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  • 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 yearslong 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 theGreen 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 drugsgenetic engineering could also be used to produce medications in the first place.

  • Certain kinds of bacteria produce enzymesproteins that speed up chemical processeswhich 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 lightbrain 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 animalsespecially 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 outcomesthat'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.

Engineers like making things better.

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