
How an Alzheimer’s ‘cabal’ thwarted progress toward a cure - KKKKkkkk1
https://www.statnews.com/2019/06/25/alzheimers-cabal-thwarted-progress-toward-cure/
======
cockatiel_day
This article is 100% true.

My first job out of college 10 years ago was in a lab focused on Alzheimer’s
research. Our Principle Investigator made an art of writing grant applications
for studies that would appear to be in line with mainstream theory, but were
really intended to test theories he actually thought were worth testing,
presented in results as an “interesting” aside. He believed the amyloid theory
had been conclusively disproven.

He explained to me that people like him work for decades, quasi-retire into
positions accepting grant applications, and have a conscious or unconscious
agenda to preserve or validate their life’s work. His money quote was “science
is like the Catholic Church, a lot of nice sentiments but full of people”.

I don’t have any evidence or examples, but I suspect this dynamic is not
limited to Alzheimer’s research.

Another anchor to research not mentioned in the article is how much sponsoring
universities take from research labs. To put a university endorsement on our
research, which is needed to be credible, the university took half (half!) our
grant money.

~~~
wavepruner
"I suspect this dynamic is not limited to Alzheimer’s research."

Agreed, I think it is a universal problem in science.

I have an illness that has been curable for decades now, but this cure is
treated with hostility by the medical establishment. I look forward to the day
when the cabal of my illness collapses. Hopefully then I will be able to talk
about what happened without people getting angry.

~~~
patmcc
How does the medical establishment benefit from not curing your illness?

~~~
mikekchar
Having experienced something that seems to be similar, imagine that you are
working on a web server. It is very slow sometimes. Your project leader is
absolutely convinced that the problem is due to multiple requests being made
to the DB at the same time. He has been lobbying to rewrite the DB layer for
some time now. He hates the archetecture that was left to him by the previous
lead developer and is absolutely sure that if he rewrites it, it will be much
faster and easier to work with.

Unfortunately, you've been profiling the code and you've found that the there
is an inordinate amount of time being spent allocating a date. It seems like
the code is pathologically looping around and hitting that date code hundreds
of thousands of times for every request. You've tried showing your lead the
code that's causing the problem. He doesn't really understand it. He doesn't
trust code profiling either. He _already knows_ what the problem is and he's
not interested in hearing any more. He ridicules you for having this stupid
theory that allocating a _date_ is slowing down the DB.

It's not that keeping the poor behaviour is benefitting him in any way. It's
more that the new solution is not _his_ solution and he's got a lot riding on
his solution being chosen (justify his code rewrite). He's kind of staked his
reputation and career with the company on his solution. If it turns out to be
something else -- especially something he's already ridiculed, he'll be toast.
He wants to get into management and management is all about politics and being
right _all the time_ (ever hear the President say, "Wow. I was certainly wrong
about that!" \-- and you can pretty much insert just about any President
there... not just the obvious one ;-) ).

That's the way I see it anyway. Doctors, just like computer programmers work
with complex systems where they are more likely to be wrong than right. I
never trust people in these positions who don't know how to be wrong. But
they/we are often placed in positions where we are not allowed to be wrong --
and some people handle those situations better than others.

~~~
rumanator
> It's not that keeping the poor behaviour is benefitting him in any way. It's
> more that the new solution is not his solution and he's got a lot riding on
> his solution being chosen (justify his code rewrite).

It might also be worth to add that he might have been subjected multiple times
to alternative theories that were refuted, and in his eyes this new outlandish
theory isn't even the most credible one on that list.

------
zosima
The article is not quite updated. Biogen did end their phase 3 trial of the
amyloid-beta antibody Aducanumab early, citing lack of efficacy. A closer look
at the numbers however appeared to reveal that they shouldn't have. And Biogen
is now filing Aducanumab for approval by FDA. [1]

All in all, there is no question that amyloid-beta is a key part of Alzheimer.
Already Alois Alzheimer, when first describing Alzheimer's disease, noted
amyloid-beta plaques as a key pathological finding. Amyloid-beta plaques are a
characteristic of the disease, and a proper Alzheimer diagnosis requires the
presence of amyloid-beta plaques.

Many variants of early-onset Alzheimer are caused by mutations either directly
in APP (the precursor to amyloid-beta) or genes intimately involved with APP-
processing (e.g. PSEN1 and PSEN2). These mutations often cause extreme levels
of amyloid-beta and amyloid plaques.

Raised levels of amyloid-beta and amyloid plaques is a necessary condition for
Alzheimer's disease, both early- and late-onset. But it's clearly not a
sufficient criteria: many people have brains full of plaques and amyloid-beta,
but little or no cognitive decline.

So the problem with Alzheimer's research is not so much the understanding that
amyloid-beta is a significant part of the story, but rather focusing on it as
the _only_ part of the story and the only conceivable solution.

[1] [https://edition.cnn.com/2019/10/22/health/biogen-
alzheimers-...](https://edition.cnn.com/2019/10/22/health/biogen-alzheimers-
drug-fda/index.html)

~~~
sampo
> All in all, there is no question that amyloid-beta is a key part of
> Alzheimer.

You are responding to an article that very much puts it into question. You
should read the article, it's not long. But it'll give some quotes:

 _“The amyloid hypothesis has been one of the most tragic stories [in] disease
research,” said neurobiologist Rachael Neve of Massachusetts General
Hospital._

And

 _Making it worse is that the empirical support for the amyloid hypothesis has
always been shaky._

~~~
zosima
Rachael Neve seems to believe, that APP (amyloid precursor protein) has a
pathological role through other means than its degradation to amyloid beta,
suggesting instead that it may have receptor-like properties [1]. Mostly, as I
understand it, from arguments of structural similarity. It's interesting, but
I know of very little solid evidence pointing that way. (And the article I
could find was quite old)

I think suggestions that amyloid beta is part of cellular defense, and that
its "designed" to stick to foreign bodies/pathogens, preventing them from
spreading in the brain, is more interesting.[2] Early-onset Alzheimer would
then be caused by amyloid beta being released erratically, while many of the
late-onset Alzheimer cases might be driven by amyloid beta in addition to some
underlying inflammatory process.

The amyloid hypothesis, strictly interpreted: that amyloid beta is highly
neurotoxic through plaque formation and is the sole cause of
neurodegeneration, is also known to be dubious and not explain many
observations very well. But that doesn't really challenge that amyloid beta
plays a significant part in the pathology. [3]

[1]
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1862818/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1862818/)

[2]
[https://www.frontiersin.org/articles/10.3389/fnagi.2018.0022...](https://www.frontiersin.org/articles/10.3389/fnagi.2018.00224/full)

[3]
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4888851/#emmm20...](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4888851/#emmm201606210-blk-0001)

------
praptak
The major and established beliefs in science usually have some fringe
competition/opposition. You can only tell in hindsight whether it's "a cabal
stifling valid criticism" or "scientists refusing to waste time on
distractions".

~~~
dhimes
This is an extremely important point. Since I was a grad student, there have
been at least 5 monumental "findings" in physics:

1\. A spinning top weighs less if it spins one way than if it spins the other

2\. A "fifth force," IIRC it was linked to baryons

3\. The climate is warming, not (as people thought) cooling

4\. Superconductivity can be achieved at high (liquid Ln2) temperatures

5\. Fusion can be achieved at low (room) temperatures ("cold fusion").

6\. Homeopathic properties of water

7\. Faster-than-light travel of neutrinos

In each case there was a rush for confirmation- tons of excitement in the
field, etc. Some were confirmed; some debunked; some remain controversial. I
read somewhere that Google is working on cold fusion?

~~~
praptak
And its physics, where I believe that it is cheaper to try weird experiments.
Even if the equipment costs are high, you can probably book 5 minutes on it to
let a grad do something seemingly silly.

In pharmacy even a simple trial on mice may take months, which translates to
$$$. Not even mentioning how expensive (and hard to get approved) a trial on
humans is. I can understand the desire to focus on the "promising" approaches
while dismissing what _looks_ like a distraction.

~~~
dhimes
The price of the experiment depends, of course, on the experiment. The point
is there was an initial excitement as well as initial skepticism. Then there
were investigations. The community eventually accepted the preponderance of
evidence. To try to do an experiment now for faster-than-light neutrinos I
would imagine would be hard, because everything we see seems to indicate that
the speed of light is a hard limit (of course, there is a lot of stuff we
can't see, at least directly...). But to convince people to fund an expensive
experiment for it would be difficult because the framework that supports the
idea that it can't happen is _nice._

It's as you say: once you have a basic working model it doesn't take
conspiracy theory to see other avenues being blocked.

The particular point the article makes, however, that journals reject articles
because of no prior publications in good journals is infuriating.

The article also mentions that funding has been limited; so hard choices had
to be made. But it does seem curious that the cause was so widely believed
before they could even make a solid diagnosis of the disease without an
autopsy examination of the brain.

------
svara
A super interesting article, but the title is pure clickbait. In this day and
age, feeding into the narrative that science is just another competitive team
sport where people compete with whatever means necessary is downright
dangerous.

Reality is much more nuanced, and the article actually does a good job of
detailing that.

In some sense this all started from the very beginning, from when Alzheimer's
disease (AD) was first described: In 1911, Alois Alzheimer found plaques in
his dementia patient's brain. [0] These plaques are what researchers would
focus on for more than the next 100 years.

Much later, the protein giving rise to the plaques (APP) was discovered and
there seemed to be good evidence for a causal role: Mice with mutated APP
developed AD.

Quoting the article:

"""

By the mid-1990s, a now-defunct San Francisco biotechnology company, Athena
Neurosciences, created the first genetically engineered mice with a mutated,
amyloid-producing human gene. The animals’ brains filled with amyloid plaques,
and their memories were destroyed. The mice were hailed as a “model for
testing therapeutic [Alzheimer’s] drugs”

"""

So we should really take this story as a cautionary tale. There was, however,
no conspiracy or "cabal". These were simply people who were convinced they
were on the right track. In a way, they were, since hereditary Alzheimer's is
caused by APP mutations, it just turns out that this isn't as important as
other ways of developing the disease.

[0]
[https://en.wikipedia.org/wiki/Auguste_Deter](https://en.wikipedia.org/wiki/Auguste_Deter)

~~~
leftyted
> In this day and age, feeding into the narrative that science is just another
> competitive team sport where people compete with whatever means necessary is
> downright dangerous.

I think that narrative is correct. We can't fix the problem if we don't
discuss it. The whole "I __believe __in science " thing (which you seem to be
pushing) is really quite silly.

Funding is a political game and the people who are best at politics tend to be
the worst at research (and vice-versa). I think this is exacerbated by the
fact that a lot of scientists are hangers-on, i.e. not capable of doing
original research. These scientists are terrified of people who _can_ do
original research since it makes them look bad (and feel bad, it's actually
depressing to think about all the people out there who are way smarter than
me).

You can imagine funding schemes that attempt to account for these issues. "For
every dollar of funding for interpretation A, earmark 25 cents for alternative
interpretations". View science as a market, something beyond our powers to
predict, then diversify your investments.

~~~
svara
I actually agree with much of what you wrote, but I think the politics of the
funding game just reflect a fundamental problem for which I don't see an
obvious solution:

Science has to be conservative, in order to protect the integrity of the
record of published findings. This can lead to a situation where a field gets
stuck in a local optimum from which progress is no longer possible, because
things that don't seem to fit are dismissed as implausible.

But you can't fix that by funding implausible things, because most of these
actually do come from people who don't know what they're talking about!

At the end of the day, the question is: can we somehow induce these necessary
paradigm shifts more quickly? I really don't know.

~~~
clairity
science doesn't have to be conservative at all, so why presume it? most
(advanced) knowledge is tentative anyway, so why not take the strategy of
accepting it all while it's uncertain? negative results are just a valuable as
advances, and contradictions are just areas begging for more research.

what you really seem to be asking is "why can't science be more efficient?"
and science shouldn't be more efficient. it should be wholly less efficient.
we should have more people searching in the dark for the implausible.

conservatism wants the safe and sure, and science is, and must be, anything
but.

~~~
bobthechef
When people say that science is conservative, what they mean is that it
progresses slowly and cautiously to built up certainty. Science is a tradition
that typically progresses incrementally and is revised incrementally (I should
say, there are many scientific traditions that proceed this way, not some
single, grand, capital S "Science!"). When anomalies occur in the experimental
results, it takes a while for them to be digested in a way that leads to model
revision and then broad acceptance. Now, that isn't to say that people can't
explore unexplored avenues or explore alternatives. They should, but that
doesn't contradict the idea that the sciences proceed conservatively.
Otherwise, you've got chaos, not science.

In any case, you're typically going to profit much more by learning from a
meticulously examined and fleshed out tradition than you are by starting from
proverbial scratch. Science wants certainty which it why, when done properly
(aye, there's the rub!), it goes to great lengths to verify things.
Conservatism, contrary to widespread misconception, is not about stagnation,
but about being careful and responsible with the stewardship of your hard won
inheritance.

~~~
clairity
you're idealizing science and literally begging the question[0], in this case,
making an _a priori_ assumption that science must proceed conservatively and
then trying to rationalize that position.

conservatism unduly burdens science by overly valuing correctness over
exploration. science advances on the latter, not the former.

be wrong, it's ok. it only adds to our scientific knowledge. we can't even
know when we're wrong without a grueling many attempts at being right.

[0]
[https://en.wikipedia.org/wiki/Begging_the_question](https://en.wikipedia.org/wiki/Begging_the_question)

------
anigbrowl
I have the impression when we read stories like this that it's not that the
leading researchers in the field are hostile to other ideas, as such, but that
they are not very well versed in economics and thus think that scarce research
funding should flow their way because giving any to other possibly-wrong
approaches would be wasteful, and likewise abandoning or discounting the
predominant theory would be a terrible mistake because of all the money that
has already gone into it (a sunk cost fallacy). Over and over we see that
expertise in one field - even a very rigorous scientific one - doesn't
immunize one from fallacious thinking in other contexts.

~~~
dba7dba
_think that scarce research funding should flow their way because giving any
to other possibly-wrong approaches would be wasteful_

I heard someone recently tell me how using _science_ to form views on topics
(social/psychology/etc) is dangerous, because science is really about funding.
AND large donors/entities who can fund science often pick science research
projects that sound cool and sexy. They may not be pushing any agenda but do
lean toward funding trendy ideas.

So really, science is often biased because of who hold the checkbooks. That
really made me think.

~~~
WalterBright
Science is funded:

1\. by desire for profit

2\. by desire for political gain

3\. by charitable impulses by people with money to spare

Each has its problems and advantages. Best if we allow all three.

~~~
birdyrooster
Does creating weapons of mass destruction count for profit, political gain,
both or something else?

~~~
saagarjha
Both, probably.

------
TrackerFF
Is Alzheimer's on the rise, or are are simply more people getting diagnosed
with it due to increased life expectancy?

A quick google search yields avg. age of diagnosis to be 80 years; 50 years
ago life expectancy in the western world was 70 years, so a bunch of people
would've probably passed from Heart Diseases and stroke back then, before
getting to the point of dementia.

So it's pretty reasonable to assume that more research went towards things
like heart diseases, etc. the past 50 years, than towards dementia and the
likes.

But now, as we see a steady decline in those things (or at least them being
the leading cause of death), we see more longevity-related diseases, like
cancer and dementia.

What I'm trying to get at here is: Yes, maybe there have been ruling forces in
academia and research that have stopped alternative theories, but wouldn't a
simpler explanation be that there have simply been more pressing issues up
until now, and we're now seeing a rise in things like dementia, due to having
deal with those previous problems.

We have dementia in one side of our family, even though most have gotten it in
their late 70s / early 80s, so I obviously hope they come up with something -
which I have no doubt will happen, the next decades.

------
raincom
It is a well known phenomenon if you have studied the history and philosophy
of sciences. Dominant paradigm(research program) writes off any anomalies
their core hypothesis faces. They will explain away these anomalies with
subsidiary hypotheses. Grants will be denied; tenures are denied; etc--all are
common to anyone participating in a research program(paradigm) that competes
with the dominant one.

------
rooundio
Unfortunately true for most scientific communities and the reason why the
current academic system is badly broken and talented young minds decide to
quit academia before even submitting a dissertation.

~~~
elfexec
Academia was always broken. Despite the current undeserved reputation as
academia being open to debate and new ideas, the opposite has always been
true. Academia has its sordid history of dogmaticism and hero-worshipping. And
progress in knowledge usually advanced in spite of academia rather than
because of it.

Go read about the battles between Newton and Hooke or even Newton and Leibniz.

The doctor who first suggested washing hand to cut down on infections in the
1800s was ridiculed and mocked by surgeons.

Scientists who brought up germ theory were mocked as quacks by doctors and
scientists who rigidly adhered to the miasma theory as gospel.

Of course white supremacy was accepted "scientific fact" for a very long time
by academia and anyone who thought otherwise would have been viewed similarly
to a flat earther today. You could argue that white supremacy would still be
"scientific fact" were it not for ww2.

My personal favorite is Georg Cantor who was mercilessly attacked by his
fellow academics within math and even without for his theories on infinite
numbers.

"The objections to Cantor's work were occasionally fierce: Leopold Kronecker's
public opposition and personal attacks included describing Cantor as a
"scientific charlatan", a "renegade" and a "corrupter of youth".[8] Kronecker
objected to Cantor's proofs that the algebraic numbers are countable, and that
the transcendental numbers are uncountable, results now included in a standard
mathematics curriculum. Writing decades after Cantor's death, Wittgenstein
lamented that mathematics is "ridden through and through with the pernicious
idioms of set theory", which he dismissed as "utter nonsense" that is
"laughable" and "wrong".[9][context needed] Cantor's recurring bouts of
depression from 1884 to the end of his life have been blamed on the hostile
attitude of many of his contemporaries,[10] though some have explained these
episodes as probable manifestations of a bipolar disorder"

[https://en.wikipedia.org/wiki/Georg_Cantor](https://en.wikipedia.org/wiki/Georg_Cantor)

"charlatan", "renegade", "corrupter of youth". Isn't it interesting how
academics attack each other like religious people attack each other? The odd
thing about some of the attacks on Cantor is that it came after his death and
after he had PROVEN his countable and uncountable infinites.

The history of academia is as nasty and vicious as any other institution. And
its gatekeepers and heroes as petty and pathetic as any you'd find anywhere
else.

~~~
zajio1am
> My personal favorite is Georg Cantor who was mercilessly attacked by his
> fellow academics within math and even without for his theories on infinite
> numbers.

I do not think this is comparable to other examples. Math is not science in
the sense that its correctness is not determined by the outside reality, only
by its internal consistency.

Different (finite vs infinite) axiomatizations leads to different classes of
math structures, so it is only a matter of custom which structures are worthy
of studying and how these 'leading' structures are defined.

And there is a point that if one studies countable structures (e.g.
arithmetics or graph theory) then using arguments from infinite set theory
(e.g. ZFC) is overkill. We do not know whether such theory is consistent and
if it is not, then most likely much simpler theories covering the countable
structures would still be consistent.

~~~
zajio1am
> so it is only a matter of custom which structures are worthy of studying

Or in other words, which proof steps are considered valid.

------
knzhou
Whenever you hear about science being a "cabal", you have to remember that
there's a huge survivorship bias. At any moment in science, there are a few
dominant hypotheses, which seem to work pretty well, and _hundreds_ of
alternative hypotheses, with only vague evidence in favor of them. The vast
majority of alternative hypotheses turn out to be completely wrong, and the
researchers pushing them are forgotten. The few that turn out to be right get
funding and recognition, exactly as many of the researchers mentioned in this
article are getting now. In fact, most criticisms of dominant paradigms in
science you read are not from outsiders, but from career scientists who are
leading the charge towards the _next_ dominant paradigm.

I say this just to point out that understanding the world is not as simple as
believing contrarians. At any moment in time, almost all contrarians are
completely wrong. Almost all paradigm shifts didn't work. Almost all anomalies
faded away.

~~~
quantified
Recall the saying that science proceeds one funeral at a time. I believe it
was coined as part of describing the shift to acceptance of plate tectonics.

~~~
btilly
It was coined by Max Plank in 1930.

I believe that it was about the acceptance of Quantum Mechanics.

Examples include that Edward Cope never accepted Darwin's theory of evolution
(even though the fossils that he found were good evidence for it), Albert
Einstein never accepted QM (even though his Nobel was for one of the key
discoveries on the way to QM), and Fred Hoyle never accepted the Big Bang
(even though he coined the phrase).

~~~
btilly
I went and found an interesting article confirming this. When a star
researcher in a field dies, the result is an increase in people entering the
field and exploring the ideas.

See
[https://news.ycombinator.com/item?id=21917047](https://news.ycombinator.com/item?id=21917047)

------
jaggednad
The article talks of journals rejecting papers because the author had already
been rejected by other journals or because the author’s prior papers were in
less-prestigious journals. This method of selecting papers is the perfect
recipe for groupthink. The names of the authors should be removed while a
paper is being reviewed—the reviewers shouldn’t know who wrote it so that
they’ll be forced to evaluate the paper on its intrinsic merits rather than
the reputation of its author. That might not solve this beta amyloid orthodoxy
problem, but it’d help at least

~~~
greglindahl
Ask people who work in any field that does have blind review, and they'll tell
you that it isn't actually blind... you can make good guesses on the author
list by examining the description of previous work, the reference list, the
style of the writing, etc etc.

~~~
monadgonad
It's still better than nothing. You can't reject a paper saying "I believe
this author is X, who has few publications in major journals" which encourages
people to assess the paper on its own merits, even if it doesn't ensure it.

------
ping_pong
This is another example of group-think in scientific research. The same thing
happened for decades where low fat diets were supposed to help for heart
disease but that has only recently been reversed after decades of
indoctrination. This happens all throughout scientific research, where science
is supposed to be immune to this, but it's obviously not. So many things we
take as gospel, only to be reversed decades later, and it has to do with how
things get funded which is unfortunately leading society the wrong way.

~~~
igorkraw
While I'm all for changing funding systems I want to point out that _there
fact we have these scandals is the system somewhat working_. Similarly to how
constant criticism of the government/large corporations isn't a sign of rot,
but of a system where improvements are still possible -as long as someone is
pointing out the problems you can fix them.

And science is not supposed to be immune to this, the culture of science is
supposed to uncover things like this/errors like this as part of a process.
The truth has a habit of shining through if you are encouraged to keep asking
questions and follow up on them.

And again, not saying the system is perfect or that calling things out is
enough. But too often comments like this get turned anti-science or "we can't
improve anything, slow decay is inevitable" cynicism (or FUD if you want to be
less charitable)

~~~
gyuserbti
This standard sentiment seems to me to be a machiavellian justification for
the status quo and for not trying to improve anything. The costs of the
problems are the problem, not whether they are eventually resolved extremely
ineffiently.

~~~
igorkraw
Yes, we can improve things, but it is important to recognise that the
scientific method and process is the best thing we have right now to figure
this stuff out. Making it more open and reliable (open acces by default, data
and code publication by default,more funding options that encourage public
participation and replication studies etc.) is definitely possible but _the
core_ is not rotten. Especially some private interests (oligarchs and those
with that ambition, "race realists" etc.) like to push the meme that something
is fundamentally broken with publicly funded science and we shouldn't trust
those ivory tower academics - often because those academics are actually able
to go for the truth instead of following the market (i.e. create
disinformation). This is what I'm pushing back against

~~~
galangalalgol
Those oligarchs and race realists have supporters within academia, when
selecting the reforms for academic process, this should be considered. Also,
acknowledging the core truth these people build their lies around is
fundamental to dismissing the whole ball of infectious meme.

------
tempsy
Hasn’t Alzheimer’s been referred to as diabetes type III? It’s inflammation of
the brain, and eating a low inflammation diet (low carb, no sugar, fasting) is
the best thing one can do to drastically reduce getting it.

~~~
creato
> It’s inflammation of the brain, and eating a low inflammation diet (low
> carb, no sugar, fasting) is the best thing one can do to drastically reduce
> getting it.

Do you have a source?

If you state something like this with such authority/in a "matter of fact" way
(and is something that seems likely to be controversial), you really should
have a source.

~~~
abgfm
Here u go:
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2769828/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2769828/)

------
ncmncm
> _those alternatives are now being explored in both basic research and
> clinical trials._

 _Some_ of those alternatives are being explored. Those of everybody driven
out of the field are not.

Is there any work on the bacterial observations?

------
rosybox
We don't seem to understand much about any of diseases that affect the brain
or nervous system. MS, Parkinson's, ALS, Huntington's disease, alzheimers, not
even essential tremors or BFS. All these futurists thinking longer lives are
just around the corner when in reality we don't jack shit about shit.
Something goes wrong with your nerves or brain, you're likely fucked and
there's little anyone can do to help you.

------
goodcanadian
"A new scientific truth does not triumph by convincing its opponents and
making them see the light, but rather because its opponents eventually die,
and a new generation grows up that is familiar with it." -Max Planck

Or, as it is more commonly put: Science advances one funeral at a time.

~~~
lincolnq
Is there an age at which you favor forcing scientists into retirement?

~~~
NotSammyHagar
It's not forced retirement that is needed, it's constant replenishing of
leaders and decision makers to let new ideas have a chance. So things can't
advance, sometimes, until the people who are invested in the old ways stop
blocking the new ways.

------
bransonf
I only learned of the flaws in the amyloid hypothesis a few weeks ago. The
single most influential thing I read was this.

[0]
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4207354/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4207354/)

~~~
twic
I studied Alzheimer's a bit during my degree, so in 2002 or so, and it seemed
pretty clear that the amyloid hypothesis was wrong even then. I had no idea it
was still the dominant paradigm.

------
LatteLazy
>Several who tried to start companies to develop Alzheimer’s cures were told
again and again by venture capital firms and major biopharma companies that
they would back only an amyloid approach.

I wonder if that's because their internal advice was from "cabal members" or
if they didn't like the fundamental science or some other reason? Maybe the
economics of (well understood) beta amyloid ideas worked better economically
than new ideas (I guess it's a big, unhedgable gamble to invest in something
that might be a cure, but won't be on the market for 20 years).

The whole point of venture capital is to fund things that "mainstream" has
rejected but rejected without good reason. That does make me wonder a bit how
good the science behind other ideas was.

------
alpineidyll3
Perhaps the most pernicious example of a common dysfunction of the grant
system and entrenchment of power in old faculty.

We hired a friend of mine exclusively to study amyloid beta spectroscopy. He
was aware that it probably didn't explain the pathology, but how else would he
get a job?

------
ekianjo
> there is not even a disease-slowing treatment.

True-ish, but Aricept is generally seen and used as a disease-slowing
treatment (even if the data is inconclusive, it is perceived this way by
physicians).

> In patients with Alzheimer's Dementia participating in clinical trials,
> administration of single daily doses of 5 mg or 10 mg of ARICEPT produced
> steady-state inhibition of acetylcholinesterase activity (measured in
> erythrocyte membranes) of 63.6% and 77.3%, respectively when measured post
> dose. The inhibition of acetylcholinesterase (AChE) in red blood cells by
> donepezil hydrochloride has been shown to correlate to changes in ADAS-cog,
> a sensitive scale that examines selected aspects of cognition. The potential
> for donepezil hydrochloride to alter the course of the underlying
> neuropathology has not been studied. Thus ARICEPT cannot be considered to
> have any effect on the progress of the disease.

> Efficacy of treatment of Alzheimer's Dementia with ARICEPT has been
> investigated in four placebo-controlled trials, 2 trials of 6-month duration
> and 2 trials of 1-year duration.

> In the 6 months clinical trial, an analysis was done at the conclusion of
> donepezil treatment using a combination of three efficacy criteria: the
> ADAS-Cog (a measure of cognitive performance), the Clinician Interview Based
> Impression of Change with Caregiver Input (a measure of global function) and
> the Activities of Daily Living Subscale of the Clinical Dementia Rating
> Scale (a measure of capabilities in community affairs, home and hobbies and
> personal care).

\- % Response

\- Intent to Treat Population n=365, Evaluable Population n=352

\- Placebo Group 10%, 10%,

\- ARICEPT tablets 5-mg Group, 18% (sig), 18% (sig)

\- ARICEPT tablets 10-mg Group, 21% (sig), 22% (sig)

Aricept does not seem to have much efficacy overall, but it makes a lot of
money for the lack of alternatives.
([https://www.medicines.org.uk/emc/product/3776/smpc](https://www.medicines.org.uk/emc/product/3776/smpc))

~~~
omgwtfbyobbq
I'm guessing the perception that it slowed Alzheimer's is because some
patients were misdiagnosed. Aricept can help with falls in Parkinson's
patients with balance problems, and in my experience seems to help with
arousal.

[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3013493/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3013493/)

Accurately diagnosing the elderly is difficult. My grandmother was diagnosed
with Alzheimer's 15-20 years ago, which was likely inaccurate. At this point
it looks like she probably has Dopa-Responsive Dystonia and may also have some
form of Vascular Dementia, some sort of CSF disorder, and possibly some other
problem that hasn't been diagnosed.

~~~
ekianjo
Yes, until recently there was no way to confirm Alzheimer with certainty until
after death. But recent imaging solutions make it possible to see the amyloid
plaques in living subjects.

~~~
omgwtfbyobbq
Can imaging differentiate between people who have plaques with and without
impairment?

[https://www.sciencedaily.com/releases/2018/08/180817093810.h...](https://www.sciencedaily.com/releases/2018/08/180817093810.htm)

------
JimBrimble35
"“Once a field commits to a particular hypothesis, the research resources —
funding, experimental models, and training — all get in line,” she wrote in a
2018 analysis. That brings backers of the dominant idea accolades, awards,
lucrative consulting deals, and well-paid academic appointments. Admitting
doubt, let alone error, would be not only be a blow to the ego but also a
threat to livelihood."

Is this not extremely controversial? It was always my belief that "not
creating a cure for X disease keeps the money flowing" was the calling card of
tinfoil hat wearing conspiracy nuts. This statement, and the following
paragraphs seem to suggest this is somewhat commonplace

~~~
internet_user
How is that controversial? That's just people for you.

------
WhompingWindows
I presented my research on Delirium, dementia, and frailty at an Alzheimer's
conference last year. There was no evidence of an Alzheimer's amyloid "cabal"
in that room. Around 90% of the work being done had to do with early
diagnosis: since this is a chronic, long-term disease, like diabetes or heart
disease, most of the research and talks were about how to diagnose and treat
EARLY, before the neurological damage has been inflicted.

In my opinion, there will probably be no silver bullet for Alzheimers, though
we may develop long-term treatments which slow the rate and severity of the
disease in those pre-disposed or in the early stages of AD.

------
kd0amg
_if alternative ideas received little funding support, it was because NIH’s
Alzheimer’s budget was woefully insufficient ($425 million in 2012, $2.4
billion in 2019)_

 _low NIH funding for Alzheimer’s from the 1980s through the 2000s is to blame
for alternative ideas languishing_

This seems like a hollow excuse. AFAIK, NIH doesn't have a mandate to put a
certain amount of funding towards one line of inquiry before funding another.

~~~
aidenn0
> This seems like a hollow excuse. AFAIK, NIH doesn't have a mandate to put a
> certain amount of funding towards one line of inquiry before funding
> another.

Rather NIH can't fund projects for the 10 most likely ideas, so it funds
projects for the 1 or 2 most likely ideas.

------
richk449
It is easy in retrospect to see that going all in on the amyloid hypothesis
was a mistake.

But that is always true once a hypothesis has been proven false (or at least
not completely true).

Is it possible to look at this as a very large “fail fast” experiment? Given
the limited funding, would it really have been better to spread it over many
hypotheses, rather than pick the most likely, and test a minimal viable
solution?

~~~
ppseafield
It's hard to see this as a fail fast experiment when:

> In more than two dozen interviews, scientists whose ideas fell outside the
> dogma recounted how, for decades, believers in the dominant hypothesis
> suppressed research on alternative ideas: They influenced what studies got
> published in top journals, which scientists got funded, who got tenure, and
> who got speaking slots at reputation-buffing scientific conferences.

It's one thing to go all-in on a hypothesis, but another to undermine other
folks' hypotheses directly. Especially when your hypothesis has not produced
any results for decades.

------
D-Coder
The author of the article, Sharon Begley, is a very good science writer. I've
seen her writing elsewhere too.

------
gardenfelder
I am reading the book "An Epidemic of Absence" by Moises Velasquez-Manoff,
which articulates a basis for everything being covered in this HN thread.
While I wish the author made better use of citations and footnotes, the
narrative seems compelling.

------
m3kw9
The article says it has nothing to do with evil or anything but it all comes
back down to money, incentives and sustaining egos.

------
JackFr
Plate tectonics. Literally ridiculed and dismissed as pseudoscience. Now we
consider it manifestly obvious.

------
cpr
Isn't this exactly the same in other areas such a cancer research?

------
m3kw9
Is like to hear some pro Amyloid researchers chime in on this.

------
Gatsky
Indeed. Nothing will save you if you have the wrong idea.

------
allovernow
>scientists whose ideas fell outside the dogma recounted how, for decades,
believers in the dominant hypothesis suppressed research on alternative ideas:
They influenced what studies got published in top journals, which scientists
got funded, who got tenure, and who got speaking slots at reputation-buffing
scientific conferences

Not quite in topic, but Is it really such a stretch to acknowledge that the
same forces in academia might bias climate science too? Except as another
commenter pointed out, it doesn't take a shadowy cabal. Just a strong trend
that individuals can believe in for ethical or moral reasons. Even when it
becomes dogmatic.

~~~
qqqwerty
I will acknowledge that those forces may be in play. But I will also ask you
to acknowledge that oil extraction has and continues to make certain people,
companies, and governments immensely wealthy and powerful and that those
groups are very interested in keeping the status quo. Those
people/companies/governments have the power and resources to finance research
into climate change that would support their narrative. And by all accounts
they have been doing that. But despite those efforts the scientific consensus
supporting climate change has remained.

So yeah, science isn't perfect and we have seen cases in the past where group
think has held back progress and discovery. But we have also seen plenty of
examples of corporations and trade groups bending and influencing the
scientific narrative to their benefit (see the low-fat discussion in this
thread). And in the case of climate change, the most monetarily interested
party is literally the wealthiest industry in the history of the world. So I
think it is safe to say that the current consensus is facing plenty of
scrutiny.

~~~
ckosidows
Does this argument prove anything? An enormous industry that wants to disprove
man-made climate change science doesn't prove climate science is iron-tight.
There are also many vested interests, at this point, in proving popular
climate science to be true. This can be companies, politicians, and even just
people who are invested in the hypothesis (either professionally or
personally).

There are industries who oppose the hypothesis that climate change is man-made
for personal reasons, but there are people on the other side who have similar
interests. There is scrutiny about man-made climate change, but I've often
seen such scrutiny lambasted by people who are too vested in the idea that man
has solely created climate change. Is it possible that, despite push-back from
oil companies, there is still group-think happening with climate change
science?

As a disclaimer I believe a significant portion of climate change is man-made
but also that part of it can be attributed to natural changes. I _definitely_
think we need to act to save ourselves from climate change. Climate change
science has a lot of momentum right now and perhaps certain ideas have been
given undue recognition or derision due to their conclusions found.

~~~
qqqwerty
The key mechanism that enables 'group think' in academia is access (or lack of
access) to funding for research. Generally, funding for research is fairly
limited relative to the number of interested researchers (ask any grad
student). The control over journal publications and conference speaking slots
is only useful in that it enables researchers to increase their odds of
receiving future funding. If one is able to get funding without those
credentials, say by going to industry players with aligned interests, then the
'academic cabals' really don't have the power and influence to be a 'cabal'.

It is worth noting, that part of the reason the Alzheimer 'cabal' existed in
the first place was because the pharmaceutical industry was willing to go
along with it. And part of the reason the 'cabal' is finally falling apart is
because the industry is no longer willing to fund the research.

Here is a fun question for you (or anyone who is skeptical). Can you name one
example where industry and academics were diametrically opposed on a
particular topic, and where it turned out that the academics were wrong? I can
point out quite a few examples where the opposite was true, but I am
struggling to think of a single example that would qualify the above prompt.

------
sillysaurusx
_The truth has a habit of shining through if you are encouraged to keep asking
questions and follow up on them._

The point is that people are actively discouraged from asking questions and
following up on them. People lose their careers and livelihoods for asking the
wrong sorts of questions.

Truth is no barrier to social backlash. In fact, questions that might be true
tend to be the ones that get people the most heated.
[https://twitter.com/a_centrism/status/1211170458902487042](https://twitter.com/a_centrism/status/1211170458902487042)

(I have no stance either way regarding that account, but it's an interesting
phenomenon that someone has to basically shroud themselves in anonymity to
present certain flavors of scientific research.)

~~~
igorkraw
On the specific topic of IQ and scientific racism, the "centrist" position of
"just asking questions" has been a cloak for agendas and not caring about the
truth for a while now. Exhibit A:
[https://mobile.twitter.com/Simon_Whitten/status/117331966332...](https://mobile.twitter.com/Simon_Whitten/status/1173319663322841088)
Exhibit B, what happens when you actually dig into the science behind the most
well known peddler of the IQ is real and important, therefore racism is
actually not a problem meme
[https://m.youtube.com/watch?v=UBc7qBS1Ujo](https://m.youtube.com/watch?v=UBc7qBS1Ujo)

Note that I'm not saying there aren't good faith inquiries to be had, but it
is _really hard_ to have these with racist agendas being pushed whole claiming
"neutral" questions.

A few observations that I would like people to keep in mind when looking at
these fields:

\- the people who complain about being "silenced" continue to find funding,
public platforms to push their research and in some cases, tenure

\- the "hard questions not being raised" seem to cluster around the question
of differences between "races" and less around whether the concept of race
actually makes sense in humans (AFAIK geneticists generally think no), whether
these differences might be socially constructed (yes, that's possible. If
there are systemic social biases against groups with genetic genes the impacts
of these will be 100% explained by the presence of these genes in data, but 0%
genetically determined as in biologically determined). And often they are then
raised to dismiss concerns about the systematic problems which might have
caused the measured problems

\- scientific racism and shoddy science in this field has a long history, and
people carry their misconceptions around. Famous examples are "objective"
written IQ tests given to barely literal test subjects, or asking trigonometry
questions, Both of which test the schooling of the subjects more than the IQ

In an inherently political field of science, denying the political nature and
implications of questions being raised and the manner in which they are raised
and trying ot claim "objectiveness" is in and of itself a political tactic.

~~~
zozbot234
There's definitely a lot of agendas being pushed. But I'm not sure why we're
being expected to trust numbers like 100% and 0% - what makes these numbers
inherently more "objective" than other possibilities such as, let's say 90%
and 10%?

~~~
igorkraw
Well in this case, because they are numbers in an example given and you are
nitpicking. In the general case, it's more complicated, but (controversial
statement ahead) truth exists,some ideas are wrong either by data or by
definition

------
g42gregory
An honest question: How does this compare to the group-think in the climate
change/global warming research? Are we similarly rejecting funding to any
research that does not fit into the common consensus? The fact that we call
some people "climate change deniers" tells me that we have an unhealthy
dynamics going on there. Will it take 30 years to get to the same point?

~~~
ivalm
> The fact that we call some people "climate change deniers" tells me that we
> have an unhealthy dynamics going on there

1\. Climate change is observable, it doesnt rely on a theory, just
measurements. Nonetheless there are a bunch of people trying to discredit what
is essentially a very well established observation.

2\. Genesis of climate change (ie is it anthropogenic) is not a direct
observable, but looking at concentrations of CO2/other gasses and where it
comes from it is not too hard to convince yourself of humans as root cause.
Again, a lot of people deny human-driven climate change despite all evidence
pointing one way.

3\. Perhaps the most uncertain are climate model predictions. I agree that
this where something might be overlooked, or maybe not.

At any rate, "climate change deniers" by and large object to (1) and (2), and
those people really have no credibility. If someone accepts anthropogenic
climate change but proposes a new model that fits observation-- more power to
them!

~~~
zorked
The biggest red flag is that "climate change deniers" aren't a fringe group of
meteorologists, but a group of politically-inclined people who also denounce
"cultural Marxism" and other crank theories.

I assume that actual expert skeptics are given a lot more respect but also get
far less exposure than deniers.

~~~
ivalm
I agree with you, but I think your argument is not a good way to engage with
skeptics because it is basically an appeal to authority, but scientists
precisely dont have much authority in their eyes.

Measuring outside temperature, however, is a lived experience for them. And
this is what we have done (in a more complicated fashion) for years now. This,
to me, is a more convincing argument.

