The Problem with America’s Lab Mice [video]

Lab mice have extremely long telomeres compared to wild mice and humans. This would theoretically make them better able to heal but more prone to cancer. This also makes them a poor model for testing the toxicity of drugs because they would be better able to deal with the damage caused by drug toxicity.

Drugs that have been developed using these mice could have a higher toxicity than the lab mice data suggests. Weinstein uses the Vioxx scandal as a possible example of such a drug.

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.

Agreed. I listened to one of their interviews on Rogan and couldn’t stand it after half an hour. It’s good to be smart but but it seems a bad character trait to be convinced of your own brilliance.

> 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.

That fixes only this one specific problem though, the breeding protocol has probably introduced a lot of biases.

> 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?

The solution to population variability is not to use variable models. That just trashes your result set.

There are enough confounding, uncontrollable variables in biology already.

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

Yes, I am aware of it, I should've been more specific.

I haven't seen anyone who is supposed to be solving this issue to be taking any steps towards improving the situation.

Respective agencies acknowledged it but (at least not to my knowledge) didn't follow up on that.

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 - "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.

Fixable and refusing to address? At the end of this I've linked a grant request from the NIH for better models, and this isn't a u ique or one of grant request. Hundreds of researchers and companies are working tirelessly on things like organ on a chip. Every drug required human trials to prove they work and could never get approved on mouse trust alone. Preclinical work will use animals up to monkeys if needed to get the best data. Neuroscience is developing brain organoids we can use that are created from actual human cells so we can move away from mice. This is millions of dollars of research being poured into this space because it turns out the scientific community does not like spending billions of dollars on failed drugs that we might have known about if we had better models. Saying the problem is fixable and that the scientific community just doesnt care is incredibly naive - it's like saying higher energy density batteries are trivially achievable but battery researchers are just too lazy right now. Its difficult, and many mainstream researchers have literally dedicated their lives to it.

https://grants.nih.gov/grants/guide/pa-files/PAR-19-369.html

>Certainly if we hold these kind of ethics we've got no excuses if an advanced alien race wants to use us in their medical experiments.

If an advanced alien wants to use us in experiments, I doubt they'd care much about what we say on the matter. And for all we know, the aliens might come from a predator background and only consider vicious species as true equals.

In the end, all non-human testing of potential treatments are meant to be fail-fast/fail-cheap. In terms of fail-fast, the timeline for seeing "lifetime" effects of a drug is far shorter in a rodent than in a human. In terms of fail-cheap, the ethical and monetary cost of a rodent suffering or dying due to unwanted effects of a drug candidate is judged to be lower than similar suffering in a human.

I do agree that lab animals aren't a resource in themselves – they're just the currently "next best" model to test in before trying a drug out in humans. In fact, mice are actually quite expensive in terms of time and money – custom-genotype mice can cost hundreds of dollars each, and that's just the up-front purchase price. The overhead of maintaining a mouse line is also quite high, with a huge loss incurred for accidental death or euthanization before they've been used as a model. When many research facilities were first shut down due to COVID lockdown this year, I heard that many labs at my university had to euthanize all their mice as they wouldn't be able to care for them. This represents a loss of months of research time and possibly thousands to tens of thousands of research dollars.

Another thing to consider is that many drug candidates that make it to the animal testing stage don't succeed with safety and/or efficacy testing. According to the FDA, 92% of pre-clinical animal tests actually fail to predict drug effectiveness in humans. This highlights a pressing need for other fail-fast/fail-cheap methods that should precede animal testing, like cell culture methods that could be used as a pre-animal screen.

If you look at it another way, groups that have a handle and understanding of a particular tool may have insight into how that tool can be used to answer a biological question. I don't think there is anything really wrong with that, but grants should be denied if they aren't proposing ways to move the field forward.

There are tons of mouse labs, however some have specialized mice or mouse systems. There are also other labs that specialize in other animal systems. These systems are nontrivial to switch between for many reasons, which I think you acknowledge. It is useful for the field in general to have access to the results of a variety of research tools that every individual wouldn't necessarily have access to.

That still doesn't mean it was secret knowledge before, the people who have use for this information could readily access it.

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.

I mean historically people would take medical folk wisdom from all sorts of sources that are probably even worse than Joe Rogan.

This reminds me of people complaining about others taking financial advice from reddit, ignoring that on average the financial advice you get from finance subs there is probably much better than the advice you get asking random friends and family -- which is a common practice.

But some comments had.