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posted by hubie on Saturday July 23 2022, @11:23PM   Printer-friendly

Two decades of Alzheimer's research may be based on deliberate fraud that has cost millions of lives

Over the last two decades, Alzheimer's drugs have been notable mostly for having a 99% failure rate in human trials. It's not unusual for drugs that are effective in vitro and in animal models to turn out to be less than successful when used in humans, but Alzheimer's has a record that makes the batting average in other areas look like Hall of Fame material.

And now we have a good idea of why. Because it looks like the original paper that established the amyloid plaque model as the foundation of Alzheimer's research over the last 16 years might not just be wrong, but a deliberate fraud.

The suspicion that something was more than a little wrong with the model that is getting almost all Alzheimer's research funding ($1.6 billion in the last year alone) began with a fight over the drug Simufilam. The drug was being pushed into trials by its manufacturer, Cassava Sciences, but a group of scientists who reviewed the drug maker's claims about Simufilam believed that it was exaggerating the potential [...] and hired an investigator to provide some support for this position.

[...] In 2006, Nature published a paper titled "A specific amyloid-β protein assembly in the brain impairs memory." Using a series of studies in mice, the paper concluded that "memory deficits in middle-aged mice" were directed caused by accumulations of a soluble substance called "Aβ*56." [...]

That 2006 paper was primarily authored by neuroscience professor Sylvain Lesné and given more weight by the name of well-respected neuroscientist Karen Ashe, both from the robust neuroscience research team at the University of Minnesota. [...]

The results of the study seemed to demonstrate the amyloids-to-Alzheimer's pipeline with a clarity that even the most casual reader could understand, and it became one of—if not the most—influential papers in all of Alzheimer's research.[...]

What intrigued Schrag when he came back to this seminal work were the images. Images in the paper that were supposed to show the relationship between memory issues and the presence of Aβ*56 appeared to have been altered. Some of them appeared to have been pieced together from multiple images. [...]

Now Science has concluded its own six-month review, during which it consulted with image experts. What they found seems to confirm Schrag's suspicions.

They concurred with his overall conclusions, which cast doubt on hundreds of images, including more than 70 in Lesné's papers. Some look like "shockingly blatant" examples of image tampering, says Donna Wilcock, an Alzheimer's expert at the University of Kentucky.

[...] And it seems highly likely that for the last 16 years, most research on Alzheimer's and most new drugs entering trials have been based on a paper that, at best, modified the results of its findings to make them appear more conclusive, and at worst is an outright fraud.

Some interesting stuff between the [...] was cut down for this summary, so I recommend reading the linked story. I also coincidentally just listened to the most recent Science podcast where they go into this in much greater detail and is well worth a listen. [hubie]


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  • (Score: 0) by Anonymous Coward on Sunday July 24 2022, @02:09PM (4 children)

    by Anonymous Coward on Sunday July 24 2022, @02:09PM (#1262628)

    If 90% of everything is crap, wouldn’t that imply that 90% of all buildings collapse under their own weight?

    We're talking about buildings, not piles of rubble, right?
    What do the fact that more than 90% of the buildings no longer exist after 100 years, and yet there a enough of them that are valuable enough to be preserved even if they can't stand on their own (like the pyramids or Stonehenge do)?

    Your Boltzmann distribution is about a closed system with only 2 variables.

    Oh really? So, that energy can take zillions of forms doesn't matter to you, eh?

    Gauss curves on the other hand are observational and representative of natural phenomena e.g. take a random sample of a 1000 people and put out a frequency distribution of weight, length, skin color or whatever biological property, and you’ll get a normal distribution.

    And this is in relation with the quality of the scientific publications exactly how?
    Are you trying to say that all humans naturally exhibit the metabolic function of producing scientific articles? Or that "weight, length, skin color or whatever biological property" are somehow correlated with the quality of the scientific articles they produce, so we can soundly extrapolate based on this correlation?

    I prefer thousands of these observations over...

    You have thousands of observations that in regards with the quality of the scientific articles? Then it shouldn't be too hard to show those numbers.
    If you don't, your assertion "is a Gauss distribution" have no basis so far.

  • (Score: 2) by quietus on Sunday July 24 2022, @02:57PM (3 children)

    by quietus (6328) on Sunday July 24 2022, @02:57PM (#1262633) Journal

    Enlighten me to the zillions of forms energy can take.

    Also: are you saying that the human brain is not biological?

    • (Score: 2) by c0lo on Monday July 25 2022, @12:27AM (1 child)

      by c0lo (156) on Monday July 25 2022, @12:27AM (#1262703) Journal

      Enlighten me to the zillions of forms energy can take.

      Some examples for you, just don't expect to list them all

      • Have the translation, rotation, vibration of the molecules for a start - especially the last one is quite useful in spectroscopy.
      • Have the different configurations the proteins fold in depending the temperature and environment - you wouldn't exist as a biological being without the functional complexity of those proteins and enzymes.
      • Have the laws that govern the speed of reaction depending on the temperature and concentration - be happy it happens this way, a world made only of elements would be boring. Some tidbits for you, on the rule of thumb about roughly doubling the speed of a reaction with every 10C increased in temperature [frostburg.edu] - it pays to know why it happens when it happens and why it's dangerous to consider it as the ultimate law of nature.
      • Have the behavior of the gasses in the gravitational field of a planet.

      Also: are you saying that the human brain is not biological?

      I can tell you've been nurtured on some degree and your behavior isn't entirely governed by your nature, but I reckon that nurture didn't go far enough. I can say this based on the fact that at least you can write (so you had some nurture) your naive and horrible simplified models of reality on S/N and your propensity of thinking they are adequate.

      The bliss of your ignorance likely feels good to you. And, from this "perspective, people" PoV, the same likely happens to the entire cohort of people on this Earth that think their ignorance is as good as the scientists' knowledge.

      ---

      As for the personal reason I chose to debate this very assertion of "Gauss distribution being applicable for professional performance": it reminds me the PHBes of this world using it in rank and yank [wikipedia.org]. It's even more reprehensible to me to see someone outside the area of scientific research using it as the gospel to characterize the quality of scientific papers: it may be so but, if you can't show me the numbers, have some decency and STFU before you draw conclusions based on not verified/demonstrated assumptions

      --
      https://www.youtube.com/watch?v=aoFiw2jMy-0
      • (Score: 2) by quietus on Monday July 25 2022, @11:53AM

        by quietus (6328) on Monday July 25 2022, @11:53AM (#1262769) Journal

        Oopsie -- there I thought that there were only really 2 forms of enery: potential energy and kinetic energy. I guess I must stand corrected here.

        As for the compliments: accepted with gratitude.

    • (Score: 3, Informative) by PiMuNu on Monday July 25 2022, @06:34PM

      by PiMuNu (3823) on Monday July 25 2022, @06:34PM (#1262857)

      To be clear, Boltzmann distribution indeed occurs in nature; it describes the probability distribution of kinetic energy of atoms in a gaseous medium having temperature T.

      Boltzmann distribution arises as a probability distribution based on the number of possible states of a gaseous medium. It's not about "forms of energy". I don't think "forms of energy" means anything.