Broken lab mice hide the harms during pharmaceutical testing (from Livestream #172)

Introduction

The speaker introduces the topic of telomeres in mice and how it affects pharmaceutical safety.

Telomere Length in Mice

• The speaker predicted that wild mice would have short telomeres, unlike laboratory mice.

• Laboratory mice have long telomeres due to selective breeding, which has implications for studying wound healing, cancer, and senescence.

• Breeding younger mice is more cost-effective for producing salable mice, but this unbalances the delicate trade-off between long telomeres reducing pathologies of aging and increasing cancer risk.

• Laboratory mice don't live long enough to get cancer due to selective breeding, making them unreliable models of cancer.

Pharmaceutical Safety Implications

• Long telomeres make laboratory mice disproportionately resilient to toxins that are not deadly but bad for the animal's tissue.

• Giving a toxin to a mouse with latent tumors may extend its life by slowing down the tumors, similar to chemotherapy in humans.

• This makes laboratory mice unreliable models for testing pharmaceutical safety since they are prone to getting tumors and can compensate for toxins.

Public Awareness

The speaker discusses how difficult it is to explain this complex issue to an audience that isn't already informed.

Challenges in Explaining the Issue

• There are many sign changes in this story that make it hard to explain to an uninformed audience.

• Researchers who work on topics like telomere and senescence don't want to hear about these issues because they challenge their existing beliefs.

• The public's job is not to discover these issues, but institutions like the FDA should be obsessed with discovering whether this is an accurate description of the universe.

Conclusion

The speaker concludes by emphasizing that pharmaceutical safety is a complex issue that requires careful consideration and research.

Importance of Pharmaceutical Safety

• The Blue Ribbon panel assembled after the Vioxx scandal put together a 300-page book called "The Future of Drug Safety," highlighting the importance of pharmaceutical safety.

• It's essential to ensure that drugs are safe for human use and not just effective in laboratory mice.

Science Journalism and the Insider's Club

In this section, Bret Weinstein discusses how science journalism has failed to report on a significant scientific discovery that was predicted 20 years ago. He argues that the scientific community is an insider's club where results are doled out to keep people in their jobs, rather than serving the public well.

Failure of Science Journalism

• Gina Colada should have called up people she interviewed for her story and asked if this discovery was predicted.

• Nicholas Wade and Carl Zimmer should have recognized that this discovery was predicted 20 years ago.

• The failure of science journalism to report on this prediction shows that it is not serving the public well.

Insider's Club Mentality

• The scientific community is an insider's club where results are doled out to keep people in their jobs.

• Review panels are stocked with friendlies, and grants are granted based on who you know rather than the quality of your work.

• If you're not part of the club, your work will never be challenged.

The Process of Discovering Truth in Science

In this section, Bret Weinstein discusses how science is supposed to be about discovering what is true, regardless of personal biases or preferences. He argues that science should not be played at a social level but rather based on evidence-based reasoning.

Discovering Truth in Science

• Science is supposed to be about discovering what is true, regardless of personal biases or preferences.

• Evidence-based reasoning should guide scientific inquiry rather than social connections or personal opinions.

• Scientists must challenge each other's work based on its merits rather than whether they like each other or agree with their conclusions.

The Significance of Evolutionary Theory

In this section, Bret Weinstein discusses the significance of evolutionary theory and how it has been validated by laboratory studies. He argues that the success of evolutionary theory should be celebrated and used to guide future scientific inquiry.

Validating Evolutionary Theory

• Evolutionary theory has made significant predictions without laboratory evidence based on theoretical reasoning alone.

• The recent discovery validates one of the major theoretical predictions from George Williams in 1967.

• This multi-generational success story should be celebrated and used to guide future scientific inquiry.

Conclusion

In this section, Bret Weinstein concludes that recent failures in science journalism and the insider's club mentality within the scientific community are concerning. He argues that science must be guided by evidence-based reasoning rather than personal biases or social connections.

Guiding Scientific Inquiry

• Recent failures in science journalism and the insider's club mentality within the scientific community are concerning.

• Science must be guided by evidence-based reasoning rather than personal biases or social connections.

• Scientists must challenge each other's work based on its merits rather than whether they like each other or agree with their conclusions.

The Importance of Hypothesis-Driven Science

In this section, the speaker discusses the importance of hypothesis-driven science and how it differs from data-driven science. He argues that without a clear hypothesis, scientific work is not a test of anything.

Hypothesis-Driven vs Data-Driven Science

• Hypothesis-driven science involves starting with a question or hypothesis and designing experiments to test it.

• Data-driven science involves collecting large amounts of data and then searching for patterns or correlations.

• Without a clear hypothesis, scientific work is not a test of anything.

• Poking around in the dark is not what science is supposed to be doing.

Telomeres in Mice

In this section, the speaker discusses an article about telomeres in mice and how it relates to the importance of hypothesis-driven science. He argues that scientists need to be careful when interpreting data and should always start with a clear hypothesis.

Telomeres in Mice

• A New York Times article reported that mice have crazy long telomeres despite having short lifespans.

• Another article explains that captive rodent breeding protocols designed to increase reproductive output simultaneously exert strong selection against reproductive senescence and virtually eliminates senescence that would otherwise favor tumor suppression.

• These animals are unreliable models of normal senescence and tumor formation safety tests employing these animals likely overestimate cancer risks and underestimate tissue damage and consequent accelerated senescence.

• Scientists need to be careful when interpreting data and should always start with a clear hypothesis.

Failure of Science Journalism

In this section, the speaker discusses the failure of science journalism and how it is related to the failure of scientists to do their job properly. The speaker also talks about how the narrative of evolutionary biology can be threatening to something that is in a position to snuff it out.

Failure at Journalism Level

• The failure is at the journalism level but first it's at the scientist level.

• Scientists are supposed to be doing science and claiming to be doing science, but they fail in their job.

• The failure of scientists leads to a failure in science journalism.

Threatening Narrative

• The narrative of evolutionary biology can be threatening to something that is in a position to snuff it out.

• This story has dramatic implications about human health and our capacity for future science.

• There are two schools of thought on what happened with the Vioxx scandal, and our school of thought has just scored a major triumph.

Importance of Track Record

In this section, the speaker emphasizes the importance of track record when making scientific claims. They discuss how Nobel Prize winners like Carey Mullis and Luke Montagne came into arguments with official sanction from their awards.

Official Sanction

• Nobel Prize winners like Carey Mullis and Luke Montagne came into arguments with official sanction from their awards.

• When you say something surprising, your track record is supposed to cause people to calibrate.

• The chances that they were wrong just because they didn't get it was pretty damn low because they had gotten it to a level that exceeded what most people do in a career.

Importance of Track Record

• The point is, you are supposed to take your track record into that battle.

• Your track record should cause people to calibrate when you say something surprising.

Cancer Protective Mechanism

In this section, the speaker talks about how the idea that we grow feeble because we have a cancer protective mechanism was not interesting to Nature's audience at first. They also discuss how this idea came from laboratory science rather than evolutionary biology.

Vindication

• It is sort of fun to have the vindication of now everybody seems interested in the idea.

• The fact that the idea came from laboratory science rather than evolutionary biology is fascinating.

The Importance of Carefulness and Thoroughness in Scientific Publication

In this section, the speaker discusses the importance of carefulness and thoroughness in scientific publication. They explain that there should be a system in place to ensure that research meets a certain standard before it is published, but unfortunately, such a system does not exist.

The Flaws in the Current System

• There is no system in place to ensure that research meets a certain standard before it is published.

• The current system is more likely to force researchers to exclude important information in order to get their work published.

• Bad science being sold by bad journalism has caused harm during the COVID pandemic.

Frustration with the Current System

• The lack of a proper system for ensuring carefulness and thoroughness is deeply frustrating for the speaker.

• The flaws in the current system are simultaneously a vindication and a slap in the face for those who value scientific rigor.

• Many have resolved to learn nothing from past mistakes, which means future problems will likely be worse.

Conclusion

• Despite these frustrations, there is still much to learn about how we can improve scientific publication.