
The Problem with America’s Lab Mice [video] - zpeti
https://www.youtube.com/watch?v=ve4q-1D_Ajo
======
Dowwie
This discussion between Joe Rogan and Bret Weinstein happened after the major
reveal (and full story) on The Portal podcast between Bret and his brother,
Eric. I _highly_ recommend listening to it:
[https://podcasts.apple.com/us/podcast/19-bret-weinstein-
the-...](https://podcasts.apple.com/us/podcast/19-bret-weinstein-the-
prediction-and-the-disc/id1469999563?i=1000462975502)

~~~
jordanpg
TL;DR please.

These brothers are smart and often interesting but they are also both audibly
quite taken with their own brilliance and often not what I want to listen to.

~~~
sradman
elindbe2 nicely summarizes Bret Weinstein's paper and the Joe Rogan clip.

Eric Weinstein's 2hr+ Portal Podcast #19 on YouTube is frustrating but I'd
summarize the "new" info from memory as:

\- math oriented older brother Eric thinks biology oriented younger brother
Bret is Nobel Prize worthy

\- yet Bret and his mouse telomere paper live in obscurity

\- reason 1: Bret chose Evergreen rather than a top tier University

\- reason 2: the science establishment is biased against disruptive ideas and
scientists

\- Carol Greider’s 2009 Nobel Prize was based on work inspired by informal
phone calls and emails from Bret

\- Bret claims that Greider failed to recognize his contribution and then
actively undermined his paper(s) through the peer review process

I wish we had TL;DR + Start/Stop Links into the original video. Long form
audio/video podcasts are both a boon and a curse since the content cannot
easily be searched or linked to.

~~~
Shoreleave
> Carol Greider’s 2009 Nobel Prize was based on work inspired by informal
> phone calls and emails from Bret

Bret is quick to point out that Dr. Greider's Nobel prize is well deserved and
for related, but earlier work. The contention is over later work.

Their conversation did inspire these findings about lab mice telomeres. But
Dr. Greider's lab decided to keep the information "in house". This means that
instead of publishing the source of the information, they can use their
knowledge to start predicting other results, and publish a full stream of
paper first. This is at 1:23:50.

------
DrAwdeOccarim
Drug development has been maturing for decades. Both industry and the agency
have had time to work out what animal models do and do not tell us. If you
develop/discover a molecule/drug that treats some disease, it's typically
found first in single-cells, then you move into higher and higher organisms.
This is the flow of development. No one thinks any mouse, even humanized mice,
are surrogates for actual clinical evidence. The whole shtick is risk
mitigation, it's amazing how far society has come in such a short period of
time where we forget non-clinical testing is not a perfect view into how a
compound will interact in a human.

~~~
mennis16
But in certain fields this current setup seems to be failing. The large
majority of clinical trials related to neuroscience fail. To the point that
pharma companies are starting to defund these departments, because the hit
probability is just not good enough to outweigh the costs. This is despite the
fact many of our treatments are woefully inadequate and often closely related
to drug discoveries made 50+ years ago. And despite the fact that the field is
well funded in academia, taking up entire departments distinct from biology.

Neuroscience is a hard problem no doubt, but I also think the current paradigm
for how basic neuroscience research is done is way too limited, and that is
impacting the viability of potential treatments that make it to clinical trial
phase.

~~~
ethbro
> _I also think the current paradigm for how basic neuroscience research is
> done is way too limited, and that is impacting the viability of potential
> treatments that make it to clinical trial phase._

Our current paradigm is optimized to avoid injuring humans at all costs,
including to the extent that it diminishes the chance of success.

By advocating for a different model, we're stating "Avoiding injuring humans
in drug discovery is not our primary concern."

Maybe that's worth it in a broader calculation, but let's be honest about what
we're talking about.

Pharma companies and regulatory bodies don't put in place billion+ dollar
trial hoops on a whim: they do so to avoid permanently injuring or killing
people with some pretty horrific side effects, to the extent we can.

~~~
throwaway0a5e
Your comment reminds me of the recent Dilbert strips where everyone is acting
like the main character doesn't care about safety because he didn't state the
implicit assumption that safety matters and someone looking for cheap virtue
points noticed and said "you didn't mention safety, why don't you care about
safety" even though he obviously cares as much as anyone else.

Nobody in this entire comment section that I have seen so far is advocating
for harming more people more frequently in the name of progress. Just because
people are asking "are there any other ways of testing drugs" and the current
testing system cares about safety does not mean that these people want to
abandon safety in order to more cheaply test drugs. Maybe we can find some
other way to test drugs that is cheaper per useful drug than the current
system and equivalent or better in terms of safety to humans.

~~~
ethbro
I didn't say that anyone wanted to abandon safety. I said that they wanted to
deprioritize safety, presumably to increase successful drug development.

> _Maybe we can find some other way to test drugs that is cheaper per useful
> drug than the current system and equivalent or better in terms of safety to
> humans._

Maybe. But we should start at a place of shared understanding.

HN is notorious for "if they just"isms with regards to other fields.

Consequently, I think it's fair to point out that the thing that most people
are lamenting (strict adherence to standards, extremely conservative trial
progression) are attached to a value (avoiding harm to humans).

If people are advocating to upend the apple cart, then they don't just get to
say "We want to continue to prioritize safety and also not do some things that
increase safety."

Personally? I'd be fine with an informed consent alternative that helped speed
through population-targeted or riskier drugs. Better to have options. But
implementing that system would have costs.

------
throwaway4666
Disclaimer: haven't seen the video (I never click any video link, sorry), but
I did read the text links provided in the thread. That said: one of the big
reason to use mice as animal models is that we've obtained a bunch of pure-
bred, homozygous lines for a bunch of different genes, and that process is
expensive and above all _lengthy_. Mice have both (a) a relatively short
generation time and (b) been experimented on for a very long time. This makes
them particularly suited for experiments involving knocked-out genes and
suchlike because you have near-perfect controls at your disposal.

Now just because we have a bunch of pure-bred homozygous mice doesn't mean
mice behave the same way as humans with respect to e.g. metabolic pathways,
immune system etc. It's just that we often don't have better models.

~~~
sradman
The problem is that the breeding protocols inadvertently created a selection
bias towards long telomeres. Mice with extra long telomeres have exceptional
tissue repair capacity while also being susceptible to tumor growth.

The supply of lab mice can be corrected to have a more natural telomere
length. All past studies that used mouse models to study the impact of drugs
are skewed to under report toxicity and over report carcinogenicity.

~~~
ardy42
> Mice with extra long telomeres have exceptional tissue repair capacity while
> also being susceptible to tumor growth....

> All past studies that used mouse models to study the impact of drugs are
> skewed to under report toxicity and over report carcinogenicity.

Could the data from long telomere mice be de-skewed to compensate for new-
understood effects the long telomeres?

~~~
AzzieElbab
I don't think it is linear. Fast tissue recovery can make side effects
unobservable

------
tomtompl
Wow, first time I see this mentioned somewhat in 'mainstream'. How is that not
talked more?

~~~
Broken_Hippo
It is a known issue, and has been talked about somewhat in 'mainstream': [1]
wired.com [2] adam ruins everything. I think it isn't talked about more
because most of us don't think about anything like this until it is brought
up, not to mention that it is a big, complicated issue that really needs folks
educated in the right areas to work out.

[1][https://www.wired.com/2016/07/science-huge-diversity-
problem...](https://www.wired.com/2016/07/science-huge-diversity-problem-lab-
rats/) [2][https://youtu.be/FHl0nIdbiLA](https://youtu.be/FHl0nIdbiLA)

~~~
rapsey
This particular issue has not been talked about in any of your links.

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gumby
This is not some secret knowledge uncovered via youtube.

Every animal model is imperfect and the various tools to try to address them
(e.g. greater genetic uniformity) have consequences as well.

If you pick the wrong model your research will fail. Even if it gets through
the pure research phase, the FDA will want justification as for why your
animal of choice is appropriate.

I had a program that required — ugh — guinea pigs. Those suckers ended up
costing $1K when all was said and done (not the cost of acquiring them,but
looking after them and running the program). Rats would have been cheaper and
mice even more but theOr immune systems could reject the pathogen we were
trying to treat; the GP was the least expensive animal it would attack. (There
turned out to be other advantages too but that was that for research). And
when it came time for the preclinical work for IND submission the agency
wanted an EMEA more expensive animal because it was a better human model.

So it’s an engineering trade off, just like any other. One controlled for when
possible. Sorry there’s no conspiracy.

~~~
rapsey
I think his point is that those mice are misleadingly bad and it is a fixable
problem that for some reason the scientific community is refusing to address.

~~~
dmatech
The scientific community often comes to an incorrect consensus, and this
consensus becomes dogma that must not be questioned because the consequences
would be too damaging to reputation/credibility/whatever.

Here's another example from a while back:

[https://news.ycombinator.com/item?id=21911225](https://news.ycombinator.com/item?id=21911225)
\- "How an Alzheimer’s ‘cabal’ thwarted progress toward a cure"

When you've got enough incentive, it's hard to resist the urge to use your
power to simply decide what is and is not allowed to be true.

~~~
vikramkr
The consensus on mice models is that they suck and we need something better,
and until we do, everything needs to he tested in humans before widespread
approval is given so we arent ever relying on mice data alone to make
regulatory decisions. Seems like a reasonable consensus to reach

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ngcc_hk
I read there is another issue with cell line as well sometimes ago.

~~~
dnautics
Many cell line stores are basically HeLa cells, and not whatever cell line
they are labeled as, because probably at some point some grad student
accidentally contaminated one petri dish with another and the HeLa s took
over. heLa cells themselves have an interesting history.

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pjc50
Does anybody have a source for this that (a) isn't video and (b) isn't Joe
Rogan?

~~~
gumby
I had never heard of Mr Rogan before but I guess I should not be surprised
that people These days seek medical advice from a comedian/martial arts
commentator. Or from a video of two people having a conversation.

~~~
rapsey
If you have never heard of Rogan then you must really be living under a rock.
It's the most popular podcast on the planet.

~~~
culturestate
Plenty of people in the world (even on HN!) don’t listen to podcasts, mate.
It’s not a globally universal cultural experience.

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pachico
Why is it that anytime someone simply points out the ethical issues about
animal rights he gets downvoted? I've seen it more than once here.

~~~
hobofan
This post has almost nothing to do with "ethical issues about animal rights".

~~~
pachico
But some comments had.

