is on DNA and RNA. I want to start with a picture of a peanut plant. Right here we have

the same peanut plant in both of these. On the left side it's being decimated by the

larvae from a corn stalk bore. The one on the right however you can see the bore sitting

right here but it's not eating the peanut. And the reason why is this one over here has

been engineered. They've actually added a gene from a bacteria called bacillus thuringiensis.

And it produces a toxin that the larvae doesn't like. So it takes a couple of bites. Quits

eating it. So there are two things that I wanted to show you with this picture. Number

one is this idea that no matter what you are, a virus, a bacteria, eukaryote, like a plant

or an animal, you have the same genetic material. And that's called DNA. The other thing that's

interesting is that humans can tamper with this. We can actually transfer DNA from one

organism to another. We can transform that organism. And that whole field is called genetic

engineering and it's exploding right now. So in this podcast I'm going to try to accomplish

five things. First of all we're going to talk about the history of DNA. How these three

experiments, the Avery-MacLeod-McCarty, the Hershey-Chase and finally the Watson-Crick-Wilkins

and Franklin experiments showed us what DNA looks like. Where it is and how it works.

Next I'll talk about how DNA is organized in chromosomes. Both prokaryotic and eukaryotic.

We'll talk about the structure of DNA and RNA. Mostly how they're different. And then

how DNA makes copies of itself. We'll then discuss the Central Dogma. How DNA is transferred

through transcription into RNA. Which is then translated into proteins which then makes

you. And then finally we're going to talk about this brave frontier of genetic engineering.

And how we can do things like transform bacteria to make important things. Especially for diabetics,

like human insulin. And so that's a lot to do. So we better get started. Let's start

way back in history with the Frederick Griffith experiment. This was in 1928. He was a medical

doctor. And so what he was looking at was bacteria. And they would do serological testing.

So they're trying to figure out what bacteria causes disease and they were using a mouse

as a lab experiment. So right here they're using streptococcus pneumoniae, they're taking

one type of that. It's called rough, because when you grow it in plates it has a rough

appearance. They would inject that into the mouse and the mouse would be happy. They'd

then inject a different type of that streptococcus, a virulent type. This one is smooth. They'd

inject it into the mouse and then it would die. And so he hasn't learned anything at

this point. He then took this evil smooth strain of streptococcus. He heat killed it.

So he heated it up. And he found when he injected that heated into the mouse, the mouse was

good to go. So we haven't learned anything yet. What he then found, and this would be

that discrepant event, is that when he took the rough strain, which normally doesn't hurt

the mouse at all, he then mixed it with the heat killed smooth strain which normally doesn't

hurt the mouse at all. The mouse died. And so what did he learn from that? Well he learned

a lot. And the big thing he learned is that there was a transforming factor. Something

was being transferred from these dead smooth strain to these live rough strain. It was

transforming them into a virulent type of a bacteria. He didn't know what it was, but

we took the next 30 years to figure out that is was DNA. And we figured out the structure

of that. So the first step came through the Avery-McCarty-MacLeod experiments. And this

is in the 30s and 40s. And what they did is looked at Fredrick Griffith's experiment and

they tried to figure out what was this transforming factor? What was being transferred from these

heat killed smooth strain over to these rough strain? And so they broke down the bacteria.

They then isolated the major molecules inside that. And so what they had was RNA. They also

had proteins. And then the last thing that they found was DNA. And we knew what DNA was.

We'd known it for you know 50 years before then. And so what they then used was enzymes

that broke down each of these. And then they'd see if you could transform the bacteria again.

So they add a ribonuclease and broke down the RNA and it still was able to transform.

They added a couple enzymes, trypsin and chimotrypsin that break down proteins. It was still able

to transform. And then they added a deoxyribonuclease which breaks down DNA and then they couldn't

transform. And so what did Avery-McCarty-MacLeod figure out? DNA was this transforming factor.

Now most of their work was largely ignored and the reason why is most scientists thought

DNA was not complex enough to be the stuff of life. It only has four different letters

and we'll talk about that in just a second. And so that couldn't be the stuff of life.

And so a lot of their work was actually ignored. But in retrospect we look back and they show

that they were the ones who figured out it was DNA. Where was the definitive answer?

Well most of the argument came form is it DNA? Or is it proteins that are actually being

transferred? And proteins are very complex. And so most of the people were thinking that

it's proteins that was the genetic material. Not DNA. And so the Hershey-Chase experiment,

sometimes called the blender experiment, used bacteriophages. And a bacteriophage is simply

a virus that infects a bacteria. It looks kind of like lunar lander. It lands on the

bacteria. It injects its hereditary material in. And then it hijacks that bacteria to make

more of the bacteriophage. And so what Hershey and Chase did, it's a really elegant experiment,

is they used two different atoms. They used in one experiment sulfur. And in this case

the sulfur is labelled red. They used a red dye to dye the bacteriophages in this experiment.

They then infect the bacteria, blend it all up. They precipitate it out and see what color

came out. Now why was it important they use sulfur? It's because sulfur is found in proteins

but it's not found in DNA. They then used a different dye to dye phosphorus. Phosphorus

is found in DNA but it's not found in proteins. And so what they were able to show is that

the only one that was doing the transforming was this green dye. That means that it was

the phosphorus. And that means that it wasn't proteins that were transferring the information.

That it was DNA. And so the Hershey-Chase experiment was definitive proof that DNA was

the hereditary material. And so this is in the 50s. And now the race is on to figure

out, not only, mostly to figure out what's the structure of DNA. How's it all work. These

are interesting people. Apparently Hershey and Chase, they worked together. Their lab

was totally silent and they just worked very effectively together. Sadly Martha Chase goes

crazy later in life. But a really cool experiment. Now we go to the ones that you're probably

familiar with. The names that you're familiar with. And that's probably Watson and Crick.

James Watson and Francis Crick are mostly given credit for discovering the structure

of DNA. But there were three other, probably even more people that played in this discovery

of this structure of DNA. One of those is Maurice Wilkins. Maurice Wilkins was really

good at x-ray crystallography. So that is taking pictures of crystalized material. It's

kind of like shining light through a chandelier and then figuring out what the structure of

the chandelier is. He was working with Rosalind Franklin. They didn't get along that well.

And Maurice Wilkins is an interesting guy. Died just a few years ago. They didn't work

well together but they had the best data out there. This is a picture of some of the, this

would be the x-ray crystallography of DNA. So they were looking at DNA and trying to

figure out its structure. If you know anything about crystallography you'd know that this

is a helix. Or it suggests the structure of a helix. Actually James Watson sat in on one

of Rosalind Franklin's secret meetings and took notes on it. And it actually helped them

to figure the structure a lot. Next we've got Erwin Chargaff. Erwin Chargaff was looking

at different organisms and studying the amount of As, Ts, Cs and Gs. And so A, G, C and T

are the four different bases that are found in DNA. And he found something unique. If

you look at for example an octopus, the amount of A, 33.2 and the amount of T is exactly

the same, about the same. And if you look at the amount of G, 17.6 and 17.1, that's about the

same as well. In other words the amount of A and the amount of T is always the same.

And the amount of G and the amount of C is always the same. We sometimes call this Chargaff's

Rule. So as you look all the way down here, like in humans, we have 29.3% A and 30% T.

Likewise we have 20% G and C. And so he didn't know what that meant, but Crick and Watson

knew that. They knew the structure of a helix coming from the work the Franklin and Wilkins.

And so they used models to figure out the structure of DNA. Why do we always have the

A and the T equal? And the G and C equal? Well if you look at the structure of DNA,

you have a backbone. This is actually a model of, this is the model that Watson and Crick

were working on. So you've got a backbone that looks like this. But then on the inside

you have your bases. And if you have an A on this side, a T will be on the other side.

And if you have a C on this side a G will be on the other side. And so the amount of

As and the amount of Ts are always equal because they bond to each other. And so this that

double helix. So Watson and Crick are given the credit for that. They actually share the

Noble prize with Maurice Wilkins. Rosalind Franklin doesn't get the Nobel Prize because

sadly she had died before then of cancer. And it was probably as a result of the x-rays

that she was using in her lab. And you can't get a Nobel prize if you die. Okay. So let's

now go to the structure. Structure of DNA. DNA doesn't just sit loose inside the nucleus.

It's organized into something called a chromosome. And so in us, in eukaryotic cells, we have

this characteristic shape of a chromosome. If you actually look at how the DNA is organized,

the DNA is wrapped around these proteins called histone proteins. And those are swirled around

other proteins and other proteins and eventually you get to the structure of the chromosome

that looks like this. Now the reason it characteristically looks like an X is that when we take a picture

of our chromosomes, this would be a picture of our chromosomes, they're usually in metaphase.

And so they usually have this characteristic X structure. What does that mean? That means

that the left side is a mirror copy of the right side. And so in a lot of my diagrams,

you'll see me drawing it, a chromosome just looking like this. With a centromere in the

middle. And that's because that's what a chromes usually looks like. It's a linear stretch.

And so in eukaryotic cells we have this long stretch of DNA wrapped around proteins and

that's where the genetic material is found. And it's really really really long compared

to the size of the actual cell itself. If we look at prokaryotic chromosomes it's different.

In a prokaryotic chromosome, the chromosome is simply loose here. It's not in a nucleus

at all. And it's also a loop. And so in us, we have a linear chromosome. In other words

it's a length with a definite end of either side. But in prokaryotics they've got just

a loop. Now the loop is wrapped around itself so it can fit in what's called the nucleoid

region of the bacteria. But it's a loop none the less. They also have extra little tiny

loops called plasmids. And those have DNA in them as well. And they carry genetic information.

And these can actually be swapped between bacteria. So it's like an extra set of genes.

Another important difference between us and bacteria is that a lot of our chromosomes

is what's called junk DNA. In other words it's DNA that's not actual genes. It's between

genes. And if you look at the DNA of a prokaryotic cell, each of those little stretches is going

to be one gene after gene after gene after gene. Now we're starting to figure out that

it's not really junk DNA. That it actually has an important function. We'll talk about

that in a different podcast.