unclear to me. Whether Dr. Das’ prior work, published before 2002, is unreliable, is also unclear to me.
It doesn’t matter how many good scientists confirmed this or that conclusion that Das published. What does matter is that HE FALSIFIED HIS DATA! Bill Sardi is Longevinex! He has a HUGE financial conflict of interest. His behavior is shameful.
Bill, again with the lack of basic knowledge, this time on clinical trials. A clinical trial for a heart attack drug works in exactly the way you describe… You take a couple hundred people, give half of them a placebo and half of them a drug, and then wait and see what happens. Some of them will die, maybe because you gave them a placebo. There’s nothing “unethical” about it, that’s just how it works for every drug bought to market. There are a couple of options that make it more ethical; in some cases, after a certain number of patients has been completed, it becomes obvious the test drug is working fantastically well, and therefore unethical to deny the new treatment to those assigned to the placebo group. So the trial gets halted and everyone gets put in the treatment group. In other cases, there is an insistence that the group not on the test drug be given the current “standard of care” instead of a placebo. This ensures everyone gets some treatment, but unfortunately it creates a “better than” standard… the new drug has to not only be as good as current care, but better. Many new drugs end up being as good as current drugs, but they don’t get approved because who needs another drug if we have a good one already? This raises the bar significantly for new drugs, especially if the current standard of care is a generic drug, so has a cost advantage over the newcomer too.
The rest of your post lurches from Das to basic science to existing drugs, and doesn’t really make a lot of sense, so excuse me if I hold off on commenting. Maybe you should be thankful… Once your colleagues over at Longevinex get wind of what trouble you seem to have gotten into here, they may not be too pleased.
Oh, still waiting for your qualifications list too 😉
Maybe Das has some kind of pull with Sardi’s company, like a seat on the board of directors or something?
No again. Every other drug on the market is not being tested against death as an end point. You are a fool.
Bill,
Read it again, he never makes that claim.
As noted by puzzled_monkey, it is bizarre that Sardi is doing to such lengths to defend Das when the sensible option, from the point of view of Longevinex’s reputation, would be to ditch Das and embrace other, non-fraudulent resveratrol researchers.
As it is he seems determined to go down with the sinking Das ship.
The ship sunk long ago. Resveratrol sales plummeted months ago once the allegations against Dr Das were published. And, yes, why would I stick my neck out if I didn’t know otherwise? You like others presume guilt. With that aside, why is there no interest in cardiac preconditioning expressed by bloggers here? It is a proven phenomenon as cardiology practices preconditioning with a pressure cuff prior to surgery. That it is mimicked with natural molecules has also been demonstrated by others. Maybe 500,000 die suddenly from a heart attack annually in the US. There is now now preventive measure for sudden-mortal heart attacks as statin drugs and aspirin have proven to be ineffective against this mortal form of heart stoppage. That I am not providing convincing evidence for cardiac preconditioning to an audience of skeptics suggests the evidence is weak or minds are closed. Which is it? The evidence demanded (double-blind placebo controlled longitudinal study) is unethical, as I have explained. You would have to compare against existing therapy and it would likely take years to determine. There is no existing trial in cardiology for resveratrol. A retrospective study as performed to validate aspirin was suggested.