Last week a new case of scientific misconduct came to light. University of Connecticut resveratrol researcher Dipak Das was accused of serious scientific misconduct. (You can read my brief post about the case or, for all the gory details, you can follow the story on Retraction Watch.)
In this post I’d like to make two fairly simple points about the case:
1. Resveratrol and Fraud, the Bigger Issue
As far as we now know, this case of scientific misconduct occurred in the lab of one researcher with, at best, a modest reputation in his field. I don’t mean to suggest that the case should not be taken seriously, but it is unclear whether it has any impact at all on the larger body of scientific research involving resveratrol and related areas. (It’s also possible that Das is only the first of dozens of rotten eggs yet to be discovered in this embryonic field.)
On the other hand, the case offers a great example of the far-reaching and dangerous fraud that so often supports the multi-billion dollar supplement industry. Because resveratrol is considered a nutritional supplement for regulatory purposes it is not subject to the rules and regulations that restrict the marketing of drugs. But, of course, all sorts of highly dramatic medical claims are made for these products. Here’s what Bill Sardi, the president of a company that makes Longevinex, a resveratrol product, claimed about reveratrol, in a statement distributed to media (attached below):
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.
The overall conclusion is that the published evidence is not sufficiently strong to justify a recommendation for the administration of resveratrol to humans, beyond the dose which can be obtained from dietary sources.
(Fun fact: one of the co-authors of the PLoS One review article was Dipak Das.)
2. Western Blots
The above quote from Bill Sardi is part of a long, rambling, often contradictory and bizarre defense of Dipak Das and resveratrol (reprinted below). Again, I have no intention of engaging all his points– I hope that regular readers of CardioBrief have been inoculated against this sort of hokum. But I do want to make sure one point doesn’t achieve any traction. The key item in the UConn report is that Das repeatedly manipulated western blot images. Sardi first argues that the western blots aren’t important at all:
The alleged faulty tests in no way altered the outcome of his research studies. The western blot test was only one of many tests used to draw scientific conclusions in published studies.
But then Sardi tries out several new explanations, in the course of a few sentences rapidly cycling through different perspectives on the western blots. First, he states that the images weren’t altered. Then he acknowledges that they were in fact altered, but that these alterations are standard practice. Then he accuses the university of willfully ignoring this “fact.”
I asked Dr. Das directly, did he altered western blot images, or directed others in his lab to do so. While his initial answer was no, meaning he had not fabricated or altered any scientific finding, altering western blot images are a common practice in laboratories for reasons other than deception. The university chose to present their findings in a derogatory manner. Dr. Das explains that editors at scientific publications commonly request researchers enhance faded images of western blot tests so they can be duplicated in their publications. Western blot tests are frequently altered to remove backgrounds, enhance contrast and increase dots-per-inch resolution so they are suitable for publication. This had been fully explained to university officials long before. [sic]
The entire statement strikes me as a great example of the pathology of someone desperately seeking to deny, refute or minimize an inconvenient truth. One statement– that editors ask researchers to “enhance” western blots– requires an immediate response. I contacted a member of the National Academy of Sciences who has published hundreds, if not thousands of western blots during the course of his distinguished career. His response was clear and unequivocal: “manipulating images is considered tampering with data.” He then clarified:
It is one thing to change the dots-per-inch (resolution) to fit a publication’s requirements – that is not crazy. But enhancing contrast and removing background is something that seems to me to be unacceptable. I certainly emphasize to students that that is unacceptable. I know of cases where students might try to ‘clean-up’ data this way and I can imagine that in some cases a PI may not realize this has been done. But I have never heard an experienced investigator claim that a journal has asked them to remove background from a blot. Now, maybe that has happened — I cannot say — but certainly NEVER to me.
Update: Tom Bartlett of the Chronicle of Higher Education talked to a number of experts in the field to determine the significance of Das’s work not the field. In addition, longtime blogger Derek Lowe posted a detailed dissection of Sardi’s statement. Both posts are worth reading.
Here is the statement from Bill Sardi, managing partner of Resveratrol Partners LLC, also known as Longevinex, a Las Vegas-based dietary supplement company:
World Without Resveratrol
Was An Award-Winning Researcher Falsely Accused Of Scientific Fraud And His Career Destroyed To Send A Message To Any Researcher Who Dares To Cooperate With Resveratrol Pill Makers?
By Bill Sardi
In recent days a clear message has been sent to laboratory investigators – cooperate with a resveratrol pill maker and your career will be over. And this is not the first time this has happened.
Leading resveratrol researcher accused of fraudulent science
If you were listening to Rush Limbaugh on the radio in the past week you heard him impugn the work of East-Indian born researcher, Dipak Das PhD., a University of Connecticut researcher widely known for his work in studying resveratrol (rez-vair-ah-troll), a red wine molecule, for heart health.
According to Limbaugh and over 300 other news agencies, Dr. Das is unequivocally guilty of doctoring tests that measure the amount of proteins in tissues, a test called a western blot. The University of Connecticut released a damning report that appears to present undeniable evidence that Dr. Das had doctored images on his office computer and published those images in a scientific journal in 2008.
The fraud that wasn’t fraud
But hold on. The alleged faulty tests in no way altered the outcome of his research studies. The western blot test was only one of many tests used to draw scientific conclusions in published studies. Furthermore, other independent labs, including the National Institutes of Health (NIH) itself, validated Dr. Das’ work, as well as researchers in Europe and Japan.
What would the motive have been to doctor the tests? University of Connecticut alleges it was grant money from the NIH. But Dr. Das alleges there had been long-standing jealously of his work within his institution dating back to 1984. He says everyone in his laboratory and many others knew of this.
University of Connecticut reviewers had brought this particular published report into question more than two years prior. Dr. Das had refuted all the allegations then. So why was it resurrected again? There is obviously more to the story.
Anonymous letters received
This writer first became aware of allegations against Dr. Das about two years ago when an anonymous letter was received in the US mail claiming that investigators were examining Dr. Das for scientific fraud. The letter originated from Farmington, Connecticut, where the University of Connecticut Health Center is located. It was type written on photocopied university letterhead.
This was certainly an odd occurrence. Dr. Das was out of the country at the time, so I contacted University officials and faxed them a copy of the letter. I said this was unusual for an outsider to receive a slanderous letter like this and I wanted to know if there truly was any investigation going on and I wanted to know who sent me this letter.
I was informed by a doctor at the university that they thought they knew who was responsible for issuing this anonymous letter. So it was someone the university knew. I later found it was an East Indian-born researcher who worked in Dr. Das’ lab who is also the informant or whistle blower in this case During subsequent investigation, I found that other research students in Dr. Das’ lab had also received similar anonymous letters alleging Dr. Das was under investigation.
Dr. Das is unpaid consultant
Since Dr. Das had volunteered to study the resveratrol pill my company makes, and test it alongside pure research-grade resveratrol, I thought that any investigation may have negative repercussions on my company. I was assured by a university official that our company was not under investigation.
Dr. Das: mentor to many
Dr. Das, who is widely known for mentoring students who later become full professors university-based research laboratories around the world, repeatedly said he wanted no money from my company. We as a company could provide some free product to test and maybe some testing supplies, but his stated desire was to test a commercially available brand of resveratrol and see it come into common use before his research career was over.
Dr. Das is 66 years of age and approaching retirement. Upon his retirement he had hoped to return to India to conduct further studies at the food and nutrition institute he established at Jadavpur University in Kolkata (the old Calcutta), the city of his birthplace.
Getting to the truth
Fortunately, I was in a unique place when the news media first blasted their reports claiming scientific fraud by Dr. Das. I was attending a meeting of resveratrol researchers in Kolkata, India and had direct access to Dr. Das, as he was in attendance at the meeting. Furthermore, two of his former laboratory students whose names are published alongside his in some papers, were also attending the meeting in Kolkata. So I could conduct an extensive inquiry of all three parties.
I first hesitated to inform Dr. Das of what was happening on a worldwide basis. I wondered how he would take the news. The delivery of a 600-page document that provided evidence of his alleged wrong-doing had already been placed on his desk at the university. The stress of all this resulted in two small strokes which he has remarkably recovered from. But this ordeal was certainly taking its toll.
I took him aside and asked if he knew that his name was in a headline story issued by over 300 news agencies around the globe, claiming he had committed scientific fraud. At the meeting in Kolkata I was informed by others that legislators in India were also considering censure of Dr. Das as he had shamed East Indian scientists around the world. The swiftness with which the news media operated and the unusual sanctions were unprecedented. It suggested this was an orchestrated hit job.
Dr. Das says all researchers alter western blot tests
I asked Dr. Das directly, did he altered western blot images, or directed others in his lab to do so. While his initial answer was no, meaning he had not fabricated or altered any scientific finding, altering western blot images are a common practice in laboratories for reasons other than deception. The university chose to present their findings in a derogatory manner. Dr. Das explains that editors at scientific publications commonly request researchers enhance faded images of western blot tests so they can be duplicated in their publications. Western blot tests are frequently altered to remove backgrounds, enhance contrast and increase dots-per-inch resolution so they are suitable for publication. This had been fully explained to university officials long before.
The other set of keys
The document produced by the university claims only Dr. Das had access to his office. That only he had the keys to his office and his computer. So he, and he alone, was responsible for the alleged western blot images that had been altered, says the university report.
But I inquired about this with the two former students attending the meeting in India. They said, no, that another party in Dr. Das’ office also had a set of keys and that this party is the very same informant who issued the anonymous letters slandering Dr. Das’ work. That informant stands to be promoted if the university fires Dr. Das. News reports claim the university will soon fire Das, if this has not already taken place.
Did Dr. Das dismiss a researcher for not cooperating?
Another allegation is that Dr. Das “de-funded” a student who conducted Western blot testing when he didn’t like the results she produced. But all three of my sources, including Dr. Das, claim this lab worker spent most of her hours working for the co-researcher who was the informant in this case and that since the worker was not doing any work on his experiments, that he removed her from his budget. The de-funding had nothing to do with the results of the western blot tests.
Students are solely responsible for data
As I drilled Dr. Das’ former students with questions, I found that lead researchers like Dr. Das do not do any lab bench experiments. Students do all the work and submit their results to him via e-mail or by directly downloading data into his computer. Dr. Das says when he is not traveling his office is open and students can enter and download data directly onto his computer. I had previously visited Dr. Das at the University of Connecticut and noticed his office door was left open and anyone could have access to his computer.
One former student told me that typically lead researchers like Dr. Das write the introduction and conclusion of experiments and the students enter all the data, before publication in scientific journals. Dr. Das, who is busy lecturing all over the globe because of his groundbreaking studies, does not directly oversee tests that are performed, and neither do most other lead researchers. The University of Connecticut report says the university holds Dr. Das responsible for all of the data. Probably most lead researchers in scientific laboratories around the globe are vulnerable to errors or even fabrication of data by their students.
Why would the university issue a report that contained erroneous and misleading information itself? Not only did another senior researcher in his lab have a set of keys, and his students widely knew of this, but also another university investigator had broken the locks on his office door and removed data from his computer as well as private information such as bank account records and his passport, according to Dr. Das.
Let’s examine the level of evidence here. An analogy could be a murder case in a court of law where prosecutors may find a gun involved in the murder in a defendant’s desk drawer, they may find his finger prints on the gun, and the bullet that killed the deceased may have come from the same gun. But this evidence is circumstantial. It does not place the accused at the site of the crime or reveal a motive. Furthermore, just how a person could be held responsible for someone else using his gun (computer) goes unexplained, but that is the university’s position. Furthermore, in this instance, the murder (intended alteration of data with intent to deceive) was never committed. The western blot test was altered only for the purpose of meeting publication requirements.
University allegations fall apart
The more I asked questions the more that the university’s allegations were falling apart. The news media, in a rush to get their story out to the world, simply reported that Dr. Das had not returned their phone calls, which was pejorative. He was in no position to answer calls at his home or office in the US as he was attending a scientific conference in India. He was blindsided by the release of the report to the news media. He could not defend himself in a timely manner. The timing of the release of the University of Connecticut report appeared to be cunningly intended to limit Dr. Das’ ability to reply to these accusations.
Just what was the motive of the university’s informant? This is where this case turns into East Indian Bollywood intrigue without the dancers and singers. According to a former student of Dr. Das, the informant, an East Indian whose career had been furthered by Dr. Das, was quite jealous of other East Indian students whom Dr. Das also favored. The student says this informant even attempted to “pour wine directly down my throat” in an attempt to inebriate her and get her to reveal negative information about Dr. Das. Well, well.
Colleagues don’t believe the university
Dr. Das says many editors at scientific journals don’t believe the University of Connecticut report. They full-well know that editing of western blot tests is common practice and that the tests in question in no way invalidate his work and were only one part of the evidence provided in his papers from which Dr. Das drew conclusions. This is the case of scientific fraud that wasn’t.
The University of Connecticut gave Dr. Das 30-days to respond to their report, but given his busy lecturing schedule, established months in advance, and given that he had refuted all prior questions asked of him, he was perplexed how to provide the university with further convincing rebuttal. I also think Dr. Das was too frightened to respond. He wrote two letters which feebly defended his work which are included in the university report. It was only when I was able to conduct an extended interview with Dr. Das that all of these other details came to light. Dr. Das was doing a poor job of defending himself.
Will Dr. Das obtain legal representation and demand embarrassing depositions from university personnel that will reveal what has been revealed in this report? An attorney called me to suggest that Dr. Das file a worldwide defamation case against the university. There is no legal recourse for Dr. Das within the State of Connecticut as the attorney general’s office there partially manages the health center where Dr. Das works.
The best way for Dr. Das to prevail in this travesty against him is to continue to work with his colleagues overseas and to write scientific papers that savvy editors of scientific publications will publish. If his colleagues publish his work, it would be fitting justice against a university and a scientific community that drew forgone conclusions and didn’t conduct a thorough investigation.
Not the first time
Was this the first time a resveratrol pill faced such back-door opposition? No. In 2004 a Harvard professor announced to the news media that he had developed a nutriceutical version of resveratrol which would soon be marketed. It became the pill my company now makes. But Harvard authorities intercepted this professor’s e-mails and phone calls and directly informed him, if he chose to work with a dietary supplement company, that he would never become tenured.
There have been other sour experiences my company has had with the research community.
- A South Florida testing lab conducted a human clinical trial of the pill my company makes and appeared to intentionally botch the study. The lab forgot to monitor whether subjects took the pills on schedule and blood samples that were sent to an outside lab were said to have been contaminated. When contacted, the outside lab said this had never occurred in their laboratory. Our company spent $60,000 for a study that produced unreportable data.
- In 2006 the University of Wisconsin gained NIH approval to test resveratrol for Alzheimer’s disease. The university had selected the pill my company makes for the study. I had met personally with the lead researcher. However, a major pharmaceutical company bought off the university and the study never commenced.
- In 2008 researchers affiliated with a major university appeared on CBS’ 60 Minutes TV program and failed to mention that the pill our company makes was found to activate 9-times more genes than plain resveratrol in a mouse study, exceeding the effect of plain resveratrol or a calorie-restricted diet. To this day these researchers refuse to lecture on this published discovery.
- In 2011 Dr. Das travelled to an out-of-state university-based animal laboratory to conduct special studies involving resveratrol and arterial health. Our company provided samples of our resveratrol pill for the test. Laboratory tissue samples obtained during these experiments were then shipped to Dr. Das’ laboratory in Connecticut, but had been completely contaminated prior to shipping. Was this another case of scientific sabotage?
Modern medicine in lock-step
Dr. Das is the man who demonstrated that resveratrol can turn a mortal heart attack into a non-mortal event and that a particular brand of resveratrol pill did this more so than plain resveratrol in laboratory mice. How many billions of dollars of heart drugs are threatened by Dr. Das’ discoveries?
Modern medicine is marching in lock-step to make sure a resveratrol pill never gains public acceptance. That is because resveratrol pills exhibit much broader biological action than any gene-targeted drug, or a drug aimed at a single cell receptor site. This is how most modern drugs are designed.
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.
The real resveratrol story
What the public heart about resveratrol in the news media in the past week is far from the real story.
Resveratrol and blindness
As many as 150,000 older Americans needlessly lost their sight in the past four years due to foot-dragging by eye doctors in prescribing resveratrol for a condition known as wet macular degeneration.
Billions of dollars in medication costs to treat this eye disease could also have been saved had the resveratrol pill my company makes been widely used as a substitute treatment.
In an NIH study our pill had been shown to exhibit six times greater effect than plain resveratrol in inhibiting the formation of abnormal blood vessels which can destroy vision at the back of the eyes.
In 2007 eye physicians discovered the resveratrol pill my company makes rapidly restored sight to patients who either refused to undergo needle injections into their eyes or who failed drug treatment. Drug treatment fails in one in six patients with macular degeneration and these patients go on to suffer permanent vision loss.
But suddenly these eye doctors denied the pill worked, they said the effect didn’t last and abandoned the use of the pill. Thereafter eye physicians began injecting a more expensive drug to treat this eye disease and began collecting billions of dollars of Medicare funds for these injections.
Mary is an 88-year old patient with wet macular degeneration who is among the first to benefit from the use of a resveratrol-based pill to save her sight. She was hospitalized at a veterans health center primarily for unstable blood pressure and her failing vision. Initially the veterans health center said our pill could not be used there because it was no an FDA-approved drug. Mary’s eye doctor appealed, having successfully treated a number of other patients with our pill. The hospital chief of staff intervened and said if the patient acquired our pill on her own, and elected to take it as a dietary supplement, there would be no objections.
Mary called our company and we rush shipped the pills. Within four days Mary was able to read the hospital meal menu for the first time. She was able to visualize her doctor’s face and see her own handwriting. As things progressed, her unstable blood pressure, which was causing her to black out, normalized. She also experienced remission of life-long migraine attacks and was later discharged from the hospital. Other therapies had failed to produce these health benefits.
Resveratrol and heart attacks
Hundreds of thousands of Americans could possibly avert a sudden mortal heart attack annually if resveratrol was substituted for aspirin among patients at high risk for heart attacks. Neither statin cholesterol-lowering drugs nor aspirin tablets prevent mortal heart attacks according to the most authoritative data. Strikingly, with all of the sophisticated pharmaceutical armamentarium against heart disease, there is not one proven way to prevent sudden-death heart attacks. Cardiologists show virtually no interest in using resveratrol in clinical practice. Outside of one non-invasive cardiology practice in Ft. Lee, New Jersey, no others are known to regularly prescribe resveratrol.
Resveratrol and cancer
If animal data can be translated to humans, countless cancer patients could have survived longer or even experienced total remissions if resveratrol were used commonly either alongside existing cancer treatments or used solely as cancer therapy. Oncologists also express no interest in using resveratrol in cancer therapy now that a major pharmaceutical company abandoned further research and development of its resveratrol drug.
A mega-dose (5000 mg) resveratrol pill induced kidney failure among patients with bone marrow cancer (multiple myeloma), which scared patients and doctors away from resveratrol pills. But a particular brand of resveratrol pill, the one my company makes, was found to be non-toxic in animal and human kidneys, even in high doses, and protected the mouse heart from damage caused an intentionally-induced heart attack while the same high dose of plain resveratrol caused damage to the rodent heart. Cardiologists and oncologists paid no attention.
A Harvard Medical School researcher laments that 8 years following the announcement that resveratrol may be the key molecule responsible for the French Paradox, the fact the French who eat a high cholesterol/high-fat diet experience a much lower rate of coronary artery disease mortality than North Americans, there is still no human trial involving resveratrol for heart disease. Resveratrol works better than aspirin, preventing blood clots, reducing inflammation, widening (dilating) blood vessels, and releasing protective chemicals before a heart attack occurs. No drug comes close to what resveratrol can do in the heart.
A researcher in the field of resveratrol suggests there is not enough human data to bring resveratrol from the laboratory bench to the hospital bedside as yet. But thousands of consumers have leaped ahead of foot-dragging researchers to experience the many health benefits posed by this miraculous small molecule found in red wine. Modern medicine is demanding evidence that it loathes to produce.
Patients are convinced
Some patients already are convinced of the health benefits of resveratrol:
Joyce Brown, age 77, of Mesquite, Nevada, was losing her sight and had undergone 17 injections of a drug directly into her eyes without success. There were no other options for Joyce Brown. All other treatment options had been exhausted. Having learned of the possibility that resveratrol may save her sight, she obtained a brand of resveratrol pill that had been uniquely shown to inhibit abnormal blood vessels that destroy the visual center (the macula) at the back of the eyes. Within days her vision was restored and she passed a driver’s license test. Her eye doctor insisted the medicine he injected was responsible for her recovery.
Her aged husband also took the pill and experienced measurably improved vision, resolution of his fragile diabetic condition and disappearance of a fluttering heart condition (atrial fibrillation) that stubbornly could not be conquered by conventional treatments.
Ed Skonezny, age 70, had none of the common symptoms of coronary artery disease. He was regularly driving a golf ball over 250 yards off the tea at his Palm Desert, California golf resort home. But a routine angiogram (dye test of coronary arteries that supply the heart with oxygenated blood) revealed narrowed coronary arteries, probably caused by a prior smoking habit years ago. One major coronary artery was 99% blocked, yet Ed experienced no angina chest pain and no damage (scarring) to his heart. Heart surgeons performed open heart surgery on this man who had no symptoms or heart damage. Doctors were totally baffled. Ed had been taking a resveratrol pill for the past few years, a resveratrol pill that had been shown in animal experiments to convert mortal heart attacks into non-mortal events, the very pill my company makes. In studies conducted by researchers at the National Institutes of Health, this resveratrol pill protected the heart prior to a blockage in a coronary artery and restored a normal gene activation pattern to heart muscle.
Dr. Orkan Stasior, in his 80s, a retired Albany, New York eye physician, developed a parotid gland tumor that oncologists said would require surgery. He began taking a resveratrol pill and some other dietary supplements and his tumor completely vanished. Surgeons persisted with the idea of surgical removal of this salivary gland even though there was no evidence of a tumor and the planned treatment does not address the cause of the disease nor has treatment been shown to meaningfully prolong survival.
Long-term controlled studies demanded
The scientific community keeps begging for long-term, controlled human studies compared against an inactive placebo pill before rushing to use resveratrol pills. But here is the crux of the situation. If a resveratrol pill is not harmful and it is the only remaining therapy after all other treatments have been exhausted, and patients face irreversible harm to their eyes or hearts unless something is done, why would modern medicine demand that studies be completed, which may take years to complete, before prescribing it for otherwise hopeless patients? How many will needlessly go blind or die of sudden heart attacks before resveratrol undergoes long-term studies?
Can you find an honest doctor to conduct studies?
As managing partner for a company that makes a resveratrol pill I have been repeatedly advised to make our pill into a drug and spend 3 or 4 years and millions of dollars to prove it works for a narrowly defined disease. But the problem is, I don’t think eye or heart physicians could be recruited to honestly conduct these studies given their foot-dragging and denial of the evidence.
When the National Institutes of Health sought to determine which of two injectable eye drugs worked the best in treating wet macular degeneration, ophthalmology drug its feet for three years before recruiting patients and then took another two years to complete the study. The drug that costs $200 (Avastin) was found to work equally well as a drug (Lucentis) that costs $1500 per injection. But eye physicians often elect to use the more expensive drug, thus gouging Medicare. Eye physicians typically inject patients 6-8 times a year and earn a fee for injecting the medication into the eye. The introduction of an oral pill would take billions of dollars away from eye physicians.
I don’t think eye physicians or cardiologists are going to conduct any study that puts them out of business.
The real story about resveratrol isn’t being told. Resveratrol isn’t being adequately studied. Will consumers see through all this subterfuge? Time will only tell.
Bill Sardi is managing partner of Resveratrol Partners LLC, dba LONGEVINEX®, a Las-Vegas-based dietary supplement company.