The DNA Double Helix Discovery — HHMI BioInteractive Video

Summary

The script narrates the groundbreaking discovery of the DNA double helix structure by James Watson and Francis Crick in the 1950s. It details their collaboration, the scientific challenges they faced, and the pivotal role of Rosalind Franklin's X-ray diffraction images. The story highlights the race against time, competition with other scientists, and the ultimate revelation of DNA's role in storing genetic information and enabling mutations, which earned them a Nobel Prize and revolutionized biology.

Takeaways

• 🌟 The discovery of DNA's structure in the 20th century was a monumental breakthrough that revolutionized our understanding of life's inheritance.
• 🔍 Traits like eye color and shape of a peapod were known to be inherited, but the method of storage and transmission of this genetic information was a profound mystery until the 1950s.
• 🧬 Scientists believed there was a special biological molecule responsible for inheritance, which had to explain both the stability and mutability of life for evolution to occur.
• 🤝 The collaboration between James Watson and Francis Crick at the Cavendish Laboratory led to one of the great discoveries of the 20th century, the structure of DNA.
• 🎓 Watson was a young American scientist with a passion for science, while Crick, an Englishman trained as a physicist, brought a fresh perspective to biological questions.
• 🧬 The idea that genes were made of DNA was not widely accepted initially, with proteins being considered more likely due to their diversity and functions within the cell.
• 🔬 X-ray crystallography was a crucial technique used to determine the molecular structure of DNA, despite being challenging and requiring interpretation of complex diffraction patterns.
• 🏆 The race to discover the structure of DNA was intense, with competitors such as Maurice Wilkins and Rosalind Franklin at King's College, and the threat of Linus Pauling's expertise in model building.
• 🔄 The first model of DNA by Watson and Crick was incorrect and met with criticism, but this failure was a part of the iterative scientific process leading to the correct model.
• 🔑 The correct model of DNA, a double helix with complementary base pairs, solved the mystery of genetic replication and provided an elegant explanation for both the stability and mutability of life.
• 🌐 The discovery of the DNA double helix was quickly recognized for its significance, leading to worldwide headlines, a Nobel Prize, and opening up new avenues for understanding life's mysteries.

Q & A

What significant scientific breakthrough occurred in the early 20th century that changed the world?

Physicists and chemists unlocked the secrets of the atom, which led to profound changes in the world.

What was the main mystery in the field of biology that remained unsolved in the early 20th century?

The main mystery was inheritance, specifically how traits were stored or transmitted from one generation to the next.

What were the special qualities that scientists believed the biological molecule responsible for inheritance must have?

The molecule needed to explain both the stability and mutability of life, allowing for the faithful transmission of traits while also enabling changes necessary for evolution.

Who were the two scientists that took up the challenge of solving the mystery of the arrangement of atoms in the molecule responsible for inheritance?

The two scientists were James Watson, an American, and Francis Crick, an Englishman.

What was the significance of the meeting between James Watson and Francis Crick?

Their meeting and subsequent collaboration led to one of the great discoveries of the 20th century, the structure of DNA.

What was the role of X-ray crystallography in the discovery of the DNA structure?

X-ray crystallography was a powerful technique used to determine the position of every atom in a molecule, which was crucial in solving the molecular structure of DNA.

Why was the initial model of DNA proposed by Watson and Crick dismissed by Rosalind Franklin?

Franklin dismissed their initial model because Watson had misremembered some key measurements, leading to an incorrect model that she quickly identified as flawed.

What was the importance of Erwin Chargaff's discovery regarding the chemical composition of DNA?

Chagaff's discovery that the amounts of adenine and thymine, and guanine and cytosine, were always equal in DNA was crucial for Watson and Crick's correct model, revealing the complementary nature of the bases.

What was the key insight that led to the correct model of the DNA double helix?

The key insight was that the sugar-phosphate backbones had to run in opposite directions with the bases on the inside, leading to the complementary pairing of adenine with thymine and guanine with cytosine.

How did the structure of the DNA double helix explain the process of genetic replication?

The complementary nature of the bases allowed for the separation of the two chains and the easy creation of new complementary copies, explaining how genetic information is replicated.

What was the reaction of the scientific community to the discovery of the DNA double helix structure?

The discovery was widely recognized as a powerful explanation for both the stability and mutability of life, and it was celebrated with a Nobel Prize nine years later.

Outlines

00:00

🧬 Unraveling the Secrets of Life: The Quest for the Structure of DNA

The script introduces the historical context of the early 20th century, where physicists and chemists had made significant strides in understanding atomic structures but the mysteries of life, particularly inheritance, remained elusive. Traits were known to be passed down through generations, yet the mechanisms behind this were unknown. Scientists hypothesized the existence of a unique biological molecule responsible for inheritance, which would need to explain both the stability and variability of life. The narrative then shifts to 1951, where two relatively unknown scientists, James Watson and Francis Crick, begin their pursuit of understanding this fundamental secret of life at the Cavendish Laboratory in Cambridge, England. Watson, a young American with a passion for science, and Crick, an English physicist turned biologist, quickly form a strong partnership based on their shared interests and desire to solve the structure of DNA.

05:02

🔬 The Challenges of DNA Research: X-ray Crystallography and Interpersonal Dynamics

This paragraph delves into the technical and interpersonal challenges faced by Watson and Crick in their quest to determine the structure of DNA. X-ray crystallography, a method crucial for solving molecular structures, was in its developmental stages and required interpreting complex diffraction patterns. The Cavendish Laboratory, known for its expertise in X-ray crystallography, was hesitant to engage in DNA research due to ongoing work at King's College in London. Maurice Wilkins, a physicist with a growing interest in biology, had initiated DNA research at King's but faced complications in his collaboration with Rosalind Franklin, a talented crystallographer who believed she should lead the project. Their conflicting views and the era's challenges for women in science created a strained partnership. Meanwhile, the threat of competition loomed with Linus Pauling, a renowned physical chemist, potentially working on DNA's structure from California.

10:03

🌀 The Race for the Double Helix: Missteps and Revelations

The script recounts Watson and Crick's initial foray into building a DNA model, which they believed to be a triple helix based on their understanding and early X-ray diffraction patterns. However, after a presentation by Rosalind Franklin, they realized their model was flawed, leading to its dismissal and their temporary prohibition from working on DNA. Despite this setback, Watson and Crick continued their research, driven by the fear of being preempted by Pauling. A pivotal moment occurred when Watson, after a visit to London and a chance encounter with Wilkins, saw Franklin's Photo 51, which revealed a clear helical pattern. This, combined with Crick's insight about the symmetry of DNA and Chargaff's rules about base pairing, led Watson to experiment with a double helix model, ultimately discovering the correct base pairing of adenine with thymine and cytosine with guanine.

15:04

🏆 The Triumph of the Double Helix: Implications and Legacy

The final paragraph celebrates the discovery of the DNA double helix and its profound impact on the field of biology. Watson and Crick's model not only fit the X-ray diffraction data and Chargaff's base pairing rules but also elegantly explained the mechanisms of genetic information storage and mutation. The complementary nature of the bases allowed for an easy replication process, solving a fundamental question in biology. The structure of DNA was published in Nature and was recognized worldwide, leading to a Nobel Prize for Watson, Crick, and Wilkins nine years later. The discovery served as a gateway to understanding life's mysteries and has continued to inspire biologists in their quest to decode the secrets of life.

Keywords

💡Inheritance

Inheritance refers to the passing of traits or characteristics from parents to their offspring. In the context of the video, it is a fundamental biological process that was not well understood until the discovery of the structure of DNA. The script mentions that everyone knew traits like the shape of a peapod or the color of eyes and hair were inherited, but the mechanism of how this information was stored or transmitted was a mystery until the work of Watson and Crick.

💡Molecule

A molecule is the smallest particle of a chemical element or compound that has the chemical properties of that element or compound. The video discusses the search for a biological molecule that could explain the process of inheritance. The molecule in question, DNA, was believed to have special qualities that allowed for the stability and mutability of life, as mentioned by Sean Carroll in the script.

💡James Watson

James Watson is an American biologist who, along with Francis Crick, is credited with discovering the structure of DNA. In the video, Watson is described as a young scientist with an intense love of science and a determination to solve the mystery of inheritance. His collaboration with Crick at the Cavendish Laboratory led to one of the great discoveries of the 20th century.

💡Francis Crick

Francis Crick was an English molecular biologist, biophysicist, and neuroscientist who, together with James Watson, made the groundbreaking discovery of the structure of DNA. The script highlights Crick's background in physics and his return to academic science after World War II, as well as his partnership with Watson and their shared interest in solving the structure of the gene.

💡X-ray Crystallography

X-ray crystallography is a technique used to determine the atomic and molecular structure of a crystal, bringing into view the arrangement of atoms in a molecule. In the video, this technique is crucial in the quest to understand the structure of DNA. The script describes how Watson and Crick used X-ray diffraction patterns to deduce the helical structure of DNA.

💡DNA

DNA, or deoxyribonucleic acid, is the molecule that carries the genetic instructions for the development, functioning, growth, and reproduction of all known living organisms. The video script discusses the discovery of DNA's structure as the key to understanding how genetic information is stored and transmitted. The script mentions that DNA was initially overlooked due to its seemingly simple composition of repeating units.

💡Genes

Genes are segments of DNA that contain the instructions for the development and function of living organisms. The concept of the gene dates back to Gregor Mendel's experiments and is central to the video's theme of inheritance. The script explains that genes are located within the nucleus of cells and are associated with structures called chromosomes.

💡Chromosomes

Chromosomes are thread-like structures consisting of DNA and protein, found inside the nucleus of animal and plant cells. They carry genetic information in the form of genes. In the video, chromosomes are mentioned as the structures within cells that contain DNA and are associated with the genetic material.

💡Mutation

A mutation is a change in the DNA sequence that can alter the genetic information within a cell. The video script explains that mutations occur when the sequence of DNA bases is changed, which is a key aspect of the evolutionary process. The discovery of DNA's structure helped to explain how such changes could occur.

💡Helix

A helix is a shape like a spiral or a coil, and in the context of the video, it refers to the structure of DNA. The script describes how Watson and Crick, along with other scientists, hypothesized that DNA might have a helical structure. Their model of the DNA double helix was confirmed by X-ray diffraction data.

💡Complementary Base Pairing

Complementary base pairing is the specific pairing of nucleotide bases in DNA, where adenine (A) pairs with thymine (T), and guanine (G) pairs with cytosine (C). This concept is central to the video's explanation of how DNA replicates. The script describes how the structure of DNA revealed by Watson and Crick showed the complementary nature of the bases, allowing for the accurate replication of genetic information.

Highlights

In the early 20th century, the secrets of the atom were unlocked, but the mystery of inheritance remained.

Scientists believed a biological molecule with special qualities was responsible for inheritance.

The molecule's 3D arrangement had to explain both the stability and mutability of life for evolution.

James Watson and Francis Crick joined forces at the Cavendish Laboratory to solve the structure of DNA.

Watson and Crick believed that DNA, not protein, was the molecule of inheritance.

X-ray crystallography was the technique used to determine the position of every atom in a molecule.

Maurice Wilkins and Rosalind Franklin at King's College were also working on DNA's structure.

Franklin's Photo 51 became one of the most famous images in biology, showing a DNA helix.

Watson and Crick initially proposed a triple helix model, which was later dismissed.

Erwin Chargaff's data on the base ratios in DNA was a crucial piece of the puzzle.

Watson's realization of base pairing (A-T and C-G) led to the correct double helix model.

The double helix structure revealed how genetic information is stored and replicated.

The complementary nature of the bases explained gene replication and mutation.

Watson and Crick's discovery was published in Nature and later awarded a Nobel Prize.

The double helix opened up a new world for biologists to decode the mysteries of life.

The discovery had a profound impact on the scientific community and the understanding of genetics.

The story of DNA's structure highlights the importance of collaboration, perseverance, and innovation in science.

Transcripts

[MUSIC PLAYING]

OLIVIA JUDSON: In the early 20th century,

physicists and chemists unlocked secrets of the atom that

changed the world forever.

[EXPLOSION]

But life remained a profound mystery.

Among life's deepest secrets was inheritance.

Everyone knew that traits like the shape of a peapod

or the color of eyes and hair were passed on from generation

to generation.

But no one knew how such information

was stored or transmitted.

Scientists were convinced that there

had to be a biological molecule at the heart of the process,

and that molecule had to have some pretty special qualities.

SEAN CARROLL: The three-dimensional arrangement

of atoms in those molecules had to explain

the stability of life, so that traits were passed faithfully

from generation to generation, and also

the mutability of life.

You have to have change in order for evolution to happen.

OLIVIA JUDSON: The challenge of solving

this mysterious arrangement of atoms, this fundamental secret

of life, was taken up in 1951 by two unknown scientists.

Less than 18 months later, they would

make one of the great discoveries

of the 20th century.

They met and joined forces of the Cavendish Laboratory

in Cambridge, England.

One was a 23-year-old American named James Watson.

ROBERT OLBY: He had a crew cut when he first

came to Cambridge.

And that was very rare in Cambridge in those days.

He liked to wear what I call gym shoes

and leave the laces untied and things like that.

He was quite an enfant terrible, I would say.

But behind that, of course, was his extreme, intense love

of science, right from his early years, and his determination.

OLIVIA JUDSON: The other was an Englishman named Francis Crick.

Trained as a physicist, his academic career

had been interrupted by the outbreak of the Second World

War.

It wasn't until 1949 that he got back into academic science.

He was anxious to make up for lost time,

and, now, interested in biology.

Crick and Watson connected instantly

when they met in 1951.

They both loved to talk science.

JAMES WATSON: Francis and I both liked ideas.

And as long as I could talk to Francis, you know,

I felt every day was worthwhile.

OLIVIA JUDSON: Crick was always ready to share his thoughts,

though he rarely did so quietly.

JAMES WATSON: Any room he was in, he

was going to make more noise than anyone else.

KAROLIN LUGER: They would constantly

throw crazy idea at each other, dismiss them,

have another idea, follow that a little further, dismiss that.

But then something comes out of left field.

So it's kind of this give and take.

FRANCIS CRICK: We did have different backgrounds,

but we had the same interests.

We both thought that finding the structure of the gene

was the key problem.

OLIVIA JUDSON: The idea of the gene

dates back to Gregor Mendel's experiments

with peapods in the 1860s.

By the 1920s, genes had been convincingly located

inside the nucleus of cells, and associated with structures

called chromosomes.

It was also known the chromosomes

are made of proteins and the nucleic acid--

deoxyribonucleic acid, or DNA.

That meant the genes had to be made of either DNA or protein.

But which was it?

Protein seemed the better bet.

There are lots of different kinds of them,

and they do lots of different stuff inside the cell.

In contrast, DNA didn't seem very interesting.

It's just repeated units of a sugar

linked to a phosphate and any of four bases.

The readiness to dismiss DNA was so entrenched

that it persisted even after Oswald Avery showed that it

can carry genetic information.

SEAN CARROLL: Avery had isolated a substance

that conveyed a trait from one bacterium to another.

And this transforming principle, as he called it,

he showed that it was not destroyed

by a protein-digesting enzyme, but was destroyed

by a DNA-digesting enzyme.

OLIVIA JUDSON: Watson and Crick were among the few who

found Avery's work persuasive.

They thought genes were made of DNA.

They also thought that solving the molecular structure

of the molecule would reveal how genetic information is

stored and passed on.

At the time, a powerful technique

for solving molecular structure was being perfected--

X-ray crystallography.

KAROLIN LUGER: At its best, X-ray crystallography

can determine the position of every single atom

in the molecule that you're analyzing with respect

to every other single atom.

OLIVIA JUDSON: Not that it's easy.

The picture you end up with is a diffraction pattern.

And to make sense of it, to work out where the atoms are,

involves interpreting lengthy calculations.

And in the 1950s, the equipment was

primitive and difficult to maintain.

The X-ray sources weren't very bright.

And on top of that, DNA is not an easy molecule to work with.

KAROLIN LUGER: Basically, picture snot.

It's kind of hard to pick it up and do stuff with it

and analyze it.

Polymers are not fun to work with from that point of view.

OLIVIA JUDSON: The Cavendish was famous for X-ray

crystallography.

But the director of the lab didn't want his stuff X-raying

DNA.

He knew that a group at King's College in London

was already doing that, and he didn't

want to be seen as competing.

JAMES WATSON: It just wasn't good manners.

OLIVIA JUDSON: The King's College scientist

who had initiated the work on DNA was Maurice Wilkins.

Like Crick, he was trained as a physicist,

and had only recently become interested

in biological questions.

Though he was drawn to the problem of the gene,

Wilkins lacked Watson and Crick's burning urgency

to find a solution.

Complicating things for Wilkins was his relationship

with his colleague, Rosalind Franklin.

She was a talented crystallographer.

But when she joined the team at King's, she

believed that she would be leading its DNA research.

KAROLIN LUGER: She had the notion

that this was her project.

He had the notion it was his project, and, if anything,

she should help him in his effort to solve the structure.

And so this is a recipe for disaster.

OLIVIA JUDSON: The times and their personalities

worked against an effective partnership.

KAROLIN LUGER: This was a time when

it was very, very hard for women in science

to be taken seriously.

And so I would imagine that Rosalind Franklin had to be,

perhaps, quite assertive.

OLIVIA JUDSON: She certainly asserted her independence.

Wilkins, by all accounts a shy man,

reluctantly agreed that they would work separately.

London is only 75 miles from Cambridge.

That means that Watson and Crick could easily keep tabs

on the work being done at King's.

But another potential competitor was thousands

of miles away in California.

Linus Pauling was renowned as the greatest physical chemist

of his generation.

He was widely admired for his ability

to build accurate models of complex molecules.

Watson and Crick were convinced that it was just

a matter of time before Pauling used this technique

to solve DNA.

Biological molecules come in a variety of shapes.

Pauling and Watson and Crick suspected

DNA might be a helix of some kind.

But if so, how were the sugar, the phosphate, and the bases

arranged?

Early in his collaboration with Watson,

Crick had worked out mathematically

what the X-ray diffraction pattern of a helical molecule

should look like.

Shortly afterwards, Watson went to London

to hear Franklin report on some of her recent work.

When he got back, he told Crick what he remembered of her talk,

and they decided to build a model.

In a few days, they had one.

It was a helix with three sugar phosphate chains on the inside

and the bases sticking out.

KAROLIN LUGER: At that time, the only interesting thing

about the DNA molecule is the bases.

And so it made perfect sense.

I mean, only an idiot would put them inside.

Because then they're hidden.

OLIVIA JUDSON: They invited Wilkins and Franklin

to come and take a look.

Unfortunately, Watson had misremembered

some of her key measurements.

Franklin saw this immediately, and quickly and derisively

dismissed their effort.

She went on to craft a mocking announcement for the death

of DNA as a helix.

It was an embarrassment that did not sit well

with the Cavendish leadership.

JAMES WATSON: We were forbidden, in a sense, to work on DNA.

OLIVIA JUDSON: The failure of the first model was painful.

But it can also be seen as just part of the scientific process.

KAROLIN LUGER: I would actually maintain

that, in order to arrive at the right solution,

you have to put out a couple of wrong ones.

And that's just the nature of discovery.

And if you're afraid of making a mistake,

you're going to fail in this business.

OLIVIA JUDSON: Through 1952, Watson and Crick

read and talked over anything and everything that

could prove relevant for their ongoing, but now underground,

quest to discover the structure of DNA.

JAMES WATSON: To me, there was only one way I could be happy--

or two ways-- solve DNA or get a girlfriend.

[LAUGHS]

And I didn't get a girlfriend, so it was solve DNA.

OLIVIA JUDSON: The year ended with Watson and Crick

thinking about DNA, Franklin taking pictures of DNA, Wilkins

avoiding Franklin, and Pauling a distant, but worrisome,

presence.

Then, in January 1953, everything changed.

News came that Pauling was indeed preparing a paper

on the structure of DNA.

Watson secured a copy of the manuscript

and found, to his great relief, the Pauling

was proposing a triple helix.

It was very similar to the one that he and Crick

had been shamed into abandoning the previous year.

Relieved, he headed to London to share the news

that the race for DNA wasn't over,

only to find that Rosalind Franklin wasn't particularly

interested in what he had to say.

ROBERT OLBY: Following his departure

from Rosalind Franklin's room, he encountered Wilkins.

And Wilkins took him into his room,

and then took out of the drawer a picture

which had been taken by Rosalind Franklin.

OLIVIA JUDSON: That picture would

become one of the most famous images

in all biology, Franklin's Photo 51.

Jim Watson recognized the diffraction pattern

immediately.

It was a helix.

And based on this, Watson thought

it might have just two chains--

a double helix.

About the same time, Francis Crick

was shown a report on Franklin's work

that included an observation on the symmetry of DNA.

This led Crick to a crucial insight

that Franklin had missed.

The two backbones had to run in opposite directions.

That led him to the conclusion that the sugar phosphate

backbones had to be on the outside with the bases inside.

So Watson started to build models again.

He experimented with pairing like with like--

adenine with adenine, thymine with thymine, and so on.

That would make each chain identical.

Watson thought that could explain how

genetic information is stored.

He thought he had the solution.

But then a Cambridge colleague told him

that the bases could not pair with themselves in that way.

And Crick pointed out that the model

didn't take account of something else that was known about DNA.

A few years earlier, another chemist interested in DNA,

Erwin Chargaff, had reported a puzzling fact

about the molecule.

KAROLIN LUGER: He analyzed the chemical composition of DNA

in different species.

And what he found is that the amount

of As-- the base adenine-- and the amount of base Ts

was always the same.

And Gs and Cs were always the same.

OLIVIA JUDSON: But no one, including Chargaff,

had figured out what those base ratios meant.

With Chargaff's data in mind, Jim Watson

went alone to the lab one Saturday morning

and started playing with cardboard cutouts.

JAMES WATSON: I began moving them around.

And I wanted an arrangement where I

had a big and a small molecule.

So how did you do it?

Somehow, you had to formed linked bonds.

So here's A and here's T. And I wanted

this hydrogen to point directly at this nitrogen.

So I had something like this.

[ZAPPING]

Oh.

So then I went to link the pair.

I wanted this nitrogen to point to this one.

And it looked like this.

[ZAPPING]

Whoa.

They look the same.

And you can push one right on top of the other.

[ZAPPING]

We knew, even if we go up to the ceiling,

we were building a tiny fraction of a molecule.

Hundreds of millions of these base

pairs in one molecule, all fitting

into this wonderful symmetry, which

we saw the morning of February 28, 1953.

OLIVIA JUDSON: The model fit the measurements,

both from the X-ray diffraction pictures

and from Chargaff's data.

But most important of all, the arrangement of the bases

immediately revealed how DNA works.

FRANCIS CRICK: The key aspects of the structure

was the complementary nature of the bases.

If you had a big one on this side,

you had to have a particularly small one on this side,

or vice versa, and so on, all the way up.

So it meant that, by separating the two chins,

you could then easily make a new complementary copy

by just obeying these pairing rules of which one

went with what.

And that solved in one blow the whole idea

of how you replicate a gene.

OLIVIA JUDSON: The structure immediately revealed

two things--

how genetic information is stored

and how changes or mutations happen.

The information is stored by the sequence of the bases.

Mutations occur when the sequence is changed.

JAMES WATSON: It's a simpler and better answer

than we ever dared hope for.

FRANCIS CRICK: And I remember an occasion when Jim gave a talk.

It's true, they gave him one or two drinks before dinner.

It was rather a short talk, because all

he could say at the end was, well, you see, he's so pretty.

He's so pretty.

JAMES WATSON: I think everyone just took joy in it,

because the field needed us.

But on the other hand, the biochemistry department

didn't invite us to give a seminar on it.

SEAN CARROLL: When the structure of the double helix

was revealed, most biologists instantly recognized the power

of the explanation before them.

Here was this beautiful molecule that

could explain both the stability of life

over huge amounts of time and its mutability in evolution.

OLIVIA JUDSON: That triumph was reported in the journal Nature.

It made headlines around the world,

and was celebrated nine years later with a Nobel Prize.

KAROLIN LUGER: That's kind of what every scientist dreams

about, to make a discovery that has this kind of impact.

SEAN CARROLL: For biologists, the discovery

of the double helix opened up a whole new world.

It was a passport to all the mysteries of life--

mysteries that biologists have been decoding ever since.

[MUSIC PLAYING]