2020-01-18
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Here's a quote from:

	The Portal -podcast

	with

	Eric and Bret Weinstein

	Published: January 16, 2020

	https://www.listennotes.com/podcasts/
	the-portal/19-bret-weinstein-the-RVBSJILtuFm/ 

I have taken some shortcuts while writing this down, but I tried
to keep the essence of the interview intact.
	
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BRET: As an undergraduate I took lots of mechanism classes.
I took a development class, I took some immunology, or
immunobiology. Anyway, I was armed with these things in an 
environment in evolutionary biology where most people were not.
Most people were in the phenomenology.

One day I happened to be in a seminar and a student was there
who was very out of place. He was studying cancer and had on a
lark decided to take an evolution seminar that looked good on
the catalogue. It wasn't right for him. He gave a talk at some
point and his talk was on his work with cancer. And frankly,
because all the other people in the room were evolutionarily
oriented, nobody was really tracking what he was saying. But
what he said struck me like a bolt of lightning. He said that
in the realm of cancer research people were looking at telomeres
which were these repeatitive sequences at the ends of 
chromosomes and they were toying with the possibility that
the fact that these telomeres shorten every time a cell divides,
that that is providing resistance to tumor formation. Very 
straightforward.

The theory of antagonistic pleiotropy was well established at
the time, but in four decades of research on the genome no one
had found a gene that matched the theory. The mechanism was
missing. I was well aware of Williams' paper at the time I saw
this talk on cancer and I knew already of the question of 
senescense [biological aging]. 

Everything came together. This was obviously the answer.
Telomere was not exactly a gene, but it was genetic and 
perfectly capable of producing exactly the effects we see in
senescense across the body.

I saw this instantly and raised my hand and tried to articulate
it. I couldn't compel a single person in the room. They couldn't
even understand what I was trying to say.

The idea is that a limit on cellular reproduction is adaptive
to protect you from cancer.

ERIC: It's a little bit of a mind bender, because what you are
telling me is that I've got to avoid immortality which can
kill me, and that the solution to not dying is death.

BRET: Yes, and what selection does is it balances these two
competing forces to give you as much vigor and longetivity
as it can.

When I went into the literature I found that people had played
around in the neighborhood but there was a particular fact which
blocked every attempt to make sense of what was going on. The fact
was that rodents were understood to have ultra-long, hypervariable
telomeres.

Mice have long telomeres and short lives, why is that? I banged 
my head on the table a couple of weeks trying to figure out what
was going on.

I begun to wonder if there was something wrong with the idea that
mice had long telomeres. Sometimes, like in Hayflick's case, 
turned out that a bunch of people were copying a wrong result so
it seemed that a lot of people had seen it. Was it that everybody
was parroting one study that mice had long telomeres? Turns out
a lot of people had tested it: Mice have long telomeres. Ten times
the length of human telomeres. It just didn't fit.

Finally it occurred to me that it was possible that what was going
on... I discovered something in trying to figure out what they
meant by mice. There's a lot of species of mice, but all the mice
we use in the lab, with the rare exception, are from one genus
and often from a particular target species.

What shocked me was that all the Mus musculus that were being used
in labs across the country and often farther afield than that
were coming from one place. Which I had no idea. There was one...

ERIC: I remember getting the phone call: "What do you know about
the Jax Lab?"

BRET: The Jax Lab, Bar Harbor, Maine, right? They seemed to be
the source of everybody's mice! It was a possibility I could not
shut down in my mind that there was something about what was
going on in Jax Lab that had resulted in the mice being sent out
to all these other laboratories...

ERIC: As if they were the representative animals...

BRET: Right, these are model organisms. People were using mice
because mice were a convenient mammal. But they are all coming
from one place. And it begun to occur to me that the one place
was not just a source of mice. It was a selective environment
that was impacting those mice. And when I dug deeper I found
that the mice were descendents of a long lineage that had lived
in captivity under the conditions of the Jax Lab. There was
something in this environment that had wildly elongated the
telomeres of these mice. That was an unbelievable idea but the 
only one I could think of that made sense of everything I had 
seen.

ERIC: It's unbelievable because of the consequences... I have not
even heard whether anyone has said "yeah, we did that, we screwed
that up". Your favourite organism of mammalian trials being
screwed up by a central facility. 

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