WEBVTT - Insulin (featuring Dr. Katrine Whiteson)

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<v Speaker 1>We as humans were scared that we were going to

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<v Speaker 1>unleash some kind of monster. What were the consequences of

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<v Speaker 1>us genetically engineering things? I mean, more recently, we've had

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<v Speaker 1>similar debates about crispers, And maybe you've heard that there

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<v Speaker 1>was even a case where a Chinese scientist used crisper

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<v Speaker 1>to genetically engineer a baby, a human that has really

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<v Speaker 1>really big ethical questions, And this was happening only in bacteria,

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<v Speaker 1>but it was the first time it had happened, and

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<v Speaker 1>we were rightfully, really thinking carefully about what the consequences

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<v Speaker 1>could be. For example, imagine you cloned a bacteria that

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<v Speaker 1>contained genes that could break down petroleum, and then you

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<v Speaker 1>unleashed that in an oil mining operation. You could really

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<v Speaker 1>cause a lot of destruction. And what if that was

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<v Speaker 1>just impossible to control and then you destroyed huge natural

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<v Speaker 1>resources unintentionally intentionally for that matter. So those were the

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<v Speaker 1>kinds of questions people were worried about.

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<v Speaker 2>Or what if it helped the bactery organize and it

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<v Speaker 2>crawled out of the vat and like extracted vengeance for

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<v Speaker 2>all the brethren that we've tortured in order to extract

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<v Speaker 2>incident from them.

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<v Speaker 1>That's a great question, but I'm pretty sure about it.

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<v Speaker 2>That's a very polite answer to a totally bonkers questionin

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<v Speaker 2>you all should have seen her face.

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<v Speaker 1>That didn't make it to the top ten list for

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<v Speaker 1>discussion out of so lamar.

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<v Speaker 3>Hi.

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<v Speaker 2>I'm Daniel. I'm a particle physicist and a member of

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<v Speaker 2>the White Senn Research Institute in Irvine, and today I'm

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<v Speaker 2>going to be an extra big fan of biology.

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<v Speaker 3>Hello, I'm Kelly Wiener Smith. Can I be like an

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<v Speaker 3>adjunct at the White sin Research Institute?

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<v Speaker 1>Like?

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<v Speaker 3>Is that what friends are called?

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<v Speaker 2>Come be a visiting professor? No problem? Yes, all right?

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<v Speaker 3>Does that come with dinner?

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<v Speaker 2>Dinner is a bonus? Yes? Plus you can add this

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<v Speaker 2>as an extra affiliation on all of your papers to

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<v Speaker 2>make you sound really.

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<v Speaker 3>Smart, fantastic. I'm go to you. I'm gonna put it

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<v Speaker 3>right on my CV. Have you ever done a show

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<v Speaker 3>with your wife before?

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<v Speaker 2>I have never done a podcast episode with Katrina, though

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<v Speaker 2>I've had lots and lots of science conversations over the

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<v Speaker 2>dinner table, so we definitely talked a lot about science

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<v Speaker 2>and board our teenagers to death. But no, I don't

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<v Speaker 2>think it's ever been recorded. So this is great for posterity.

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<v Speaker 3>Well, and I'm excited because we have talked on the

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<v Speaker 3>show often about how, you know, since she studies microbiome stuff,

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<v Speaker 3>sometimes you find bags of poop in your freezer and

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<v Speaker 3>stuff like that, and I feel like it's really important

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<v Speaker 3>for people to like put a voice to those stories.

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<v Speaker 3>And today that's gonna happen.

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<v Speaker 2>You just want another poop in the freezer ally on

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<v Speaker 2>the show to outvote me. That's what's going on here, really,

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<v Speaker 2>I do.

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<v Speaker 3>I want the gross votes to outnumber the people who

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<v Speaker 3>are squeamish. And also I like, you know, pushing the

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<v Speaker 3>envelope in the direction of gross so that I don't

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<v Speaker 3>seem as gross, you know, Like, mostly I want Zach

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<v Speaker 3>to realize how lucky he is. Yeah, that there's not

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<v Speaker 3>bags of poop in the freezer like the dead bird.

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<v Speaker 3>Not a big deal.

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<v Speaker 2>All right, Well, welcome to the podcast where we pretend

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<v Speaker 2>to be talking about science, but really we're doing marital therapy.

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<v Speaker 3>Well, and on today's show, we're very lucky to have

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<v Speaker 3>Katrina come on to talk to us about diabetes and

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<v Speaker 3>the history of insulin production and the future of insulin production.

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<v Speaker 3>And she was amazing. She had a lot of incredible insights.

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<v Speaker 2>Yeah, I think a lot of people think they understand

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<v Speaker 2>diabetes generally, but there's a lot of really fascinating biochemistry

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<v Speaker 2>and a lot of nuance there, and a lot to

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<v Speaker 2>understand about the daily life of somebody with diabetes. And

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<v Speaker 2>it's kind of amazing that until about one hundred years ago,

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<v Speaker 2>diabetes was a death sentence. You got diabetes and you

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<v Speaker 2>were dead a couple years later. And now because of

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<v Speaker 2>amazing biologists, we can save the lives of all those kids,

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<v Speaker 2>and people like my wife can grow up and be

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<v Speaker 2>like a professor and had kids and live a full life.

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<v Speaker 2>It's really kind of an amazing testament to what science

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<v Speaker 2>can do.

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<v Speaker 3>And I'm not going to release any spoilers here, but

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<v Speaker 3>there were at least two things she talked about where

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<v Speaker 3>I was like, I thought I knew and I was

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<v Speaker 3>totally wrong. And so I think we're gonna have a

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<v Speaker 3>good episode of sort of dispelling rumors or myths about diabetes.

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<v Speaker 2>All right, Well, then, without further ado, let's welcome my

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<v Speaker 2>favorite scientist at the whites And Research Institute. So then

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<v Speaker 2>today it's my great pleasure to welcome to the podcast.

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<v Speaker 2>Co president of the White Sun Research Institute and winner

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<v Speaker 2>of the whites In Research Prize as Professor Katrina whites

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<v Speaker 2>In at uc Irvine Katriina, Welcome to the podcast.

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<v Speaker 1>Thank you.

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<v Speaker 3>I'm so excited you're here.

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<v Speaker 1>I didn't even know about those awards, but I will.

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<v Speaker 2>I guess I'll go update your CV right now.

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<v Speaker 3>Update your tenure packet, all the things.

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<v Speaker 2>Yeah, but we did just invite Chain onto the podcast

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<v Speaker 2>to joke around with her. We invited her on because

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<v Speaker 2>she's a deep expert in today's topic.

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<v Speaker 3>So today we're talking about bioengineering bacteria, we're talking about diabetes,

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<v Speaker 3>we're talking about lydia villa comarov and it's going to

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<v Speaker 3>be an amazing conversation and we're super excited to have

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<v Speaker 3>you here.

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<v Speaker 1>Thank you.

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<v Speaker 3>So by the end of the episode, we're going to

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<v Speaker 3>get to bacteria producing pharmaceutical components. But let's start by

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<v Speaker 3>talking about diabetes. What are the mechanisms underlying diabetes.

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<v Speaker 1>Well, that's a really good question, and actually even just

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<v Speaker 1>using the word diabetes already doesn't give you quite enough

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<v Speaker 1>information to be able to answer that question, because there's

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<v Speaker 1>two really different forms of diabetes. I guess we could

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<v Speaker 1>go back to ancient times when the word first arose,

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<v Speaker 1>and in that time we understood that sugar was involved

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<v Speaker 1>and that not being able to process sugar was involved.

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<v Speaker 1>We've actually known that for hundreds of years, so you

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<v Speaker 1>could think of glucose as maybe the first biomarker. There

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<v Speaker 1>were really interesting ways that people would detect that someone

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<v Speaker 1>had diabetes. It's actually diabetes melitis, and the words mean

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<v Speaker 1>that you're losing water due to sugar. And people would

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<v Speaker 1>take urine and put it out to see if the

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<v Speaker 1>ants were attracted to it. They would taste the urine

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<v Speaker 1>to see if it was sweet, and that would give

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<v Speaker 1>them a clue that you had this wasting disease where

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<v Speaker 1>your body couldn't process sugar. And like, probably the first

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<v Speaker 1>thing that pops into mind when you think of diabetes

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<v Speaker 1>in modern times is it's associated with obesity, But actually

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<v Speaker 1>diabetes is a wasting disease. It means that you can't

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<v Speaker 1>get energy from sugar and you actually starve to death

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<v Speaker 1>while drowning with lots of sugar in your blood. So

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<v Speaker 1>I think that's just actually really amazing and usually counterintuitive.

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<v Speaker 1>When I'm teaching, I sometimes show images of the children

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<v Speaker 1>who would die from diabetes before the insulin was discovered,

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<v Speaker 1>and they are emaciated because they're unable to get any

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<v Speaker 1>energy from the sugar that they're eating. So to back up,

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<v Speaker 1>I mean, there's two main kinds of diabetes. The first one,

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<v Speaker 1>type one diabetes for a while even called juvenile diabetes,

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<v Speaker 1>is when your immune system kills the cells in your

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<v Speaker 1>pancreas that make insulin, so you're no longer able to

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<v Speaker 1>access sugar. So you eat sugar. It gets into your blood,

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<v Speaker 1>but the key that allows the sugar to be used

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<v Speaker 1>by your cells is just totally missing.

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<v Speaker 2>And so you're saying, insulin is that key. Insulin is

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<v Speaker 2>a thing that takes sugar from your blood and into

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<v Speaker 2>your cells exactly.

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<v Speaker 1>Insulin is a protein like ham, but it's acting like

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<v Speaker 1>a little it's a little robot. It's a little key

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<v Speaker 1>that actually summons the transporters that help glucose get into

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<v Speaker 1>your cell up to the surface and then the gates

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<v Speaker 1>open and the sugar can get into the cells. Without that,

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<v Speaker 1>the sugar just sits in your blood and the cells starve.

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<v Speaker 3>Is there a toxic effect of the sugar building up

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<v Speaker 3>as well? Or is it just that you're starving? Is

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<v Speaker 3>the main problem the long term?

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<v Speaker 1>The sugar in your blood is super toxic. But those

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<v Speaker 1>are kind of like decade long problems. So if you're

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<v Speaker 1>dealing with starving in the course of weeks or months,

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<v Speaker 1>then the decade long problem of too much sugar in

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<v Speaker 1>your blood is just not something to worry about. But yes, hope,

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<v Speaker 1>too much sugar in your blood is definitely toxic. And

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<v Speaker 1>I think that's the part that's more famous about diabetes

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<v Speaker 1>right now, because most diabetes in our time, ninety percent

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<v Speaker 1>of diabetes is what we called type two diabetes, and

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<v Speaker 1>it can be lifestyle associated, but amazingly, it's actually more genetic.

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<v Speaker 1>It's more inherited to get type two diabetes. So about

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<v Speaker 1>ninety percent of the diabetes in the world right now

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<v Speaker 1>emerges usually later in life, and it's not because you

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<v Speaker 1>don't have insulin. You could actually have plenty of insulin,

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<v Speaker 1>it's just not working very well, so your body is

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<v Speaker 1>resistant to the use of the insulin. That's associated with

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<v Speaker 1>metabolic syndrome, but actually can be quite genetic. You can

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<v Speaker 1>be a very healthy, thin looking person and still get

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<v Speaker 1>type two diabetes. So that's also a bit of a

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<v Speaker 1>misnomertis always assume it's associated with lifestyle, but in the

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<v Speaker 1>case of type two diabetes, if it is arising because

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<v Speaker 1>of obesity, you can reverse it if you eat less carbs,

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<v Speaker 1>exercise more, and in general it don't overload the system

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<v Speaker 1>that depends on insulin. You can resensitize your body to

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<v Speaker 1>the insulin that it can make, and you can also

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<v Speaker 1>take medicines that make the insulin more effective.

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<v Speaker 2>All right, so let me recap for the non biologists.

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<v Speaker 2>You eat a ham sandwich, your body turns some of

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<v Speaker 2>that into sugar, puts it into your blood, but then

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<v Speaker 2>your cells and your body, like your muscles, can't access

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<v Speaker 2>it from your blood without insulin, this thing that takes

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<v Speaker 2>it from the blood into the cells. And type one

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<v Speaker 2>diabetes is when your body kills the cells to produce insulin,

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<v Speaker 2>so you just don't have it. Type two is when

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<v Speaker 2>you still have insulin, but because of some metabolic things,

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<v Speaker 2>it's not working as well, or it's just not.

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<v Speaker 1>As effective, or you just don't have enough. Yeah, that's

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<v Speaker 1>about right. There's a lot of nuances you will not

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<v Speaker 1>be surprised to hear. For example, your brain, which uses

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<v Speaker 1>about twenty percent of the glucus in your body, doesn't

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<v Speaker 1>really depend on insulin in the same way. So I

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<v Speaker 1>find that kind of amazing that your brain is just

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<v Speaker 1>like this constant machine that's using a lot of the

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<v Speaker 1>sugar in your blood. It's like the main reason it's

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<v Speaker 1>so important that our blod glucose levels are maintained at

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<v Speaker 1>a certain level, otherwise your brain doesn't function. So that's

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<v Speaker 1>kind of independent of the insulin. And then there's other

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<v Speaker 1>really cool exceptions, like your muscles, especially during exercise, they're

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<v Speaker 1>extra sensitive to being able to get glucose in. So

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<v Speaker 1>there are extreme examples, Like there's a story about a

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<v Speaker 1>guy one hundred years ago before there was really insulin,

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<v Speaker 1>who kept himself alive with like a really crazy exercise

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<v Speaker 1>regiment and he had like amazing muscle mass and he

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<v Speaker 1>kind of like extended his capacity to metabolize his diet

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<v Speaker 1>even though he didn't have much insulin. So it's kind

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<v Speaker 1>of interesting we didn't do more of that, but on average, yeah,

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<v Speaker 1>without insulin, your blood will be full of sugar and

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<v Speaker 1>your cells will be starving. And if you look at

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<v Speaker 1>a picture of a kid who died from type one

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<v Speaker 1>diabetes before nineteen twenty one, when insulin was discovered, they

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<v Speaker 1>look emaciated, which is just terrible so.

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<v Speaker 2>You're starving, but your blood is filled with sugar and

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<v Speaker 2>your pea is filled with sugar. You just don't have

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<v Speaker 2>access to it. So it's like being hungry at a buffet.

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<v Speaker 2>It's crazy.

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<v Speaker 1>Yeah, exactly.

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<v Speaker 3>Do you know this story of how we discovered insulin.

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<v Speaker 1>Yeah, I mean, there's actually a lot of really good

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<v Speaker 1>stories around that. It was a slow process like science

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<v Speaker 1>often is, because we got a lot of important clues

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<v Speaker 1>even maybe half a century before the discovery of insulin,

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<v Speaker 1>Like we knew for a long time, hundreds of years

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<v Speaker 1>that it was related to glucose. So then by the

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<v Speaker 1>eighteen eighties in Germany, there were scientists who figured out

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<v Speaker 1>that if you removed the pancreas from a dog, it

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<v Speaker 1>would cause essentially the symptoms of diabetes.

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<v Speaker 2>What were they doing. Were they just like taking random

0:11:31.240 --> 0:11:32.760
<v Speaker 2>organs out of dogs one at a time to see

0:11:32.760 --> 0:11:35.080
<v Speaker 2>what happens, Like, let's see what happens that dogs don't

0:11:35.080 --> 0:11:36.920
<v Speaker 2>have a heart. Oh that didn't work very well.

0:11:37.679 --> 0:11:41.120
<v Speaker 1>Yeah, I guess that's not diabetes related. Good question. I mean,

0:11:41.320 --> 0:11:43.480
<v Speaker 1>you know it could be that like some unlucky dog

0:11:43.559 --> 0:11:46.040
<v Speaker 1>got kicked by a cow or hit by There weren't

0:11:46.080 --> 0:11:47.760
<v Speaker 1>cars in those days, but hit by a horse.

0:11:47.800 --> 0:11:50.320
<v Speaker 3>I guess we did do some pretty awful things to

0:11:50.360 --> 0:11:52.800
<v Speaker 3>animals in the past. It wouldn't surprise me if there

0:11:52.840 --> 0:11:54.719
<v Speaker 3>were a series of experiments we were like, how do

0:11:54.800 --> 0:11:56.480
<v Speaker 3>they do without this? How about without that?

0:11:56.880 --> 0:11:59.640
<v Speaker 2>In the past, biologists are still doing horrible things to animals,

0:11:59.679 --> 0:12:00.959
<v Speaker 2>and the name of science.

0:12:00.720 --> 0:12:04.320
<v Speaker 3>We have to go through complicated protocols and institutions and

0:12:04.440 --> 0:12:08.440
<v Speaker 3>prove that those animals are needed for scientific discovery these days.

0:12:08.480 --> 0:12:10.240
<v Speaker 3>But that could be a whole different episode.

0:12:09.920 --> 0:12:11.920
<v Speaker 2>Unless you want to do experiments on your own children,

0:12:11.960 --> 0:12:13.720
<v Speaker 2>in which case you don't have to ask an IRB,

0:12:14.200 --> 0:12:15.840
<v Speaker 2>but you should ask your husband.

0:12:17.160 --> 0:12:19.720
<v Speaker 1>But if you're the parent, you could also ask yourself,

0:12:19.840 --> 0:12:27.199
<v Speaker 1>especially if it's like something very low risk. This is

0:12:27.240 --> 0:12:29.000
<v Speaker 1>a case where I could try to look up the

0:12:29.080 --> 0:12:31.440
<v Speaker 1>eighteen eighty nine story that I have in my brain

0:12:31.480 --> 0:12:34.319
<v Speaker 1>about the pancreas. But anyway, somehow they realized that there

0:12:34.400 --> 0:12:38.560
<v Speaker 1>was a connection between pancreas being missing and diabetes. So

0:12:38.679 --> 0:12:41.040
<v Speaker 1>then that sounds like the kind of thing where it

0:12:41.040 --> 0:12:43.160
<v Speaker 1>shouldn't have taken more than a couple of months to

0:12:43.200 --> 0:12:47.080
<v Speaker 1>go from knowing it was the pancreas to extracting insulin

0:12:47.160 --> 0:12:49.400
<v Speaker 1>from the pancreas so that you could save all these

0:12:49.559 --> 0:12:52.840
<v Speaker 1>kids who were dying from diabetes. But it wasn't until

0:12:52.880 --> 0:12:57.280
<v Speaker 1>nineteen twenty one, twenty two that we finally extracted insulin

0:12:57.320 --> 0:13:00.520
<v Speaker 1>from the pancreas. A lot of that time went to

0:13:01.240 --> 0:13:05.360
<v Speaker 1>figuring out how to purify the insulin protein away from

0:13:05.440 --> 0:13:08.840
<v Speaker 1>all the other digestive enzymes and proteins that are also

0:13:08.920 --> 0:13:11.640
<v Speaker 1>produced by the pancreas. So you know, your pancreas is

0:13:11.679 --> 0:13:14.520
<v Speaker 1>this organ that's there to help you digest stuff. One

0:13:14.559 --> 0:13:18.600
<v Speaker 1>of its main jobs is to produce proteins that break

0:13:18.679 --> 0:13:22.240
<v Speaker 1>down our food, and those are also made of protein.

0:13:22.360 --> 0:13:26.240
<v Speaker 1>So basically the pancreas is full of stuff that destroys insulin,

0:13:26.400 --> 0:13:29.880
<v Speaker 1>since insulin is also a protein, so like separating those

0:13:29.880 --> 0:13:32.480
<v Speaker 1>things away from each other. It took forty years or

0:13:32.559 --> 0:13:34.559
<v Speaker 1>thirty years. That's a really hard thing to do. Now,

0:13:34.600 --> 0:13:36.080
<v Speaker 1>that's the kind of thing we're really good at, but

0:13:36.120 --> 0:13:38.280
<v Speaker 1>in those days we had to invent a bunch of

0:13:38.320 --> 0:13:39.480
<v Speaker 1>techniques to get good at that.

0:13:39.520 --> 0:13:42.280
<v Speaker 2>It's amazing to me how recently we have like any

0:13:42.320 --> 0:13:45.720
<v Speaker 2>idea what big organs in our body do. Like before that,

0:13:45.760 --> 0:13:47.360
<v Speaker 2>we're just like we don't know this is just a

0:13:47.360 --> 0:13:50.320
<v Speaker 2>blob of meat like stuff that seems to be important.

0:13:50.640 --> 0:13:52.360
<v Speaker 1>What I think is amazing is that when we don't

0:13:52.440 --> 0:13:55.200
<v Speaker 1>know what something does, we assume it's irrelevant. So like

0:13:55.559 --> 0:13:58.680
<v Speaker 1>we're always saying that the spleen and the appendix, for example,

0:13:58.960 --> 0:14:02.040
<v Speaker 1>serve no purpose. You know, you listen to them telling

0:14:02.120 --> 0:14:04.280
<v Speaker 1>you in the hospital when you're getting your appendix out, like, hey,

0:14:04.320 --> 0:14:06.320
<v Speaker 1>you don't need this, It'll be no big deal. I

0:14:06.320 --> 0:14:08.520
<v Speaker 1>find that really funny that when we don't understand something,

0:14:08.520 --> 0:14:11.560
<v Speaker 1>we just say it's irrelevant. Like that is definitely not true.

0:14:11.679 --> 0:14:14.800
<v Speaker 1>In the case of the appendix, having your appendix there

0:14:14.840 --> 0:14:17.520
<v Speaker 1>as a reservoir for gut bacteria is like the difference

0:14:17.559 --> 0:14:19.880
<v Speaker 1>between life and death. To be able to recede your

0:14:20.160 --> 0:14:23.640
<v Speaker 1>gut microbiome and be protected from infection in the future.

0:14:23.760 --> 0:14:26.320
<v Speaker 1>That was like clearly important enough that we developed an

0:14:26.400 --> 0:14:28.000
<v Speaker 1>organ and hung onto it, you know, and.

0:14:27.960 --> 0:14:29.960
<v Speaker 3>The evidence for that is really good now, right, that

0:14:29.960 --> 0:14:32.880
<v Speaker 3>that is the appendix's role to hold onto those bacteria.

0:14:33.040 --> 0:14:35.560
<v Speaker 1>I mean, it's a hypothesis that's hard to prove, right

0:14:35.600 --> 0:14:38.440
<v Speaker 1>because it's very context dependent. But if you think about

0:14:38.440 --> 0:14:41.360
<v Speaker 1>the context of human history, that seems like a very

0:14:41.400 --> 0:14:42.400
<v Speaker 1>relevant context.

0:14:42.560 --> 0:14:45.280
<v Speaker 2>It's biology. So the answer is it depends.

0:14:46.440 --> 0:14:49.960
<v Speaker 3>It's true. It's true. So they opened up the pancreas,

0:14:50.000 --> 0:14:52.000
<v Speaker 3>they've been able to divide out the different proteins that

0:14:52.040 --> 0:14:54.440
<v Speaker 3>are in there. How do you get from art I've

0:14:54.480 --> 0:14:57.760
<v Speaker 3>divided out the proteins to actually treating the disease. Was

0:14:57.760 --> 0:14:58.920
<v Speaker 3>that a pretty easy step?

0:14:59.440 --> 0:15:02.520
<v Speaker 1>That's a real cool question. And this all happened at

0:15:02.520 --> 0:15:05.440
<v Speaker 1>a university. It was at the University of Toronto, and

0:15:05.480 --> 0:15:09.120
<v Speaker 1>there was a medical student there that summer, Best, and

0:15:09.160 --> 0:15:12.920
<v Speaker 1>he was working with a lab supervisor, Banting. So Banting

0:15:12.960 --> 0:15:15.600
<v Speaker 1>and Best are the famous team who discovered insulin that

0:15:15.640 --> 0:15:19.680
<v Speaker 1>summer in Toronto. The second they had it purified out,

0:15:19.800 --> 0:15:23.360
<v Speaker 1>they started treating a dog who had had their pancreas

0:15:23.400 --> 0:15:26.640
<v Speaker 1>taken out, and they were able to keep a dog

0:15:26.680 --> 0:15:30.640
<v Speaker 1>alive for a couple of months using the dog insulin extract,

0:15:30.640 --> 0:15:33.440
<v Speaker 1>which was pretty crude. In the meantime, they also worked

0:15:33.480 --> 0:15:36.760
<v Speaker 1>on better purifying insulin from cows and that's when they

0:15:36.800 --> 0:15:39.680
<v Speaker 1>started considering using it to treat a child. And they

0:15:39.680 --> 0:15:41.120
<v Speaker 1>actually moved to this really quickly.

0:15:41.720 --> 0:15:42.240
<v Speaker 3>Interesting.

0:15:42.520 --> 0:15:44.880
<v Speaker 1>I would say that would still happen today because it

0:15:44.880 --> 0:15:48.200
<v Speaker 1>would definitely be a life or death circumstance. We still

0:15:48.240 --> 0:15:51.400
<v Speaker 1>have these compassionate use exemptions from the FDA, the Food

0:15:51.440 --> 0:15:53.680
<v Speaker 1>and Drug Administration. In fact, I use those for our

0:15:53.720 --> 0:15:57.560
<v Speaker 1>phage therapy trials, where if somebody has no other options,

0:15:57.640 --> 0:16:00.720
<v Speaker 1>we'll allow you to do with something more experimental. But

0:16:00.840 --> 0:16:03.920
<v Speaker 1>that means that this like lab guy, a med student

0:16:04.080 --> 0:16:08.920
<v Speaker 1>who was certainly not a professional at making medicines, was

0:16:09.000 --> 0:16:11.280
<v Speaker 1>just taking this extract they made in the lab. And

0:16:11.320 --> 0:16:13.840
<v Speaker 1>the first boy they treated was a Canadian boy at

0:16:13.880 --> 0:16:17.080
<v Speaker 1>the hospital at the University of Toronto. He was fourteen

0:16:17.240 --> 0:16:19.920
<v Speaker 1>and he was wasting away because he didn't have any insulin,

0:16:20.800 --> 0:16:23.800
<v Speaker 1>and he went from being very very ill with very

0:16:23.840 --> 0:16:27.560
<v Speaker 1>high blood sugar to doing much better, like within hours,

0:16:27.960 --> 0:16:31.000
<v Speaker 1>and then really soon after that. There's an image that

0:16:31.200 --> 0:16:33.800
<v Speaker 1>I think is super iconic to anybody who knows about

0:16:33.800 --> 0:16:36.280
<v Speaker 1>the discovery of insulin, and it's an image of a

0:16:36.400 --> 0:16:39.360
<v Speaker 1>nurse with a cart and maybe a doctor next to them,

0:16:39.680 --> 0:16:42.440
<v Speaker 1>and the story goes that they went into this ward

0:16:42.480 --> 0:16:45.320
<v Speaker 1>of the hospital that had thirty comatose children with type

0:16:45.320 --> 0:16:48.360
<v Speaker 1>one diabetes, and the parents were there, and then they

0:16:48.400 --> 0:16:51.640
<v Speaker 1>injected this very experimental cocktail they had made in the

0:16:51.720 --> 0:16:54.920
<v Speaker 1>lab into those thirty kids and they all woke up,

0:16:55.720 --> 0:16:58.320
<v Speaker 1>and you know, that was a really big moment in

0:16:58.360 --> 0:17:00.840
<v Speaker 1>science and must have been amazing for the parents who

0:17:00.880 --> 0:17:03.760
<v Speaker 1>really had no reason to hope their kids had any

0:17:03.840 --> 0:17:04.879
<v Speaker 1>chance of getting better.

0:17:05.240 --> 0:17:06.919
<v Speaker 2>I mean, if your kid is wasting away and the

0:17:06.960 --> 0:17:09.800
<v Speaker 2>doctor says, hey, we're going to inject this experimental dog

0:17:09.920 --> 0:17:12.720
<v Speaker 2>organ juice into your kid, you might just be like, yes,

0:17:12.800 --> 0:17:13.720
<v Speaker 2>do anything please?

0:17:13.880 --> 0:17:15.440
<v Speaker 1>Right? Yeah, exactly.

0:17:15.960 --> 0:17:19.160
<v Speaker 2>But how did we know that dog pancreas would produce

0:17:19.240 --> 0:17:22.239
<v Speaker 2>dog insulin which humans could use. Isn't it possibility that

0:17:22.280 --> 0:17:24.640
<v Speaker 2>like dog insulin could be different from human insulin.

0:17:25.440 --> 0:17:27.600
<v Speaker 1>Yeah, that's a really good point. I mean, I guess

0:17:27.680 --> 0:17:29.800
<v Speaker 1>we tried it and learned in the moment that first

0:17:29.880 --> 0:17:33.720
<v Speaker 1>fourteen year old was injected with insulin, we figured that out.

0:17:33.760 --> 0:17:38.320
<v Speaker 1>And we now know that the insulins across animals have

0:17:38.440 --> 0:17:43.399
<v Speaker 1>really shared features. So you know, animals that have guts

0:17:43.480 --> 0:17:48.040
<v Speaker 1>also have insulin basically, so insulin is very conserved. This system,

0:17:48.040 --> 0:17:50.960
<v Speaker 1>which might seem quite delicate, is being used across the

0:17:51.000 --> 0:17:55.800
<v Speaker 1>animal kingdom, and in general, the insulins are pretty exchangeable, so.

0:17:55.840 --> 0:17:58.159
<v Speaker 2>You could like extract insulin from a hummingbird and use

0:17:58.200 --> 0:17:59.120
<v Speaker 2>it on a person.

0:18:00.000 --> 0:18:02.800
<v Speaker 1>Well, hummingbird. Wow, you'd need a lot of hummingbirds. That's

0:18:02.840 --> 0:18:07.000
<v Speaker 1>a good question, but yeah, I think so. There was

0:18:07.040 --> 0:18:10.879
<v Speaker 1>actually a Czech couple, Eva and Victor Saxel, who fled

0:18:11.080 --> 0:18:15.440
<v Speaker 1>Nazi occupied Czechoslovakia in nineteen forty. She was teaching English

0:18:15.440 --> 0:18:18.159
<v Speaker 1>in Shanghai when her symptoms of diabetes developed when she

0:18:18.200 --> 0:18:20.920
<v Speaker 1>was around nineteen or twenty years old. By then, highly

0:18:20.920 --> 0:18:24.359
<v Speaker 1>purified insulin from cows was available in the pharmacies of Shanghai,

0:18:24.840 --> 0:18:27.320
<v Speaker 1>and people were living pretty healthy lives in the nineteen

0:18:27.359 --> 0:18:30.919
<v Speaker 1>forties when they had access to insulin. But then when

0:18:30.960 --> 0:18:34.320
<v Speaker 1>the Japanese occupied, those pharmacies shut down and Eva was

0:18:34.359 --> 0:18:36.439
<v Speaker 1>in a really tough spot. How was she going to

0:18:36.480 --> 0:18:40.119
<v Speaker 1>survive without access to insulin from pharmacies. And so this

0:18:40.240 --> 0:18:44.080
<v Speaker 1>is really an amazing tale of survival because Eva and

0:18:44.160 --> 0:18:46.359
<v Speaker 1>Victor they actually figured out they got their hands on

0:18:46.400 --> 0:18:48.959
<v Speaker 1>a book showing the method that Banting and Best had

0:18:49.000 --> 0:18:52.359
<v Speaker 1>developed for purifying insulin out of the pancreas. They didn't

0:18:52.359 --> 0:18:55.160
<v Speaker 1>have dogs or cows, but they figured out that they could.

0:18:55.480 --> 0:18:58.040
<v Speaker 1>They were knitting socks and selling them to get money

0:18:58.040 --> 0:19:01.920
<v Speaker 1>to buy water buffalo pancreases, and first they figured out

0:19:01.920 --> 0:19:04.719
<v Speaker 1>how to get the water buffalo insulin for Eva, but

0:19:04.760 --> 0:19:07.760
<v Speaker 1>they actually made enough to sustain hundreds of people with

0:19:07.840 --> 0:19:11.200
<v Speaker 1>diabetes in the ghetto of Shanghai. So hundreds of people

0:19:11.240 --> 0:19:14.040
<v Speaker 1>survived for the years of World War two depending on

0:19:14.119 --> 0:19:16.600
<v Speaker 1>the insulin that Eva and her husband were purifying out

0:19:16.640 --> 0:19:19.240
<v Speaker 1>of the water buffalo pancreas. It's really amazing.

0:19:19.480 --> 0:19:20.440
<v Speaker 3>Oh that's interesting.

0:19:20.960 --> 0:19:24.640
<v Speaker 1>There's another story like that in Chile of a husband

0:19:24.680 --> 0:19:28.000
<v Speaker 1>who learned how to extract insulin from any kind of animal,

0:19:28.240 --> 0:19:30.360
<v Speaker 1>and he was helping his wife survive. And I think

0:19:30.440 --> 0:19:33.440
<v Speaker 1>the issue actually was that she would develop immunity to

0:19:33.600 --> 0:19:36.399
<v Speaker 1>one kind of insulin, and not because of the insulin itself,

0:19:36.400 --> 0:19:38.760
<v Speaker 1>but the extract is never pure, so she basically would

0:19:38.760 --> 0:19:41.840
<v Speaker 1>develop allergies to the extract. So then he would move

0:19:41.880 --> 0:19:43.679
<v Speaker 1>on to another kind of animal. And I think she

0:19:43.720 --> 0:19:46.520
<v Speaker 1>didn't have access to pharmaceutical grade insulin, so he was

0:19:46.560 --> 0:19:47.880
<v Speaker 1>helping her survive that way.

0:19:48.160 --> 0:19:51.120
<v Speaker 2>Because insulin doesn't cure diabetes, right, it just helps get

0:19:51.160 --> 0:19:53.959
<v Speaker 2>the sugar across the cells. Right now, you need a

0:19:54.000 --> 0:19:56.320
<v Speaker 2>constant supply of insulin, right, Like, how long will the

0:19:56.359 --> 0:19:59.840
<v Speaker 2>type one diabetic live if insulin supply just gets shut off.

0:20:00.520 --> 0:20:02.640
<v Speaker 1>Yeah, just a couple days, And so you hear those

0:20:02.680 --> 0:20:05.119
<v Speaker 1>stories about the kids wasting away over the course of

0:20:05.160 --> 0:20:07.080
<v Speaker 1>a year or two. And that's at the beginning of

0:20:07.119 --> 0:20:10.359
<v Speaker 1>the disease when they still make some insulin. But somebody

0:20:10.400 --> 0:20:13.800
<v Speaker 1>who has developed long term type one diabetes and has

0:20:13.800 --> 0:20:15.960
<v Speaker 1>been dependent on insulin for a long time, they literally

0:20:16.000 --> 0:20:19.080
<v Speaker 1>have no insulin. And then it's not actually a matter

0:20:19.119 --> 0:20:21.719
<v Speaker 1>of starvation, like you wouldn't live long enough to starve

0:20:22.680 --> 0:20:25.280
<v Speaker 1>with type one diabetis and no insulin, because your blood

0:20:25.280 --> 0:20:28.240
<v Speaker 1>sugar would go very high. And then you go into

0:20:28.320 --> 0:20:31.680
<v Speaker 1>a state that's called ketosis, where your body starts producing

0:20:31.760 --> 0:20:35.960
<v Speaker 1>key tones, basically wasting away your muscles to get energy,

0:20:36.440 --> 0:20:39.719
<v Speaker 1>and that process produces a lot of acid, and you

0:20:39.760 --> 0:20:41.960
<v Speaker 1>basically die from the acid in your blood. It's like

0:20:41.960 --> 0:20:43.600
<v Speaker 1>when you hit the wall in a marathon and you

0:20:43.640 --> 0:20:45.960
<v Speaker 1>don't have any more glucose from your liver and muscles.

0:20:46.000 --> 0:20:48.639
<v Speaker 1>Your liver and muscles have glycogen stores, and so then

0:20:48.680 --> 0:20:51.000
<v Speaker 1>your body turns to breaking down the protein of your

0:20:51.080 --> 0:20:54.480
<v Speaker 1>muscles to get energy, and that process produces keytnes, which

0:20:54.480 --> 0:20:56.560
<v Speaker 1>are acidic, and then you die from the acid in

0:20:56.600 --> 0:20:57.080
<v Speaker 1>your blood.

0:20:57.600 --> 0:21:00.360
<v Speaker 2>So we can survive if we extract insulin from these

0:21:00.359 --> 0:21:02.800
<v Speaker 2>poor animals. But that's a destructive process, right You can't

0:21:02.800 --> 0:21:05.840
<v Speaker 2>extract insulin from a dog without killing the dog, or

0:21:05.920 --> 0:21:06.199
<v Speaker 2>can you?

0:21:06.480 --> 0:21:08.159
<v Speaker 1>The way it's done, as far as I know, has

0:21:08.200 --> 0:21:10.840
<v Speaker 1>always been destructive. And so I mean, this could lead

0:21:10.880 --> 0:21:13.520
<v Speaker 1>us to another interesting conversation about like, well, okay, we

0:21:13.560 --> 0:21:15.919
<v Speaker 1>made this discovery, so then how did we actually produce

0:21:16.000 --> 0:21:18.639
<v Speaker 1>enough insulin to keep the diabetics of the world alive

0:21:18.680 --> 0:21:22.359
<v Speaker 1>who need it every couple hours, you know, not just days.

0:21:23.280 --> 0:21:26.040
<v Speaker 3>And that seems like a great topic to ponder, And

0:21:26.080 --> 0:21:44.800
<v Speaker 3>we'll return to it after the break and we're back.

0:21:44.840 --> 0:21:47.040
<v Speaker 3>And so we had just finished discussing how it had

0:21:47.040 --> 0:21:49.800
<v Speaker 3>been figured out how you can extract the insulin protein

0:21:49.960 --> 0:21:52.879
<v Speaker 3>from deceased animals, and now we're talking about starting to

0:21:52.960 --> 0:21:55.239
<v Speaker 3>scale up so that we can provide this in an

0:21:55.280 --> 0:21:56.440
<v Speaker 3>industrial sort of way.

0:21:56.600 --> 0:21:59.159
<v Speaker 2>I have another question before we talk about industrial production

0:21:59.240 --> 0:22:02.080
<v Speaker 2>of insulin, which is a naive question, like if it's

0:22:02.119 --> 0:22:04.720
<v Speaker 2>about the pancreas producing insulin and your pancreas is not

0:22:04.760 --> 0:22:07.520
<v Speaker 2>making one, why can't you do a pancreas transplant, like

0:22:07.520 --> 0:22:09.840
<v Speaker 2>we can do a heart transplant or a kidney transplant

0:22:10.320 --> 0:22:12.199
<v Speaker 2>or other kinds of transplants. And why can't I just

0:22:12.520 --> 0:22:14.840
<v Speaker 2>get the pancreas from a human corpse and put it

0:22:14.880 --> 0:22:17.399
<v Speaker 2>into a diabetic and cure their diabetes.

0:22:18.240 --> 0:22:20.679
<v Speaker 1>You can do that actually, and you know, Canada has

0:22:20.720 --> 0:22:23.320
<v Speaker 1>been so important in all these diabetes developments and the

0:22:23.480 --> 0:22:27.680
<v Speaker 1>Edmonton Protocol was developed also in Canada. Point is, yes,

0:22:27.800 --> 0:22:30.680
<v Speaker 1>you can transplant a pancreas into a person, but then

0:22:30.720 --> 0:22:34.400
<v Speaker 1>you have to give them immunosuppressants. In order to survive

0:22:34.720 --> 0:22:37.920
<v Speaker 1>after an organ transplant, you have to take immunosuppressive drugs,

0:22:38.440 --> 0:22:41.600
<v Speaker 1>which mean that your risk of cancer and infectious disease

0:22:41.680 --> 0:22:43.960
<v Speaker 1>become very high. So to do that to a young

0:22:43.960 --> 0:22:47.560
<v Speaker 1>person who otherwise has a healthy life expectancy is dooming

0:22:47.600 --> 0:22:50.000
<v Speaker 1>them to a less healthy and shorter life.

0:22:50.160 --> 0:22:51.720
<v Speaker 3>I assume who would you do that for.

0:22:51.840 --> 0:22:54.480
<v Speaker 1>Then there's one context where it happens a lot, which

0:22:54.520 --> 0:22:57.240
<v Speaker 1>is really cool, which is if you have kidney failure,

0:22:57.280 --> 0:22:59.800
<v Speaker 1>which is also more common in people with diabetes, and

0:23:00.080 --> 0:23:03.159
<v Speaker 1>doing a kidney transplant, you can do a tandem transplant

0:23:03.200 --> 0:23:05.399
<v Speaker 1>of kidney and pancreas, and you have to take the

0:23:05.440 --> 0:23:08.679
<v Speaker 1>immunister presence anyway for the kidney transplant, so then you

0:23:08.720 --> 0:23:11.679
<v Speaker 1>get a bonus of no longer being diabetic, which is

0:23:11.680 --> 0:23:13.760
<v Speaker 1>great because it also protects the kidney. So that's a

0:23:13.840 --> 0:23:17.040
<v Speaker 1>really cool procedure, which is pretty common that people get

0:23:17.080 --> 0:23:19.560
<v Speaker 1>a kidney and a pancreas transplant together.

0:23:19.880 --> 0:23:21.840
<v Speaker 2>All right, So if you don't get a pancreas transplant,

0:23:21.840 --> 0:23:24.320
<v Speaker 2>you need your steady supply of insulin. And we were saying,

0:23:24.320 --> 0:23:26.600
<v Speaker 2>we don't want to just keep killing dogs in order

0:23:26.680 --> 0:23:29.359
<v Speaker 2>to in order to extract the insulin from their pancreas,

0:23:29.680 --> 0:23:32.320
<v Speaker 2>or rats of China or whatever, So then tell us

0:23:32.320 --> 0:23:35.240
<v Speaker 2>about how we produce insulin without killing all of our

0:23:35.240 --> 0:23:36.040
<v Speaker 2>furry friends.

0:23:36.160 --> 0:23:40.040
<v Speaker 1>Well, for many years between around nineteen twenty something and

0:23:40.400 --> 0:23:44.439
<v Speaker 1>the nineteen eighties, we relied on animals that we produce

0:23:44.520 --> 0:23:47.600
<v Speaker 1>for food, so cows and pigs were our main source

0:23:47.600 --> 0:23:51.239
<v Speaker 1>of insulin for all those years, and so that scaled up.

0:23:51.240 --> 0:23:54.879
<v Speaker 1>In the nineteen twenties. There were two main companies that emerged,

0:23:54.920 --> 0:23:56.919
<v Speaker 1>and there's lots of stories about how the patents all

0:23:56.960 --> 0:24:00.720
<v Speaker 1>worked out, but basically Eli Lilly in Indiana became the

0:24:00.880 --> 0:24:04.720
<v Speaker 1>US leader in producing insulin, and Novo Nordisk in Denmark

0:24:04.800 --> 0:24:07.879
<v Speaker 1>became the European leader and making insulin. Currently there's a

0:24:07.920 --> 0:24:11.399
<v Speaker 1>third producer, so Nofi, they're French. Ninety percent of the

0:24:11.400 --> 0:24:13.800
<v Speaker 1>insulin in the world is still produced by those three companies.

0:24:13.840 --> 0:24:16.600
<v Speaker 1>And initially all their insulin was coming from animals, and

0:24:16.640 --> 0:24:22.159
<v Speaker 1>so you would get pig pancreas or cow pancreas from butchers.

0:24:22.880 --> 0:24:25.800
<v Speaker 1>It became a very refined process, and I think it

0:24:25.880 --> 0:24:30.000
<v Speaker 1>took you know, a crazy amount of pig pancreas. I mean,

0:24:30.160 --> 0:24:33.320
<v Speaker 1>you know, it was like a thousand pounds of pancreas

0:24:33.359 --> 0:24:36.320
<v Speaker 1>would would lead to one pound of insulin being produced.

0:24:36.359 --> 0:24:39.040
<v Speaker 1>It took a lot of purification and so and we

0:24:39.160 --> 0:24:42.760
<v Speaker 1>kept that going, and this supply was quite widespread and

0:24:42.880 --> 0:24:45.680
<v Speaker 1>a lot of people's lives were sustained with that insulin.

0:24:45.880 --> 0:24:48.040
<v Speaker 1>I don't think we could have kept scaling up. So

0:24:48.119 --> 0:24:51.720
<v Speaker 1>it's very good we had an early and amazing advance

0:24:51.880 --> 0:24:55.600
<v Speaker 1>and changing how we produced insulin around the eighties. But yeah,

0:24:55.640 --> 0:24:59.040
<v Speaker 1>for all those years we were collecting pigs and cow

0:24:59.160 --> 0:25:04.119
<v Speaker 1>pancreas from butcher an extracting insulin from there. And actually

0:25:04.160 --> 0:25:06.679
<v Speaker 1>we know a few people like Daniel, our friend Mones.

0:25:07.040 --> 0:25:10.639
<v Speaker 1>His mom she worked at Nova NOORDESK and she was

0:25:10.680 --> 0:25:13.359
<v Speaker 1>one of the people who developed those procedures, or at

0:25:13.400 --> 0:25:16.960
<v Speaker 1>least she was involved, I know in extracting insulin from pigs.

0:25:17.000 --> 0:25:19.159
<v Speaker 1>A lot of people were involved in making that happen.

0:25:19.320 --> 0:25:21.199
<v Speaker 2>I wonder if that was complicated for some folks, like

0:25:21.240 --> 0:25:24.840
<v Speaker 2>people who were vegetarians but diabet and then they had

0:25:24.840 --> 0:25:27.520
<v Speaker 2>to essentially use this animal product. Or what if you

0:25:27.560 --> 0:25:30.000
<v Speaker 2>were like Hindu and didn't want to use cow insulin,

0:25:30.119 --> 0:25:32.879
<v Speaker 2>or your Muslim and you didn't want to use pig insulin. Yeah,

0:25:33.000 --> 0:25:35.240
<v Speaker 2>could people like choose which animal it came from.

0:25:35.560 --> 0:25:38.159
<v Speaker 1>Yeah? I never had to use animal insulin myself, so

0:25:38.240 --> 0:25:40.480
<v Speaker 1>I don't know, but yes, I think you could choose

0:25:41.320 --> 0:25:44.600
<v Speaker 1>which animal source it came from. That was part of

0:25:44.640 --> 0:25:47.560
<v Speaker 1>the what you knew about the product. That's one very

0:25:47.560 --> 0:25:50.560
<v Speaker 1>big issue. Another big issue is that people would typically

0:25:50.600 --> 0:25:54.080
<v Speaker 1>develop sensitivities or allergies to it over time, and then

0:25:54.119 --> 0:25:56.479
<v Speaker 1>it would be less effective. It was a solution in

0:25:56.520 --> 0:25:59.200
<v Speaker 1>many ways, and there are people who lived for decades

0:25:59.520 --> 0:26:02.639
<v Speaker 1>taking and cow insulin, but it wasn't as easy to

0:26:02.720 --> 0:26:04.800
<v Speaker 1>keep that going your whole life because a lot of

0:26:04.840 --> 0:26:07.640
<v Speaker 1>people developed sensitivities like allergies, you mean.

0:26:07.480 --> 0:26:09.880
<v Speaker 2>Like your immune system is responding because it's like, hey,

0:26:09.920 --> 0:26:12.479
<v Speaker 2>this is a cow product, not something from inside the body.

0:26:12.960 --> 0:26:15.400
<v Speaker 1>Yeah, I don't even think it was the insulin itself.

0:26:15.480 --> 0:26:17.800
<v Speaker 1>And despite all the purification I just talked about, I

0:26:17.800 --> 0:26:21.320
<v Speaker 1>think it was hard to remove everything allergenic about it,

0:26:21.400 --> 0:26:23.600
<v Speaker 1>so then you would develop immunity.

0:26:23.920 --> 0:26:27.520
<v Speaker 3>Were there any concerns about diseases passing from pigs and

0:26:27.560 --> 0:26:30.320
<v Speaker 3>cows to people or the purification process or to cleared

0:26:30.359 --> 0:26:30.680
<v Speaker 3>that out.

0:26:31.080 --> 0:26:34.080
<v Speaker 1>That's a really cool question, and there were actually concerns.

0:26:34.119 --> 0:26:36.080
<v Speaker 1>I don't think we even knew about it at the time,

0:26:36.200 --> 0:26:39.400
<v Speaker 1>but now there's a lot of concern about preon diseases,

0:26:39.600 --> 0:26:43.800
<v Speaker 1>and so actually diabetics are sometimes excluded from blood donation

0:26:44.000 --> 0:26:47.639
<v Speaker 1>and other kind of organ transplant because of concern for

0:26:47.760 --> 0:26:52.000
<v Speaker 1>preon diseases, especially coming from cows. So yeah, people who

0:26:52.520 --> 0:26:54.919
<v Speaker 1>have been having a lot of animal products like that,

0:26:55.080 --> 0:26:59.080
<v Speaker 1>in theory could have been exposed to preon diseases, which

0:26:59.119 --> 0:27:01.440
<v Speaker 1>I think were less and at that time, also because

0:27:01.440 --> 0:27:04.840
<v Speaker 1>of agricultural practices, like I think preon diseases became more

0:27:04.880 --> 0:27:08.920
<v Speaker 1>common towards the end of the twentieth century because we

0:27:08.920 --> 0:27:13.719
<v Speaker 1>were doing all this like feed animal waste, like chopped

0:27:13.800 --> 0:27:17.640
<v Speaker 1>up animal bits to the animals themselves, and that would

0:27:17.720 --> 0:27:21.720
<v Speaker 1>kind of concentrate the chances of preon diseases developing. And

0:27:21.760 --> 0:27:24.120
<v Speaker 1>that's better now. We know not to do that now.

0:27:24.600 --> 0:27:27.800
<v Speaker 3>And so you indicated in the nineteen eighties something changed.

0:27:28.000 --> 0:27:29.639
<v Speaker 3>What was the thing that changed.

0:27:29.480 --> 0:27:32.439
<v Speaker 1>Well, it's so amazing to me that this happened as

0:27:32.480 --> 0:27:34.800
<v Speaker 1>early as it did in the eighties. But we actually

0:27:34.800 --> 0:27:38.680
<v Speaker 1>figured out how to produce human insulin by fermenting it

0:27:38.720 --> 0:27:43.000
<v Speaker 1>in bacteria and sometimes yeast by the early eighties, and

0:27:43.080 --> 0:27:47.280
<v Speaker 1>so this was connected to the first genetically engineered organisms.

0:27:47.960 --> 0:27:50.560
<v Speaker 1>In the fifties and sixties, we made the discovery of DNA.

0:27:50.640 --> 0:27:54.200
<v Speaker 1>We understood the central dogma that DNA was the storage

0:27:54.240 --> 0:27:58.000
<v Speaker 1>material of biology and that it was a blueprint for

0:27:58.200 --> 0:28:02.280
<v Speaker 1>producing RNA and then protein insulin is a protein. You know,

0:28:02.320 --> 0:28:05.600
<v Speaker 1>it was only a decade or maybe twenty years after

0:28:05.640 --> 0:28:08.240
<v Speaker 1>we understood that that we were really making use of

0:28:08.240 --> 0:28:11.440
<v Speaker 1>that information, which I think is really cool. So by

0:28:11.480 --> 0:28:14.399
<v Speaker 1>the seventies, the hotbed of a lot of this activity

0:28:14.480 --> 0:28:19.040
<v Speaker 1>was California and also Boston. People were starting to clone

0:28:19.320 --> 0:28:21.119
<v Speaker 1>and like they were starting to be able to, like,

0:28:21.520 --> 0:28:24.879
<v Speaker 1>you know, use little molecular scissors to chop out a

0:28:24.920 --> 0:28:28.159
<v Speaker 1>piece of DNA from a bacteria and replace it with

0:28:28.240 --> 0:28:31.320
<v Speaker 1>another piece of DNA that encoded something you were interested in.

0:28:32.200 --> 0:28:34.000
<v Speaker 1>And so it's kind of interesting to me to think

0:28:34.040 --> 0:28:37.360
<v Speaker 1>about how these molecular biologists who were more like theoreticians

0:28:37.400 --> 0:28:39.880
<v Speaker 1>about the biology almost these weren't like doctors who were

0:28:39.920 --> 0:28:42.520
<v Speaker 1>thinking about solutions so much. But they're like, Hey, I

0:28:42.520 --> 0:28:45.520
<v Speaker 1>wonder what a good important protein to try to clone

0:28:45.520 --> 0:28:47.200
<v Speaker 1>would be. And they're like, hey, insulin. A lot of

0:28:47.240 --> 0:28:50.240
<v Speaker 1>people need that. Let's try that. And so one of

0:28:50.280 --> 0:28:53.600
<v Speaker 1>the first things that was involved in these early cloning

0:28:53.640 --> 0:28:56.480
<v Speaker 1>projects just to demonstrate, like, hey, can we clone stuff

0:28:56.520 --> 0:29:00.480
<v Speaker 1>in bacteria was insulin and so in the seven we

0:29:00.520 --> 0:29:03.520
<v Speaker 1>started to do that kind of cloning. And then around

0:29:03.600 --> 0:29:07.000
<v Speaker 1>the mid seventies there was this moment where everyone realized, like,

0:29:07.080 --> 0:29:08.920
<v Speaker 1>oh my god, what are we doing. If I, like

0:29:09.000 --> 0:29:13.040
<v Speaker 1>complete these experiments, have I just created something that could

0:29:13.120 --> 0:29:15.560
<v Speaker 1>go on and replicate and cause a lot of destruction.

0:29:15.720 --> 0:29:18.680
<v Speaker 1>And so there was actually a meeting in a Sillamart, California.

0:29:19.320 --> 0:29:21.880
<v Speaker 1>I think it was around nineteen seventy seven. We all

0:29:22.000 --> 0:29:26.200
<v Speaker 1>know this meeting, the Silamar meeting about the safety of

0:29:26.640 --> 0:29:30.920
<v Speaker 1>genetic engineering basically, and maybe one hundred and fifty people

0:29:30.920 --> 0:29:34.640
<v Speaker 1>were there, mostly scientists, but politicians too, and they had

0:29:34.640 --> 0:29:37.360
<v Speaker 1>a real look in the mirror, like what are we

0:29:37.440 --> 0:29:40.320
<v Speaker 1>doing and is this safe? And everybody halted their work

0:29:40.440 --> 0:29:43.160
<v Speaker 1>until the meeting so that we could decide what to do.

0:29:44.000 --> 0:29:47.280
<v Speaker 1>And during that meeting there were a lot of discussion

0:29:47.280 --> 0:29:49.680
<v Speaker 1>about whether it was okay, and in the end there

0:29:49.680 --> 0:29:52.480
<v Speaker 1>were rules around what you were allowed to do, but

0:29:52.640 --> 0:29:55.720
<v Speaker 1>it was decided that you could indeed proceed with cloning,

0:29:56.360 --> 0:30:02.480
<v Speaker 1>especially under controlled circumstances. So the project for cloning insulin

0:30:02.600 --> 0:30:05.360
<v Speaker 1>was one of the ones that halted until after that meeting,

0:30:05.720 --> 0:30:08.800
<v Speaker 1>and then once the decision was made that it was

0:30:08.840 --> 0:30:13.480
<v Speaker 1>okay to proceed, then the scientists continued with their cloning projects.

0:30:13.480 --> 0:30:15.920
<v Speaker 1>And so I think it was about around nineteen seventy eight,

0:30:15.920 --> 0:30:18.240
<v Speaker 1>which is also the year I was born, that the

0:30:18.320 --> 0:30:20.840
<v Speaker 1>first insulin cloning project was completed.

0:30:21.320 --> 0:30:23.080
<v Speaker 3>So when I hear the word clone, I think of

0:30:23.200 --> 0:30:25.480
<v Speaker 3>like copying and pasting and organism.

0:30:25.560 --> 0:30:25.920
<v Speaker 1>Mm hmm.

0:30:26.360 --> 0:30:30.240
<v Speaker 3>Is it you're essentially copying and pasting bacteria that now

0:30:30.280 --> 0:30:32.239
<v Speaker 3>have the human insulin gene. Is that the right way

0:30:32.280 --> 0:30:32.840
<v Speaker 3>to think about it?

0:30:33.160 --> 0:30:37.320
<v Speaker 1>Yeah, exactly, So the human insulin gene was copied and

0:30:37.440 --> 0:30:41.240
<v Speaker 1>pasted into a bacteria, and then they asked the bacterial

0:30:41.320 --> 0:30:44.400
<v Speaker 1>cell to grow and produce the insulin. Now, I just

0:30:44.440 --> 0:30:46.600
<v Speaker 1>made it sound really simple like there was just only

0:30:46.640 --> 0:30:48.680
<v Speaker 1>one thing that had to be copied in But to

0:30:48.720 --> 0:30:51.480
<v Speaker 1>be honest, a lot of genetic engineering had to happen

0:30:51.680 --> 0:30:53.880
<v Speaker 1>so that the insulin could be produced. They had to

0:30:53.920 --> 0:30:56.040
<v Speaker 1>make sure that all the ingredients were there, that it

0:30:56.160 --> 0:31:00.360
<v Speaker 1>was in a spot that the bacterial sell again its

0:31:00.360 --> 0:31:03.640
<v Speaker 1>own needs, was producing this protein. You know, it's not

0:31:03.680 --> 0:31:05.960
<v Speaker 1>like the bacteria needed the insulin, So they had to

0:31:06.000 --> 0:31:08.760
<v Speaker 1>kind of rewire some of the metabolic pathways to force

0:31:08.840 --> 0:31:11.520
<v Speaker 1>that to happen. So, to be honest, it was a

0:31:11.520 --> 0:31:15.560
<v Speaker 1>combination of real savvy and luck that insulin could be

0:31:15.600 --> 0:31:18.880
<v Speaker 1>produced that way. A lot of bacteria don't have the

0:31:18.960 --> 0:31:23.720
<v Speaker 1>right tools for making other kinds of modifications to proteins

0:31:23.720 --> 0:31:26.520
<v Speaker 1>that are common in eukaryotic cells, and so the fact

0:31:26.560 --> 0:31:28.720
<v Speaker 1>that they could do that a little bit was luck.

0:31:28.920 --> 0:31:32.320
<v Speaker 1>And when we look back at which bacteria were initially

0:31:32.440 --> 0:31:36.200
<v Speaker 1>chosen for some of these cloning projects, they were just random,

0:31:36.280 --> 0:31:39.120
<v Speaker 1>Like the most common Ecoli, the kind of bacteria this

0:31:39.200 --> 0:31:42.000
<v Speaker 1>was done and is called ecoli assure Shia coli. And

0:31:42.040 --> 0:31:44.680
<v Speaker 1>there's this really famous strain of E. Coli ecol I

0:31:44.840 --> 0:31:46.880
<v Speaker 1>K twelve that was the one that was used in

0:31:46.880 --> 0:31:51.040
<v Speaker 1>this project. And E. Coli K twelve was isolated from

0:31:51.040 --> 0:31:54.760
<v Speaker 1>a Stanford patient who had some kind of infectious disease.

0:31:54.800 --> 0:31:58.960
<v Speaker 1>I think diphtheria just randomly taken from this person's gut,

0:32:00.080 --> 0:32:02.800
<v Speaker 1>and then it happened to have properties that were good

0:32:02.840 --> 0:32:05.440
<v Speaker 1>for cloning. Like I have equal IK twelve in my lab.

0:32:05.520 --> 0:32:08.240
<v Speaker 1>All biologists no equal IK twelve, but it's just like

0:32:08.320 --> 0:32:11.680
<v Speaker 1>a random Standford patient from the nineteen twenties ecoli.

0:32:12.080 --> 0:32:14.280
<v Speaker 2>I have some basic questions about how this works, like

0:32:14.320 --> 0:32:17.240
<v Speaker 2>why are we using bacteria? Is it just like the

0:32:17.320 --> 0:32:20.680
<v Speaker 2>simplest unit that we think we could still genetically engineer.

0:32:21.200 --> 0:32:24.400
<v Speaker 2>Why can't we genetically engineer dogs to make human insulin?

0:32:24.680 --> 0:32:27.480
<v Speaker 1>I mean, I think we were using bacteria thinking that

0:32:27.480 --> 0:32:30.120
<v Speaker 1>that would be a really great way to scale up

0:32:30.440 --> 0:32:34.080
<v Speaker 1>and not have a combination of ethics and safety and

0:32:34.120 --> 0:32:37.280
<v Speaker 1>just production. How great is it if the same way

0:32:37.320 --> 0:32:39.960
<v Speaker 1>you brew beer you can brew insulin. You know, that

0:32:40.120 --> 0:32:43.120
<v Speaker 1>was the thinking. We're good at producing things with bacteria.

0:32:44.040 --> 0:32:48.680
<v Speaker 1>Yogurt beer beer is mostly yeast, but still bread. We

0:32:48.800 --> 0:32:53.360
<v Speaker 1>have microbial fermentation for food production really down, So the

0:32:53.440 --> 0:32:56.760
<v Speaker 1>idea was to pivot that towards making medicines.

0:32:57.000 --> 0:33:00.360
<v Speaker 2>I see, so bacteria can't make cute puppy eyes, care

0:33:00.400 --> 0:33:03.160
<v Speaker 2>about growing them up and slaughtering them all for our.

0:33:03.040 --> 0:33:05.880
<v Speaker 1>Insulin, sure, I mean that's one way of looking at it.

0:33:05.960 --> 0:33:11.240
<v Speaker 1>But also just from a purely energy climate and finance perspective,

0:33:12.160 --> 0:33:15.800
<v Speaker 1>bacteria are very efficient, so you know it's going to

0:33:15.880 --> 0:33:17.040
<v Speaker 1>be quick and.

0:33:17.880 --> 0:33:20.920
<v Speaker 3>Much more short generation times.

0:33:20.680 --> 0:33:24.320
<v Speaker 1>Yes, exactly, E Coli double in twenty minutes. I still

0:33:24.360 --> 0:33:28.160
<v Speaker 1>think that a batch of insulin is not an overnight process,

0:33:28.240 --> 0:33:33.040
<v Speaker 1>like I think even in modern insulin production factories it

0:33:33.120 --> 0:33:35.440
<v Speaker 1>probably takes like a month or two to go from

0:33:35.680 --> 0:33:39.920
<v Speaker 1>the overnight culture of the bacteria producing the insulin to

0:33:40.080 --> 0:33:42.760
<v Speaker 1>like all of the different processing steps. Insulin is a

0:33:42.800 --> 0:33:47.520
<v Speaker 1>really complicated protein because it's so you know, powerful, which

0:33:47.720 --> 0:33:50.440
<v Speaker 1>you know, with great power comes great responsibility. Too much

0:33:50.480 --> 0:33:53.760
<v Speaker 1>insulin can very quickly kill you in our own bodies.

0:33:53.800 --> 0:33:57.280
<v Speaker 1>Our insulin is produced in an inactive form, and it

0:33:57.320 --> 0:34:01.640
<v Speaker 1>has to be cleaved to become active. And so the

0:34:01.680 --> 0:34:04.720
<v Speaker 1>insulin that's produced in the bacteria initially also is in

0:34:04.760 --> 0:34:07.320
<v Speaker 1>that inactive form, and then all that processing that would

0:34:07.320 --> 0:34:09.680
<v Speaker 1>normally happen in someone's body has to happen in the

0:34:09.680 --> 0:34:12.680
<v Speaker 1>factory so that the form that you inject is already active.

0:34:12.719 --> 0:34:15.839
<v Speaker 1>So there's a lot of complex steps there. And if

0:34:15.840 --> 0:34:17.440
<v Speaker 1>you were to try to take it out of puppies,

0:34:17.440 --> 0:34:19.640
<v Speaker 1>I think that would be way less effective. I mean,

0:34:19.880 --> 0:34:23.600
<v Speaker 1>the number of cows we needed to produce enough insulin

0:34:23.640 --> 0:34:27.919
<v Speaker 1>to support humanity was becoming untenable. Like there weren't enough

0:34:27.920 --> 0:34:29.800
<v Speaker 1>cows to make all the insulin, even though we have

0:34:29.880 --> 0:34:32.480
<v Speaker 1>a crazy appetite for meat and beef, but we still

0:34:33.040 --> 0:34:35.920
<v Speaker 1>couldn't probably sustain all the diabetics who needed insulin.

0:34:36.160 --> 0:34:38.040
<v Speaker 2>And why do we need to build this in a

0:34:38.120 --> 0:34:40.920
<v Speaker 2>life form anyway? Like we know how to do chemistry,

0:34:40.960 --> 0:34:43.200
<v Speaker 2>I mean I don't, but some people do. Why can't

0:34:43.200 --> 0:34:45.799
<v Speaker 2>you just like stick the atoms together and build this

0:34:45.880 --> 0:34:48.600
<v Speaker 2>thing out of little lego pieces, you know, synthesize the

0:34:48.640 --> 0:34:49.239
<v Speaker 2>thing in the lab.

0:34:49.719 --> 0:34:51.600
<v Speaker 1>Yeah, I like that idea. And there is a thing

0:34:51.719 --> 0:34:56.680
<v Speaker 1>called cell free extract production that people sometimes use these days.

0:34:56.760 --> 0:34:59.560
<v Speaker 1>I think it just is convenient and handy that these

0:34:59.600 --> 0:35:03.880
<v Speaker 1>bacteria in a way are great little factories. They already

0:35:03.880 --> 0:35:06.560
<v Speaker 1>know how to make copies of themselves. So I think

0:35:07.160 --> 0:35:10.200
<v Speaker 1>from an efficiency perspective, I mean, how great is it

0:35:10.280 --> 0:35:12.880
<v Speaker 1>that the bacteria you just give them a little glucose

0:35:12.920 --> 0:35:15.799
<v Speaker 1>and they go figure all that stuff out for themselves.

0:35:15.840 --> 0:35:19.440
<v Speaker 1>Otherwise you'd have to manufacture thousands and thousands of different

0:35:19.440 --> 0:35:23.239
<v Speaker 1>components that the bacteria otherwise just build for themselves, and.

0:35:23.239 --> 0:35:25.600
<v Speaker 2>They're self replicating, which is much more than our grad

0:35:25.600 --> 0:35:26.239
<v Speaker 2>students can do.

0:35:27.640 --> 0:35:29.440
<v Speaker 1>I mean, to be honest, to the way we produce

0:35:29.480 --> 0:35:32.680
<v Speaker 1>a lot of the things you might consider putting into

0:35:32.760 --> 0:35:36.920
<v Speaker 1>a sell free artificial manufacturing process, we'd probably get them

0:35:36.960 --> 0:35:39.239
<v Speaker 1>from microbial production to a lot of the things that

0:35:39.280 --> 0:35:42.880
<v Speaker 1>we produce that way we do with the help of microps.

0:35:42.640 --> 0:35:44.720
<v Speaker 2>Like cheese. I don't think I want to eat lab

0:35:44.960 --> 0:35:51.600
<v Speaker 2>synthesized cheese either. We actually have a friend who was

0:35:51.640 --> 0:35:54.640
<v Speaker 2>working on plant free food and he give us a

0:35:54.640 --> 0:35:59.080
<v Speaker 2>taste from like chemically synthesized butter, and it wasn't good. No,

0:35:59.280 --> 0:36:02.600
<v Speaker 2>I didn't like it. No mascrecy, but it wasn't better.

0:36:02.719 --> 0:36:04.840
<v Speaker 2>But what I have one more question, simple, which is

0:36:05.040 --> 0:36:08.320
<v Speaker 2>you talk about inserting these genes into the bacteria to

0:36:08.360 --> 0:36:10.319
<v Speaker 2>make it do its thing, which makes it feel like

0:36:10.320 --> 0:36:13.239
<v Speaker 2>the bacteria is some sort of computer and you're just

0:36:13.239 --> 0:36:15.000
<v Speaker 2>like changing the program and you're like, hey, can you

0:36:15.040 --> 0:36:17.920
<v Speaker 2>make this instead of that? Is it as simple as that?

0:36:17.960 --> 0:36:19.360
<v Speaker 2>Can you go a little bit into the detail of

0:36:19.440 --> 0:36:22.120
<v Speaker 2>like how do we know how to write this code?

0:36:22.160 --> 0:36:24.000
<v Speaker 2>And then how do we take the code and actually

0:36:24.080 --> 0:36:26.239
<v Speaker 2>put it into the genome? Right, it's not as simple

0:36:26.280 --> 0:36:29.160
<v Speaker 2>as like logging into the bacteria and editing the files.

0:36:29.440 --> 0:36:31.880
<v Speaker 2>You need to actually like put it into the DNA.

0:36:31.920 --> 0:36:33.120
<v Speaker 2>How do we know how to do any of that?

0:36:33.520 --> 0:36:35.960
<v Speaker 1>Yeah? What a good question. I'm not sure I know

0:36:36.040 --> 0:36:38.680
<v Speaker 1>all the answers, but I can tell you that one

0:36:38.680 --> 0:36:41.680
<v Speaker 1>of the first proteins that we ever even figured out

0:36:41.719 --> 0:36:44.520
<v Speaker 1>what the sequence of it was was insulin. And so

0:36:44.960 --> 0:36:47.440
<v Speaker 1>that's at the protein level, like the sequence of amino

0:36:47.480 --> 0:36:50.479
<v Speaker 1>acids that you need to make insulin, that's what makes

0:36:50.520 --> 0:36:55.320
<v Speaker 1>insulin insulin. From there, the protein sequence could have lots

0:36:55.320 --> 0:36:58.560
<v Speaker 1>of different DNA sequences that lead to the same protein

0:36:58.560 --> 0:37:01.840
<v Speaker 1>sequence because we have redund and see in the genetic code.

0:37:01.920 --> 0:37:06.200
<v Speaker 1>So usually you have three nucleotide bases encoding an amino

0:37:06.239 --> 0:37:10.880
<v Speaker 1>acid for a protein sequence, and there's many combinations of

0:37:10.960 --> 0:37:13.600
<v Speaker 1>DNA that would lead to the right sequence for the protein.

0:37:14.280 --> 0:37:18.320
<v Speaker 1>I actually don't know how they chose what DNA sequence

0:37:18.520 --> 0:37:21.440
<v Speaker 1>to initially clone into the E. Coli. In theory, it

0:37:21.480 --> 0:37:24.200
<v Speaker 1>could be that they just this is not how they

0:37:24.200 --> 0:37:25.640
<v Speaker 1>did it because they didn't have the right tools to

0:37:25.640 --> 0:37:27.160
<v Speaker 1>do this. But in theory, it could be that they

0:37:27.160 --> 0:37:28.920
<v Speaker 1>were just like, oh, well, we know what protein sequence

0:37:28.960 --> 0:37:32.400
<v Speaker 1>we want, so therefore any of these bajillion different DNA

0:37:32.400 --> 0:37:35.120
<v Speaker 1>sequences will work, So we'll just artificially synthesize one of

0:37:35.120 --> 0:37:38.360
<v Speaker 1>those and do it from there. We could do that today.

0:37:38.400 --> 0:37:41.560
<v Speaker 1>That's actually pretty easy thing to do. I've often thought

0:37:41.560 --> 0:37:44.840
<v Speaker 1>about that, Like, if you knew something you wanted to produce,

0:37:45.520 --> 0:37:49.000
<v Speaker 1>you could synthesize the piece of DNA and send it

0:37:49.000 --> 0:37:51.880
<v Speaker 1>to a yogurt manufacturer anywhere in the world, and they

0:37:51.880 --> 0:37:54.200
<v Speaker 1>could make vast quantities of a protein that you were

0:37:54.200 --> 0:37:56.800
<v Speaker 1>interested in if you could get the cells to cooperate.

0:37:56.840 --> 0:37:58.120
<v Speaker 1>I mean, there's a few things that would be hard

0:37:58.120 --> 0:38:00.440
<v Speaker 1>about it, but yeah, I think they must have known

0:38:00.520 --> 0:38:04.680
<v Speaker 1>this sequence for human DNA and then physically got in

0:38:04.760 --> 0:38:08.200
<v Speaker 1>their hands on that and chopped it out and then

0:38:08.320 --> 0:38:11.520
<v Speaker 1>like physically we use the word ligation, it just means

0:38:11.560 --> 0:38:15.440
<v Speaker 1>like pasting it into the bacteria, and it wasn't just that,

0:38:15.600 --> 0:38:18.040
<v Speaker 1>And a lot of this happened also with the company Genentech.

0:38:18.680 --> 0:38:21.480
<v Speaker 1>I'm sure that many people know more about this history

0:38:21.560 --> 0:38:23.920
<v Speaker 1>than I do. But some of it is proprietary, right

0:38:24.000 --> 0:38:28.680
<v Speaker 1>because it was happening at a company, some of it anyway.

0:38:28.719 --> 0:38:32.840
<v Speaker 1>And so they cloned the human DNA sequence, copied it

0:38:32.840 --> 0:38:36.239
<v Speaker 1>into the bacterial cell, and just fired the bacteria up

0:38:36.280 --> 0:38:36.960
<v Speaker 1>to produce it.

0:38:37.320 --> 0:38:39.719
<v Speaker 3>So now you've got the bacteria with the code, and

0:38:39.760 --> 0:38:41.720
<v Speaker 3>you figured out how to get them to be running

0:38:41.719 --> 0:38:44.040
<v Speaker 3>that code all the time, so they're making more insulin. Yeah,

0:38:44.160 --> 0:38:48.120
<v Speaker 3>is that insulin accumulating inside the bacteria or do they

0:38:48.160 --> 0:38:50.799
<v Speaker 3>excrete it? How do we get it after that?

0:38:51.120 --> 0:38:54.200
<v Speaker 1>That's a really good question, and I think there's actually

0:38:54.239 --> 0:38:56.400
<v Speaker 1>several ways you could do that, and I would not

0:38:56.480 --> 0:38:59.759
<v Speaker 1>be surprised if both of those options are happening in

0:39:00.000 --> 0:39:03.080
<v Speaker 1>various factories in the world right now. One way it

0:39:03.080 --> 0:39:06.279
<v Speaker 1>can happen often when a bacterial cell is confronted with

0:39:06.360 --> 0:39:08.239
<v Speaker 1>like a crazy amount of something it doesn't quite know

0:39:08.239 --> 0:39:10.920
<v Speaker 1>what to do with, it pumps it into a little

0:39:10.920 --> 0:39:13.799
<v Speaker 1>compartment called a vacuole, and it just like makes little

0:39:13.880 --> 0:39:16.799
<v Speaker 1>pouches of it. That's my understanding for the main thing

0:39:16.840 --> 0:39:19.040
<v Speaker 1>that happens is that you get these little pouches of

0:39:19.080 --> 0:39:22.320
<v Speaker 1>the vacuoles from the cells, and then the next step

0:39:22.480 --> 0:39:25.400
<v Speaker 1>is to pop the cells, pull out all those vacuoles,

0:39:25.480 --> 0:39:28.320
<v Speaker 1>and then get the insulin from there. So I'm pretty

0:39:28.320 --> 0:39:30.839
<v Speaker 1>sure that's the main way that it's done these days

0:39:30.840 --> 0:39:34.440
<v Speaker 1>from E. Coli. Not all insulin is made in bacteria

0:39:34.560 --> 0:39:37.480
<v Speaker 1>and ecoli. There's I think maybe twenty or thirty percent

0:39:37.520 --> 0:39:39.320
<v Speaker 1>of the insulin that's manufactured in the world is in

0:39:39.440 --> 0:39:42.840
<v Speaker 1>yeast and sachromics service. And then it's going to be

0:39:42.920 --> 0:39:45.439
<v Speaker 1>yet another process. And so yeah, theory, you could make

0:39:45.480 --> 0:39:49.680
<v Speaker 1>the cell excrete the insulin into the liquid, which might

0:39:49.840 --> 0:39:52.759
<v Speaker 1>make your process easier, but since insulin's a protein and

0:39:52.800 --> 0:39:56.600
<v Speaker 1>it can get broken down by enzymes that eat proteins,

0:39:56.680 --> 0:39:58.359
<v Speaker 1>in a way, you might be better off having it

0:39:58.440 --> 0:40:02.279
<v Speaker 1>be in a protected pouch that you could just pull

0:40:02.320 --> 0:40:04.359
<v Speaker 1>those aside and get the insulin out.

0:40:04.640 --> 0:40:07.760
<v Speaker 3>I don't think I've thought before about the complicated process

0:40:07.800 --> 0:40:10.319
<v Speaker 3>of acquiring this stuff after the bacteria has made it.

0:40:10.360 --> 0:40:12.480
<v Speaker 3>Like I guess i'd imagine, like you know, you skim

0:40:12.520 --> 0:40:14.440
<v Speaker 3>the top and there's the insulin and you stick it

0:40:14.480 --> 0:40:17.919
<v Speaker 3>into needles. But yeah, I mean extracting all of those vacules, Yeah,

0:40:17.920 --> 0:40:20.160
<v Speaker 3>and popping them doesn't sound like easy work.

0:40:20.320 --> 0:40:24.200
<v Speaker 1>No, that's a sophisticated process. And then the protein sequence

0:40:24.239 --> 0:40:28.560
<v Speaker 1>still contains extra bits that make it inactive on purpose,

0:40:28.680 --> 0:40:30.759
<v Speaker 1>so that it's not in our bodies. We don't want

0:40:30.760 --> 0:40:33.200
<v Speaker 1>it to be active exactly when it's produced. It's like

0:40:33.360 --> 0:40:37.719
<v Speaker 1>unleashed and activated very intentionally, So to get it to

0:40:37.760 --> 0:40:40.120
<v Speaker 1>be in that active form takes yet more steps.

0:40:40.520 --> 0:40:42.359
<v Speaker 3>All right, awesome, So we're going to take a break now,

0:40:42.360 --> 0:40:43.839
<v Speaker 3>and when we get back from the break, we're going

0:40:43.880 --> 0:40:50.160
<v Speaker 3>to hear about lydia Villa Komorov's contribution to this field.

0:41:04.200 --> 0:41:07.520
<v Speaker 3>All right, and we're back. So it's Women's History month.

0:41:07.560 --> 0:41:10.920
<v Speaker 3>We're trying to feature some amazing women that most people

0:41:10.960 --> 0:41:14.040
<v Speaker 3>have perhaps not heard of. And you agreed to come

0:41:14.080 --> 0:41:17.000
<v Speaker 3>on the show and talk to us about lydia Villa Comarov.

0:41:17.640 --> 0:41:19.360
<v Speaker 3>What was her contribution to this field.

0:41:19.800 --> 0:41:22.759
<v Speaker 1>Well, lydia Villa Comorov was a grad student in the

0:41:22.840 --> 0:41:26.280
<v Speaker 1>nineteen seventies during this era where we were just figuring

0:41:26.360 --> 0:41:29.000
<v Speaker 1>out that we could clone bacteria. So not only did

0:41:29.000 --> 0:41:32.239
<v Speaker 1>we understand the central dogma, the way that molecular biology

0:41:32.320 --> 0:41:34.840
<v Speaker 1>is encoded. We were now starting to be able to

0:41:34.920 --> 0:41:35.640
<v Speaker 1>manipulate it.

0:41:36.160 --> 0:41:38.080
<v Speaker 3>Interesting, So a few.

0:41:37.840 --> 0:41:40.640
<v Speaker 1>People had done anything in this area. Right around the

0:41:40.680 --> 0:41:44.640
<v Speaker 1>time that doctor Villa Komarova finished her PhD from MIT

0:41:44.800 --> 0:41:47.760
<v Speaker 1>in nineteen seventy five and she embarked on a really

0:41:47.840 --> 0:41:51.200
<v Speaker 1>bold post doc at Harvard. It was to clone the

0:41:51.280 --> 0:41:54.480
<v Speaker 1>human insulin gene into bacteria. It was so bold that

0:41:54.520 --> 0:41:57.320
<v Speaker 1>Harvard actually asked them to stop. They paused the project

0:41:57.400 --> 0:42:02.400
<v Speaker 1>for fear of ethical consideration for what the consequences of

0:42:02.600 --> 0:42:05.640
<v Speaker 1>humans cloning things could be. So she actually continued her

0:42:05.719 --> 0:42:08.600
<v Speaker 1>project at Cold Spring Harbor. There were lots of failures.

0:42:08.719 --> 0:42:11.040
<v Speaker 1>I think that was a really tough post doc, but

0:42:11.200 --> 0:42:14.640
<v Speaker 1>ultimately she succeeded. I think that was around nineteen seventy eight,

0:42:14.760 --> 0:42:18.440
<v Speaker 1>and by the early eighties there was commercially available human

0:42:18.440 --> 0:42:23.080
<v Speaker 1>insulin that had been synthesized in bacteria, and her project

0:42:23.400 --> 0:42:27.760
<v Speaker 1>was to clone the gene for insulin into E. Coli,

0:42:28.040 --> 0:42:32.120
<v Speaker 1>the bacteria. So she has a paper in PNAS, the

0:42:32.160 --> 0:42:35.600
<v Speaker 1>Proceedings of the National Academy of Science, and in that

0:42:35.680 --> 0:42:40.040
<v Speaker 1>paper she demonstrates that you can pull the insulin gene

0:42:40.160 --> 0:42:44.480
<v Speaker 1>from humans, clone it into bacteria and get the bacterial

0:42:44.520 --> 0:42:48.680
<v Speaker 1>cells to replicate. So it was a big step, not

0:42:48.880 --> 0:42:51.799
<v Speaker 1>just that this was an idea, but that it could

0:42:51.880 --> 0:42:55.040
<v Speaker 1>actually be done, and everyone had their eyes on this happening.

0:42:55.200 --> 0:42:59.160
<v Speaker 1>It was considered risky and important enough that her project

0:42:59.200 --> 0:43:02.520
<v Speaker 1>was halted as these considerations about the ethics were being

0:43:02.520 --> 0:43:06.880
<v Speaker 1>discussed at the ASILAMAR meeting, and after the ASILAMAR meeting

0:43:07.160 --> 0:43:10.239
<v Speaker 1>she was allowed to proceed. And it all happened very

0:43:10.280 --> 0:43:13.439
<v Speaker 1>fast because her paper was already published in nineteen seventy eight,

0:43:13.480 --> 0:43:15.760
<v Speaker 1>and I think the Assillamar meeting was only in nineteen

0:43:15.800 --> 0:43:18.680
<v Speaker 1>seventy seven, So I bet that was intense. I bet

0:43:18.719 --> 0:43:19.920
<v Speaker 1>she was working hard with.

0:43:20.040 --> 0:43:22.640
<v Speaker 2>What ethics concerns do we have? Because, as we said earlier,

0:43:22.640 --> 0:43:26.280
<v Speaker 2>bacteria can't make peppy eyes, so what are the ethical issues.

0:43:26.600 --> 0:43:29.440
<v Speaker 1>It was a very new idea that humans could clone things,

0:43:29.480 --> 0:43:33.600
<v Speaker 1>that we could decide what the DNA that a creature

0:43:33.719 --> 0:43:37.160
<v Speaker 1>encoded was. And in some ways, I don't think it's

0:43:37.200 --> 0:43:40.960
<v Speaker 1>different than agriculture, not just farming of crops, but I

0:43:41.000 --> 0:43:43.680
<v Speaker 1>mean dog breeding or horse breeding or anything where you

0:43:43.880 --> 0:43:47.640
<v Speaker 1>select for traits that you care about and then intentionally

0:43:47.760 --> 0:43:52.319
<v Speaker 1>push a population towards having specific traits that we had

0:43:52.360 --> 0:43:56.200
<v Speaker 1>always only done that in the context of selection, where

0:43:56.280 --> 0:43:59.960
<v Speaker 1>all of the reproducing was happening by itself, or you know,

0:44:00.160 --> 0:44:02.280
<v Speaker 1>what you might consider a natural way, in the sense

0:44:02.320 --> 0:44:04.759
<v Speaker 1>that you were just like picking out the peas that

0:44:04.800 --> 0:44:07.239
<v Speaker 1>had the color you were excited about and crossing those,

0:44:07.280 --> 0:44:09.480
<v Speaker 1>and then you get more, and after hundreds of years

0:44:09.520 --> 0:44:13.319
<v Speaker 1>you can't even recognize the organism compared to where it started.

0:44:12.960 --> 0:44:16.080
<v Speaker 2>From the way we transformed corn from like a tiny

0:44:16.080 --> 0:44:18.920
<v Speaker 2>little grain to this like hugely productive.

0:44:18.520 --> 0:44:21.719
<v Speaker 1>Food, for example, exactly, or like watermelons, or you know

0:44:21.760 --> 0:44:27.360
<v Speaker 1>something where watermelons weren't these like amazing, gicy, genormous fruits

0:44:27.400 --> 0:44:31.279
<v Speaker 1>when we first found them, right, We cultivated that, and

0:44:31.400 --> 0:44:35.799
<v Speaker 1>the consequences of the cultivation are obviously encoded in the

0:44:35.840 --> 0:44:39.040
<v Speaker 1>genome and in some ways not really different than cloning

0:44:39.080 --> 0:44:43.360
<v Speaker 1>something on purpose. In fact, we're not that good at cloning.

0:44:43.440 --> 0:44:47.600
<v Speaker 1>Like cloning requires us as humans to decide what pieces

0:44:47.640 --> 0:44:51.239
<v Speaker 1>of DNA belong in an organism, and we typically are

0:44:51.320 --> 0:44:54.000
<v Speaker 1>kind of bad at that. It's interesting. I went to

0:44:54.040 --> 0:44:57.840
<v Speaker 1>grad school in an era where rational design of proteins

0:44:57.920 --> 0:45:00.719
<v Speaker 1>was really popular and a lot of people's projects were

0:45:00.760 --> 0:45:03.640
<v Speaker 1>like looking at protein sequences and being like, oh, I

0:45:03.680 --> 0:45:06.040
<v Speaker 1>think we should put an alanine there, and that's going

0:45:06.080 --> 0:45:08.520
<v Speaker 1>to make this work better. That kind of thing, and

0:45:08.600 --> 0:45:11.240
<v Speaker 1>typically it didn't actually work better. So in some ways,

0:45:11.239 --> 0:45:15.040
<v Speaker 1>I think we've come to respect that evolution and allowing

0:45:15.120 --> 0:45:17.600
<v Speaker 1>natural selection to happen is if in some ways, a

0:45:17.640 --> 0:45:20.359
<v Speaker 1>more powerful way to pull off things you want to do.

0:45:21.040 --> 0:45:24.719
<v Speaker 1>But you would never get insulin production through evolution. I mean,

0:45:25.000 --> 0:45:28.120
<v Speaker 1>bacteria would never produce insulin. So it's actually a really

0:45:28.160 --> 0:45:31.200
<v Speaker 1>great case for genetic engineering. It was a very cool

0:45:31.239 --> 0:45:35.080
<v Speaker 1>problem that lydia Villa comorov took on because it was

0:45:35.160 --> 0:45:38.440
<v Speaker 1>so effective and it really would never have happened without cloning.

0:45:39.280 --> 0:45:41.880
<v Speaker 1>So your question was how did it come to be

0:45:42.000 --> 0:45:45.440
<v Speaker 1>that this was an ethical problem? And the real issue

0:45:45.560 --> 0:45:49.120
<v Speaker 1>was just that we as humans were scared that we

0:45:49.120 --> 0:45:52.239
<v Speaker 1>were going to unleash some kind of monster. What were

0:45:52.280 --> 0:45:57.520
<v Speaker 1>the consequences of us genetically engineering things? I mean, more recently,

0:45:57.560 --> 0:46:00.680
<v Speaker 1>we've had similar debates about crispers, and you've heard that

0:46:00.719 --> 0:46:04.239
<v Speaker 1>there is even a case where a Chinese scientist used

0:46:04.239 --> 0:46:08.800
<v Speaker 1>Crisper to genetically engineer a baby, a human that has really,

0:46:08.840 --> 0:46:13.120
<v Speaker 1>really big ethical questions, And this was happening only in bacteria,

0:46:13.320 --> 0:46:15.359
<v Speaker 1>but it was the first time it had happened, and

0:46:15.400 --> 0:46:19.000
<v Speaker 1>we were rightfully, really thinking carefully about what the consequences

0:46:19.000 --> 0:46:23.319
<v Speaker 1>could be. For example, imagine you cloned a bacteria that

0:46:23.480 --> 0:46:27.359
<v Speaker 1>contained genes that could break down petroleum, and then you

0:46:27.440 --> 0:46:31.480
<v Speaker 1>unleashed that in an oil mining operation. You could really

0:46:31.520 --> 0:46:33.719
<v Speaker 1>cause a lot of destruction. And what if that was

0:46:33.840 --> 0:46:39.240
<v Speaker 1>just impossible to control and then you destroyed huge natural

0:46:39.239 --> 0:46:43.040
<v Speaker 1>resources unintentionally or intentionally for that matter. So those were

0:46:43.080 --> 0:46:44.879
<v Speaker 1>the kinds of questions people were worried about.

0:46:45.120 --> 0:46:47.120
<v Speaker 2>Or what if it helped the bacteria organize and it

0:46:47.160 --> 0:46:50.120
<v Speaker 2>crawled out of the vat and like extracted vengeance for

0:46:50.239 --> 0:46:53.160
<v Speaker 2>all the brethren that we've tortured in order to extract

0:46:53.200 --> 0:46:54.000
<v Speaker 2>insulin from them.

0:46:54.440 --> 0:46:56.600
<v Speaker 1>That's a great question, but I'm pretty sure they didn't

0:46:56.600 --> 0:46:57.400
<v Speaker 1>talk about it.

0:46:57.160 --> 0:47:00.360
<v Speaker 2>That's a very polite answer to a totally bunkers question.

0:47:00.680 --> 0:47:03.760
<v Speaker 2>You all should have seen her face.

0:47:04.880 --> 0:47:07.080
<v Speaker 1>That didn't make it to the top ten list for

0:47:07.160 --> 0:47:08.280
<v Speaker 1>discussion out of Solomar.

0:47:08.520 --> 0:47:10.480
<v Speaker 2>I bet there were some science fiction writers there. They

0:47:10.480 --> 0:47:12.120
<v Speaker 2>would have come up with that scenario. It didn't take

0:47:12.120 --> 0:47:13.640
<v Speaker 2>me very long to think about it.

0:47:15.280 --> 0:47:17.799
<v Speaker 3>I think there was a recent ant Solomar meeting that

0:47:17.880 --> 0:47:20.520
<v Speaker 3>was sort of inspired by then prior meeting. So you

0:47:20.560 --> 0:47:23.719
<v Speaker 3>mentioned the ethical issues associated with Crisper. Yeah, but I

0:47:23.719 --> 0:47:26.680
<v Speaker 3>think they like literally had another Ansilomar meeting with like

0:47:26.760 --> 0:47:29.560
<v Speaker 3>similar goals to figure out what direction.

0:47:30.000 --> 0:47:32.080
<v Speaker 1>I think it's next month, Oh is it? Yeah? I

0:47:32.080 --> 0:47:33.719
<v Speaker 1>think it's next week. I think you guys could have

0:47:33.760 --> 0:47:36.359
<v Speaker 1>this episode coincide or we could look into that. That'd

0:47:36.400 --> 0:47:38.840
<v Speaker 1>be cool. Yeah, because my friend Jen Martini was invited,

0:47:38.840 --> 0:47:40.600
<v Speaker 1>but she couldn't go because she's teaching, and I know

0:47:40.680 --> 0:47:42.160
<v Speaker 1>she doesn't start teaching until.

0:47:41.880 --> 0:47:44.640
<v Speaker 3>Next week's I mean maybe we should have a whole

0:47:44.680 --> 0:47:47.879
<v Speaker 3>episode on the ethical implications of Crisper too. That yeah,

0:47:48.000 --> 0:47:48.920
<v Speaker 3>important and timely.

0:47:49.040 --> 0:47:51.080
<v Speaker 2>So how ballsy was it for her to take on

0:47:51.120 --> 0:47:53.920
<v Speaker 2>this project because if it didn't work, she could ended

0:47:54.000 --> 0:47:56.520
<v Speaker 2>up with basically nothing, no result. I mean, this was

0:47:56.560 --> 0:47:58.719
<v Speaker 2>like really swinging for a home run, wasn't it.

0:47:59.040 --> 0:48:01.640
<v Speaker 1>Yeah, that's a really good question. It'd be fun to

0:48:01.800 --> 0:48:03.960
<v Speaker 1>talk to the people who are around at that time.

0:48:04.120 --> 0:48:05.920
<v Speaker 1>I don't think I would give this to a student

0:48:05.960 --> 0:48:09.520
<v Speaker 1>as their only project. It does seem really risky. But yeah,

0:48:09.520 --> 0:48:12.120
<v Speaker 1>if you look at the people involved, like who her

0:48:12.280 --> 0:48:15.719
<v Speaker 1>bosses were and who their collaborators were. You know, they

0:48:15.760 --> 0:48:18.800
<v Speaker 1>were used to taking on really big projects and hitting

0:48:18.840 --> 0:48:22.920
<v Speaker 1>for home runs. So that's what you do in Boston, Yeah, exactly.

0:48:25.239 --> 0:48:27.480
<v Speaker 3>So what came for her after this? So she did

0:48:27.520 --> 0:48:30.520
<v Speaker 3>this amazing breakthrough, was the first person to do this

0:48:30.600 --> 0:48:32.560
<v Speaker 3>amazing thing. What did she do after that?

0:48:32.920 --> 0:48:35.359
<v Speaker 1>She stayed in science. Actually, she made a really good

0:48:35.440 --> 0:48:38.360
<v Speaker 1>use of her science education, and she went on to

0:48:38.480 --> 0:48:41.560
<v Speaker 1>work on not just insulin, but other hormones that are

0:48:41.800 --> 0:48:44.719
<v Speaker 1>related to insulin. Some of them are called insulin like

0:48:44.800 --> 0:48:49.200
<v Speaker 1>growth factors. It's a really complex field that I honestly

0:48:49.440 --> 0:48:52.160
<v Speaker 1>couldn't tell you too much about what all the implications are,

0:48:52.200 --> 0:48:55.040
<v Speaker 1>but I do know that she ran a lab and

0:48:55.120 --> 0:48:59.200
<v Speaker 1>spent many years studying hormones that are related to insulin.

0:48:59.400 --> 0:49:01.560
<v Speaker 1>And so she stayed in that field. And she also

0:49:02.280 --> 0:49:05.520
<v Speaker 1>really put a lot of energy into being a role

0:49:05.600 --> 0:49:08.440
<v Speaker 1>model and a leader for other people who wanted to

0:49:08.480 --> 0:49:14.680
<v Speaker 1>become scientists. She'd encountered definitely roadblocks herself, considering that most

0:49:14.840 --> 0:49:18.320
<v Speaker 1>institutions wouldn't even accept women as applicants to graduate school

0:49:18.360 --> 0:49:20.799
<v Speaker 1>when she was applying, and so she became a co

0:49:20.920 --> 0:49:24.480
<v Speaker 1>founding member of the Society for the Advancement of Chicanos

0:49:24.560 --> 0:49:28.600
<v Speaker 1>and Hispanics and Native Americans and Science or SACNAS, And

0:49:28.600 --> 0:49:30.800
<v Speaker 1>that was back in the nineteen seventies, and I actually

0:49:30.800 --> 0:49:33.719
<v Speaker 1>didn't know that. I personally have had a lot of

0:49:33.760 --> 0:49:37.080
<v Speaker 1>students who have been supported by SAKNAS to go to conferences.

0:49:37.120 --> 0:49:40.360
<v Speaker 1>They have meetings every year. I work at UC Irvine,

0:49:40.360 --> 0:49:43.799
<v Speaker 1>which is a Hispanic serving institution, and a lot of

0:49:43.800 --> 0:49:46.080
<v Speaker 1>our students have gone to those meetings and had a

0:49:46.120 --> 0:49:49.000
<v Speaker 1>really good time. So I think that's really cool she

0:49:49.080 --> 0:49:49.560
<v Speaker 1>founded that.

0:49:50.080 --> 0:49:52.799
<v Speaker 2>And why isn't she a zillionaire? I mean, I know

0:49:52.880 --> 0:49:56.200
<v Speaker 2>that this technology is the foundation of like billions of

0:49:56.280 --> 0:49:59.520
<v Speaker 2>dollars of annual profit for Nova Noordis and Eli Lilly.

0:50:00.040 --> 0:50:01.920
<v Speaker 2>Why isn't she elon Musk?

0:50:02.239 --> 0:50:04.799
<v Speaker 1>What a good question. I don't know the details of

0:50:04.920 --> 0:50:07.640
<v Speaker 1>what kind of IP they tried to get for the

0:50:07.840 --> 0:50:11.120
<v Speaker 1>technique that they developed. I also know that genen Tech

0:50:11.280 --> 0:50:13.600
<v Speaker 1>was really involved, and so actually an important thing to

0:50:13.600 --> 0:50:15.239
<v Speaker 1>say is that, you know, so her paper came out

0:50:15.239 --> 0:50:18.000
<v Speaker 1>in nineteen seventy eight, she didn't keep up with this

0:50:18.239 --> 0:50:22.240
<v Speaker 1>specific feel. I know that genen Tech was the company

0:50:22.280 --> 0:50:27.440
<v Speaker 1>that really developed the possibility of producing insulin in bacteria.

0:50:28.280 --> 0:50:30.840
<v Speaker 1>My sense is that what she did was proof of concept,

0:50:31.000 --> 0:50:34.560
<v Speaker 1>I see, which was critical because it made people ready

0:50:34.600 --> 0:50:37.719
<v Speaker 1>for the idea. But my guess is that genen Tech

0:50:37.800 --> 0:50:41.280
<v Speaker 1>went on and developed the technology in its own specific

0:50:41.360 --> 0:50:44.720
<v Speaker 1>way that could then have ip that stayed within the company.

0:50:44.880 --> 0:50:47.680
<v Speaker 2>Isn't there like fast acting and long acting with insulin stuff.

0:50:48.160 --> 0:50:50.440
<v Speaker 1>Her paper came out in nineteen seventy eight, and I

0:50:50.480 --> 0:50:52.919
<v Speaker 1>know that by nineteen eighty two the Food and Drug

0:50:52.920 --> 0:50:56.720
<v Speaker 1>Administration had approved human insulin to be given to people.

0:50:57.400 --> 0:50:59.640
<v Speaker 1>I was diagnosed with type one diabetes in nineteen eighty

0:50:59.680 --> 0:51:02.480
<v Speaker 1>four and I never took animal insulin. I only got

0:51:02.520 --> 0:51:05.239
<v Speaker 1>the human insulin at that time. It was just the

0:51:05.280 --> 0:51:08.080
<v Speaker 1>straight up human insulin sequence. It hadn't been modified to

0:51:08.120 --> 0:51:11.680
<v Speaker 1>have new properties. But that's pretty amazing that we scaled

0:51:11.680 --> 0:51:15.600
<v Speaker 1>that up for humanity that quickly. And so the insulins

0:51:15.600 --> 0:51:19.520
<v Speaker 1>that I took with like regular insulin, is still produced

0:51:19.520 --> 0:51:23.880
<v Speaker 1>today and I used it for twelve years, like multiple

0:51:23.920 --> 0:51:27.920
<v Speaker 1>injections daily, And now if you go to Walmart, you

0:51:27.960 --> 0:51:30.560
<v Speaker 1>can actually buy that kind of insulin for twenty five dollars.

0:51:30.600 --> 0:51:33.120
<v Speaker 1>This is probably the most important thing I'm saying like

0:51:33.239 --> 0:51:35.560
<v Speaker 1>ever anytime I have an audience, I say this because

0:51:35.560 --> 0:51:38.600
<v Speaker 1>it could really save lives that you can buy regular

0:51:38.680 --> 0:51:42.280
<v Speaker 1>human insulin at Walmart. It's intended for cats and dogs

0:51:42.280 --> 0:51:45.000
<v Speaker 1>who have diabetes. But it's exactly the insulin that I

0:51:45.120 --> 0:51:49.080
<v Speaker 1>used for many years, and it cost twenty five dollars

0:51:49.520 --> 0:51:51.760
<v Speaker 1>and you don't need a prescription. It's just over the counter.

0:51:51.880 --> 0:51:54.080
<v Speaker 1>You can just go to Walmart and buy this insulin

0:51:54.600 --> 0:51:57.000
<v Speaker 1>and it's exactly the same bottle as the one that

0:51:57.040 --> 0:51:59.520
<v Speaker 1>I used in the nineteen eighties. So, starting in the

0:51:59.600 --> 0:52:03.480
<v Speaker 1>nineteen eight e we scaled up fermentation of human insulin

0:52:03.920 --> 0:52:07.160
<v Speaker 1>to be available for all people. I wouldn't say access

0:52:07.200 --> 0:52:11.440
<v Speaker 1>is perfect, but it's pretty good. Like there's definitely parts

0:52:11.480 --> 0:52:13.600
<v Speaker 1>of the world where you can buy insulin at a

0:52:13.640 --> 0:52:16.279
<v Speaker 1>pretty reasonable cost. I'm sure you've heard a lot about

0:52:16.280 --> 0:52:18.360
<v Speaker 1>the cost of insulin, Like if you cross the border

0:52:18.360 --> 0:52:20.640
<v Speaker 1>into Mexico, you can buy this insulin at a very

0:52:20.680 --> 0:52:24.960
<v Speaker 1>reasonable cost too. It wasn't until the nineties that engineered

0:52:25.040 --> 0:52:27.920
<v Speaker 1>insulins that have different kinetics, like they can be faster

0:52:28.000 --> 0:52:31.400
<v Speaker 1>and slower. Those came out in the nineties. The slower

0:52:31.400 --> 0:52:34.680
<v Speaker 1>insulins were available earlier, like the insulin you can buy

0:52:34.680 --> 0:52:37.560
<v Speaker 1>at Walmart. There's a slower one too, that's called NPH,

0:52:37.560 --> 0:52:40.319
<v Speaker 1>and that didn't require crazy bioengineering or I don't know,

0:52:40.400 --> 0:52:42.120
<v Speaker 1>they've somehow figured that out way earlier.

0:52:42.280 --> 0:52:45.480
<v Speaker 3>Why would you want faster and slower insulin, Well.

0:52:45.360 --> 0:52:49.160
<v Speaker 1>The regular insulin it takes a few hours to become active.

0:52:49.320 --> 0:52:55.799
<v Speaker 1>So the insulin exists in little trimers around zinc molecules

0:52:55.960 --> 0:52:58.799
<v Speaker 1>in a dimer. So there's two zinc molecules that each

0:52:58.840 --> 0:53:01.439
<v Speaker 1>have three insulin molecules attached to them, So there's six

0:53:01.560 --> 0:53:05.279
<v Speaker 1>insulin molecules all hanging out together. You have to wait

0:53:05.320 --> 0:53:08.040
<v Speaker 1>for them to dissociate because the insulin is only active

0:53:08.040 --> 0:53:11.880
<v Speaker 1>as a monomer by itself, So when you inject regular insulin,

0:53:12.480 --> 0:53:15.479
<v Speaker 1>you have to wait one hour for it to even

0:53:15.520 --> 0:53:19.879
<v Speaker 1>start working at all, and it doesn't peak until three hours. Now,

0:53:19.880 --> 0:53:22.520
<v Speaker 1>when you eat your food, it doesn't come in immediately either,

0:53:22.719 --> 0:53:25.600
<v Speaker 1>But regular insulin is too slow for an average meal,

0:53:25.680 --> 0:53:28.640
<v Speaker 1>so most people would have to either inject their insulin early,

0:53:29.120 --> 0:53:32.480
<v Speaker 1>but that's kind of dangerous. Imagine you inject your insulin,

0:53:32.800 --> 0:53:35.360
<v Speaker 1>but you're like your food is late, or you're on

0:53:35.400 --> 0:53:36.960
<v Speaker 1>a walk and you forget to eat or you know,

0:53:37.000 --> 0:53:38.960
<v Speaker 1>something like that. If your blood seger goes too low,

0:53:39.280 --> 0:53:42.840
<v Speaker 1>you die from low blood sugar immediately. It's like the

0:53:42.880 --> 0:53:45.799
<v Speaker 1>most common cause of death in people with type one diabetes.

0:53:46.600 --> 0:53:48.799
<v Speaker 1>So that's really really something you have to be careful with.

0:53:48.880 --> 0:53:52.160
<v Speaker 1>So having your insulin kinetics not really matching when you

0:53:52.200 --> 0:53:57.320
<v Speaker 1>need the insulin is both for convenience and basic survival,

0:53:57.600 --> 0:54:01.440
<v Speaker 1>really really important. There was a big arms race between

0:54:01.480 --> 0:54:05.960
<v Speaker 1>Eli Lilly and Novonordisk in the nineties to rationally design

0:54:06.040 --> 0:54:09.960
<v Speaker 1>insulins that had different properties, and they both succeeded in

0:54:10.000 --> 0:54:13.560
<v Speaker 1>slightly different ways. And now you can buy insulin that

0:54:14.120 --> 0:54:18.560
<v Speaker 1>falls apart more easily. Those dimers on the trimers of

0:54:18.600 --> 0:54:21.720
<v Speaker 1>the zinc are not as stable, so they fall apart

0:54:21.920 --> 0:54:24.200
<v Speaker 1>more quickly. And now when you inject the insulin, it

0:54:24.239 --> 0:54:28.000
<v Speaker 1>starts to become active within minutes and peaks within an hour,

0:54:28.520 --> 0:54:33.200
<v Speaker 1>which matches how people eat much better. So it's safer

0:54:33.480 --> 0:54:36.280
<v Speaker 1>and a little bit easier to keep your blood sugar

0:54:36.320 --> 0:54:38.680
<v Speaker 1>within range. But matching the kinetics of your food with

0:54:38.719 --> 0:54:41.200
<v Speaker 1>the kinetics of your insulin is just a major challenge.

0:54:41.440 --> 0:54:43.960
<v Speaker 3>So is it still the case that today people with

0:54:44.000 --> 0:54:46.800
<v Speaker 3>diabetes need to be really careful about, like what kinds

0:54:46.960 --> 0:54:50.040
<v Speaker 3>of insulin that they're injecting. Has it gotten easier over time?

0:54:50.120 --> 0:54:51.680
<v Speaker 3>I feel like I heard once that there are these

0:54:52.160 --> 0:54:54.040
<v Speaker 3>things that can attach to your body that sort of

0:54:54.120 --> 0:54:56.160
<v Speaker 3>do all the measuring for you. What is it like today.

0:54:56.840 --> 0:54:59.840
<v Speaker 1>Well, so there's been big changes both in how we

0:55:00.040 --> 0:55:04.040
<v Speaker 1>deliver insulin and how we monitor blood sugar. So we

0:55:04.120 --> 0:55:06.719
<v Speaker 1>haven't talked about blood sugar monitoring at all in any

0:55:06.760 --> 0:55:08.959
<v Speaker 1>of this, but I'll bring up that, you know, we've

0:55:09.000 --> 0:55:13.080
<v Speaker 1>known for centuries how to detect glucose and urine, but

0:55:13.120 --> 0:55:15.560
<v Speaker 1>that's very old information. By the time the sugar hits

0:55:15.600 --> 0:55:18.480
<v Speaker 1>your urine, that's like happened hours ago, and you can't

0:55:18.480 --> 0:55:20.520
<v Speaker 1>really take that sample and demand quite in the same

0:55:20.520 --> 0:55:22.640
<v Speaker 1>way as you can take a blood sample. So we

0:55:22.719 --> 0:55:25.759
<v Speaker 1>started poking our fingers to get blood sugar measurements. Those

0:55:26.080 --> 0:55:29.240
<v Speaker 1>devices started being available at home in the nineteen eighties

0:55:29.880 --> 0:55:32.279
<v Speaker 1>and then for about ten or fifteen years. We now

0:55:32.280 --> 0:55:34.840
<v Speaker 1>have these sensors that you can put a little sensor

0:55:34.880 --> 0:55:37.319
<v Speaker 1>on your arm and you get blood sugar information every

0:55:37.360 --> 0:55:41.279
<v Speaker 1>five minutes. So those sensors help you see what your

0:55:41.320 --> 0:55:45.160
<v Speaker 1>blood sugar is. We also have both injections for insulin

0:55:45.239 --> 0:55:49.279
<v Speaker 1>and also insulin pumps. So the pump will deliver insulin

0:55:49.800 --> 0:55:52.240
<v Speaker 1>at rates that you tell it to give you the insulin.

0:55:52.719 --> 0:55:55.959
<v Speaker 1>But none of this is happening without a lot of thought.

0:55:56.200 --> 0:55:58.080
<v Speaker 1>There's not like a machine that just takes care of

0:55:58.120 --> 0:56:00.440
<v Speaker 1>it for you. A lot of people when they see

0:56:00.440 --> 0:56:03.040
<v Speaker 1>an insulin pump imagine like, oh, that must be so

0:56:03.160 --> 0:56:05.279
<v Speaker 1>nice that like, oh, the AI is taking care of

0:56:05.280 --> 0:56:07.960
<v Speaker 1>your bl chicker for you, And that's not the case

0:56:08.000 --> 0:56:10.160
<v Speaker 1>at all. Insulin pumps just do what you tell them

0:56:10.200 --> 0:56:10.440
<v Speaker 1>to do.

0:56:10.719 --> 0:56:12.799
<v Speaker 3>That is what I imagined. Thanks for clarifying that.

0:56:13.000 --> 0:56:15.160
<v Speaker 1>Even my doctors, like if I go to the eye doctor,

0:56:15.200 --> 0:56:17.400
<v Speaker 1>they're like, oh, it must be some nice having your

0:56:17.440 --> 0:56:19.360
<v Speaker 1>pump doing that for you. But I mean, no, the

0:56:19.440 --> 0:56:21.640
<v Speaker 1>pump is not operating independently.

0:56:22.080 --> 0:56:24.640
<v Speaker 2>And talk per a minute about why that's a hard problem.

0:56:24.680 --> 0:56:26.640
<v Speaker 2>I mean, people might be thinking, well, you have a

0:56:26.680 --> 0:56:28.360
<v Speaker 2>sense of that tells you how much glucose you have,

0:56:28.440 --> 0:56:31.000
<v Speaker 2>and you have insulin which brings the glucose down. Why

0:56:31.000 --> 0:56:33.080
<v Speaker 2>can't you just you know, fit a straight line to

0:56:33.160 --> 0:56:35.520
<v Speaker 2>that and descide how much insulin I have? Why do

0:56:35.560 --> 0:56:38.120
<v Speaker 2>you need a human brain in the loop there or

0:56:38.120 --> 0:56:39.280
<v Speaker 2>why is it a hard problem.

0:56:39.560 --> 0:56:41.799
<v Speaker 1>There's a lot of reasons it's a hard problem. A

0:56:41.840 --> 0:56:44.239
<v Speaker 1>big one is that the way that we're giving the

0:56:44.280 --> 0:56:49.759
<v Speaker 1>insulin just subcutaneously means that it's slow. So you know,

0:56:49.800 --> 0:56:52.879
<v Speaker 1>when you eat, your pancreas is exactly in the right

0:56:52.880 --> 0:56:56.000
<v Speaker 1>place at the right time, sensing the glucose as it's

0:56:56.040 --> 0:56:59.920
<v Speaker 1>getting released from your digestion. So then not only do

0:56:59.960 --> 0:57:03.080
<v Speaker 1>you get real time information, but you also have the

0:57:03.080 --> 0:57:05.920
<v Speaker 1>insulin being delivered exactly where you need it. So when

0:57:05.960 --> 0:57:09.160
<v Speaker 1>you take insulin subcutaneously, it takes like a good half

0:57:09.200 --> 0:57:13.400
<v Speaker 1>an hour to dissolve and become active. I guess. Another

0:57:13.440 --> 0:57:17.240
<v Speaker 1>really important thing to say is that the insulin's activity

0:57:17.320 --> 0:57:20.840
<v Speaker 1>is affected by your own activity. So if you're exercising,

0:57:20.880 --> 0:57:23.320
<v Speaker 1>the insulin that you're taking will do a lot more work.

0:57:23.920 --> 0:57:27.360
<v Speaker 1>And your own pancrease has more than one hormone. It

0:57:27.400 --> 0:57:31.080
<v Speaker 1>has insulin and also glucagon, so it's a two component system.

0:57:31.360 --> 0:57:34.720
<v Speaker 1>Insulin drives your blood sugar down, Glucagon drives your blood

0:57:34.760 --> 0:57:38.760
<v Speaker 1>sugar up. So what glucagon does is it releases the

0:57:38.800 --> 0:57:41.760
<v Speaker 1>glycogen stores in your liver and muscle to raise your

0:57:41.760 --> 0:57:44.960
<v Speaker 1>blood sugar. So if this dangerous thing starts to happen

0:57:45.000 --> 0:57:47.960
<v Speaker 1>that your insulin drives your blood sugar too low. Then

0:57:48.000 --> 0:57:50.800
<v Speaker 1>the glucagon can pick it up from the floor and

0:57:50.840 --> 0:57:53.120
<v Speaker 1>save your life so you don't die from low blood sugar.

0:57:54.120 --> 0:57:56.800
<v Speaker 1>Our insulin pumps don't have glucagon in them. Glucagon is

0:57:56.840 --> 0:58:00.360
<v Speaker 1>a really delicate hormone. There's about one hundred companies there

0:58:00.360 --> 0:58:03.560
<v Speaker 1>engineering more stable glukug on. Maybe we'll have that soon,

0:58:03.720 --> 0:58:06.480
<v Speaker 1>but right now the pumps just have insulin. There is

0:58:06.520 --> 0:58:09.200
<v Speaker 1>a company that's trying to make a two component pump

0:58:09.280 --> 0:58:12.400
<v Speaker 1>that also has glucagon, but anyway, that doesn't happen yet.

0:58:12.760 --> 0:58:15.960
<v Speaker 1>So there's a number of reasons, like you could, in theory,

0:58:16.040 --> 0:58:19.120
<v Speaker 1>use the glucose information, the old information you're getting from

0:58:19.120 --> 0:58:22.240
<v Speaker 1>the sensor in your arm, and have that direct the

0:58:22.280 --> 0:58:26.560
<v Speaker 1>dosing of the insulin from your pump. However, your pump

0:58:26.600 --> 0:58:29.280
<v Speaker 1>doesn't know if you're about to go running, or if

0:58:29.320 --> 0:58:31.880
<v Speaker 1>you are sick, or you know. The amount of insulin

0:58:31.920 --> 0:58:35.280
<v Speaker 1>you need is affected by easily forty two factors that

0:58:35.360 --> 0:58:38.400
<v Speaker 1>most of them can't be measured, and so you need

0:58:38.480 --> 0:58:41.840
<v Speaker 1>your brain to synthesize all those factors and think through

0:58:41.840 --> 0:58:43.840
<v Speaker 1>the decision of how much insulin you need, and.

0:58:43.800 --> 0:58:46.040
<v Speaker 2>You don't trust chat GPT to make those decisions for

0:58:46.080 --> 0:58:46.479
<v Speaker 2>you yet.

0:58:46.600 --> 0:58:49.400
<v Speaker 1>I mean, I wouldn't mind like chatting with chat GPT

0:58:49.520 --> 0:58:52.480
<v Speaker 1>about it and getting ideas, but I would definitely want

0:58:52.520 --> 0:58:54.400
<v Speaker 1>to be the one who's the buck stops with me

0:58:54.480 --> 0:58:55.680
<v Speaker 1>when it comes to that decision.

0:58:55.720 --> 0:58:57.640
<v Speaker 2>All right, So then our last question is what do

0:58:57.680 --> 0:59:00.240
<v Speaker 2>you see happening in the future, like in ten year

0:59:00.280 --> 0:59:03.120
<v Speaker 2>and fifty years, in one hundred years, what's going to

0:59:03.280 --> 0:59:06.920
<v Speaker 2>change about our treatment of diabetes or understanding of the

0:59:06.920 --> 0:59:08.200
<v Speaker 2>biochemical processes.

0:59:08.440 --> 0:59:12.560
<v Speaker 1>Well, there's biological and engineering fronts to talk about, and

0:59:12.600 --> 0:59:14.920
<v Speaker 1>actually I should make a really big shout out to

0:59:15.000 --> 0:59:19.040
<v Speaker 1>the group of people who are engineering devices. There's even

0:59:19.120 --> 0:59:22.560
<v Speaker 1>groups of people who have built algorithms that do take

0:59:22.640 --> 0:59:25.760
<v Speaker 1>the information from the glucose sensors and use it to

0:59:25.840 --> 0:59:29.320
<v Speaker 1>dose the insulin. Sometimes they're called loopers. They're closing the loop.

0:59:29.960 --> 0:59:32.960
<v Speaker 1>Many of those algorithms are open source, and people are

0:59:33.040 --> 0:59:37.919
<v Speaker 1>having good results with better blood sugar control using those algorithms.

0:59:37.960 --> 0:59:41.560
<v Speaker 1>It takes a really tech savvy person and somebody who

0:59:42.000 --> 0:59:44.080
<v Speaker 1>you know. In my case, I go running every day

0:59:44.520 --> 0:59:47.760
<v Speaker 1>and I don't think those algorithms take exercise into account

0:59:47.880 --> 0:59:50.080
<v Speaker 1>in a way that works for me. So that's why

0:59:50.120 --> 0:59:54.080
<v Speaker 1>I personally am not using the looping algorithms, although I'm interested.

0:59:54.160 --> 0:59:56.120
<v Speaker 1>So if there's someone out there who's into looping, like,

0:59:56.320 --> 0:59:59.400
<v Speaker 1>my mind is open. So there are people making really

0:59:59.400 --> 1:00:02.120
<v Speaker 1>big progress on the algorithms, I think those are going

1:00:02.160 --> 1:00:05.400
<v Speaker 1>to be a really big frontier that our algorithms are

1:00:05.440 --> 1:00:07.840
<v Speaker 1>going to get better and better. Some of the major

1:00:07.880 --> 1:00:11.800
<v Speaker 1>insulin pump companies have soft versions of those algorithms with

1:00:11.880 --> 1:00:13.960
<v Speaker 1>a lot of safety on them, where they keep the

1:00:14.480 --> 1:00:17.760
<v Speaker 1>average blood sugar values a little higher to give you

1:00:17.800 --> 1:00:21.439
<v Speaker 1>a safety buffer. So that's starting to happen already. In fact,

1:00:21.480 --> 1:00:24.040
<v Speaker 1>the pump I use has a soft algorithm like that that,

1:00:24.760 --> 1:00:27.040
<v Speaker 1>especially for sleeping at night when there's not as many

1:00:27.080 --> 1:00:29.200
<v Speaker 1>different changes going on, it can do a really good

1:00:29.280 --> 1:00:31.640
<v Speaker 1>job of helping you keep your blood sugar in control.

1:00:32.240 --> 1:00:35.120
<v Speaker 1>So that's already getting better. I'd say the engineering front

1:00:35.160 --> 1:00:39.640
<v Speaker 1>will include better sensors, better algorithms. If we had glucagon,

1:00:39.800 --> 1:00:42.440
<v Speaker 1>then that will also close the loop and help to

1:00:42.480 --> 1:00:46.360
<v Speaker 1>make the measurements better overall, though, I mean, humans are

1:00:46.360 --> 1:00:49.280
<v Speaker 1>really complex. Like one of my favorite results recently showed

1:00:49.280 --> 1:00:52.760
<v Speaker 1>how people eating exactly the same meal one week apart

1:00:53.160 --> 1:00:56.680
<v Speaker 1>and wearing a continuous glucose monitor had different blood sugar

1:00:56.720 --> 1:00:59.840
<v Speaker 1>responses to the same meal, which I think highlights that

1:01:00.080 --> 1:01:03.760
<v Speaker 1>challenge of why it has to be pretty thoughtful how

1:01:03.800 --> 1:01:06.440
<v Speaker 1>you are dosing insulin even for the same meal and

1:01:06.480 --> 1:01:08.720
<v Speaker 1>the same person. You can't assume it's going to work

1:01:08.720 --> 1:01:12.439
<v Speaker 1>the same way each time. But then on the biology front,

1:01:12.480 --> 1:01:16.360
<v Speaker 1>there's also really big progress. So we have been learning

1:01:16.440 --> 1:01:21.000
<v Speaker 1>how to direct the program of stem cells and differentiating

1:01:21.000 --> 1:01:23.360
<v Speaker 1>them into different kinds of cells that we can use

1:01:23.400 --> 1:01:26.760
<v Speaker 1>for different kinds of medicine. There's a whole arm of

1:01:26.800 --> 1:01:32.760
<v Speaker 1>research towards building pancreatic beta cells, the ones that secrete insulin,

1:01:33.600 --> 1:01:37.360
<v Speaker 1>so that they could be transplanted. The first versions of

1:01:37.400 --> 1:01:41.400
<v Speaker 1>these have required people to take immunosuppressants, just like for

1:01:41.480 --> 1:01:45.480
<v Speaker 1>a pancreased transplant, so it didn't feel as exciting to me,

1:01:46.200 --> 1:01:49.800
<v Speaker 1>but that's actually starting to get better, and there are

1:01:50.000 --> 1:01:54.880
<v Speaker 1>efforts towards making hypoimmune, so like not giving an immune

1:01:54.880 --> 1:01:59.040
<v Speaker 1>response cells, so that people could get transplants with these

1:01:59.080 --> 1:02:01.720
<v Speaker 1>kind of cells and not have to take imminosuppressants and

1:02:01.760 --> 1:02:05.920
<v Speaker 1>potentially have them work to control their blood sugar. I

1:02:05.920 --> 1:02:08.240
<v Speaker 1>don't know, it's interesting to me to imagine trusting a

1:02:08.280 --> 1:02:11.600
<v Speaker 1>little renegade group of cells to do that. But you know,

1:02:11.720 --> 1:02:13.959
<v Speaker 1>that will get tested and we'll know a lot more

1:02:14.080 --> 1:02:17.080
<v Speaker 1>those are. On the treatment front, there's another whole aspect

1:02:17.200 --> 1:02:20.240
<v Speaker 1>to talk about, which is, you know, the way that

1:02:20.360 --> 1:02:23.560
<v Speaker 1>type one diabetes develops, at least your immune system starts

1:02:23.600 --> 1:02:27.080
<v Speaker 1>to attack your pancreas. This process can take a couple

1:02:27.040 --> 1:02:30.320
<v Speaker 1>of years. A lot of people when they're diagnosed, imagine that.

1:02:30.600 --> 1:02:32.200
<v Speaker 1>You know, oh, I got a cold and then I

1:02:32.240 --> 1:02:34.440
<v Speaker 1>got diabetes, or I took finals and I was all

1:02:34.440 --> 1:02:37.040
<v Speaker 1>stressed out and that caused my diabetes. But really it

1:02:37.080 --> 1:02:39.440
<v Speaker 1>was just the straw that broke the camel's back. And

1:02:39.520 --> 1:02:41.280
<v Speaker 1>this was a process that was going on for a

1:02:41.320 --> 1:02:44.760
<v Speaker 1>couple of years, and then a stressful circumstance made you

1:02:44.840 --> 1:02:47.920
<v Speaker 1>need more insulin, so then the system couldn't support you anymore.

1:02:48.520 --> 1:02:52.520
<v Speaker 1>But now there's actually a treatment for people who are

1:02:52.720 --> 1:02:55.320
<v Speaker 1>just starting to build the antibodies that are killing their

1:02:55.320 --> 1:03:01.520
<v Speaker 1>pancreatic cells, and that treatment will basically target and slow

1:03:01.600 --> 1:03:04.480
<v Speaker 1>down the immune process. It's called tea yield. And we

1:03:04.520 --> 1:03:08.520
<v Speaker 1>actually have a friend whose son was caught early because

1:03:08.520 --> 1:03:10.640
<v Speaker 1>he had a really savvy mom who understood what was

1:03:10.720 --> 1:03:13.640
<v Speaker 1>going on, and she helped him get that treatment, and

1:03:13.680 --> 1:03:16.320
<v Speaker 1>it's supposed to delay the onset of his type one

1:03:16.400 --> 1:03:19.880
<v Speaker 1>diabetes for several years. So he's probably still on that path,

1:03:20.600 --> 1:03:22.680
<v Speaker 1>but I could imagine us getting even better at that.

1:03:22.800 --> 1:03:25.080
<v Speaker 1>And to be honest, the reason I became a microbiome

1:03:25.160 --> 1:03:30.360
<v Speaker 1>scientist is that we know that the diagnosis of autoimmune

1:03:30.360 --> 1:03:34.919
<v Speaker 1>diseases is becoming more and more frequent. EXAMA allergies, type

1:03:34.920 --> 1:03:37.920
<v Speaker 1>one diabetes, a lot of autoimmune diseases are becoming more common,

1:03:38.680 --> 1:03:42.400
<v Speaker 1>and we don't exactly know why. It's clearly a change

1:03:42.440 --> 1:03:45.880
<v Speaker 1>in our immune development and the exposures we have in

1:03:45.920 --> 1:03:50.720
<v Speaker 1>early life. And for example, most babies born in human

1:03:50.840 --> 1:03:55.480
<v Speaker 1>history were breastfed and their guts became dominated by a

1:03:55.520 --> 1:03:59.000
<v Speaker 1>biffidobacteria that's good at helping break down the breast milk fibers,

1:03:59.840 --> 1:04:03.360
<v Speaker 1>and that's now missing from most people in the industrialized world.

1:04:04.080 --> 1:04:06.600
<v Speaker 1>So there are big studies right now to try to

1:04:06.640 --> 1:04:10.800
<v Speaker 1>reintroduce that biffodobacteria and see if it helps us reduce

1:04:11.000 --> 1:04:14.920
<v Speaker 1>our incidence of autoimmune diseases. So the easiest disease to

1:04:14.920 --> 1:04:17.720
<v Speaker 1>study is ezema in some ways because it emerges within

1:04:17.760 --> 1:04:19.800
<v Speaker 1>the first year or so of life, and they're now

1:04:19.920 --> 1:04:22.880
<v Speaker 1>are big studies using biffidobacteria to see if we can

1:04:22.920 --> 1:04:26.320
<v Speaker 1>reduce those diseases. But there's also right now there's a

1:04:26.360 --> 1:04:29.480
<v Speaker 1>big study in Europe across five countries with more than

1:04:29.480 --> 1:04:32.200
<v Speaker 1>a thousand people who are from families who are a

1:04:32.200 --> 1:04:34.720
<v Speaker 1>little bit more at risk for developing type one diabetes,

1:04:35.320 --> 1:04:38.479
<v Speaker 1>and they're introducing that biffodobacteria. So it's going to take

1:04:38.680 --> 1:04:41.000
<v Speaker 1>like probably ten years until we have the beginnings of

1:04:41.040 --> 1:04:43.880
<v Speaker 1>the answer, because type one diabetes can happen in childhood

1:04:43.920 --> 1:04:48.600
<v Speaker 1>or even adulthood. But we're gonna know if these changes

1:04:48.640 --> 1:04:52.240
<v Speaker 1>in microbiome exposure that put us on a better immune

1:04:52.240 --> 1:04:57.200
<v Speaker 1>development course could help to reduce the incidence of type

1:04:57.200 --> 1:05:00.160
<v Speaker 1>one diabetes. So it might be akin to vaccination in

1:05:00.200 --> 1:05:05.720
<v Speaker 1>the future that we intentionally develop our microbial exposures to

1:05:05.760 --> 1:05:08.520
<v Speaker 1>direct the way our immune systems develop so we don't

1:05:08.600 --> 1:05:11.240
<v Speaker 1>end up with all these autoimmune diseases.

1:05:11.720 --> 1:05:13.240
<v Speaker 2>All right, Well, it sounds like a lot of potential

1:05:13.240 --> 1:05:15.400
<v Speaker 2>progress and lots of different directions. I hope that young

1:05:15.440 --> 1:05:18.600
<v Speaker 2>scientists out there are excited about working in all of

1:05:18.640 --> 1:05:22.240
<v Speaker 2>these angles and taking big risks like Lydia did.

1:05:22.720 --> 1:05:24.919
<v Speaker 3>Yeah, thanks for being on the show, kut Ri enough,

1:05:25.000 --> 1:05:25.640
<v Speaker 3>that was awesome.

1:05:25.800 --> 1:05:26.200
<v Speaker 1>Thank you.

1:05:26.320 --> 1:05:28.200
<v Speaker 2>I'm going to nominate you for next year's White Sin

1:05:28.320 --> 1:05:30.840
<v Speaker 2>Research Award as well, even that you've twenty five years ago.

1:05:30.880 --> 1:05:37.880
<v Speaker 1>Now I'm going to nominate you. You. I mean, I

1:05:37.920 --> 1:05:41.080
<v Speaker 1>think it's amazing that our society has produced all this

1:05:41.160 --> 1:05:44.440
<v Speaker 1>insulin to keep so many people with diabetes alive. And

1:05:44.480 --> 1:05:46.560
<v Speaker 1>we could do better with the access. But I mean,

1:05:46.640 --> 1:05:49.840
<v Speaker 1>considering that it's like water for so many people to

1:05:50.040 --> 1:05:52.480
<v Speaker 1>depend on the insulin, it's kind of amazing that we've

1:05:52.560 --> 1:05:53.680
<v Speaker 1>kept these systems going.

1:05:54.120 --> 1:05:56.640
<v Speaker 2>All right. Well, thanks very much, China, and thanks everybody

1:05:56.760 --> 1:05:57.560
<v Speaker 2>for listening.

1:06:04.840 --> 1:06:08.680
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1:06:08.720 --> 1:06:11.160
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