Doudna and Charpentier – the science superheroes of CRISPR

Boom Advent #10 – Famous Scientists

Think of your favourite food. How could it be any better? What about your favourite animal? Could you improve it? Or how about a dangerous disease – what if we could make it a slight irritation instead? The power to do this is all trapped up inside the genes of the plants, animals, bacteria, viruses and fungi that make up our world. It’s starting to look like in the future we will have the tools to shape those genes so maybe we can have chips from the chippy that are actually a superfood, a dog that lives as long as you do, and diseases that we can easily control or treat. All of that is thanks to the work of two incredible scientists: Charpentier and Doudna, and the technology called CRISPR.

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DNA

Try and write down everything about yourself. How many fingers do you have? Do you have fingernails? What colour is your hair? Your eyes? Do you like the taste of coriander or brussels sprouts? This is going to be a very long list indeed, isn’t it….

But there are answers to all of those questions and a billion more – we know that because your hair doesn’t change colour each day, you still have fingernails in the evening and usually the foods you like stay pretty much the same until you get older!

The secret to keeping track of all those things is your DNA. It’s a bit long list of information that can be used to build you. Your body uses your DNA to replace old bits of your body to keep you looking fresh.

A problem comes when you think how much information there must be to keep track of absolutely everything you need to not only stay alive but also be totally unique from everybody else on the planet! The answer to that problem is that you have a lot of DNA – the big long list is about 6.4 billion bits of information long.

There’s so much of it that you can even extract it and see DNA!

The whole list together is called your genome. Being able to change just a small section of this 6,400,000,000 long list of information would be a huge breakthrough. That’s exactly what Charpentier and Doudna’s discovery of CRISPR technology is allowing. We’re getting to that…

Genome

Let’s pretend that all of the information about you – contained in your DNA – is written down in a books. Put all of those books together – every single bit of information about you – into a big bookshelf and you have the complete instructions on how to make another you. Your genome is the full set of DNA.

So this CRISPR breakthrough by Charpentier and Doudna is like being able to go into a library and finding anywhere that a certain sentence appears. It’s quite amazing when you think just how many books and how long some of those books are in the library!

Gene

Let’s look for a specific piece of information – whether or not you like brussels sprouts.

We can go to the bookshelf and find a shelf labelled ‘Chromosome 7’. On that shelf we will find a book called ‘TAS2R38‘. If we find DNA in that book that gives instructions for “CCGCGTGTG” then your sense of taste will really pick up one some molecules in the sprouts that make them taste awful! If the instructions say “GCTGTTATC” you might like them after all!* You can try and use “CCGCGTGTG” as an excuse at Christmas to get out of eating sprouts if you like. Let us know how it goes.

One book in this case is one gene. A gene contains all the DNA to give the information for a specific thing.

Genotype

Whether your book TAS2R38 has “CCGCGTGTG” or “GCTGTTATC” is called your genotype. It basically means that your big list of information in your DNA has the instructions for one characteristic or another. So for example you could have the information that codes for brown hair – so your genotype would be for brown hair.

Phenotype

Life is never simple. Just because you have a certain set of instructions doesn’t mean your body will follow them perfectly! Maybe there’s a clash in two different sets of instructions somewhere. Sometimes you might have a genotype for a certain characteristic but you might not show it outwardly.

You could have the genotype to be really tall but you hate milk and brussels sprouts so you don’t grow to be really tall. Your phenotype is what your body actually does rather than what the gene’s instructions say it should do.

Hereditary

You didn’t write these instructions out or choose which genes you wanted. Your parents did it all for you! Half of your DNA comes from one parent and half comes from the other. The two sets of DNA from your parents get all smashed together and mixed up and you get half of each!

This means you have a bit of information from one parent and a bit from another – so you’ll be a bit like both but not necessarily exactly the same as either!

This can be good if your parents are super-smart olympic sprinting world-renowned artists. There can be problems though – if your parents are carriers of a genetic disease then that can be passed down to you as well. Some things about you as a person are hereditary – that means they have been passed down to you from your parents.

Gene Editing – the Slow Way

We mentioned right at the start the idea of giving living things around us superpowers. Things like healthier food and incredible pets.

Sweetcorn

Sweetcorn hasn’t always been the amazing bright yellow, easy to grow megacrop that it is today. It used to be a tough, tiny cob. Ancient civiliations in modern day Mexico took the best of that bad bunch of almost-foods and bred those together. Since breeding takes a mixture of the DNA information from each parent there’s a chance that you’ll get the tastiness from one parent with the fast growth of the other parent! Over time you slowly make the corn sweeter, faster growing and bigger. It takes a really long time though. We’re talking thousands of years to make big changes.

Flyball Superheroes

Have you ever heard of flyball? It’s the pinnacle of dog sports. There is a rule that one member of the flyball team has to be something other than a Border Collie. That’s because border collies are just so good at the sport they really dominate! Of course, they weren’t bred to do flyball exactly…

Dogs have been domesticated from wolves over thousands of years of human history. What we know of today as dogs actually have a lot in common with each other despire their looking so different! We’ve bred the best dogs for certain tasks together for so long that the gene pool is pretty shallow.

Having a shallow gene pool makes it really easy to quickly select the parents with desirable traits. That means we can create entire new breeds of dogs within just a few decades – spaniels for example were just one type of dog 400 years ago but now there are a span of spaniels! Springers, cockers, King Charles, etc. That’s to say nothing about how fast the Cockerpoo or Goldendoodle have popped into breeding branding!

Over years and years and years we choose which genes we want these animals and plants to have. We do this by choosing the animals with the phenotype we want and breeding them together to select for the genotype we need.

Gene Editing – the Fast Way

If we want to create real super powers then we’re going to need a faster way to select the genes we want. Selective breeding relies on too much chance! What if there was a way to change the genetic information to exactly what we want? Thanks to Doudna and Charpentier’s discovery – CRISPR – there might just be…

Let’s go back to our analogy of books. Remember that all of the you-code in your DNA is organised into books – genes. What about if you didn’t like a particular scene in a book? Say a character dying in Harry Potter – how could you change that? You’d need to know exactly where the death happens, find that part, cut the paper out where the passage with the morbid act occurs, and replace the hole you’ve cut out with a new piece of paper with a new bit of story in it. Perhaps one where a few wizards randomly decide to leave the Battle of Hogwarts right in the middle of the action and go live on a farm instead.

In gene terms – we’ll need to locate a specific section of the genetic code, cut the DNA out, and insert a new section of code.

You can see why this is often called ‘genetic scissors‘.

What is CRISPR

CRISPR (pronounced: criss-purr) is the confusing name for these genetic scissors. It relies on the defence mechanisms developed by bacteria in their fight against viruses! (Yes, bacteria can get infections too).

Bacteria use a combination of strands of genetic material – the CRISPR bit – and a protein called Cas9. Turning this CRISPR protein combo into a useful tool is what makes Doudna and Charpentier so impressive.

The Bacteria-Virus Arms Race

Viruses don’t just infect people – they also go after bacteria. Bacteria are constantly trying to get new weapons to fight off viruses all while viruses develop new ways to sneak inside the bacteria! Once a virus gets inside another organism it will trick the cell it has just infected to make more viruses – using the instructions written in its genetic code.

If you want to defend against a virus, one way would be to rip up all of those instructions before the viruses have a chance to replicate! The problem with that is that the host cell also uses genetic codes to give instructions for all the stuff it needs to be alive too. That means we can’t just destroy all the DNA we find – we need to be really careful to only select the virus’ genetic material.

One defence mechanism the bacteria have uses fancy gene-searching tools we know as CRISPR. The bacteria learn how to recognise the genetic material of the virus and make a copy of a piece of viral DNA. The combination of the protein Cas and this copy of the viral RNA is a weapon with a seek and destroy mission.

The deadly bookmark

Back to our book analogy. Going back to our idea of changing the story in the book so your favourite character doesn’t die or the Red Wedding is just “the Wedding” (I can’t do anything about S8, sorry), the first step is knowing what we’re looking for. If you have the exact text you’re looking for you can scan through the book until your text matches the part of the book. Boom – we’ve identified the position in the book we need to change. That’s when the tools come in to snip out the section of the book we need to change.

This is exactly how the CRISPR-Cas combo cooperates. It can search through any genetic material it comes across and if an exact match to the ‘text’ that it has is found – and the tools get to work.

What tools are available?

So we’ve got a method of getting to the genes we want to target. That on its own isn’t very useful! We need to do something to those genes when we get there. That’s where the breakthrough of Charpentier and Doudna training CRISPR to do exactly what they want comes in.

The simplest thing to do is just remove the section we don’t like. If you remove the instructions in the genes, the organism can’t follow the instructions! This means that if we knew which gene caused a hereditary condition we could go on a seek-and-destroy mission for that gene and just remove it, hopefully preventing a person from ever developing the phenotype – actually having the disease.

More complicated still, you could look to swap out the code in one place for a different code to make a different genotype and hopefully a different phenotype. This is where things get a bit contentious. Technically it would be possible to edit and change the DNA of a person or other living organism to give them an exact genotype – like designing a person.

I don’t think that anyone would argue that being able to remove the genotype that causes a horrible disease is a bad thing. We could really help and treat people and improve their lives. Designing a child to have characteristics that you might like? Adding a patchwork of manufactured DNA into the genes they inherit from their parents though – that might be a bit more questionable.

Who discovered CRISPR?

Emmanuelle Charpentier and Jennifer Doudna are the two superheroes of science are the people we will be thanking in a few years’ time when CRISPR starts to have massive and positive impacts on our society. Charpentier is from France and Doudna is from America. They became friends while attending a conference and decided to work together from then on.

That is possibly the part of this whole story that I find most inspiring. When scientists come together and collaborate, amazing things happen!

You can read lots more about Charpentier and Doudna, and CRISPR, in this article: Two women share chemistry Nobel in historic win for ‘genetic scissors’.

Why is it a big deal that they won the Nobel Prize?

You mean other than it being the NOBEL PRIZE?

Charpentier and Doudna ‘s breakthrough – training CRISPR to do what we want it to – could be absolutely massive to the future. It could mean that we can design those superhero animals and plants we mentioned at the start or just hit ‘delete’ on entire diseases. But besies that, this is the first time that two women have been awarded a Nobel prize without a man also being included.

I can’t say it better than one of the prize winners herself when asked about this being the first time that two women have shared the prize without a man in sight:

“I wish that this will provide a positive message specifically for young girls who would like to follow the path of science… and to show them that women in science can also have an impact with the research they are performing.”

Professor Emmanuelle Charpentier – source: BBC

CRISP-huh, what is it good for?

Aside from the inspiration these scientists will provide to millions of young girls who love science, the genetic scissors has the ability to do so much. It might allow scientists to cure or prevent inherited diseases, or provide new treatments for cancer. We have already witnessed the creation of a vaccine for Covid-19 in less than a year, but the power of CRISPR might allow us to changes lives within weeks or months. Whenever you hear ‘CRISPR’ don’t forget to say thank you to Charpentier and Doudna!

Not only might you be able to eat foods your genes would have prevented you from doing, but there will be loads of it. In addition, they will also taste super.

*We’ve gone with the most common ‘codon’ for each of the amino acids in question here for simplicity.