3 ms·

This is a bit against Hacker News rules so I'm going to say this once and only once. You run around commenting on many diverse fields that no single human could

This is a bit against Hacker News rules so I'm going to say this once and only once. You run around commenting on many diverse fields that no single human could possibly be an expert on simultaneously. These comments come with a consistent attitude: your position is obviously right, and only evil or self-interested establishments stand in the way of that being acknowledged. There are many other human beings who are just as smart as you or smarter, and just as invested in truth and goodness. Is it likely that you have the royal road to these things?

ncmncm 4y ago
I do not, in fact, comment on the overwhelming majority of topics. Here I have asked earnest questions. It is a fact that every drug tried to interfere with amyloids, over decades, failed miserably, if not actually made things worse. Why do you object to my asking them?
- civilized 4y ago
  "What will happen when my beliefs are proven true" isn't really a question, in the same way that "do you still beat your wife" isn't really a question.
  - ncmncm 4y ago
    We have literal decades of evidence that interfering with amyloid synthesis has no desirable effect on Alzheimer's patients. That is painfully and (expensively!) clearly the way to bet. Is it possible, in principle, that by some miracle a magical new way of interfering with amyloid synthesis will turn out to fix everything? Sure. But the question remains the same. What would they all move on to, then? They should be moved onto that thing right away. Something where actually getting somewhere useful is not important. If I were hiring biochemists, I own I would not count an amyloid research background in an applicant's favor. If you can see some reason to think otherwise, please explain. ("Not easily frustrated", maybe?) Recall that we are discussing tens of billions of tax dollars poured down that rathole. All the comments posted in response to the fraud just assumed that fooling with this or that amyloid was still the key. There was no hint of doubt about their program, evident. Somebody should be asking questions about a future direction. Criticizing me for asking it is criticizing exactly the wrong person. The people who should have been asking the unpleasant questions, and deserve sharp criticism for not asking them, are the ones still dispensing themselves NIH grants.
    - civilized 4y ago
      Have a look at the comments on this post and let me know what you think after that. https://www.alzforum.org/news/community-news/sylvain-lesne-who-found-av56-accused-image-manipulation https://www.alzforum.org/news/community-news/sylvain-lesne-w... Starting with just Dr. Ashe's comment at the top: > Based on my published work (Liu et al., 2015; Ashe, 2020), it is clear that there are two general forms of Aβ, type 1 and type 2. One particular form of type 1 (referred to in our papers as Aβ*56 and in the Science article as “toxic oligomers”) was shown by my lab and others to impair memory function in mice. The type 2 form of Aβ is the one found in amyloid plaques. It is this latter form that drug developers have repeatedly but unsuccessfully targeted. There have been no clinical trials targeting the type 1 form of Aβ, the form which my research has suggested is more relevant to dementia. Mr. Piller erroneously conflated the two forms of Aβ. There's a lot of interesting comments after Ashe's as well.
      - ncmncm 4y ago
        I read through all of the comments before I posted, as I noted: "what I got from the comments there" and "all the comments posted in response to the fraud...". Assuming I lied about that violates HN guidelines. Too. A careful reading shows Ashe is still talking about mouse amyloids, i.e., something never shown, over decades and $billions, to have anything to do with how Alzheimer's develops in humans. There is plenty of failure and blame to go around. They clearly don't need your help dodging it. And you did not answer, or even address, any of my questions.
        civilized 4y ago
        Dismissing mouse models is silly. Lots of successful medical research has turned on evidence from mouse models. Any Alzheimer's research paradigm you prefer will use them too if pursued seriously. I don't know if anything amyloid beta will pan out, but none of your statements or questions seem to illuminate the matter at all. They seem loaded with unevidenced presupposition. And I don't track your comments about what you've read or not read, only whether the comments seem to reflect knowledge from the reading. I would like the discussion to be informed by the experts, so I brought in the experts. That's all there is to it.

ncmncm 4y ago

I do not, in fact, comment on the overwhelming majority of topics. Here I have asked earnest questions. It is a fact that every drug tried to interfere with amyloids, over decades, failed miserably, if not actually made things worse. Why do you object to my asking them?

civilized 4y ago
"What will happen when my beliefs are proven true" isn't really a question, in the same way that "do you still beat your wife" isn't really a question.
- ncmncm 4y ago
  We have literal decades of evidence that interfering with amyloid synthesis has no desirable effect on Alzheimer's patients. That is painfully and (expensively!) clearly the way to bet. Is it possible, in principle, that by some miracle a magical new way of interfering with amyloid synthesis will turn out to fix everything? Sure. But the question remains the same. What would they all move on to, then? They should be moved onto that thing right away. Something where actually getting somewhere useful is not important. If I were hiring biochemists, I own I would not count an amyloid research background in an applicant's favor. If you can see some reason to think otherwise, please explain. ("Not easily frustrated", maybe?) Recall that we are discussing tens of billions of tax dollars poured down that rathole. All the comments posted in response to the fraud just assumed that fooling with this or that amyloid was still the key. There was no hint of doubt about their program, evident. Somebody should be asking questions about a future direction. Criticizing me for asking it is criticizing exactly the wrong person. The people who should have been asking the unpleasant questions, and deserve sharp criticism for not asking them, are the ones still dispensing themselves NIH grants.
  - civilized 4y ago
    Have a look at the comments on this post and let me know what you think after that. https://www.alzforum.org/news/community-news/sylvain-lesne-who-found-av56-accused-image-manipulation https://www.alzforum.org/news/community-news/sylvain-lesne-w... Starting with just Dr. Ashe's comment at the top: > Based on my published work (Liu et al., 2015; Ashe, 2020), it is clear that there are two general forms of Aβ, type 1 and type 2. One particular form of type 1 (referred to in our papers as Aβ*56 and in the Science article as “toxic oligomers”) was shown by my lab and others to impair memory function in mice. The type 2 form of Aβ is the one found in amyloid plaques. It is this latter form that drug developers have repeatedly but unsuccessfully targeted. There have been no clinical trials targeting the type 1 form of Aβ, the form which my research has suggested is more relevant to dementia. Mr. Piller erroneously conflated the two forms of Aβ. There's a lot of interesting comments after Ashe's as well.
    - ncmncm 4y ago
      I read through all of the comments before I posted, as I noted: "what I got from the comments there" and "all the comments posted in response to the fraud...". Assuming I lied about that violates HN guidelines. Too. A careful reading shows Ashe is still talking about mouse amyloids, i.e., something never shown, over decades and $billions, to have anything to do with how Alzheimer's develops in humans. There is plenty of failure and blame to go around. They clearly don't need your help dodging it. And you did not answer, or even address, any of my questions.
      - civilized 4y ago
        Dismissing mouse models is silly. Lots of successful medical research has turned on evidence from mouse models. Any Alzheimer's research paradigm you prefer will use them too if pursued seriously. I don't know if anything amyloid beta will pan out, but none of your statements or questions seem to illuminate the matter at all. They seem loaded with unevidenced presupposition. And I don't track your comments about what you've read or not read, only whether the comments seem to reflect knowledge from the reading. I would like the discussion to be informed by the experts, so I brought in the experts. That's all there is to it.