As some scientists worked to control life
at the scale of global agriculture, others
worked in a different direction.
The mid-1900s was a period of reexamination
of one of our big questions: what, exactly,
is life?
Let's talk DNA and Biotech!!!
[Intro Music Plays]
Although the story is complex, it’s often
simplified to one big “discovery” of DNA
made in 1953 by two dudes who won Nobels.
… There were other people involved.
By the 1940s, researchers knew that the cell
nucleus contained thread-shaped structures
called chromosomes that played a critical
role in cell division.
Chromosomes seemed to be made of a mixture
of protein and other stuff.
And this other key stuff was a molecule made
out of carbon, hydrogen, nitrogen, and phosphorus.
This was deoxyribonucleic acid, or DNA.
Isolated, DNA looks kind of like white powder.
But no one knew DNA’s structure.
A molecule’s structure—the way it fits
together—tells us about how it works, and
maybe how to redesign it.
In 1944, Austrian physicist Erwin Schrödinger—the
cat guy—published a short book called What
is Life?, reviewing this deceptively simple
question.
Scientists knew that there must be a unit
of heredity, the “gene,” that must be
part of the chromosomes.
Schrödinger examined the laws of physics,
determining that the gene must be very small,
only a few thousand atoms in size.
It must vary.
Yet it must be orderly and not give rise to
too many mutations.
So Schrödinger threw down the challenge:
how does this “gene” physically encode
the information that defines life?
He argued that this was among the most interesting
questions facing science.
And he suggested that one of the people best
poised to answer it was biophysicist Max Delbrück.
Delbrück ran a loosely organized network
of researchers at Cold Spring Harbor Laboratory,
Caltech, and elsewhere called the Phage Group.
The Group worked with viruses that parasite
bacteria, called bacteriophages.
Viruses are just nucleic acids in little protein
robot-bodies.
The Phage Group did important work on how
life works at a small scale, using radioactive
tracers inside viruses.
But even they couldn’t tell if it was the
DNA part or the protein part of the virus
that took over the bacterium.
And no one could explain how either physically
encoded information.
So by 1950, the pressure to understand DNA
was on… even though not everyone was convinced
that DNA was the physical substrate of heredity
at all!
Despite this uncertainty, scientists set out
to win this race.
The most famous was American chemist Linus
Pauling—who went on to join the short list
of people with two Nobel Prizes!
Pauling was an obvious choice because in 1951
he characterized the alpha helix structure
of common proteins.
He used an empirical approach, X-ray crystallography:
X-rays—which have wavelengths much smaller
than visible light—pierce molecules, then
scatter, making a diffraction pattern that
reveals information about the molecule’s
shape.
Crystallography is an incredibly finicky technique.
But Pauling correctly showed how common proteins
fold up into elegant little spirals.
He then decided to tackle DNA—guessing incorrectly
that it was made up of three helices.
Also in the race was James Watson, a brilliant,
young, and brash American biochemist.
“Brash” is the historian's euphemism for
“sexist jerk.”
He was a member of the Phage Group and a fan
of Schrödinger’s What is Life?
Watson traveled to the University of Cambridge’s
Cavendish Laboratory.
There, he partnered with English biophysicist
Francis Crick, who became one of the great
theorists of modern biology.
Watson and Crick’s approach was modeling
DNA—asking which atoms went where, based
on the laws of chemistry and physics.
Now, if you read Watson’s best-selling autobiography,
The Double Helix, you’d think he and Crick
did the heavy lifting in discovering the structure
of DNA.
You wouldn’t know that Harvard University
Press refused to publish his book because
of its potentially libelous characterization
of their collaborators!
ThoughtBubble, shows us another side of the
story:
Watson cast English chemist Rosalind Franklin
as the villain.
Franklin worked at King’s College London,
not the Cavendish.
And she was Jewish.
And she was… also… a woman.
She also went to a talk by Watson and Crick
and tore apart their suggested model of DNA.
The head of the Cavendish was humiliated, forbidding them from more DNA modeling.
You see, Franklin was a leading expert in
X-ray crystallography.
Her photographs had shown that there were
two forms of DNA: A, which is dry and crystalline,
and B, which is wet—how DNA looks in living
cells.
This discovery was a fundamental step in understanding
DNA.
(We now know there is a third form, Z-DNA.)
Then in 1952, Franklin made one of the most
famous photographs in science: Photo 51.
It shows a clear “X” pattern—the signature
of a helix, or spiral-stair shape.
But Franklin didn’t know that the deputy
director of her lab,
Maurice Wilkins, was secretly passing her
notes and images to Watson and Crick.
The rest became history…
In 1953—working on their model, reviewing
facts about the four nucleic acids in DNA,
or bases, and looking at Franklin’s images—Watson
and Crick realized DNA must be a double helix.
And that the bases must be paired so that
the As equal the Ts and the Gs match the Cs.
The zipper shape of the double helix allows
DNA to transmit information from generation
to generation with few copying errors: a cellular
machine “unzips” the staircase down the
middle, and figures out one half of a base
pair by looking at the other.
If one base is an A, it must connect to a
T. Simple!
Watson and Crick invited Franklin to Cambridge
to review their work.
She immediately acknowledged that it was correct.
She just didn’t know how much they had relied
on her own work!
Thanks Thoughtbubble,
After publishing their model and the data
backing it up, Watson and Crick became scientific
celebrities.
Franklin, however, died prematurely of cancer,
likely due to her work with X-rays.
And the Nobel Prize is not awarded posthumously.
So in 1962, Watson, Crick, and Wilkins shared
the Nobel without acknowledging the debt they
owed to Franklin.
But, in part because Watson described Franklin
so horribly in his book—he called Franklin
“Wilkins’s assistant!”—historians
went back and researched her life, writing
her back into the role of protagonist in the
story of DNA.
So a scientific object like DNA is assembled
out of other scientific objects such as X-ray
images, textbooks, and three-dimensional models
of tin and cardboard—but also erroneous
ideas such as Pauling’s triple helix, as
well as relationships and competitive drives
for fame.
With DNA revealed, life itself could theoretically
now be not only “read” but “programmed.”
Remember, this was around the same time as
the birth of computing!
So DNA became a machine-language “program”
to make RNA, which became an assembly-language
“program” for making proteins, which are
what life is made out of.
This process was thought to be quite computer-like,
moving only in one direction—from DNA to
RNA to proteins.
This rule, first expressed by Crick, is the
Central Dogma of Genetics.
We now know it’s more complicated, but the
essential idea is useful.
The question after 1953 was another how—the
genetic code.
DNA has four nucleic acid “letters”—A,
T, G, and C, with a U instead of a T in RNA.
But how do these code for the twenty amino-acid
“letters” of the proteins that we’re
made out of?
Some of the DNA discoverers went back to the
theoretical drawing board.
In 1954, Watson and Soviet-American physicist
George Gamow founded the “RNA
tie club” to figure it out.
And Gamow, Crick, and others did important
theoretical work.
But in 1961, biochemists Marshall Nirenberg
and Heinrich Matthaei cracked
the first piece of the code.
And, over the 1960s, other biochemists figured
out the rest, including how RNA works.
Also in 1953, University of Chicago chemist
Stanley Miller and his advisor Harold Urey
produced amino acids, the building
blocks of life, out of an electrified broth
of not-living nutrients.
The Miller–Urey experiment supported the
idea that all life on earth arose in a primordial
soup of basic nutrients, billions of years
ago.
Some scientists, though—including Crick!—found
this unlikely, and thought life on earth probably
came from outer space.
An idea called panspermia.
The discoveries of 1953 marked a new era in
biology.
Evolution now had a molecular basis: mutations
are copy errors in DNA.
Rare, but inevitable.
Mutations give rise to the variation that
Darwin and Wallace described.
Molecular techniques revolutionized the study
of evolution.
Species were regrouped by the similarity of
their DNA, not their visible physical structures.
Crabs, for example, evolved several times,
millions of years apart.
It turns out that having armor-skin and claw
hands, and being able to digest literal trash
is super useful in different watery environments!
Another use of the newly deciphered genetic
code was industrial.
Arguably, biotechnology had been around for
a while.
Beer, after all, is made using engineered
strains of brewers’ yeast.
But this process takes a long time and involves
strain selection, or picking types of yeast
with useful properties—not molecular-scale
editing.
After 1953, scientists started looking for
genes connected to traits of interest.
The problem was, knowing what genes code for
what traits wasn’t useful without having
a way to move those genes around.
So biotech took off in the early 1970s in
San Francisco, after Paul Berg, Stanley Cohen,
and Herbert Boyer published the results of
experiments with recombinant DNA or rDNA—new,
synthetic sections of DNA made by cloning
sections from one organism’s genome into
another.
With rDNA, scientists could splice sequences
of DNA.
Berg became the first person to join DNA from
two different species in one microbe.
rDNA allowed scientists to copy the genes
involved in the creation of the important
hormone insulin, which regulates how much
sugar the body has in its bloodstream, into
bacteria and yeast.
Before rDNA, people with diabetes had to get
insulin from pigs or other animals, but synthetic
insulin is more pure.
Industrial genetic engineering exploded.
In 1980, the Supreme Court of the United States
heard a landmark case called Diamond v. Chakrabarty
The question was whether or not a company
could patent a bioengineered lifeform—a
microbe designed to eat up spilled oil.
SCOTUS said yes: if you engineer an organism’s
genome, then it becomes a technology.
And, by 1980, the biotech industry also had
its first initial public offerings, or IPOs.
Several companies launched with massive valuations.
And universities—especially around San Francisco
and Boston—began to view their scientific
discoveries as major sources of money.
They set up offices of technology transfer
or licensing.
Scientific knowledge—and life itself—became
potential technologies.
Next time—we’ll look at how biological
technologies changed medicine and agriculture.
It’s time for the birth of Big Pharma, GMOs,
and IVF.
Crash Course History of Science is filmed
in the Dr. Cheryl C. Kinney studio in Missoula,
Montana and it’s made with the help of all
this nice people and our animation team is
Thought Cafe.
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