#timeline of peach cultivation
Explore tagged Tumblr posts
Note
I've got to say, I've been doing a lot of research on Italy recently and I literally can't stop thinking about your boys. I'm over here trying to read about whatever Crusade and my brain is just a constant loop of "isn't Machete a cardinal? And Vasco was from like Verona, right?" Not super conducive to learning anything, but I am enjoying myself and thought you should know.
Thank you for your lovely art and for sharing your darlings <33
That's adorable ;^; But also sorry the lads keep distracting you, hah.
I'd argue that getting invested in your characters and their stories and having to do background research for them is actually a great way to accumulate knowledge about various subjects. Often it's stuff you probably would never get around to reading about otherwise. I'm not saying it's always information you'll have many practical uses for, but learning about new things is fun and it's beneficial to you and your brain in the long run.
Vasco is from Florence actually! It's usually considered to be the birthplace and the main hub of the entire Renaissance movement. Leonardo da Vinci, Botticelli and Michelangelo lived and influenced there and Dante Alighieri (author of The Divine Comedy/Dante's Inferno) was florentine as well, albeit he lived several centuries prior to them.
#Verona is a stunning historically significant city as well but it's a bit too far from Rome in this case#nowadays the fastest train ride from Rome to Florence takes around a hour and a half it looks like#travelling was slow and took a lot of effort in the 1500's but it was still a manageable distance#answered#nnnnnnnothingtoseehere#for real though the stuff you end up googling when you try to piece together a character is pretty funny#like#the evolution of breeches#history of bathtubs#history of sofas#timeline of peach cultivation#the cost of gyrfalcons#winemaking techniques#ear infections on dogs#how Italian surnames are formatted#the rise and fall of the Medici dynasty#are there any beaches near Venice#can you survive being stabbed in the liver#can you survive a hemlock poisoning#can you survive severe malaria
164 notes
·
View notes
Text
Manga/Manhua/Webcomic recommendations I have
These are either REAL gay or REAL Femdom you know. Maybe not in the erotic department, but in the Feelings~
So I’m recommending these cause I think they deserve more recognition and attention. If they do, the artist may get more big bucks to keep the ball rolling.
A lot of these are Chinese based novels that I got into after falling in love with Mo Dao Zu Shi and all of Mxtx’s works. I’ll link them, tell you guys the chapter number, and rate them so you guys can get an idea of what they’re like.
College Student Empress, +32 Chapters
https://manganelo.com/manga/ho922575
9/10 Okay, talk about a smart dom. She is such a babe and so clever, I love her. She somehow gets reincarnated into an empress and has to brains her way out of not being assassinated by an unknown attacker while also maintaining the life of said empress. Art is gorgeous, surprisingly the hair styles are really cool. The only downside is that the emperor is a whiny immature little man child that everyone consecutively agrees to punch in the face. Maybe he’ll transform into a nice passive sub one day. Also, beautiful women everywhere and the MC is hilarious.
To Be Or Not To Be, +56 Chapters
https://manganelo.com/manga/ox920326
9/10 Ahh, this is a good one. The cover is very misleading actually. Another gets reincarnated into a royals body, this time around business man gets reincarnated into an emperor’s body of a book he reads who is supposed to be the villain. Very Scum Villain esque. Let's see, lovely art, great characters, very gay, plenty book subversions cause of that gay. And what- ah, what’s this?
Lesbians?! In my 2020?! The year of Lesbians?!
Devil Wants To Hug, +56 Chapters
https://manganelo.com/manga/vb920111
8/10 A soulmate sort of story. Lovely characters, nice conflict, very very gay. Demons, gods, cultivators, the likes. Some fun amnesia thrown in there for the mix! Art is pretty in its own style. I personally really like when all the characters become chibis. Those are actually the first chibis that I have ever found to be cute.
I Accidentally Saved The Jianghu’S Enemy, +9 Chapters
https://manganelo.com/manga/cj923095
7/10 This one’s kind of fun. Both main characters are kind of little shits if I’m being honest and I like them for it. Gives off a very Mo Dao Zu Shi vibe to it. The boy in red is like Xue Yang and Wei Wuxian mixed really nicely together. It’s basically about a medical practitioner with a shady past saves the life of evil boy who is super shady. It doesn’t have much in the way of chapters right now, but the art style is very pretty and I can’t wait to see where it goes.
As Lovely As The Peach Blossoms, +24 Chapters
https://manganelo.com/manga/et923098
6.5/10 Very cute. Very soft. Different than the rest of the other stories in a way, plot wise. Art style isn’t amazing, but it is pleasant and gentle. There is a smidge of homophobic actions, but it’s easy to push through. Its about these two who have known each other for a long time, finally get reunited.
Silent Lover, +19 Chapters
https://manganelo.com/manga/jw922352
6/10, whaaa, is that a bad ranking. Nah, not really. There are other ones I have read that aren’t on this list at all and are no good! Now this one does have its strengths and weakness. Firstly the strengths, good plot, good characters, especially the antagonist, she is such a BITCH, I love her. Art style is very pretty. There is crossdressing and gay shit galore. Set in some timeline of ancient China. I honestly relate to the MC and find him to be very reasonable even if OTHERS think he’s too wimpy. Now, flaws. Uhh, it’s one of those stories where the top is pretty terrible at first and abusive. I think it’s some sort of romanticized theme that I’m seeing in a lot of these East Asian Stories. Makes me con-cerned. Thankfully it doesn’t last too long, as expected.
Villain Initialization, +60 Chapters
https://manganelo.com/manga/mc922174
10/10 would recommend! Holy shit, this one is so fucking funny and relatable. You got super powers, you got second chances at repeating your life, you got a villain- you got a hero maybe becoming... you know 😳. The art is awesome, all the ladies are god damn hot, the villain’s super suit fits in all the right places. Holy moly, I hope this gets adapted into something cause it is that fucking gooooddd!
#Devil Wants To Hug#Silent Lover#I Accidentally Saved The Jianghu’S Enemy#As Lovely As The Peach Blossoms#To Be Or Not To Be#College Student Empress#manhua#manga#comic#webcomic#just my opinions
116 notes
·
View notes
Note
Hello, related to Erha. I just read that Peach Blossom in China is other term for a "love affair"? (between lovers, not in the adulterated sense. ) Now, everytime I read Peach Blossom wine in the novel, I wonder if Meatbun have given this thought to Moran in a subtle way, when he offers the wine to Chu Wanning. and if Yuheng thought about this too, as well the first time that's why he cherished the wine in his two lifetimes?
First off, just wanted to say Erha asks are my favorite asks so thanks, Anon!
That is a neat fact, I did not know that. I am sure Meatbun totally enjoyed putting the tongue-in-cheek hint with this, just as she did with all the comments that CWN is a man made of wood and not flesh and blood.
Not sure about whether CWN thought about it though, at least not when Mo Ran first brought it to him because we all know what thin face he has and if that connotation has occurred to him, he’d have been hella embarrassed and acting out - I mean, remember the sheer mountains of crankiness driven by thirst in the Farm arc? And even in the 1.0 timeline, he’d withdraw into his armor whenever he thought of liking Mo Ran. I think this early on, he liked Mo Ran for his kindness and the way he radiated so much joy and warmth - there is a running motif of Chu Wanning being always cold and Mo Ran being a human furnace - which btw, it just occurred to me, is twice brilliant on Meatbun’s part: it contrasts with TXJ being always cold and seeking warmth in Chu Wanning (showing both this isn’t “true” Mo Ran and how desperately cold TXJ must be, to seek warmth in a man who usually doesn’t have enough of his own) AND isn’t there a constant line running through 2ha about BBBFs being cultivation furnaces? Meatbun, you mad genius!
Anyway, this got off track, sorry. But yes, I don’t think this early on CWN ever thought of Mo Ran romantically, not in the way he did in the 1.0 timeline where he wistfully liked him and certainly not the way he did in 2.0 timeline where Yuheng Elder finally discovered hormones. (His feelings in 1.0 timeline read pretty asexual to me, and even if romantic, driven more by longing than any desires of the flesh.) So I am not sure he’d ever have caught the meaning; especially since he’s well-educated but awfully unworldly so I am not sure he’d have even known the term. I do think that he is fond of that wine because he associates it with Mo Ran and Mo Ran giving it to him (with his own money!) and so it becomes a special thing for him.
Side note - I honestly don’t know if Mo Ran thought about the meaning of it when he gave it to CWN. He’s probably a lot more likely to know the term, having been brought up in a brothel (and in the world, in general) and he clearly acquired very strong feelings for him very quickly though honestly because of the multiple timelines and the fact that Shi Mei magically scooped out parts of his brain and personality for fun on a repeated basis, I honestly have no idea what stage of it happened when and when it went from admiration to love to carnal to whatever. Like - that early on, Mo Ran clearly worships the ground CWN walks on but is it romantic love per se? I honestly don’t know. And then of course he forgets he gave it to him :(
This has turned into a giant non-answer, sorry, but it did make me happy to contemplate all that!
18 notes
·
View notes
Text
@jennifersnape asked : Ok, Ok ... in the meantime I have to apologize immediately for my English, it is not my first language nor the second to tell the truth so if there are errors, incomprehensible things ... sorry!
So, I've watched the two series and I'm trying to read the books but ... I'm having a little trouble about some things. So, questions! Both on books and on the TV series.What exactly is Dong Hua Dijiun? From what I understand he has brought together and pacified the various kingdoms but ... he is not the creator, right? There is a "Divinity", someone more powerful than he has created the whole, would be the father of Mo Yuan?
How many and which clans exist?
At one point in 3L3WPB SiMing says that he controlled their fate and that they weren't meant to be together, but there is nothing with the Rock of the Thrice, right? That was one storyline that wasn't part of the Canon, right?(I admit that this thing of the 2 TV series has me very confused since in one they do things and in the other there is no mention of it. luckily I landed here!)
As for the future ... Hem, I know the next books are all about other poies but, we'll see / read more about Dong Hua Dijiun and Bai Fengjiu, right? They won't leave us completely in the dark what happens to them? And, will there be more Drama there? That is, will they continue to shoot TV series about this universe, with the same actors? Why, I admit that I have a very slight crush on Vengo Gao in the role of Dong Hua.
Ok, I think we are too many questions for the moment. Thank you!
First off, wow, you really beat even Admin Ro out for length here. That’s wild. Second off, I’ll be answering these questions in the order which you asked them, so here goes!
1) Donghua Dijun is an ancient god born out of the spiritual energy of the universe. Nourished by the springs of Bi Hai Cang Ling, it’s said he bust out of a rock fully formed as a kid. He wasn’t the head of the fight that brought together and pacify the various kingdoms, even if he was part of that fight and commanded armies in it. That distinction goes to Mo Yuan, god of war. But - no, Donghua is not the creator of the universe. According to origin myth, if we have to trace a rough creator, that would be God Pangu. Father God (father of Mo Yuan, as you put it) is a god that came after that and raised the mountains and the seas out of the created universe.
2) At the beginning of the universe there were five clans in existence in the Four Seas and Eight Wildernesses: the Celestial Clan, the Demon Clan, the Ghost Clan, the Sprite Clan and the Human Clan. Then, with some passage of events, the Human Clan was sent to the ten billion mortal realms apart from the realms.
3) The Stone of Three Lifetimes (rough translation directly from the Chinese in my Head) does not, in fact, exist in canon. It was a gimmick specifically designed for DongFeng’s arc in the Peach Blossoms drama, due to the fact that the production team who did that drama did not have the copyright to Pillow Book. In the Pillow Book novel there is a “Fate Stone,” but that stone doesn’t actually dictate anyone’s fate, but rather transcribes it, I guess, is the best way I can explain that? Also Siming doesn’t control the fate of the immortals, he only controls the fate of the mortals.
4) There’s an extra chapter out right now that tells us what happened to them - to sum up succinctly, Feng Jiu wakes up, and Donghua at the moment is attempting to regain his powers while being with his family by going into secluded cultivation five months out of every year. That translation is still coming but at the moment Admin Ro has a test every week and she can’t spare the brain cells. As for being a part of the other novels - as Lotus Step timeline is currently fifty thousand years before Peach Blossoms even started and nothing else has been written yet, it’s really up in the air. We do know that Lotus Step timeline intersects with Pillow Book timeline (according to the extra, God Zuti has been reinstated to her role ten years after Pillow Book ends), though we have no idea what it means in terms of cameos. In short, as we put in the FAQ - don’t get your hopes up.
5) Currently there’s been no “next drama” planned because Lotus Step novel isn’t even finished yet. However, I really doubt when/if the next drama is shot, it’ll be with the same cast. An adaptation might take another 3-5 years at least and by then everyone in the current cast might be too old to fit these parts except Yuan Yuxuan, and at that point it’s a question of whether or not she’s gotten popular enough to pull sponsors. Also it’s unlikely that the actors would want to reprise the roles again - Reba (who plays Feng Jiu) was hesitant about taking the Pillow Book script for this reason, and Mark Zhao (who plays Yehua) has straight refused to play Yehua ever again.
Vengo...is at a turning point in terms of his career. He’s 38, which really means he’s quickly aging out of “fast” light romance/xianxia romance/historical romance/the like of scripts. What he needs right now are projects that solidify his acting career/serious dramatic roles that look good on a resume that will give him a better pool of future scripts in the ages of 40 and beyond. But yeah, it’s unlikely (and probably not good for his career) for him to be reprising a role in this series. If you would like to see more of him, please check out Living Toward the Sun, which premiered just last year and also be on the look out for Sword Snow Stride (coming up in 2021).
#jennifersnape#donghua dijun#three lives three worlds the pillow book#admin ro answers#((im sorry i get passionate about the acting careers of everyone around here))#((i just want everyone to thrive in the years to come so I can see them on my screen!!!))
16 notes
·
View notes
Text
From now until November, we’ll be spotlighting some of our MHHE registered authors. Want to make art for them? Register here! Artists who register before July 6th get early access to claims.
MHHE Author Spotlight: Page161of180
What piece of work best represents your writing style, and how would you briefly describe it?
I think that my most representative piece is one called "You're a Story (I Can Follow)". It's a take on the Orpheus and Eurydice myth, that involves Eliot rescuing Quentin from the Underworld after the events of season four-- which, *heavy sigh*, I wrote in the middle of season four, before I realized how badly I would eventually a crave a story that gets Quentin back.
I think it speaks clearly to the things I like to do as a writer: the plot is there but not overly complex, the focus is on the characters (specifically Eliot and Quentin) and how they understand themselves and each other and who they are to each other, there are just an absolutely gratuitous number of flashbacks and memories and little moments that show the truth of any relationship (in my view), it's deep in the feels but ends joyfully, and it takes as both thesis statement and rallying cry that the beating heart of love is knowing someone really damn well and taking care of them as best you can, even if you are a full disaster every time you try to express it.
One of my favorite bits, which takes place near the start of the story, when Eliot is trying to convince himself that Quentin is actually following him out of the Underworld, follows below. If you want to know how I see Eliot in his relationship to Quentin (that is: desperately romantic and desperately dysfunctional about it), this is all you really need to read:
He cleared his throat once. It would have been almost comically affected, except for the fact that he actually did need to clear the choking lump that had formed if he was going to get a word out. “The thought occurs,” he said, keeping his voice deliberately casual, “that if we’re going to make it up however many stairs are in the Underworld Branch without me losing what’s left of my mind, the whole ‘ascending in silence’ thing isn’t going to cut it. I know there’s not much you can do about that at the moment--”
He grabbed the banister to cover the tremor in his hand, “--so you’ll just have to suffer through my sparkling conversation. Fortunately, I’ve cultivated a real gift for speaking to imaginary versions of you recently. And on the off chance you’ve bailed on the whole enterprise already, we’ll just-- chalk this up to the stage of the grieving process where I go full season 5 - season 6 hiatus Spike.”
Eliot actually could feel Q, then, but he knew it wasn’t coming from behind him, but inside him, the shard of Q that was a part of him, always, even all the months Eliot had repressed him. The part that was always watching Eliot with disappointed (but unsurprised) eyes as Eliot pretended every little thing about Q didn’t make him want to carve a shelter out of his body for this reckless little stormcloud of a man, with his awful clothes and embarrassing earnestness and the eyelashes that Eliot honest-to-God couldn’t not kiss every. Single. Time. he’d watched them flutter while Q flew apart with Eliot’s name in his mouth.
“Sorry,” Eliot said quietly, letting out a sigh. “I told myself that I was going to be better--” braver “--if I ever . . . saw you. Again. Ever so slightly less full of my own bullshit. But this is--”
Nothing like he thought it would be , for starters. In his relentless planning for what he’d do when he was free, he’d imagined what he’d say if Q was happy, if Q was furious, if Q had already fucked off and married Alice and they had 2.5 magical prodigies and Q hadn’t even thought of Eliot in thirteen years of however the fuck much time had passed. But never had he considered coming back to find Q-- gone . It hardly would have been conducive to maintaining his sanity. Nor had he considered what it would be like to find Q but to have lost the words . To be too chickenshit to say them, sure. To fumble them, abso-fucking-lutely. But to have mortgaged them away?
“-- it’s hard, Q,” he finally settled on. “It’s just-- really hard.”
He could imagine the Q behind him, and the Q inside him, both furrowing their brows.
“Oh stop it,” he shushed, in the familiar way born of having the time to learn every one of a person’s textbook moves. “You know you’re always worth it. To me.”
And: bonus answer! While I think "You're a Story" is probably my most representative work overall, it is a bit mournful in tone until the ending, so perhaps not the best representative of what my MHHE work will be like! For that, I'd recommend, "The Honor of Your Presence," which is the fully indulgent, outsider-POV, Queliot wedding piece that my heart needed: . A snippet (and strong contender for my absolute favorite piece of dialogue that I've written) follows below:
“Fine,” King Quentin says. “Forget the whole ‘obey’ thing. What about just love and honor ? That’s-- unobjectionable, right?”
King Eliot doesn’t answer immediately, and because he is wearing one of his looser tunics today, without the high-collared jackets he prefers, Rafe can see that the pulse in his throat begins to pound at a pace not unlike the palace’s fleet of messenger bunnies.
“Seriously,” King Quentin sighs.
“It’s not that it’s objectionable , per se,” King Eliot says, his voice a note higher than normal. Rafe might say it was verging on the hysterical, were that a word that could be fairly applied to a king. “Isn’t it just-- a bit gauche to come out and say it? What happened to preserving the mystery?”
What piece of work are you most proud of and why?
While I'm embarrassingly attached to everything I've written in this fandom (because I'm embarrassingly attached to the characters themselves), I think my personal proudest moment is a piece called "A Little Disguised, or a Little Mistaken". On one level, this is all about Eliot and Quentin's memory-wipe personas Nigel and Brian meeting and falling in love like the nonsensical soulmates that they are. But on another level, it's also about the parts of Eliot and Quentin that are immutable and come through no matter what, and the way that they keep making the same mistakes with each other (and getting the same things right) across their various timelines and identities. It's also, in large measure, about Jane Austen, for reasons. If you want to know what me writing a no-magic, modern AU romcom would look like (cough cough, MHHE!, cough), the first three-quarters of this are a pretty good indication.
“What can I make you tonight? And keep in mind-- we’re celebrating.”
That was right, Nigel’s text had said he had good news. Well, at least one of them did.
“Um. Something, like, fruity?”
Nigel smirked and it made Brian want to simultaneously slide to the floor and also reach over and pull Nigel in by the collar, but he did neither.
“Okayyy,” Nigel said. “Do I get anything more to go on?”
Brian shrugged one shoulder. “Surprise me.”
Nigel’s hands, always deft and sure, fumbled the glass for a moment, but he recovered it. “Why don’t you tell me what you don’t like,” he said once he had.
Nothing you’re offering , Brian wanted to say. But instead he cleared his throat and said, “Uh. Peaches, I guess? I don’t like them.”
Nigel nodded. “What don’t you like about them?”
They hurt to eat , Brian thought. “Too sweet, I guess,” he said instead.
“I’ll take your word for it,” Nigel said, already starting to gather ingredients.
“You’ve never eaten a peach?”
Nigel shook his head as he started muddling something with something else. “Allergic. Even the smell’s kind of overpowering, though. I get how they could be too much.”
As Nigel poured and shook and stirred, Brian watched entranced and a little sad that something Nigel did so naturally was so dangerous for him. Or maybe it wasn’t natural at all. Maybe Nigel was just a much better actor than New York had given him credit for.
Nigel finished his creation and placed it on a napkin, before sliding it across the bar to Brian. It was reddish-gold in color, shading down to a deeper purple-red at the bottom of the glass.
“Gin fizz with a plum shrub,” he said to Brian’s inquisitive look. “Anyway. Brace yourself. Good news incoming.”
What tropes can we look forward to in your MHHE fic?
Let's see . . . There's going to be about a millisecond of enemies-to-lovers, but let's be real-- these two are far too charmed by each other to stay enemies for long. Not sure any of the following are within the strict definition of "tropes," but they're among my personal favorites, so you can go ahead and expect some gratuitous cuddling of a puppy, some deep-meaningful-late-night-talks-even-though-we've-only-just-met (time is an illusion! they bond fast!), so so so much expressing of thinly-veiled feelings through artistic expression, and actively pining while also actively sleeping together. Also, am I going snow these ridiculous gentlemen in? (I'm going to snow these ridiculous gentlemen in.)
Fuck, Marry, Kiss (under the mistletoe) with three Magicians characters of your choice!
My fully honest answer is Eliot, Eliot, and Eliot. But my even more honest answer is that I'd rather sit back with a cup of tea and a plate of gingerbread cookies and sigh with deep appreciation while Quentin handles all of Eliot's mistletoe needs.
19 notes
·
View notes
Photo
New Post has been published on https://fitnesshealthyoga.com/what-is-crispr-cas9-the-revolutionary-gene-editing-tech-explained/
What is CRISPR-Cas9? The revolutionary gene-editing tech explained
Until very recently if you wanted to create, say, a drought-resistant corn plant, your options were extremely limited. You could opt for selective breeding, try bombarding seeds with radiation in the hope of inducing a favourable change, or else opt to insert a snippet of DNA from another organism entirely.
But these approaches were long-winded, imprecise or expensive – and sometimes all three at the same time. Enter CRISPR. Precise and inexpensive to produce, this small molecule can be programmed to edit the DNA of organisms right down to specific genes.
The development of cheap, relatively easy gene-editing has opened up a smorgasbord of new scientific possibilities. In the US, CRISPR-edited long-life mushrooms have already been approved by authorities while elsewhere researchers are toying with the idea creating spicy tomatoes and peach-flavoured strawberries.
But the game-changing technology could have the biggest impact when it comes to human health. If we could edit out the troublesome mutations that cause genetic diseases – such as haemophilia and sickle-cell anaemia – we could put an end to them altogether. The path for human gene-editing is littered with controversies and tough ethical dilemmas, however, as the news in late 2018 that – against all ethical guidance – a Chinese scientist had secretly created the first gene-edited babies.
Here’s everything you need to know about the complex and sometimes controversial technology driving the gene-editing revolution.
What is CRISPR?
CRISPR evolved as a way for some species of bacteria to defend themselves against viral invaders. Each time they faced a new virus, bacteria would capture snippets of DNA from that virus’ genome and create a copy to store in its own DNA. “They gather a set of sequences that they’ve been exposed to,” says Malcolm White, a biologist at the University of St Andrews, “these [bacteria] essentially carry a little library in their genome.”
To stick with the library analogy, these snippets of viral DNA were like little books – each one containing the data that allowed the bacterium to recognise and quickly kill off a virus next time it invaded. And in-between these chunks of useful DNA there are slightly less useful chunks of repetitive DNA keeping them separate – like a kind of molecular bookend.
These repeating segments of DNA are what gives CRISPR its name – Clustered Regularly Interspaced Short Palindromic Repeat – but it’s really the bits between these repeats that make CRISPR so useful. These useful bits are, somewhat unhelpfully, called spacers, and each one contains a reference to the DNA of a virus the bacteria (or its ancestors) had come across in the past. When a previously unseen virus attacks the bacterium, it adds another spacer to its library of previous attacks.
When a virus from that same species attacks again, the spacer corresponding to that virus’ genome swings into action. It’s a bit like the way that our own immune systems can recognise a flu virus if we’ve had that year’s flu vaccine. The spacer sequence is turned into RNA – a molecule that contains messages from DNA – and hunts down the corresponding piece of viral DNA. Once it finds it, an enzyme attached to the RNA string acts as a pair of biological scissors, cutting the target DNA and rendering the virus harmless.
You might have heard this system referred to as CRISPR-Cas9 as well as just plain CRISPR. In this case, the Cas9 bit refers to the enzyme used to cut the target DNA. “We can programme [Cas9] very easily to target one DNA sequence and to be very specific so it won’t cut anything that’s even similar in sequence,” says White. There can be other kinds of enzymes involved in gene-editing – Cas12 and Cpf1 for example – but all of them work in the same basic way.
How does it work?
Of course, all this is only useful if you’re a bacterium. So how do we turn an anti-virus defence mechanism into something that could let us edit human genomes at will?
Rather than relying on bacteria to create the molecules for them, scientists have worked out how to create their own versions of the CRISPR molecules in the lab. To start with, they need to work out the section of DNA that they want to target. For a condition sickle-cell anaemia, which is caused by a fault in a single gene, this is relatively easy, since we’ve already sequenced the gene that causes this disease and so know exactly the genetic code that we’re trying to target.
The banana is dying. The race is on to reinvent it before it’s too late
Before we get down to the business of unzipping and chopping up DNA, it’s worth getting to grips with the basics of how DNA is structured. Holding together the familiar DNA double-helix are four different nitrogen bases: adenine (A), thymine (T), guanine (G) and cytosine (C). The ordering of these bases determines everything about us, genetically-speaking. Eye colour, how tall we’re likely to be, whether we’re susceptible to certain diseases, it’s all written out in base pairs in our genetic code.
Like teeth on a zipper, these bases always pair up with their complementary base. A always pairs with T while G always pairs with C, over and over again until you’ve got to the three billion base pairs that make up the human genome.
But DNA isn’t much use staying locked up in a double helix – it needs to get that information out there and into the cell where it can be used to create proteins, which are the building blocks of pretty much everything in our bodies. To do to this, DNA unzips itself, breaking apart those base pairs until they’re flapping about in the cell.
These flapping, momentarily unpaired base pairs match up with short segments of RNA which contain their own own bases. RNA shares three bases with DNA – G, C and A – but T is alway replaced by U (uracil). Similar base-pairing rules apply, so an exposed DNA G base will pair with an RNA C base while a DNA A base will pair with a U. If you have an exposed DNA sequence of GAC, for example, you’ll end up with an RNA sequence of CUG.
Scientists use these basic principles to create their own CRISPR molecules which, as we pointed out above, are short stretches of RNA. All you need to do is open up a stretch of interesting-looking DNA – like the bit that contains the mutation that leads to sickle-cell anaemia – and build the complementary RNA sequence, with DNA-chopping enzyme attached. It’s a bit like starting with one side of a zipper and using that to build the corresponding but opposite side of the zipper that neatly fits into it.
Once you’ve got your CRISPR molecules, you need them to get your target cell. Luckily, viruses love nothing more than injecting stuff into other cells, so popping CRISPR molecules into otherwise benign viruses is one particularly useful way of introducing CRISPR into cells that’s already been put to work with in numerous studies involving mice.
Now CRISPR-Cas9 can really get to work. The Cas9 enzyme starts by unzipping bits of the DNA double helix while the RNA molecule sniffs its way along the exposed base pairs looking for a perfect match. Once the perfect match is found, Cas9 cuts out the troublesome gene before repairing the remaining bits of DNA. Other enzymes can add in insert genes instead of deleting them, but the basic process of unzipping, recognising and editing remains the same across different CRISPR molecules.
What is CRISPR used for?
CRISPR is particularly attractive to the agricultural industry, which is always looking for a way to engineer disease- and weather-resistant crops which will increase yields and, subsequently, their profit margins. In October 2015, plant biologists at Pennsylvania State University in the US presented US Department of Agriculture (USDA) regulators with button mushrooms that had been edited so they go brown a lot more slowly than normal mushrooms.
A year later, the USDA confirmed that the same mushrooms would be cultivated and sold without having to pass through the agency’s regulatory process for genetically-modified foods. Now, non-browning mushrooms are hardly the most thrilling foodstuff, granted, but this USDA is a pretty big deal because it hints that CRISPR-edited crops might be able to sidestep some of the environmental backlash levelled at GMO crops.
And it’s not just mushrooms getting the CRISPR love. In Australia, one scientist has already used CRISPR to make bananas resistant to a deadly fungus threatening to decimate the world’s crop of the fruit, while others are working on using the technology to create naturally decaffeinated coffee or finally engineer the perfect tomato.
Timeline: When was CRISPR discovered?
2005
After characterising CRISPR in 1993, Francisco Mojica at the University of Alicante in Spain became the first to hypothesise that the DNA sequences were part of bacteria’s adaptive immune system.
2007
Scientists at Danisco, a Danish food research firm, proved experimentally that CRISPR was part of a bacterial immune system and that Cas9 inactivates the invading virus.
2011
Emmanuelle Charpentier’s group at Umeå University in Sweden demonstrates the role of tracerRNA in guiding Cas9 to its cellular target.
2012
Emmanuelle Charpentier and Jennifer Doudna at the University of California, Berkeley simplify the CRISPR system by fusing together different elements into a single, synthetic guide
Although the agricultural world provides some of the furthest-along examples of CRISPR in action, the stakes are much higher when it comes to human health. Animal studies are already underway to use CRISPR to tackle sickle-cell anaemia and haemophilia – two promising candidates for CRISPR-treatment because they’re determined by a relatively small number of mutations. In the case of sickle-cell anaemia, the condition is caused by just the mutation of a single base pair in one gene.
The more genes involved in a condition, the harder it becomes to use CRISPR as a potential solution. “There are not many human diseases where only one gene is mutated,” says White. Certain cancers, for instance, are linked to multiple mutations in different genes, and often the link between genetic mutations and cancer risk are poorly understood so there’s no guarantee that – even if we could use CRISPR to fix faulty genes – that’d it’d be any kind of panacea for cancer.
Why is CRISPR controversial?
Late last year, He Jiankui, a researcher the Southern University of Science and Technology in Shenzhen shocked the scientific world when he claimed responsibility for the world’s first CRISPR-edited human beings. He reportedly took embryos from couples where the father was HIV-positive and the mother HIV-negative and used CRISPR to edit the gene controlling a protein channel that HIV uses to enter cells.
The experiment – which was detailed in a YouTube video, not a peer-reviewed journal – was widely condemned by scientists. “It’s been widely acknowledged that the science is not yet ready for clinical application,” says Sarah Chan, a bioethicist and director of the Mason Institute for Medicine, Life Sciences and the Law at the University of Edinburgh said at the time. “More has to be done to resolve uncertainties, and to try and understand the risks.”
Although the He study does violate clear ethical boundaries, it does raise one of the big ethical conundrums when it comes to CRISPR. The problem is that it’s not that easy to use CRISPR to change your genome once you’re an adult – you’d need to find some way of introducing the molecules to every single target cell.
This is perhaps achievable for conditions like sickle-cell anaemia, where you only need to change the DNA in red blood cells. By using CRISPR to edit bone marrow – where red blood cells are produced – you might be able to target a relatively small percentage of cells and still fix the condition.
But if you want to change a person’s entire genome, you need to edit their DNA when they’re little more than a tiny cluster of cells. This leads to all kinds of ethical issues. Why stop at identifying and chopping out genetic diseases, for instance, if we could also tweak an embryo’s DNA so the resulting baby was more likely to be intelligent, or good-looking?
“What if we wanted to change future life span, or intelligence, or Alzheimer’s disease potential or whether they go bald when they get to middle age,” says White. “Societies going to have to come to terms with what we want – it’s not up to scientists.”
Although human gene-editing raises some of the biggest ethical questions, things aren’t an awful lot clearer when it comes to agriculture. In July 1018, the European Court of Justice threw the future of gene-edited crops into doubt when it confirmed that CRISPR-edited crops would not be exempt from existing regulations limiting the cultivation and sale of genetically-modified crops.
Crops that have been genetically-modified – usually by inserting a gene from one organism into another – have long been sidelined in Europe, despite their popularity in other parts of the world. Despite a scientific consensus that GM foods are safe to eat, headlines warning of ‘frankenfood’ and lobbying from environmental groups helped keep GM crops away from human consumption.
But agricultural advocates for CRISPR hoped that the new gene-editing technology would provide an opportunity to redress this balance. The ECJ ruling means that any CRISPR-edited food that is to be grown or sold in the EU must pass stringent safety tests that non-edited crops (or crops made using certain techniques like radiation mutation) do not have to face. For now, at least, one of the biggest barriers facing CRISPR isn’t science, but public relations.
More great stories from WIRED
– Why the UK’s porn block is one of the worst ideas ever
– Wedding shaming Facebook groups are the real-life Mean Girls
– Glasgow cured violence by treating it as a health epidemic
– Upgrade your sound with our guide to the best headphones
– The best Black Mirror episodes ranked
Get the best of WIRED in your inbox every Saturday with the WIRED Weekender newsletter
!function(f,b,e,v,n,t,s) if(f.fbq)return;n=f.fbq=function()n.callMethod? n.callMethod.apply(n,arguments):n.queue.push(arguments); if(!f._fbq)f._fbq=n;n.push=n;n.loaded=!0;n.version='2.0'; n.queue=[];t=b.createElement(e);t.async=!0; t.src=v;s=b.getElementsByTagName(e)[0]; s.parentNode.insertBefore(t,s)(window, document,'script', 'https://connect.facebook.net/en_US/fbevents.js'); fbq('init', '181847449123027'); fbq('track', 'PageView');
Source link
0 notes