From: C. Glenn Begley
Sent: Sunday, October 27, 2024 5:01 PM
Dear Dr Nebert,
THANK YOU for your prompt response.
It would be interesting to know what role (if any) the NHI OSI played in this investigation because the OSI has had some negative press recently that questions the value of having the OSI at all.
Other countries (including Australia), look to the OSI as an example of best international practice regarding scientific integrity policies, but it remains unclear (at least to me) whether the OSI is really able to fulfil its mandate.
THANK YOU again for sharing this,
Warmest regards,
C.Glenn Begley
From: Nebert, Daniel (nebertdw)
Sent: Sunday, October 27, 2024 4:04 PM
Subject: Dark clouds forming in NIA over Alzheimer and Parkinson disease
Dear Professor Begley,
I see no mention of the NIH Office of Scientific Integrity (OSI) being involved — but I would be extremely surprised if they’re not — especially because this is a problem internal to the NIH.
The National Institutes of Health (NIH) comprises 27 different components called Institutes and Centers (there are 24 Institutes and 3 Centers); each has its own specific research agenda, often focusing on particular diseases or body systems. All 24 Institutes receive their funding directly from Congress, and administrate their own budgets. The National Institute of Aging (NIA) is one of these 24 Institutes.
The NIH OSI is not considered as one of the 27 Institutes and Centers of the NIH; the OSI it is a separate office within the NIH that oversees scientific integrity policies across all the institutes and centers (and worldwide funding) — rather than being a distinct research entity itself.
DwN
From: C. Glenn Begley
Sent: Sunday, October 27, 2024 12:34 AM
Dear Dr Daniel Nebert,
Thank you for highlighting this topic. This matter is really scandalous but sadly very common in many publications. Your description of the details was extremely helpful to understand what had been going on. Do you know if the NIH Office of Research Integrity was ever involved in this case?
I agree that we need to have severe consequences for these types of behaviours. These people should lose the privilege to supervise students and postdoctoral fellows. Furthermore, they should not be able to apply for any further NIH grants in the future, and they should have to re-pay the funds that they had received over the prior years.
It might be a long time before we see “the punishment that fits the crime,” but, as more of these stories emerge, hopefully we are getting closer to the time when these behaviours will be treated seriously.
Thank you again and best wishes,
C.Glenn Begley, MB, BS, PhD, FRACP, FRCPA, FRCPath, FAHMS
Clinical Hematologist and Medical Oncologist, Melbourne, Australia
From: paul stidolph
Dan,
One of the biggest problems of such revelations is that we are becoming inured to them. This story should have been headline news, but I have neither seen nor heard anything about it in the national press — despite massive interest by the general public on the subject of Alzheimer Disease.
Paul Stidolph, MD
U.K. physician, retired
From: Nebert, Daniel
Sent: Saturday, October 26, 2024 6:12 PM
Xiang,
Your comments made me ponder that perhaps it’s time for all reputable journals to reject Western blots as unequivocal evidence for confirmation of a specific normal protein or variant protein — when NGS combined with GEO analysis has become so readily available and so much more trustworthy.
Ray, and Divaker,
Yes, it’s time for criminal investigations of fraud and corruption in science, combined with sufficiently severe punishment that fits the egregiousness of the crime. But — for the most part (in science as well as in politics, over the past 20-30 years) have we EVER seen this happen?
DwN
From: Choubey, Divaker (choubedr)
Sent: Thursday, October 24, 2024 7:35 AM
Hi Dan,
Thank you for sharing these very troublesome findings uncovering research misconduct by a prominent neuroscientist — who was trusted by the scientific community and the NIH to lead research efforts, funded with a huge amount of money to improve our understanding of the neurodegenerative diseases, AD and PD. It will take years to clean up the scientific mess created by these studies with falsified data probably intermingled with some truthful data. Therefore, I believe the scientific community needs to pressure NIH to take appropriate action to discourage others in the future to consider a similar research approach.
Best,
Divaker
ivaker Choubey, Ph D, Professor Emeritus
Dept of Environmental and Public Health Sciences, University of Cincinnati
From: Ray D’Alonzo
Sent: Wednesday, October 23, 2024 4:57 AM
Dan,
Wow! I know you monitor these things with personal interest. This has got to be the most egregious example in GEITP that I’ve seen to date. One has to wonder if it calls for pressing criminal charges. This kind of thing will not stop unless the punishment matches the offense.
Ray
Professor Emeritus
Chemistry, Procter & Gamble; University of Massachusetts, Amherst
From: Zhang, Xiang
Sent: Tuesday, October 22, 2024 6:37 PM
Hi Dr. Nebert,
I don’t like the Western blot; it’s a biased assay which can be easily manipulated. Those who reuse their images are the laziest of people — and that’s why they get caught
I like Next Generation Sequencing (NGS) much better [NGS is a modern method that can sequence millions of DNA fragments simultaneously, which is much faster and more cost-effective than traditional sequencing techniques]: this is mostly an unbiased analysis at the global level. Those who design the experiments are unlikely to be the ones who prepare the samples; those who prepare the samples are unlikely to be the ones who process the samples for NGS; and those who run the NGS are unlikely to be the ones who analyze the data. On top of all this, the raw data these days will be uploaded to Gene Expression Omnibus (GEO) [This is a public repository that archives and distributes high-throughput sequencing data. GEO is an open-access archive of high-throughput functional genomic data, including all array-based applications and some high-throughput sequencing data.] for peer inspection.
Regards,
Xiang Zhang, PhD
Professor and Director
Genomics, Epigenomics and Sequencing Core | University of Cincinnati
(nebertdw)
Sent: Tuesday, October 22, 2024 5:45 PM
From time to time, these GEITP pages select a flagrant case of fraud in scientific research — something that seems to have been rarely seen (in our opinion) — before about 1990. This sad story comes from inside the prestigious Intramural Program of the National Institutes of Health (NIH).
The U.S. Congress in 2016 approved a large amount of funds for Alzheimer disease research. In response, the National Institute on Aging (NIA) appointed veteran brain researcher Eliezer Masliah to be NIA’s key leader for the effort. Dr. Masliah accepted the offer to lead NIA’s Division of Neuroscience — whose budget ($2.6 billion in the last fiscal year) dwarfs that of all the rest of NIA combined. As a leading federal ambassador to the research community and chief adviser to NIA Director Richard Hodes, Masliah was expected to gain tremendous influence over the study and treatment of neurological conditions in the U.S. and beyond. Masliah saw this promotion as the pinnacle of his rising career; he told the online discussion group “Alzforum” that “the golden era of Alzheimer research” had arrived, and he was eager to help NIA direct these newly-gained research funds. “I am fully committed to this effort. It is an historical moment.”
Masliah appeared to be an ideal selection. The physician and neuropathologist had conducted research at the University of California San Diego (UCSD) for decades; and his drive, curiosity, and productivity had driven him into the top ranks of scholars on Alzheimer and Parkinson disease. His roughly 800 research papers, many on how those maladies damage synapses (the junctions between neurons) have made him one of the most-cited scientists in his field. His extensive work on topics including alpha-synuclein — a protein linked to both diseases — has continued to influence basic and clinical science.
Over the past 2 years, however, questions have arisen about some of Masliah’s research. An investigation by Science magazine has now found that “scores of his lab studies at UCSD, and more recently at NIA are riddled with apparently falsified Western blots (images used to show the presence of specific normal vs abnormal proteins) and micrographs of brain tissue. Numerous images seem to have been inappropriately reused within and across papers, sometimes published years apart in different journals, describing divergent experimental conditions.
After Science brought initial concerns about Masliah’s work to their attention, forensic analysts specializing in scientific work who had previously worked with Science, produced a 300-page dossier revealing a steady stream of suspect images between 1997 and 2023 in 132 of his published research papers: “In our opinion, this pattern of anomalous data raises a credible concern for research misconduct and calls into question a remarkably large body of scientific work,” they concluded.
Neither Masliah — nor the various drug companies, universities, or federal agencies that were provided the dossier — have so far rejected or challenged any of the numerous examples of possible misconduct despite having been given the material more than 2 weeks ago. On 26 Sept 2024, the NIH released a statement saying that, following an investigation, it had “confirmed findings of research misconduct” against Masliah for “falsification and/or fabrication involving reusing and relabeling of figure panels” in two publications. According to their statement, Masliah no longer serves as NIA’s neuroscience division director, but NIH declined to further clarify his employment status.
The lengthy story is detailed in the attached pdf file, which all GEITP’ers are welcome to read at their leisure. ☹
DwN
Science 27 Sept 2024; 385: 1406-1412
THANK YOU for your prompt response.
It would be interesting to know what role (if any) the NHI OSI played in this investigation because the OSI has had some negative press recently that questions the value of having the OSI at all.
Other countries (including Australia), look to the OSI as an example of best international practice regarding scientific integrity policies, but it remains unclear (at least to me) whether the OSI is really able to fulfil its mandate.
THANK YOU again for sharing this,
Warmest regards,
C.Glenn Begley
Dear Professor Begley,
I see no mention of the NIH Office of Scientific Integrity (OSI) being involved — but I would be extremely surprised if they’re not — especially because this is a problem internal to the NIH.
The National Institutes of Health (NIH) comprises 27 different components called Institutes and Centers (there are 24 Institutes and 3 Centers); each has its own specific research agenda, often focusing on particular diseases or body systems. All 24 Institutes receive their funding directly from Congress, and administrate their own budgets. The National Institute of Aging (NIA) is one of these 24 Institutes.
The NIH OSI is not considered as one of the 27 Institutes and Centers of the NIH; the OSI it is a separate office within the NIH that oversees scientific integrity policies across all the institutes and centers (and worldwide funding) — rather than being a distinct research entity itself.
DwN
From: C. Glenn Begley
Sent: Sunday, October 27, 2024 12:34 AM
Dear Dr Daniel Nebert,
Thank you for highlighting this topic. This matter is really scandalous but sadly very common in many publications. Your description of the details was extremely helpful to understand what had been going on. Do you know if the NIH Office of Research Integrity was ever involved in this case?
I agree that we need to have severe consequences for these types of behaviours. These people should lose the privilege to supervise students and postdoctoral fellows. Furthermore, they should not be able to apply for any further NIH grants in the future, and they should have to re-pay the funds that they had received over the prior years.
It might be a long time before we see “the punishment that fits the crime,” but, as more of these stories emerge, hopefully we are getting closer to the time when these behaviours will be treated seriously.
Thank you again and best wishes,
C.Glenn Begley, MB, BS, PhD, FRACP, FRCPA, FRCPath, FAHMS
Clinical Hematologist and Medical Oncologist, Melbourne, Australia
From: paul stidolph
Sent: Friday, October 25, 2024 2:21 AM
Dan,
One of the biggest problems of such revelations is that we are becoming inured to them. This story should have been headline news, but I have neither seen nor heard anything about it in the national press — despite massive interest by the general public on the subject of Alzheimer Disease
Paul Stidolph, MD
U.K. physician, retired
Xiang,
Your comments made me ponder that perhaps it’s time for all reputable journals to reject Western blots as unequivocal evidence for confirmation of a specific normal protein or variant protein — when NGS combined with GEO analysis has become so readily available and so much more trustworthy.
Ray, and Divaker,
Yes, it’s time for criminal investigations of fraud and corruption in science, combined with sufficiently severe punishment that fits the egregiousness of the crime. But — for the most part (in science as well as in politics, over the past 20-30 years) have we EVER seen this happen?
DwN
From: Choubey, Divaker
Sent: Thursday, October 24, 2024 7:35 AM
Hi Dan,
Thank you for sharing these very troublesome findings uncovering research misconduct by a prominent neuroscientist — who was trusted by the scientific community and the NIH to lead research efforts, funded with a huge amount of money to improve our understanding of the neurodegenerative diseases, AD and PD. It will take years to clean up the scientific mess created by these studies with falsified data probably intermingled with some truthful data. Therefore, I believe the scientific community needs to pressure NIH to take appropriate action to discourage others in the future to consider a similar research approach.
Best,
Divaker
Divaker Choubey, Ph D, Professor Emeritus
Dept of Environmental and Public Health Sciences, University of Cincinnati
From: Ray D’Alonzo
Sent: Wednesday, October 23, 2024 4:57 AM
Dan,
Wow! I know you monitor these things with personal interest. This has got to be the most egregious example in GEITP that I’ve seen to date. One has to wonder if it calls for pressing criminal charges. This kind of thing will not stop unless the punishment matches the offense.
Ray
Professor Emeritus
Chemistry, Procter & Gamble; University of Massachusetts, Amherst
From: Zhang, Xiang
Sent: Tuesday, October 22, 2024 6:37 PM
Hi Dr. Nebert,
I don’t like the Western blot; it’s a biased assay which can be easily manipulated. Those who reuse their images are the laziest of people — and that’s why they get caught
I like Next Generation Sequencing (NGS) much better [NGS is a modern method that can sequence millions of DNA fragments simultaneously, which is much faster and more cost-effective than traditional sequencing techniques]: this is mostly an unbiased analysis at the global level. Those who design the experiments are unlikely to be the ones who prepare the samples; those who prepare the samples are unlikely to be the ones who process the samples for NGS; and those who run the NGS are unlikely to be the ones who analyze the data. On top of all this, the raw data these days will be uploaded to Gene Expression Omnibus (GEO) [This is a public repository that archives and distributes high-throughput sequencing data. GEO is an open-access archive of high-throughput functional genomic data, including all array-based applications and some high-throughput sequencing data.] for peer inspection.
Regards,
Xiang Zhang, PhD
Professor and Director
Genomics, Epigenomics and Sequencing Core | University of Cincinnati
From: Nebert, Daniel (nebertdw)
Sent: Tuesday, October 22, 2024 5:45 PM
From time to time, these GEITP pages select a flagrant case of fraud in scientific research — something that seems to have been rarely seen (in our opinion) — before about 1990. This sad story comes from inside the prestigious Intramural Program of the National Institutes of Health (NIH).
The U.S. Congress in 2016 approved a large amount of funds for Alzheimer disease research. In response, the National Institute on Aging (NIA) appointed veteran brain researcher Eliezer Masliah to be NIA’s key leader for the effort. Dr. Masliah accepted the offer to lead NIA’s Division of Neuroscience — whose budget ($2.6 billion in the last fiscal year) dwarfs that of all the rest of NIA combined. As a leading federal ambassador to the research community and chief adviser to NIA Director Richard Hodes, Masliah was expected to gain tremendous influence over the study and treatment of neurological conditions in the U.S. and beyond. Masliah saw this promotion as the pinnacle of his rising career; he told the online discussion group “Alzforum” that “the golden era of Alzheimer research” had arrived, and he was eager to help NIA direct these newly-gained research funds. “I am fully committed to this effort. It is an historical moment.”
Masliah appeared to be an ideal selection. The physician and neuropathologist had conducted research at the University of California San Diego (UCSD) for decades; and his drive, curiosity, and productivity had driven him into the top ranks of scholars on Alzheimer and Parkinson disease. His roughly 800 research papers, many on how those maladies damage synapses (the junctions between neurons) have made him one of the most-cited scientists in his field. His extensive work on topics including alpha-synuclein — a protein linked to both diseases — has continued to influence basic and clinical science.
Over the past 2 years, however, questions have arisen about some of Masliah’s research. An investigation by Science magazine has now found that “scores of his lab studies at UCSD, and more recently at NIA are riddled with apparently falsified Western blots (images used to show the presence of specific normal vs abnormal proteins) and micrographs of brain tissue. Numerous images seem to have been inappropriately reused within and across papers, sometimes published years apart in different journals, describing divergent experimental conditions.
After Science brought initial concerns about Masliah’s work to their attention, forensic analysts specializing in scientific work who had previously worked with Science, produced a 300-page dossier revealing a steady stream of suspect images between 1997 and 2023 in 132 of his published research papers: “In our opinion, this pattern of anomalous data raises a credible concern for research misconduct and calls into question a remarkably large body of scientific work,” they concluded.
Neither Masliah — nor the various drug companies, universities, or federal agencies that were provided the dossier — have so far rejected or challenged any of the numerous examples of possible misconduct despite having been given the material more than 2 weeks ago. On 26 Sept 2024, the NIH released a statement saying that, following an investigation, it had “confirmed findings of research misconduct” against Masliah for “falsification and/or fabrication involving reusing and relabeling of figure panels” in two publications. According to their statement, Masliah no longer serves as NIA’s neuroscience division director, but NIH declined to further clarify his employment status.
The lengthy story is detailed in the attached pdf file, which all GEITP’ers are welcome to read at their leisure. ☹
DwN
Science 27 Sept 2024; 385: 1406-1412