[BostonCard]

I think the image analysis software can tell you where the origin and where the destination is, even for “white” space, as local differences in contrast and brightness make it look like there is an edge at the destination.

BC

[BostonCard]

I think the image analysis software can tell you where the origin and where the destination is, even for “white” space, as local differences in contrast and brightness make it look like there is an edge at the destination.

BC

[dabigv13]

Exactly so. It is concerning because there may have been "signal" in the lower right area that was pasted over with basically white space from the other green highlighted areas

Too many mistakes in this post to respond to them all but just to start that is not the reason for concern. It's not that there was data in the lower right that was covered up.

What is concerning is that the blots for the 3A figure largely do not seem to be actually shown as they are just copy/pasted areas of who knows what.

The blots to check whether the vector only transfected cells, DCC netrin receptor transfected cells, or myc-tagged (a way of tagging a protein with a different protein to allow detection via an antibody to the myc epitope) UNC5H2 receptor netrin receptor transfected cells produced an antibody reaction with their corresponding antibodies in the western blot. 

It's a control experiment that is necessary to demonstrate so we can interpret the rest of the figure, which purports to show what happens when both DCC and UNC5H2 are both expressed at the same time in presence of netrin and whether they form a complex.

To support the conclusions in the rest of the figure, the blots should show no bands, and they don't, but as they were all copy pasted, we know for sure that the experiments the figure purports to show are not actually shown.

It's probable that the experiments would indeed show a negative result. But you have to show your work in science, and rather than do that, in this figure somebody just pasted in the results rather than showing us actual experimental results. Not a concern that someone pasted over contradictory results

[dabigv13]

Exactly so. It is concerning because there may have been "signal" in the lower right area that was pasted over with basically white space from the other green highlighted areas

Too many mistakes in this post to respond to them all but just to start that is not the reason for concern. It's not that there was data in the lower right that was covered up.

What is concerning is that the blots for the 3A figure largely do not seem to be actually shown as they are just copy/pasted areas of who knows what.

The blots to check whether the vector only transfected cells, DCC netrin receptor transfected cells, or myc-tagged (a way of tagging a protein with a different protein to allow detection via an antibody to the myc epitope) UNC5H2 receptor netrin receptor transfected cells produced an antibody reaction with their corresponding antibodies in the western blot. 

It's a control experiment that is necessary to demonstrate so we can interpret the rest of the figure, which purports to show what happens when both DCC and UNC5H2 are both expressed at the same time in presence of netrin and whether they form a complex.

To support the conclusions in the rest of the figure, the blots should show no bands, and they don't, but as they were all copy pasted, we know for sure that the experiments the figure purports to show are not actually shown.

It's probable that the experiments would indeed show a negative result. But you have to show your work in science, and rather than do that, in this figure somebody just pasted in the results rather than showing us actual experimental results. Not a concern that someone pasted over contradictory results

[martyup]

The blots to check whether the vector only transfected cells, DCC netrin receptor transfected cells, or myc-tagged (a way of tagging a protein with a different protein to allow detection via an antibody to the myc epitope) UNC5H2 receptor netrin receptor transfected cells produced an antibody reaction with their corresponding antibodies in the western blot. 

I have no idea of what is being said in this paragraph, but it sure sounds political.

[martyup]

The blots to check whether the vector only transfected cells, DCC netrin receptor transfected cells, or myc-tagged (a way of tagging a protein with a different protein to allow detection via an antibody to the myc epitope) UNC5H2 receptor netrin receptor transfected cells produced an antibody reaction with their corresponding antibodies in the western blot. 

I have no idea of what is being said in this paragraph, but it sure sounds political.

[Goose]

What is concerning is that the blots for the 3A figure largely do not seem to be actually shown as they are just copy/pasted areas of who knows what.

The blots to check whether the vector only transfected cells, DCC netrin receptor transfected cells, or myc-tagged (a way of tagging a protein with a different protein to allow detection via an antibody to the myc epitope) UNC5H2 receptor netrin receptor transfected cells produced an antibody reaction with their corresponding antibodies in the western blot. 

It's a control experiment that is necessary to demonstrate so we can interpret the rest of the figure, which purports to show what happens when both DCC and UNC5H2 are both expressed at the same time in presence of netrin and whether they form a complex.

To support the conclusions in the rest of the figure, the blots should show no bands, and they don't, but as they were all copy pasted, we know for sure that the experiments the figure purports to show are not actually shown.

It is fair to say that since any copy and paste went on, we have reason to question any part of the figure being genuine. It may be totally a "dry lab" that has nothing to do with the actual experiment that was done. I must admit I resist that conclusion for two reasons, one emotional and one practical.

The emotional one is that nobody with any shred of integrity could justify creating a totally "computer generated" figure and passing it off as the result of an experiment. As I see it, there are only three reasons to do this: 1) you did the experiment and the results contradicted your conclusions. You therefore created a bogus .jpg to mislead everybody. This is a "worst case" IMHO. 2) you didn't actually do the experiment and faked it. You are still misleading everybody as to the data but perhaps not quite as much. 3) You did the experiment, it supported your conclusion, but you can't find the blot or any photos of it. You therefore created a bogus .jpg and mislead everybody not about the correctness of your conclusion but the provenance of the data. To me, every one of these things is totally and unambiguously inadmissible. You have to be at best a totally amoral scientist to do them. You know you are intentionally misrepresenting the data. I therefore look for other conclusions that don't require this as more probable.

The practical one is that it makes no sense to create from whole cloth a result that looks so different from its "twin" on the left. The easiest way to make an unremarkable fake would be to copy a background like the top of the left side figure, paste it twice, go find the same "signal" blob that was used in the "current" fake, paste it at the right molecular weight, and you are done. No additional cutting and pasting needed. You also have a figure that raises no questions why it is clearly "different" in background level. Yes, you can also add the qualification that the scientist is both a) immoral, and b) not real good at faking data, but that adds another dimension.

I therefore don't treat it as a given that all of the data in the right hand figure is fake. I can easily imagine that the blot got damaged or something similar. It is a lot easier to justify (to yourself anyway) "cleaning up" a photo that really does represent the experimental data than it is to justify generating an entirely fake result. There is no way of knowing where the non-duplicated data in the .jpg came from. They could be "genuine" As far as I know, there is no way to know that the pink square data and green square data was not actually "original" to the bottom right of the .jpg, and have been copy-pasted elsewhere. If that isn't correct, please point me to where that is refuted. (Do their edges conclusively not match the data around them)? It may not have changed the result in a meaningful way. Is that morally "better"? Not much IMHO but at least the entire thing isn't a fake. What was the reason to do this? I don't know. In any case, it significantly alters the .jpg There may be "actual experimental results" in there but some areas clearly aren't.

It's probable that the experiments would indeed show a negative result. But you have to show your work in science, and rather than do that, in this figure somebody just pasted in the results rather than showing us actual experimental results. Not a concern that someone pasted over contradictory results

Agree, you have to show your work, warts and all.

[Goose]

What is concerning is that the blots for the 3A figure largely do not seem to be actually shown as they are just copy/pasted areas of who knows what.

The blots to check whether the vector only transfected cells, DCC netrin receptor transfected cells, or myc-tagged (a way of tagging a protein with a different protein to allow detection via an antibody to the myc epitope) UNC5H2 receptor netrin receptor transfected cells produced an antibody reaction with their corresponding antibodies in the western blot. 

It's a control experiment that is necessary to demonstrate so we can interpret the rest of the figure, which purports to show what happens when both DCC and UNC5H2 are both expressed at the same time in presence of netrin and whether they form a complex.

To support the conclusions in the rest of the figure, the blots should show no bands, and they don't, but as they were all copy pasted, we know for sure that the experiments the figure purports to show are not actually shown.

It is fair to say that since any copy and paste went on, we have reason to question any part of the figure being genuine. It may be totally a "dry lab" that has nothing to do with the actual experiment that was done. I must admit I resist that conclusion for two reasons, one emotional and one practical.

The emotional one is that nobody with any shred of integrity could justify creating a totally "computer generated" figure and passing it off as the result of an experiment. As I see it, there are only three reasons to do this: 1) you did the experiment and the results contradicted your conclusions. You therefore created a bogus .jpg to mislead everybody. This is a "worst case" IMHO. 2) you didn't actually do the experiment and faked it. You are still misleading everybody as to the data but perhaps not quite as much. 3) You did the experiment, it supported your conclusion, but you can't find the blot or any photos of it. You therefore created a bogus .jpg and mislead everybody not about the correctness of your conclusion but the provenance of the data. To me, every one of these things is totally and unambiguously inadmissible. You have to be at best a totally amoral scientist to do them. You know you are intentionally misrepresenting the data. I therefore look for other conclusions that don't require this as more probable.

The practical one is that it makes no sense to create from whole cloth a result that looks so different from its "twin" on the left. The easiest way to make an unremarkable fake would be to copy a background like the top of the left side figure, paste it twice, go find the same "signal" blob that was used in the "current" fake, paste it at the right molecular weight, and you are done. No additional cutting and pasting needed. You also have a figure that raises no questions why it is clearly "different" in background level. Yes, you can also add the qualification that the scientist is both a) immoral, and b) not real good at faking data, but that adds another dimension.

I therefore don't treat it as a given that all of the data in the right hand figure is fake. I can easily imagine that the blot got damaged or something similar. It is a lot easier to justify (to yourself anyway) "cleaning up" a photo that really does represent the experimental data than it is to justify generating an entirely fake result. There is no way of knowing where the non-duplicated data in the .jpg came from. They could be "genuine" As far as I know, there is no way to know that the pink square data and green square data was not actually "original" to the bottom right of the .jpg, and have been copy-pasted elsewhere. If that isn't correct, please point me to where that is refuted. (Do their edges conclusively not match the data around them)? It may not have changed the result in a meaningful way. Is that morally "better"? Not much IMHO but at least the entire thing isn't a fake. What was the reason to do this? I don't know. In any case, it significantly alters the .jpg There may be "actual experimental results" in there but some areas clearly aren't.

It's probable that the experiments would indeed show a negative result. But you have to show your work in science, and rather than do that, in this figure somebody just pasted in the results rather than showing us actual experimental results. Not a concern that someone pasted over contradictory results

Agree, you have to show your work, warts and all.

[cardcrimson]

Apparently, in the fraud case against Stanford Prof Cohen, Stanford lied, er, issued false statements to the Daily. The Daily dug deeper and proved they were indeed false. What a tangled web Stanford is weaving all over the place. . .. 

https://stanforddaily.com/2023/01/02/sta...raud-case/

Great that true investigative journalism isn't dead. Good for the Daily.

[cardcrimson]

Apparently, in the fraud case against Stanford Prof Cohen, Stanford lied, er, issued false statements to the Daily. The Daily dug deeper and proved they were indeed false. What a tangled web Stanford is weaving all over the place. . .. 

https://stanforddaily.com/2023/01/02/sta...raud-case/

Great that true investigative journalism isn't dead. Good for the Daily.

[Mick]

Publish or perish means scientific advancement has ground to a halt, says this article.

Cutting edge of science is blunter than ever | National Post

[Mick]

Publish or perish means scientific advancement has ground to a halt, says this article.

Cutting edge of science is blunter than ever | National Post

[TonyLima]

Nowhere else on the planet would you get this discussion on a sports board.  IMHO this is a testimonial to the quality of Stanford grads.  I'm just a dumb economist, but I know enough about statistics to appreciate this discussion.  Thanks to everyone who contributed.

[TonyLima]

Nowhere else on the planet would you get this discussion on a sports board.  IMHO this is a testimonial to the quality of Stanford grads.  I'm just a dumb economist, but I know enough about statistics to appreciate this discussion.  Thanks to everyone who contributed.

[dabigv13]

https://www.washingtonpost.com/education...stigation/

A panel of prominent experts is taking part in the review of Stanford University’s president over possible research misconduct claims, a special committee of the university’s board of trustees announced Friday.

The special committee is reviewing allegations that research papers co-authored years ago by Marc Tessier-Lavigne, an internationally known neuroscientist who has led the university since 2016, might contain altered images.

The five scientists, all members of the National Academy of Sciences or National Academy of Medicine or both, include a Nobel laureate, a former president of Princeton University and a former provost of Harvard University. The panel has begun its evaluation and does not have a set timeline for completing the work.

[dabigv13]

https://www.washingtonpost.com/education...stigation/

A panel of prominent experts is taking part in the review of Stanford University’s president over possible research misconduct claims, a special committee of the university’s board of trustees announced Friday.

The special committee is reviewing allegations that research papers co-authored years ago by Marc Tessier-Lavigne, an internationally known neuroscientist who has led the university since 2016, might contain altered images.

The five scientists, all members of the National Academy of Sciences or National Academy of Medicine or both, include a Nobel laureate, a former president of Princeton University and a former provost of Harvard University. The panel has begun its evaluation and does not have a set timeline for completing the work.

[82lsju]

https://www.washingtonpost.com/education...stigation/

A panel of prominent experts is taking part in the review of Stanford University’s president over possible research misconduct claims, a special committee of the university’s board of trustees announced Friday.

The special committee is reviewing allegations that research papers co-authored years ago by Marc Tessier-Lavigne, an internationally known neuroscientist who has led the university since 2016, might contain altered images.

The five scientists, all members of the National Academy of Sciences or National Academy of Medicine or both, include a Nobel laureate, a former president of Princeton University and a former provost of Harvard University. The panel has begun its evaluation and does not have a set timeline for completing the work.

The members of the scientific panel are (in alphabetical order):

• [b]Hollis Cline[/b], Ph.D.
  Chair, Department of Neuroscience, Scripps Research Institute; Director, Dorris Neuroscience Center, Scripps Research Institute; Hahn Professor of Neuroscience, Scripps Research Institute; Member, National Academy of Sciences 
  
• [b]Kafui Dzirasa[/b], M.D., Ph.D.
  Howard Hughes Medical Institute Investigator and K. Ranga Rama Krishnan Associate Professor of Psychiatry and Behavioral Sciences, Biomedical Engineering, Neurobiology, and Neurosurgery, Duke University; Member, National Academy of Medicine 
  
• [b]Steven E. Hyman[/b], M.D.
  Distinguished Service Professor and Harald McPike Professor of Stem Cell and Regenerative Biology, Harvard University; Provost Emeritus, Harvard University; Director of the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard; Member, National Academy of Medicine 
  
• [b]Randy Schekman[/b], Ph.D.
  Howard Hughes Institute Investigator and Professor of Cell and Developmental Biology, University of California, Berkeley; 2013 Nobel Laureate in Physiology/Medicine; Member, National Academy of Sciences; Member, National Academy of Medicine 
  
• [b]Shirley M. Tilghman[/b], Ph.D.
  Professor of Molecular Biology and Public Affairs Emerita, Princeton University; President Emerita, Princeton University; International Member, National Academy of Sciences; Member, National Academy of Medicine 
  

https://boardoftrustees.stanford.edu/special-committee/

[82lsju]

https://www.washingtonpost.com/education...stigation/

A panel of prominent experts is taking part in the review of Stanford University’s president over possible research misconduct claims, a special committee of the university’s board of trustees announced Friday.

The special committee is reviewing allegations that research papers co-authored years ago by Marc Tessier-Lavigne, an internationally known neuroscientist who has led the university since 2016, might contain altered images.

The five scientists, all members of the National Academy of Sciences or National Academy of Medicine or both, include a Nobel laureate, a former president of Princeton University and a former provost of Harvard University. The panel has begun its evaluation and does not have a set timeline for completing the work.

The members of the scientific panel are (in alphabetical order):

• [b]Hollis Cline[/b], Ph.D.
  Chair, Department of Neuroscience, Scripps Research Institute; Director, Dorris Neuroscience Center, Scripps Research Institute; Hahn Professor of Neuroscience, Scripps Research Institute; Member, National Academy of Sciences 
  
• [b]Kafui Dzirasa[/b], M.D., Ph.D.
  Howard Hughes Medical Institute Investigator and K. Ranga Rama Krishnan Associate Professor of Psychiatry and Behavioral Sciences, Biomedical Engineering, Neurobiology, and Neurosurgery, Duke University; Member, National Academy of Medicine 
  
• [b]Steven E. Hyman[/b], M.D.
  Distinguished Service Professor and Harald McPike Professor of Stem Cell and Regenerative Biology, Harvard University; Provost Emeritus, Harvard University; Director of the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard; Member, National Academy of Medicine 
  
• [b]Randy Schekman[/b], Ph.D.
  Howard Hughes Institute Investigator and Professor of Cell and Developmental Biology, University of California, Berkeley; 2013 Nobel Laureate in Physiology/Medicine; Member, National Academy of Sciences; Member, National Academy of Medicine 
  
• [b]Shirley M. Tilghman[/b], Ph.D.
  Professor of Molecular Biology and Public Affairs Emerita, Princeton University; President Emerita, Princeton University; International Member, National Academy of Sciences; Member, National Academy of Medicine 
  

https://boardoftrustees.stanford.edu/special-committee/

[82lsju]

some additional info in today's Daily

https://stanforddaily.com/2023/01/18/nob...an-18-2023

[82lsju]

some additional info in today's Daily

https://stanforddaily.com/2023/01/18/nob...an-18-2023

[fullmetal]

For all the reasons given by the anonymous sources in the article, this looks terrible.  If I wanted to cover things up and bluff my way through a scandal...I'd be doing what MTL is doing. 

MTL is probably too busy covering his rear to be handling the Muir situation properly, imo...or the Katie Meyer situation for that matter.  Thoroughly compromised.

[fullmetal]

For all the reasons given by the anonymous sources in the article, this looks terrible.  If I wanted to cover things up and bluff my way through a scandal...I'd be doing what MTL is doing. 

MTL is probably too busy covering his rear to be handling the Muir situation properly, imo...or the Katie Meyer situation for that matter.  Thoroughly compromised.

[Mick]

For all the reasons given by the anonymous sources in the article, this looks terrible.  If I wanted to cover things up and bluff my way through a scandal...I'd be doing what MTL is doing. 

MTL is probably too busy covering his rear to be handling the Muir situation properly, imo...or the Katie Meyer situation for that matter.  Thoroughly compromised.

If he's that compromised, then the board should pressure him to step aside.

[Mick]

For all the reasons given by the anonymous sources in the article, this looks terrible.  If I wanted to cover things up and bluff my way through a scandal...I'd be doing what MTL is doing. 

MTL is probably too busy covering his rear to be handling the Muir situation properly, imo...or the Katie Meyer situation for that matter.  Thoroughly compromised.

If he's that compromised, then the board should pressure him to step aside.

[BostonCard]

I agree that he should probably go on leave (from being President) while the investigation is ongoing, but I don't think that is the norm.  I think it is clear that there are differing views among differing people, including some who have publicly supported MTL.  I continue to believe that the allegations are serious, that it is possible that he committed fraud and that he should not be president (or even a faculty member) in the University, but also that it is possible that the investigation will clear him of the most serious concerns.

I continue to believe that we don't want a University President micromanaging how healthcare is delivered to students.  Hell, we largely don't want the University President micromanaging the Athletics Department for that matter, except inasmuch as his vote is needed for major conference decisions.  The problem, of course, is that I don't have a ton of confidence in Provost Drell either.

BC

[BostonCard]

I agree that he should probably go on leave (from being President) while the investigation is ongoing, but I don't think that is the norm.  I think it is clear that there are differing views among differing people, including some who have publicly supported MTL.  I continue to believe that the allegations are serious, that it is possible that he committed fraud and that he should not be president (or even a faculty member) in the University, but also that it is possible that the investigation will clear him of the most serious concerns.

I continue to believe that we don't want a University President micromanaging how healthcare is delivered to students.  Hell, we largely don't want the University President micromanaging the Athletics Department for that matter, except inasmuch as his vote is needed for major conference decisions.  The problem, of course, is that I don't have a ton of confidence in Provost Drell either.

BC

[gailtate]

I agree that he should probably go on leave (from being President) while the investigation is ongoing, but I don't think that is the norm.  I think it is clear that there are differing views among differing people, including some who have publicly supported MTL.  I continue to believe that the allegations are serious, that it is possible that he committed fraud and that he should not be president (or even a faculty member) in the University, but also that it is possible that the investigation will clear him of the most serious concerns.

I continue to believe that we don't want a University President micromanaging how healthcare is delivered to students.  Hell, we largely don't want the University President micromanaging the Athletics Department for that matter, except inasmuch as his vote is needed for major conference decisions.  The problem, of course, is that I don't have a ton of confidence in Provost Drell either.

BC

Respect is an entitlement. Confidence and admiration are earned.

[gailtate]

I agree that he should probably go on leave (from being President) while the investigation is ongoing, but I don't think that is the norm.  I think it is clear that there are differing views among differing people, including some who have publicly supported MTL.  I continue to believe that the allegations are serious, that it is possible that he committed fraud and that he should not be president (or even a faculty member) in the University, but also that it is possible that the investigation will clear him of the most serious concerns.

I continue to believe that we don't want a University President micromanaging how healthcare is delivered to students.  Hell, we largely don't want the University President micromanaging the Athletics Department for that matter, except inasmuch as his vote is needed for major conference decisions.  The problem, of course, is that I don't have a ton of confidence in Provost Drell either.

BC

Respect is an entitlement. Confidence and admiration are earned.

[82lsju]

from The Daily

In 2009, Marc Tessier-Lavigne, then a top executive at the biotechnology company Genentech, was the primary author of a scientific paper published in the prestigious journal Nature that claimed to have found the potential cause for brain degeneration in Alzheimer’s patients. “Because of this research,” read Genentech’s annual letter to shareholders, “we are working to develop both antibodies and small molecules that may attack Alzheimer’s from a novel entry point and help the millions of people who currently suffer from this devastating disease.”

But after several unsuccessful attempts to reproduce the research, the paper became the subject of an internal review by Genentech’s Research Review Committee (RRC), according to four high-level Genentech employees at the time; two were senior scientists and two were scientists who also served as executives. Three spoke on the condition of anonymity because of the sensitivity of the allegations and non-disclosure agreements. The scientists, one of whom was an executive who sat on the review committee and all of whom were informed of the review’s findings at the time due to their stature at the company, said that the inquiry discovered falsification of data in the research, and that Tessier-Lavigne kept the finding from becoming public.

Tessier-Lavigne denies both allegations. Genentech said in a statement that “as part of our diligence related to these allegations, we reviewed the records from that November 2011 RRC meeting and saw no allegations of fraud or wrongdoing.” The company acknowledged that “given that these events happened many years ago … our current records may not be complete.”

https://stanforddaily.com/2023/02/17/int...eb-17-2023

[82lsju]

from The Daily

In 2009, Marc Tessier-Lavigne, then a top executive at the biotechnology company Genentech, was the primary author of a scientific paper published in the prestigious journal Nature that claimed to have found the potential cause for brain degeneration in Alzheimer’s patients. “Because of this research,” read Genentech’s annual letter to shareholders, “we are working to develop both antibodies and small molecules that may attack Alzheimer’s from a novel entry point and help the millions of people who currently suffer from this devastating disease.”

But after several unsuccessful attempts to reproduce the research, the paper became the subject of an internal review by Genentech’s Research Review Committee (RRC), according to four high-level Genentech employees at the time; two were senior scientists and two were scientists who also served as executives. Three spoke on the condition of anonymity because of the sensitivity of the allegations and non-disclosure agreements. The scientists, one of whom was an executive who sat on the review committee and all of whom were informed of the review’s findings at the time due to their stature at the company, said that the inquiry discovered falsification of data in the research, and that Tessier-Lavigne kept the finding from becoming public.

Tessier-Lavigne denies both allegations. Genentech said in a statement that “as part of our diligence related to these allegations, we reviewed the records from that November 2011 RRC meeting and saw no allegations of fraud or wrongdoing.” The company acknowledged that “given that these events happened many years ago … our current records may not be complete.”

https://stanforddaily.com/2023/02/17/int...eb-17-2023

[fullmetal]

Background reading on older, potentially invalid Alzheimer's research data and investigative pathways: 
https://www.science.org/content/blog-pos...es-it-mean

[fullmetal]

Background reading on older, potentially invalid Alzheimer's research data and investigative pathways: 
https://www.science.org/content/blog-pos...es-it-mean

[BostonCard]

Since that article, this I no longer correct:

7. Those trials have failed. But every single Alzheimer’s trial has failed. I think that any ultimate explanation of Alzheimer’s disease is going to have to include beta-amyloid as a big part of the story - but if attacking the disease from that standpoint is going to lead to viable treatments, we sure as hell haven’t been seeing it. We have to put money and effort down on other hypotheses and stop hammering, hammering, hammering on beta-amyloid so much. It isn’t working.

https://www.nejm.org/doi/full/10.1056/NEJMoa2212948

CONCLUSIONS

Lecanemab reduced markers of amyloid in early Alzheimer’s disease and resulted in moderately less decline on measures of cognition and function than placebo at 18 months but was associated with adverse events. Longer trials are warranted to determine the efficacy and safety of lecanemab in early Alzheimer’s disease. (Funded by Eisai and Biogen; Clarity AD ClinicalTrials.gov number, NCT03887455. opens in new tab.)

The amyloid hypothesis is controversial, but the success of lecanemab does suggest amyloid likely is at least a partial contributor to the pathophysiology of Alzheimer's disease.

BC

[BostonCard]

Since that article, this I no longer correct:

7. Those trials have failed. But every single Alzheimer’s trial has failed. I think that any ultimate explanation of Alzheimer’s disease is going to have to include beta-amyloid as a big part of the story - but if attacking the disease from that standpoint is going to lead to viable treatments, we sure as hell haven’t been seeing it. We have to put money and effort down on other hypotheses and stop hammering, hammering, hammering on beta-amyloid so much. It isn’t working.

https://www.nejm.org/doi/full/10.1056/NEJMoa2212948

CONCLUSIONS

Lecanemab reduced markers of amyloid in early Alzheimer’s disease and resulted in moderately less decline on measures of cognition and function than placebo at 18 months but was associated with adverse events. Longer trials are warranted to determine the efficacy and safety of lecanemab in early Alzheimer’s disease. (Funded by Eisai and Biogen; Clarity AD ClinicalTrials.gov number, NCT03887455. opens in new tab.)

The amyloid hypothesis is controversial, but the success of lecanemab does suggest amyloid likely is at least a partial contributor to the pathophysiology of Alzheimer's disease.

BC

[dabigv13]

Yikes! Throw the bum out! He's already apparently orchestrated one cover-up, Stanford needs to get their shit together on this and suspend MTL like they should've a long time ago.

The review committee found that “lab data had been falsified,” Maurer recalled being told, in a communication using those exact words. He was unable to provide the document to The Daily because he had to relinquish all company emails when he departed Genentech for another biotechnology company. But he said he was certain that the word “falsification” was used to describe the errors in the paper.

The Daily has not located a written document detailing the committee’s findings, but the four scientists, who were all familiar with the conclusions of the review, described the findings, and their accounts were consistent. Genentech did not provide documents detailing the conclusions of the review.

Neal, Tessier-Lavigne’s lawyer, wrote that “the Paper’s original results were accurately reported.” In response to questions from The Daily about whether, even aside from the concerns raised by scientists that the results of experiments had been falsified, four panels of the paper appeared to contain visible duplications and whether this constituted inaccurate reporting, Neal wrote: “Dr. Tessier-Lavigne first saw reference to those allegations yesterday, when he saw the new post in PubPeer,” an online site where scientists identify issues in published papers. “Dr. Tessier-Lavigne is looking into those issues.” (Schrag, in reviewing the 2009 paper, noted several panels that were supposed to represent different experiments but appeared to contain the same result. He posted his concerns on PubPeer. Elisabeth Bik, a prominent research misconduct investigator, independently identified the same alleged duplications when she reviewed the paper at the request of The Daily).

Fraudsters usually don't just do it once. Looks like another instance of MTL copying images.

Tessier-Lavigne, who wrote a response to several followup questions The Daily sent after the initial letter from his lawyer, wrote that “I understand that Genentech has also communicated to you that [the review] did not raise issues.” Genentech did not say that the review raised no issues and declined several times to answer questions about whether the review had uncovered any issues.

LOL

Nikolaev received a Columbia Ph.D. in 2005 and published one of the most cited Alzheimer’s papers of the decade. Social media posts and Nikolaev’s LinkedIn show that he departed Genentech in 2011 and spent the year after he left the company taking pre-med classes at Washtenaw Community College in Michigan, before enrolling in Florida Atlantic University’s medical school. He now works in Weston, Fla. as a radiation oncologist.

Also lol

[dabigv13]

Yikes! Throw the bum out! He's already apparently orchestrated one cover-up, Stanford needs to get their shit together on this and suspend MTL like they should've a long time ago.

The review committee found that “lab data had been falsified,” Maurer recalled being told, in a communication using those exact words. He was unable to provide the document to The Daily because he had to relinquish all company emails when he departed Genentech for another biotechnology company. But he said he was certain that the word “falsification” was used to describe the errors in the paper.

The Daily has not located a written document detailing the committee’s findings, but the four scientists, who were all familiar with the conclusions of the review, described the findings, and their accounts were consistent. Genentech did not provide documents detailing the conclusions of the review.

Neal, Tessier-Lavigne’s lawyer, wrote that “the Paper’s original results were accurately reported.” In response to questions from The Daily about whether, even aside from the concerns raised by scientists that the results of experiments had been falsified, four panels of the paper appeared to contain visible duplications and whether this constituted inaccurate reporting, Neal wrote: “Dr. Tessier-Lavigne first saw reference to those allegations yesterday, when he saw the new post in PubPeer,” an online site where scientists identify issues in published papers. “Dr. Tessier-Lavigne is looking into those issues.” (Schrag, in reviewing the 2009 paper, noted several panels that were supposed to represent different experiments but appeared to contain the same result. He posted his concerns on PubPeer. Elisabeth Bik, a prominent research misconduct investigator, independently identified the same alleged duplications when she reviewed the paper at the request of The Daily).

Fraudsters usually don't just do it once. Looks like another instance of MTL copying images.

Tessier-Lavigne, who wrote a response to several followup questions The Daily sent after the initial letter from his lawyer, wrote that “I understand that Genentech has also communicated to you that [the review] did not raise issues.” Genentech did not say that the review raised no issues and declined several times to answer questions about whether the review had uncovered any issues.

LOL

Nikolaev received a Columbia Ph.D. in 2005 and published one of the most cited Alzheimer’s papers of the decade. Social media posts and Nikolaev’s LinkedIn show that he departed Genentech in 2011 and spent the year after he left the company taking pre-med classes at Washtenaw Community College in Michigan, before enrolling in Florida Atlantic University’s medical school. He now works in Weston, Fla. as a radiation oncologist.

Also lol

[johnbar]

Wow, this does look really bad.  I expect MTL will be leaving to pursue other opportunities some time soon.

[johnbar]

Wow, this does look really bad.  I expect MTL will be leaving to pursue other opportunities some time soon.

[BostonCard]

FYI, MTL subsequently published a paper disproving his own hypothesis:

https://pubmed.ncbi.nlm.nih.gov/24806669/

However, in two distinct APP transgenic models of AD, we did not observe any alteration in the formation of amyloid plaques, gliosis, synaptic loss, or cognitive behavioral deficits with genetic deletion of DR6, though we did observe a transient reduction in the degree of microglial activation in one model. Our results support the view that DR6 functions with APP to modulate synaptic density in the adult CNS, but do not provide evidence for a role of DR6 in the pathophysiology of AD.

BTW, the RRC at Genentech really is a routine review; there is nothing sinister about the fact that his review went before the RRC.

BC

[BostonCard]

FYI, MTL subsequently published a paper disproving his own hypothesis:

https://pubmed.ncbi.nlm.nih.gov/24806669/

However, in two distinct APP transgenic models of AD, we did not observe any alteration in the formation of amyloid plaques, gliosis, synaptic loss, or cognitive behavioral deficits with genetic deletion of DR6, though we did observe a transient reduction in the degree of microglial activation in one model. Our results support the view that DR6 functions with APP to modulate synaptic density in the adult CNS, but do not provide evidence for a role of DR6 in the pathophysiology of AD.

BTW, the RRC at Genentech really is a routine review; there is nothing sinister about the fact that his review went before the RRC.

BC