Engineers like making things better.
From mechanical parts to electronic circuitry:
if it can be improved, somewhere an engineer is
working on making it more useful to the world.
Of course, the goal of all this is to make
our lives better.
But there’s another way in which life, in
the sense of living organisms, can be tailored
to our benefit.
At the boundaries of engineering and scientific
research, genetic engineers are working with
the very blueprints of life: DNA.
By editing DNA and the genes contained within
it, the field of genetic engineering is allowing us to
change the nature of living beings.
That can sound a little scary, and it’s
certainly not without its controversy.
But done correctly, it could help us create more food,
design new materials, treat or cure diseases, and even
improve people’s lives before they’re born.
[Theme Music]
The world of genetic engineering revolves around DNA:
a molecule found in nearly all the cells of
most living things, which governs how those
cells grow and function.
At its simplest, it consists of two, long sugar
phosphate strands that spiral around one
another in the famous double helix formation.
And it’s what links those two spirals together
that determines the genetic content of DNA.
Four types of molecules, called bases, make up
the biological code that stores information on the
structure of cells and how they operate.
The sequence of those bases makes up
the organism’s genes.
And if the organism reproduces, it passes
on some or all of those genes.
There’s a lot of cellular machinery that goes into
translating the code from DNA into the proteins that
carry out different functions within a living being.
But as you probably know, the end result is that
different genes produce different characteristics
in different living things.
Through millions of years of evolution and genetic
inheritance, differences in DNA are why a tiger has
stripes but a jaguar has spots,
or why sunflowers and roses have
different types of petals.
And humans have been tinkering with that
DNA for thousands of years – long before
we even knew it existed.
The most widespread example is the food we
obtain from crops.
People have selectively cultivated crops and
bred them to be bigger, yielding more food.
That’s essentially the same as picking crops
with the right genes.
We’ve also tried to make them more resilient
to problems like diseases or a lack of rainfall.
As for animal DNA, we bred wolves into domesticated
dogs more than 10,000 years ago.
So in some ways, genetic engineering has gone
on for millenia.
But one of the pioneers of modern genetic
engineering was American geneticist Norman
Borlaug.
In 1944, Borlaug was hired by the International
Maize and Wheat Improvement Center to, well,
improve maize and wheat.
Wheat is the third most-consumed cereal crop
in the world, so improving its yield would have
a huge impact.
Borlaug and his team tried some traditional
crop breeding techniques to make wheat more
resistant to diseases like stem rust,
which is caused by a fungus that shrivels
the stems of plants and can even kill them.
And to an extent, they were successful, but
the new disease-resistant wheat plants came
from wheat that had long, thin stems.
The new crops inherited those traits, too,
which caused them to fall over,
which interferes with their growth and can
reduce the final yields of the crops by up to 50%!
So, Borlaug and his colleagues used their
background in genetics
to cross-breed the new wheat with a shorter, Japanese
variety that was more resistant to falling over –
a trait that they successfully introduced into
the disease-resistant kind.
Wheat that doesn’t fall over might not sound
like the most amazing of accomplishments.
But Borlaug’s wheat was developed at just
the right time to prevent a catastrophic famine
from happening in India and Pakistan.
In 1962, Borlaug and his fellow scientists introduced
their new wheat to those countries, doubling the crop
yields in the region over the next decade.
The achievement became known as the “Green
Revolution.”
As a direct result of Borlaug’s work, it’s
estimated about 300 million people were
rescued from starvation,
and he was awarded the Nobel Peace
Prize for his work in 1970.
So genetic engineering has already changed
the world for the better in significant ways.
And today’s techniques give genetic engineers
an even more accurate and powerful toolkit for
tackling other challenges.
In addition to addressing food shortages,
we could tweak the development of certain
plants for the production of biofuels,
like ethanol derived from corn or
genetically engineered algae.
In fact, algae can be engineered to produce
more than just fuel.
If we can edit the right genes, we could create
large amounts of what are known as diatoms.
Diatoms are special forms of algae with cell
walls made of silica.
They’re literally living in glass houses!
That special property gives diatoms lots of
applications in nano-engineering.
They can be arranged onto surfaces to
produce biosensors, used to detect explosives,
or sent to deliver drugs inside the body.
Genetic engineering could help synthesize
and manipulate diatoms more efficiently.
And the medical benefits aren’t limited to delivering
drugs – genetic engineering could also be used to
produce medications in the first place.
Certain kinds of bacteria produce enzymes – proteins
that speed up chemical processes – which can, in turn,
produce the chemicals used in pharmaceutical drugs.
For example, the enzyme P450 is used to
create drugs for cancer treatment, but it’s
naturally produced by plants.
By inserting the genes of a P450-producing plant into bacteria, researchers can create factories of genetically engineered bacteria that generate P450 in greater amounts.
This type of strategy can make the drug production
process much more efficient – a similar method is
already used to produce insulin, for example.
Even better than treating diseases would be
stopping them from happening in the first place.
Which brings us to one of the more controversial
uses of genetic engineering: genetic treatments
for unborn animals, including humans.
Certain diseases are caused by issues in an
organism’s DNA.
Mutations happen when there’s a glitch in
the DNA-copying process and the base pairs
in the gene aren’t transcribed perfectly.
In humans, for example, mutations can lead to
heart conditions like hypertrophic cardiomyopathy,
which thickens some of the muscles in the
heart, stopping it from pumping blood efficiently
and forcing the heart to work harder.
If we could edit the DNA in an embryo to fix
a mutation or delete a carrier gene for a disease,
it would prevent the disease from being
there when the person was born and grew up.
On a genetic level, it’s like removing an
entire disease.
Of course, many are concerned that genetic engineering
would be used to modify humans for other traits, from
the color of their hair and eyes to their intelligence.
And whether or not that’s something we want
to do as a species is still being debated.
But modern methods are far from delivering that
kind of control, while certain diseases are already
being tackled with current techniques.
So genetic engineering has an enormous amount
of potential.
But the real challenge comes from how we actually
chop and change genes.
There are a few different ways geneticists do this,
but two breakthrough techniques have blown the doors
open in genetic engineering over the last decade:
Optogenetics and CRISPR.
Optogenetics involves modifying cells to make
them sensitive to light – brain cells, for example.
Understanding the human brain is an enormous
challenge, one that the National Academy of Engineering
in the US has made one of their Grand Challenges for
the 21st Century.
And one of the major obstacles is that we still
don’t know exactly what each cell in the brain does.
Since the human brain has certain structures similar
to those in other animals – especially mammals –
studying the brains of those animals
can help build a better model of our own.
Essentially, we need to be able to turn individual brain cells on and off and see how that affects an animal’s behavior to help understand how neurons work together throughout the body.
Changing the variables and measuring the outcomes
– that’s the heart of scientific testing.
Brain cells have certain proteins on their surfaces
called ion channel receptors, which are chemical
channels into the cell that act like switches.
They activate or deactivate brain cells when
a chemical, like a neurotransmitter, hits them.
Here’s where it gets clever.
Viruses are usually bad news for the organisms
they’re being hosted in.
Certain viruses can attack a cell’s DNA
and insert rogue bits of genetic code, making
the cell malfunction.
But because some viruses can introduce DNA
to cells, they can also be put to good use
for genetic engineering purposes.
For example, viruses modified to carry certain bits of
DNA can give a cell light sensitive proteins, called
opsins, embedded in its ion channel receptors.
Do that to brain cells in, say, a rat, and you can turn
those cells on and off by beaming pulses of light directly
to the cell using fiber optic cables.
Researchers have already used this technique
to study the motion circuits in the brains of mice,
even controlling their motion.
They’ve also manipulated cells that govern
sleep in fruit flies, waking them up and putting
them to sleep with flashes of light.
Both the motor cortex in mice and the sleep cycle
in fruit flies have parallel structures in humans,
so optogenetics offers a powerful way to
model human brain physiology.
Another star genetic engineering technique uses
chunks of bacterial DNA called Clustered Regularly
Interspaced Short Palindromic Repeats.
To avoid that mouthful, the technique is referred
to simply as CRISPR editing.
CRISPR can edit DNA in a way that’s easier
to customize, and can both remove particular
genes from a cell and add new ones.
It relies on on a defense mechanism found
in bacteria to defend against viruses.
Bacteria like E. coli produce certain proteins
that fight off viruses attacking the cell.
When they succeed in fighting off the invaders,
enzymes in the cell actually take parts of the virus
DNA and store it within the cell.
If another virus attacks later on, the bacteria produce special attack enzymes, known as Cas9, that carry around those stored bits of viral genetic code like a mug shot.
When Cas9 enzymes come across a virus, they
see if the virus contains genetic information that
matches the mug shot.
If it’s a match, the Cas9 enzyme chops up
the virus’s DNA to neutralize the threat.
These mechanisms are exactly what genetic
engineers need:
the ability to store and recognize portions of
genetic code on a microbiological level, and to
cut DNA and add parts of it where needed.
So, with CRISPR-Cas9, genetic engineers have
an incredibly versatile toolkit for editing genes in living beings.
So, among other things, CRISPR could help
cure diseases like cancer, sickle cell disease,
and certain kinds of muscular dystrophy.
In theory, all you have to do is remove the
mutations and put in the correct, healthy
DNA sequence.
There are lots of other approaches genetic
engineers can use, too, but CRISPR is one of the most
popular ones being used in research right now.
Still, CRISPR is far from perfect in its current
form.
Changing DNA isn’t consequence-free, and if done
incorrectly, it can even cause the very genetic diseases
and mutations researchers want to cure.
So there’s a long way to go before we’re
fully genetically engineering humans on the
DNA level.
But in the future, techniques like these may lead to cures
for all kinds of diseases, and like so many fields of
engineering, improve a lot of people’s quality of life.
In this episode, we looked at genetic engineering.
We saw that DNA was the underlying mechanism
for how genes are inherited by living things and how
it determines an organism’s features.
We saw how selective breeding can improve agricultural
practices, and the potential DNA-level engineering could
have on other fields of engineering.
Finally, we saw how optogenetics and CRISPR
have opened up new ways for genetic engineers
to change the DNA inside living cells.
In our next episode we’re gonna be combining
two awesome things: food & engineering.
Crash Coruse Augmented Reality Poster
available now at DFTBA.com
Crash Course Engineering is produced in association
with PBS Digital Studios, which also produces
Deep Look, a show that explores big scientific
mysteries by going very, VERY small.
See the unseen at the very edge of our visible
world, from eye popping mantis shrimp to blood
sucking mosquitos.
Check it out at the link in the description.
Crash Course is a Complexly production and
this episode was filmed in the Doctor Cheryl C.
Kinney Studio with the help of these wonderful people.
And our amazing graphics team is Thought Cafe.
