#they confirm it because they both have the same birthmark on their balls or something

[buginateacup]

Laszlo's obviously been on such a journey of wanting to connect with humanity over the last couple of seasons I can only think how funny it would be if he decided to track down the descendants of his bastard children he fathered as a human and discovered Guillermo was one of them

[bts-hyperfixation]

Soulmates

JJK X Reader soulmate AU

Warnings: Minor character death(car crash, only mentioned nothing graphic), Drinking

I don’t know if this is what you (the requester) were going for? this is somehow where I ended up

Everyone in this world has a soulmate. Someone that is meant to complete them and make them feel whole.

Your other half can be identified by the matching birthmark hidden somewhere on their body. There are also a lot of people whose marks are so close to matching that it almost feels like the real thing… almost. Sadly, many don’t ever get to experience the love of their true soulmate, so they settle for the closest they can get.

Jungkook was convinced he was one of the lucky few. Looking at her made his heart feel like it was going to burst. Every time he saw her the world got brighter, the birds started singing a little louder, and his stress nearly melted away entirely … nearly. But at 17 no one is going to pay attention to nearly.

Their birthmark’s matched so closely, each sporting a small puzzle piece on opposite wrists. You wouldn’t even bat an eyelid at the loved-up pair as they walked together hand in hand. And he loved her so completely, and her him, that they never thought to question it. Madly in love until the day she died.

Jungkook spent weeks almost comatose when the news of her car crash reached him. Couldn’t move, eat, sleep. To lose your soulmate so young was said to be a fate worse than never finding them at all. Even after coming through the other side people could tell he wasn’t the same carefree young boy he had been, most likely never would be again. His eyes’ looked far older than his years now, his soft features much more angular.

Three months after her death he resolve to never fall in love again, happy in the knowledge that he got to know her even for such a short amount of time.

….

You met Jungkook at a party. Someone from Uni decided that 24 was the right age for a big birthday bash. They hired out an entire club and set up a series of activities for people to enjoy. A mechanical ball on the main floor, a ball pit to the side, a BBQ in the smoking area, and a bouncy castle in the downstairs 90’s themed area. It really was an amazing event. You however spent most of your time watching the quiet Korean boy in the corner, every time his eyes met yours you felt compelled to move to him, talk to him, dance with him, anything that would get his attention on you. At the time you put it down to the alcohol. It took you exactly 3 and a half drinks to pick up the courage and interrupt his current conversation.

He was very sweet, really sweet considering he clearly didn’t want to be talking to you. It was evident in the way his eyes shifted and the nervous playing with his sleeves, still you persevered. Something about him wouldn’t let you give up, not yet at least. Your saving grace came when your favourite band came blaring over the speakers. “PRETTYMUCH” aren’t an underrated band per say but it’s difficult to find someone who knows them in your circle, so when Jungkook’s face lit up at the same time as yours you knew you had your in. So with the Phases remix blaring through the club you took your opportunity.

“I love this song!” You took his hand and pulled him on to the dance floor before you really realised that’s what you are doing. To start with he was frozen, a little shocked by your boldness, but as you gave it your all he joined in, loosening up for the first time that entire night. After that it was a lot easier to talk to him, you actually went into the smoking area to talk more about shared music interests.

After you went to get a drink you got caught up with some others and he came to find you. It felt like an electric shock when he’d grabbed your hand to get your attention, but there were a lot of balloons around so that would explain the residual electricity. By the time the party was over, and the club was closing, you didn’t want to leave him, not just now but ever. You found yourselves wandering around aimlessly, talking about nothing until the sun came up. Looking back it was then you decided Jungkook was it for you. You had never really believed in the soulmate tradition until you met him.

Weeks go by of you texting back and forth. You found out the reason he was so into music was because he was a musician himself, he even promised to perform for you sometime. A lot of promises were made in those messages.

‘There’s this amazing Restaurant in the city’ you claimed promising to take him with you next time.

‘I really want to see this movie’ he said promising to pay for tickets when it came out.

‘We should go see this band together’ The number one promise between the two of you, quickly racking up a lot of different acts to see together.

So when one of those bands turned up on the roster for the local you’d bought tickets immediately sending him the confirmation. Your stomach had fluttered thinking about seeing him in person again. And so you counted down the days as they passed. Picked and repicked your outfit. Talked yourself in and out of going. Eventually the day arrived. The doorbell signalling his arrival was deafening, ringing out through your small studio apartment. You took a few deep breaths before opening the door.

He was flawless, your tipsy memory hadn’t done him justice. A broad chest draped in a white long sleeve tee, ripped skinnies straining against his thighs, his hair swept into a James Dean quiff. You might’ve laughed at the way your outfits had accidently matched (a black crop with white skinnies) had you been capable of making a noise.

“Ready to go?” He asked nervously, rubbing the back of his neck. You’d nodded, blushing when you realised you had been staring.

It was a short bus ride into the town centre. Spent in relatively comfortable silence arms brushing against one another in the limited space on the crowded vehicle. The club was packed wall to wall when you got inside, no hope of getting to the front of the crowd, or so you’d thought. Jungkook grabbed your hand winked at you and began heading in the opposite direction of the stage. He led you up some back stairs and on to a balcony you hadn’t ever noticed before.

“I’ve played here before, almost no one knows this is here, but it will give us the perfect view.” He dropped your hand in favour of leaning over the railing. You couldn’t help but feel cold at the loss. The performance was great, you found yourselves screaming lyrics back and forth at one another. Some people had cottoned on to your little hiding spot and soon it became as packed as the rest of the club. Whether he was trying to protect you from the others or he was pushed there you will never know, but Jungkook ended up caging you to the railing, head resting on your shoulder.

After the show you’d decided it was time to ask him how he felt. The club was still busy, but the two of you had been in a quiet corner on your own nursing drinks and chatting aimlessly.

“Do you believe in soulmates?” You asked, broaching the topic carefully. You watched closely for his reaction, but he gave nothing away. Instead he just shrugged.

“I did once.” It was too blunt, you knew you should’ve stopped but you couldn’t, now you’d decided to tell him it was like verbal diarrhoea.

“I didn’t think I did, I mean I’ve never seen any ‘matching birthmarks’ and every couple I know is perfectly happy… but then I met you and I keep thinking about it, and you, and how I feel about you.” You watched as his face goes from pensive to a deer caught in the headlights.

“I… I have to leave now.” He got up and ran into the crowd before you even had a chance to reach for him. He dipped through a back entrance of the club and into the night before you could even push through the first layer of people.

The ride home had seemed a lot longer. Holding back tears had proved extremely difficult. Of all the reactions he could’ve given you that might’ve been the worst one. Somehow you found yourself thinking even him laughing in your face might’ve been better. You left the lights in your studio switched off that night. Made a beeline for your bed and passed out face down.

It would’ve felt like a bad dream when you woke up… if it hadn’t been for the crusty mascara tracking down your cheeks. You’d picked up your phone from where it lay abandoned next to you. Battery on 12%. You’d decided then it’d be best to run damage control, at least save the friendship.

Y/N: I’m sorry about last night…

You hadn’t expected his reply to be quick, so it’d surprised you when the typing bubbles appeared immediately; and furthered your sadness when they disappeared moments later without a message.

For days you spiralled. Going over the moment again and again in your head. Each replay turning the memory into something worse than the original.

Eventually you plucked yourself out of bed, deciding to face the problem head on and talk to the friend that invited you both to their birthday in the first place.

She met you at a café downtown during her lunch break. It was obvious by your red rimed eyes and sniffling nose that you had been crying but she was nice enough to ignore it for the most part. You caught up on her life for a little while until you physically couldn’t hold back anymore.

You told her exactly what had happened between you and JK, watching as her expression got both more understanding and pitying as you got closer to the end. Whatever you thought she was going to tell you was no where close to the story you got. You sat mouth wide open as she told you about the accident, and the way it affected Jungkook. It made you want to cry all over again. You didn’t know what to say once she had finished, stewing in your own thoughts for a while. The main thought that kept coming to the front of your mind was one that made you feel so evil. But you had to get it out

“What if she wasn’t really his soulmate. What if he was never meant for her” Its barely above a whisper but your friend heard it.

“He truly believes that she was” She replied squinting at you. Her break ended shortly after that leaving you alone with your thoughts.

…

It’s almost a month later when you see Jungkook again. Hadn’t heard a single thing from him since the concert but at least you knew why.

This time it was someone pool party. You honestly hadn’t been expecting to see him there. Didn’t even know you had mutual friends past that one girl. You didn’t think twice about your birthmark when you stripped down to your two piece. Why would you? Everyone has one. You were lay out on a sun-lounger with a drink when you spotted him. Tucked away in a corner once again, the only difference this time was his attention was already on you. He looked as good as ever, hair damp and slicked back, Long-sleeved neoprene shit covering his torso but trunks showing off his amazing thighs. You’d forced yourself to look away form him but could still feel the intensity of his gaze on you.

Eventually you couldn’t take it anymore, too hot under the sun and his stare you decided to change out of your swimsuit into a sundress for the evening. Heading inside you found your way into someone’s bedroom to get changed. Perhaps you should’ve checked to see if the door the locked though, because just as you had wiggled out of the bikini top Jungkook burst into the room.

“Ah shit… Sorry… I um.” His hand had flown in front of his eyes as he’d slammed the door shut behind him and you’d immediately reached for the flimsy dress pulling it over you torso so he could reopen his eyes.

“What in the actual fuck Jungkook?” you whisper screamed not wanting to draw attention to the two of you hidden away.

“I’m sorry, I didn’t mean to, I didn’t think… I just needed to see…”

“See what?! My boobs? I think you managed that one perv. You haven’t spoken to me in weeks and now all of a sudden you can’t wait long enough to knock.” You came across a lot meaner than you had meant, you just hadn’t been prepared for him to want to speak to you again.

“No I’m sorry I’ll go, this was a bad idea, I was probably seeing things anyway.” He mumbled looking sheepishly at the floor/

“No wait it’s okay, I really want to apologise don’t leave.” You took a deep breath and waited for his eyes to meet yours properly. When they did you could see the shock behind them.

“Why do you need to apologise? I’m the one that ran off, I never even told you why and I fucked up and I’m sorry I just…” You reached for him then, wanting nothing more than to comfort him and then realised it wasn’t your place, arm dropping heavily back to your side. “I felt so guilty with you, not because of you, because of me.” You nodded in understanding.

“I found about your soulmate after I confessed to you. I’m so sorry I didn’t know. I never would’ve brought it up if I had known you had already found yours.” You’d broken eye contact with him then unable to watch the sadness in his eyes and not be able to do anything about it.

“That’s why I felt so guilty though because the way I feel about you is so similar to the way I felt about her, how I still feel about her deep down. I was so confused because you’re only supposed to get one soulmate, and if I could feel the same way about you in such a short time… it just feels like I’m betraying her by loving you.” He stepped forward reaching for your chin and forced you to meet his gaze. “The today when I saw your birthmark on your thigh I could’ve cried.” He uses his free hand to unzip the shirt he’d been wearing. He pulled his left arm from the sleeve exposing his birthmark to you. A puzzle piece to fit perfectly into your own.

You’d gasped at the revelation you were right. He was meant to be yours. And yet it didn’t feel right. The anguish on his face was clear, the internal fight he had obviously been having with himself ever since the concert.

“Letting yourself love me now doesn’t mean you loved her any less” you whispered, allowing yourself to move even closer to him, wrapping him in your arms. He’d nuzzled into your neck allowing tears to stream down his cheeks and onto your shoulder. You’d felt every bit of stress leave his body as he cried. Emotions he hadn’t even know he had been holding onto, finally letting himself really breath since he had lost her all those years ago.

You’d lost track of the time, just stood with him, holding him until the final few sniffles came. His cheeks had been puffy by and red when he pulled away, wiping his face on the sleeve still on his right arm.

“Do you want to leave? We can go back to mine” You’d asked carefully, not willing to let him go home alone after feeling like that. He’d nodded weakly, sliding his arm back into the shirt before taking your hand in his. You’d headed for the door only to be brought back by the hand he had on yours. He’d pulled you so close you could see the flecks of gold in his irises, watched your reaction before leaning in and kissing you. It was salty with left over tears, but you wouldn’t change you first kiss for the world. Everything felt like it clicked into place in that moment, the world tilted on its axis. The exchange was short lived, a chaste peck followed by a few smaller pecks before he let you lead him all the way home.

Masterlist

[starlessskies94]

A Second Chance (Arthur/FReader)

So this is inspired by a recent ask I saw to @reddeadmort about Francis Sinclair time traveling to bring back a cure for Arthur and I love the idea as crazy as it sounds...so I wrote this. It’s terrible but I can dream right??

It was over finally over; everyone had gotten away. Moving on to live a better life just as you and Arthur had wanted. The deceivers were dead and the innocent that fell could finally rest. But as you stood in front of the small cabin in the woods; the rain thrashing against the trees lines and soaking you through to the bone, you knew you couldn’t turn back now.

“Y/N...” Arthur croaked, his lungs straining with each breath as he raised a trembling hand upon your shoulder. “You don’t know if this’ll even work. Ain’t no one here ‘sept for a woman and her kid.”

You turned to look at him, eyes like stone. Unshaken. Unblinking. Taking in the sick and weakened man before you. The man you loved...the man you were determined to save.

“Yes. I’ve already spoken to him and he agreed to help. For a price.”

He was struck with yet another coughing fit; choking on the very air he breathed and your heart clenched at the sight of it.

“Ain’t-“ he coughed again, clearing his throat to catch his breath. “Ain’t worth paying anything for, Y/N.” He wheezed. “I’m a lost cause.”

You slipped your hand in his; the large paw dwarfing your own as you guided him forward towards the wooden steps that led towards the door.

You’re worth it. You thought to yourself. Voice and heart too broken at this point to utter any more words on the matter. Knocking on the door you both waited...or rather you did. Arthur wasn’t expecting anything to happen. Didn’t even think anyone would answer. So it was rather surprising when a very odd looking; very familiar man opened the door.

“Good morning Miss; come on in friends, take a load off.” The man smiled jauntily. “I’ve been expecting you!”

Francis Sinclair. Certainly a man Arthur hadn’t expected to ever see again. Dressed just as strangely as he had been before, his bright eyes crinkled around the edges as he grinned; that same unique birthmark creasing with friendly gesture.

“Your lady here has been writing to me for some time Mr Morgan! A real dolly she is too!” He stated as they followed him inside. “Told me all about your condition and what she wanted to do about it and that was enough to really razz my berries!”

The two of you could barely keep with the pace Sinclair was babbling but you stayed silent none the less. Somewhat take aback by the mess that filled the cabin.

Notebooks and journals all laid out on the table in the center. Strange drawings pinned to the walls and across the windows, blocking out the sunlight. The cabin itself only illuminated by the warming glow of candles. Arthur sat himself down on the nearest chair; his strength waning from the ride you’d taken to get there.

Waving a dismissive hand at the concern on your face as you kneeled beside him.

Francis of course hadn’t noticed a thing; continuing his rambling at a hundred miles a minute with his back turned to the pair of you. Restless hands sifting through loose papers in front of him.

“Took me a while to collar my find but after racking the old noodle, I was able to get what I needed and cut out before the heat was really on!”

“Do you have any idea what this lunatic is talking about?” Arthur said lowly in your ear as you shared a look with the outlaw. You shook your head but moved forward to speak regardless.

“Mr Sinclair. I have what you asked for.” You said firmly and loudly enough to grab the young man’s attention.

He turned swiftly, almost jumping toward you. His bubbling energy quite contagious as you held back a smile of amusement.

“Marvellous doll!” The man jubilated rushing off to the side to receive the very thing you’d come for. Practically snapping the thick notebook from your grasp; trading it for the small satchel he held. Before once again turning his back and quickly began scanning through the pages.

“Ah we’re on the up and up see! Really getting something started now I got the rest of these doll!” He looked up to be greeted by the blank looks on both your and Arthur’s faces. The two of you still clearly having no idea what he was talking about.

But Francis just chuckled and sent a charming wink your way.

“Probably find me a bit of an odd ball right? No to worry my friends...not to worry. Say Sport, your girl is real good to get you this stuff! Wasn’t easy either I can tell you.” Arthur leaned back in his seat as Sinclair addressed him, the confusion still sat upon his frowned brows.

“Just make you take it all okay Sport? Be a really pain in the neck to get more!”

With that the two of you left. Arthur still questioning what the hell was going on and what exactly Sinclair had given you. But you said nothing and waited until you got back to town. To the quiet of your hotel room away from prying eyes.

Opening the bag and emptying the contents down onto the bed, leaving Arthur stunned at what he was looking at.

Boxes and boxes of large tablets and capsules; small vials of clear liquids along with the smallest vaccine needle he had ever seen.

And you both decided that in that moment...Arthur Morgan died from his illness. Albert Miller however was a strong and healthy young man of thirty eight, living out by the base of the mountains. Living the peaceful life you both deserved.

Your small homestead growing larger with the livestock and the crops that grew by the side of the cabin. The fresh hunted kills hung in the barn ready to be prepared for the winter to come.

You’d visited a doctors office a good year after giving Arthur the medicine. The man preceding to throw you out for wasting his valuable time when he’d confirmed that Arthur was perfectly fit and healthy. And although you were pretty sure the man thought you and Arthur insane from the giddy looks on your faces at the incredible news...you didn’t care.

Just as you didn’t care how Francis Sinclair’s strange medicines had cured Arthur.

Because they had. And that’s all that mattered.

[nightblink]

Blink Reads Oathbringer - Chapters 13-16

Chapter Thirteen – Chaperone

I’d be tempted by a balcony too, Shallan, especially one bound to have a great view.

It’d be good for Shallan to be able to Lightweave herself into Veil without needing sketches beforehand. It’s a good limitation to have on her powers, especially at first, but she’s going to need more flexibility.

Thank the Heralds that Sebarial and Palona are looking out for you to make sure that you do things like eat. You’re the type that gets submerged in your art or whatever you’re doing and somehow ignores the body’s pleas for sustenance.

…that’s not Palona.

He’s so distracted upon seeing her that he stumbles – what happened to your coordination, Kholin? [cackles] But he “didn’t even have the decency to blush” – yeah, he was probably too busy appreciating-

You did invite him in.

Oh hello little tidbits – “born under the sign of the nine”? Wait, isn’t nine the bad number in Vorin theology? That… does not assuage my worries for you in the slightest. At least having a birthmark is benign, and dear lord, is that an attempt to invite her into your rooms while you’re half-dressed? Adolin. Propriety, young man!

Dopey grin is canon.

‘Ash’s eyes’ – is that a new swearing-by-the-Heralds, or one we’ve heard before?

‘She’d traveled to the ancient city of the Knights Radiant, but compared to Adolin’s affection, all the sights of Urithiru were dun spheres.’ Be still my shipper heart

Plopping right down onto the floor with all their food, it’s such a comfortable atmosphere!

Shallan, I know you have new detail to add to your fap material, but later, okay?

Oh now he starts blushing and worrying about propriety. Now that his brain’s caught up with the rest of him, the Alethi Sensibilities are coming out.

SHALLAN. wOW girl, you are thirsty. (I don’t think he’d mind)

‘Fake it ‘til you make it’ really does help, Shallan, at least it did/does so for me. Glad to see you’re reaping the benefits – enough to have it recognized by others!

Oh no, oh nooo, she’s spiraling again…

I don’t think he entirely believed that answer.

“A Shallanspren.” Pretty much, yeah.  omg Adolin don’t poke poor Pattern. Das rude. I’m imagining his fractals going all spiky in annoyance.

“Inappropriate? Such as… dividing by zero?” Pattern you are amazing

I’m so happy that she can find happiness, be happy, content, able to revel in this sort of little moment that can never be captured. Shallan needs little moments like this in her life, spots of brightness to hold onto when the dark feels like it’s overwhelming

Come on, Shallan, come on, try the men’s food, you know you want to-!

Well. Adolin likes spicy-as-fuck dishes, confirmed.

PATTERN OH MY G O D

“accidentally” pATTERN that’s not how it works and fucking hell, I’m laughing too hard to be at my desk for this

“NO MATING.” Dead, I’m just dead, Send me off to the Farplane now

(he probably saw what you were imagining in your head earlier, Shallan. It’s your own fault, really)

!!! He noticed how she felt in the meeting and thought he’d help try to rectify that! Goddamn it you two have such a great dynamic

Thank you Brandosando for confirming again that Adolin is highly educated despite being illiterate - a future HIghprince has to know how to run their princedom, after all. Those ardents must have had fits trying to get him to sit down and pay attention, though (I’m still of the mind that he’s ADHD and nothing has popped up to contradict this so far)

Aaand there’s the pacing.

yOU TWO. Both wanting this to work but almost unsure of your own worth to each other, cradling that warmth of hope and spark of affection that’s maybe even growing to love

“You only ruined the wrong ones, you see.” that’s not the greatest appeal to his logic but damn if it doesn’t work. AND HE GOES IN FOR THE KISS-

“No mating!”

Pattern you are a gem

 Chapter Fourteen - Squires Can’t Capture

‘They were playing cards.’ Yeaaaaaah, they must have escaped Odium’s influence somehow. But how?

‘What in Damnation’s depths?’ another good swear to remember!

Workform, then. 

I flip the page and FUCKING HELL I thought I was tossed into a Cthulu or White Wolf Black Spiral Dancers sourcebook for a moment before the details resolved themselves out of the greater picture.

 ‘Shallan’s Sketchbook - Corridor’? ....dude. That. Shallan. Shallan. That is not at all like the style we saw you use in previous books. That is a Coping Sketch.

We were definitely wrong about how the Everstorm would hit the parshmen, at least for right now. These aren’t Voidbringers - or at least they’re not mindless, probably not controlled either? What is going on

Wait- was that a spren?

Best option, Kaladin. Good choice.

(I think.)

Chapter Fifteen - Brightness Radiant

So the second body was found in the same area as well as being the same manner of murder? I can’t remember if that area ‘belonged’ to one of the Highprinces or not

The fidgeting with the ball only enhances/reinforces my ADHD headcanon for him

I know they’re (supposedly) looking at all the options, but that’s not terribly convincing, Adolin. [winces] And while he’s right, Shallan, he just has information you don’t. Damning information.

Oooo, Shallan’s going to investigate, isn’t she. Veil time? Veil time?

Oh no Adolin what are you going to say, are- are you actually working yourself up to tell her?

...maybe. Toeing the cultural boundaries is certainly something to be unsure of especially for Vorins, but... perhaps.

(Blame him, Shallan. You’re going to be tasting spice for days.)

Ohhhh no no no, this is bringing up things she’s been trying to repress even though she can’t, Adolin come on, use that uncanny insight of yours-!

The snark would be funny if it were actually playful instead of a deflecting tactic.

[winces] Shallan, I know you’re fighting your PTSD right now, but that thought was really classist.

[buries face in hands] Adolin this is not a good time, I know you’re excited, you want to share this with her and your mind is set, but Shallan is not up for this right now. This could trigger a full on panic attack.

That is... a way to cope. Fake it til you make it. And it’s another personality inside her, she’s just strengthening it, bringing it to the forefront. But she’s once again avoiding facing the issue - because if she faces it she’ll shatter.

(They’re opposites in that way - Adolin facing the problem directly, Shallan deflecting. Very firebender vs waterbender mentality.)

Oh, Pattern.

This is going to bottle up inside until she breaks. Again.

...can he tell the difference, I wonder? She’s still Shallan, but... a different aspect of Shallan.

HAH, that little shove! Oh, I’m flashing back to kung fu practice years ago...

[SNORTS] Zahel, they know you too well. (If you’d ever tried that with Vivenna, she would not be having it.)

He’s been doing this since he was six, Shallan, cut him a little slack. He’s internalized the ‘mysticism’ and it makes sense on a deep level to him, at least.

He’s right about the unlearning, Shallan. Just trust him.

But don’t cut him any slack for the chicken.

part of it might be from being a duelist but I swear that part of it is more

“She knew that passion - she’d felt what it was to be alive with interest, to be consumed by something so fully that you lost yourself to the wonder of it. For her it was art, but watching him, she thought that the two of them weren’t so different.” - @heliokrantor LOOK LOOK WE WROTE ALMOST THIS E X A C T THING IN ‘BEFORE THE DUEL’ . Just. an entire fic of it. [highfives] Fuckyeah.

And at the end, she finds peace. 

Chapter Sixteen - Wrapped Three Times

So. Does that make the Honorblades Splinters of Honor?

TELL US ABOUT THE REQUIREMENTS FOR PLATE, STORMFATHER. At least what Oathlevel a Radiant can get/materialize/whatever it at!

Frightened? The Stormfather can feel fear? On the sort of level that a human/Parshendi/mortal can feel emotion?

At least Navani is staying occupied by rolling up her sleeves and taking on civil engineering projects. (They’ll certainly need it.) I’d thought she was a conceptual mechanical engineer, but apparently her interests are broader than just that!

Dalinar is being v e r y careful about the amount of unbridled power he allows himself, and after seeing the flashbacks I can only think thank god.

Did Stormfather just confirm that he was a Cognitive Shadow, or was that pure metaphor?

Is... is this guard giving Dalinar shit for not obeying his own directives? Dude, you have steel-plated balls.

....are you one of Lopen’s ‘cousins’.

A watch! How common are those? Probably not at all, but how did Nanavi get it? Was she the one who managed to engineer a clock down to watch-size?

Oooof, that heresy is hitting you in unexpected ways. Even your own swordmaster ardents don’t want much to do with you anymore.

And then, of course, there’s Zahel. Hi Vasheeeeer. You gonna reveal yourself anytime during this series?

Please continue confusing the Rosharans with your Nalthian turns of phrase. It’s vastly entertaining.

wrESTLING? I. Well. Okay then. Barechested, tight-pantsed wrestling it is, then. ‘Vehah match’, note to remember what that’s called.

I wonder, if you hadn’t stopped reaching for the Thrill, would you have been able to grasp it? Or does the Nahel bond prevent it from taking hold?

OH OH STORMLIGHT. YES. DO THE THING DALINAR DO THE THING BREATHE THE LIGHT

Or not. Fair fight, that’s respectable.

You were enjoying the sight Navani, don’t try to say otherwise.

‘GEMHEART’ AS AN ENDEARMENT. AAAAAAAHHHHH.  It's like telling one "not only are you the greatest and most beautiful of gems, one who holds the light of my life, but also I would fight armies and chasmfiends for you". I love it. Give me more of this.

Three monarchs for the Iri - two kings and a queen. Are they joint rulers? Poly? Or do they all rule over separate parts of Iri? I’m inclined to think the latter since apparently it’s only the queen that has influence over foreign policy.

Ooo, are you going to try to bully your ardents into speaking with you, Dal? 

“I was merely one in a long line of idiots given the ability to kill people too easily. Well at least you can recognise and admit that.

Navani, you should know by now that it’s easier for the men of your family to think when they’re in motion. All of them, including Dalinar.

“Alethkar has not been relevant in the world since the Sunmaker’s fall.” Yeaaaah, you’ve all been warring amongst yourselves in your divided princedoms - you’ve not even been a real kingdom and therefore a power on the world scale up until the unification, and then after Gavilar dies you took all your Highprinces over to fight another, rather pointless war. It’s no wonder the rest of the world won’t leap when you call.

Oooo, shit, all of Iri-Rira is still salty over the Alethi getting Adolin’s Plate? Damn.

hello reference for how to wear takama. I’m keeping you too.

“You sound like your niece!” “I’ll take that as a compliment.” 10/10 here for Dalinar questioning his faith while still keeping faith

!!!! Conscious surgebinding! There’s Adhesion, but we still need to know what on Roshar Tension does. I’m still drawing a blank on that one. Sanderson please don’t keep us in the dark for too long on this one.

!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!

he heard he wife’s name

Evi

(your brother’s death wasn’t what broke you. it was hers. and now, with your spren filling the cracks in your soul, you’re starting to remember)

[theharvestersbook]

06: Proteans

Meredith opened her palm and looked at her birthmark.  Then, she looked up at her mother.  "Mama," she whispered, "am I a freak?"   "No baby.  You are more special than you can imagine."  Maya patted Meredith's hand and hugged her.  Maya hesitated for a moment, looked at Meredith's hand, and then at Papa Gill, who nodded.  Ready or not, it was time.   Maya looked around and saw that Sam, Hamish, Neha and Kaikane were all watching her and Meredith intently.  Waiting.  She smiled wistfully and said, "The time has come,' the Walrus said, 'To talk of many things: Of shoes, and ships, and sealing-wax, Of cabbages, and kings, And why the sea is boiling hot...'" "What’s that, Mama?” “A very old poem, Mer," Maya smiled at her daughter.  She stood up, took a deep breath, and looked up at the harvesters.  "Come with me," she said as she started below deck, "I want to show you all something."   The harvesters looked at each other with a shared feeling of destiny.  No one said anything, but they all seemed to know. So, one by one, they got up and followed Maya below deck.   "Each of you have been having dreams lately," said Maya as they gathered by one of the stern compartments near the engines. It was a unique feature of the Queen Caretta that, thanks to Papa Gill's constant tinkering, her engines made no sound.  And while there were other sounds coming from the engine room, mostly gentle whirring and a subtle, smooth vibration, it was easy to hear Maya speak in a normal tone. “Maybe you’ve been hearing voices in the water as well," She continued, "or having strange visions that you cannot explain." The harvesters all looked at each other in hesitant surprise.  How could Maya possibly know that all of them had been having dreams about suffocating and a strange, beautiful city?  They hadn't even told each other, because the dreams had been so strong, so vivid, each of the harvesters had been secretly worried that they might be going crazy.   Maya didn't wait for a confirmation.  She knew the truth.  "You're frightened to tell anyone because you think no one will believe you," she said as she looked directly at each harvester, "or worse, you're worried that someone will believe you, and think you're a freak."   She turned, and pointed her finger directly at Meredith.  "I'm telling you right now that I believe you, and you are not a freak.  You're all miracles." She turned to put her hand on the compartment door latch.  She hesitated for a moment, and then turned to look at everyone again. "You are different,” she nodded.  “But you are all so much more special than you realize." Then, she pushed the door open and a warm, orange glow filled the corridor.   Immediately, each of the harvesters reacted.  Meredith raised her hand to her temple as her head started buzzing and clicking madly.  Sam raised her hands to cover her ears.  Hamish and Neha both flinched and squinted their eyes.  Kaikane put a hand to his head as if he had been gripped by a sudden headache. Seeing her friends' reactions, Meredith realized that she wasn't the only one who had been struggling.  Sam's moodiness, Kai's nervousness, Hamish's acting out and Neha's indifference; all of her friends had been struggling.  She just hadn't paid attention to them.  She assumed that she was the only one who was having a hard time. Maya stepped into the orange glow of the compartment.  "C'mon," she waved, "No one's going to hurt you."  The harvesters crowded around the hatchway and peered into the compartment. It was warmer in the compartment than in the hatchway, and humid.  Sticky, even.  In the center of the room, was what looked like a cluster of murderballs.  But they weren't.  They were softer than murderballs, almost like balls of dough.  There was a gooey webbing holding them all together, and they pulsed, slowly, with an orange glow.  Meredith knew immediately what they were. "Eggs," she thought out loud to no one. Maya raised her eyes.  "Yes, Mer.  They're eggs, of a sort." "But what kind of eggs?" asked Neha, still rubbing her head. "Well, not really eggs.  They’re Protean stasis pods," answered Maya, very matter-of-factly, like they should've all known what Protean stasis pods were. "The same kind you came from," she added with a slight smile. Hamish laughed.  "I'm sorry, Maya.  But you're saying I came from one of those?"  He said, jokingly, as he pointed at the stasis pods, "Like a chicken?" "Yes," replied Maya, "That is precisely what I'm saying."  She said it with such a frankness that Hamish stopped laughing and swallowed hard instead.  Maya looked around at the other Harvester faces.  "You're all children of Proteus.  These," she waved her hand at the glowing pods, "are also children of Proteus." "But Mama, who's Proteus?" asked Meredith. “Proteus is our home, Mer," Maya said gently, "A long time ago, our home, Proteus, was attacked, and our only option was to escape and hide.  So, we escaped by placing our daemons in these stasis pods, and hiding the pods in clutches around the world.” “What’s a daemon?” asked Hamish, who had become very serious and curious by now. “A daemon is a spirit, an internal, inspiring force.  Your daemon is your essence, your soul," Maya answered.  She turned and looked at the pods, " Each pod contains the daemon of a single Protean, waiting to be reborn.  The combined memory, knowledge and culture of the entire Protean race is contained in these pods." "The dreams you've each been having, that's your subconscious, your daemon, trying to push your Protean memories and knowledge into your conscious mind.  The older you get, the more powerful your dreams will become, until finally, you'll Rush." "What do you mean, rush?" Sam interrupted, holding up her hand.  "What's a rush?" Maya considered this for a moment, and then said, "Your Rush is when you become completely aware of your Protean self; your daemon presents itself to you.  All your stored memories and knowledge will move from subconscious to conscious, your g..." Maya hesitated for a moment and looked at everyone.  No one said a word as they stared in disbelief at Maya. "Lot's of things are going to happen at your Rush," she said softly.  "I can't explain everything now.  You'll just have to go through your Rush to understand.  And in the meantime, you're gonna have to trust me." She hesitated, and added, "Without an experienced Protean to mentor you through the Rush, it could overwhelm you, drive you mad, or even kill you."  She looked at Sam.  “So don’t think you can Rush by yourself.” Maya allowed her words to sink in.  The room pulsed with the silent orange glow from the stasis pods. "So, that means there are experienced Proteans," Hamish quietly deduced.  "At least, I hope there are, cause I don't want to go crazy." "Too late," said Sam. There was a soft chuckle from the harvesters, except Meredith, who was thinking hard.   Neha looked intently at Maya and asked the obvious question, "Are you a Protean?" "I am.  And so is Papa Gill.  He brought me out of stasis after a huge storm destroyed the clutch I was a part of." "Then which clutch did he come from?" "He didn't.  Papa Gill has a different story.  When Proteus was lost, clutches of stasis pods were hidden all over the world.  Papa Gill has been searching for, and protecting, the clutches ever since then.” “Are you saying Papa Gill came from Proteus?” Maya nodded. “Geez,” said Sam, “how old is he?” “Old.” "So, after we were all hidden in our stasis pods, in various, secret clutches around the world, Papa Gill’s been patrolling the oceans, and watching over our clutches?" asked Sam. “Yep,” nodded Maya. "What about my gills, Mama?" asked Meredith.  She reached up and touched her neck and shoulder.  "I had gills when I was in the water, when I, when I drowned.  Now they're gone.  Will they come back?  Does everyone else have them?" Hamish and Sam both unconsciously reached up and touched their necks. "Yes, we all have gills,” replied Maya.  “They retract when we breathe air.  They only reveal when we’re in water.  You'll learn how to use them after your Rush." "Well, then why do you and Papa Gill use portagills to dive?  Why not just use your, uh, real gills?" asked Hamish. Sam smacked Hamish on the back of the head.   "Because, stupid," she chided, "It wouldn't really look too normal.  Now, would it?" Hamish rubbed the back of his head and gave Sam a look of irritation. "You're hiding!" Neha snapped her fingers.  "You don't want anyone to know about you, about us, about uh, Proteans.  So, you pretend to be human.  But, why?  Why are we hiding?" Everyone looked at Maya with a new concern. "Are we in danger?" asked Sam. "Neha, I'm impressed.  Yes, we are hiding.  And we are in danger, Sam.  But more importantly, these stasis pods," she waved her hand over the cluster of glowing orbs, "they are in grave danger.  And we must help them." "Well, what do?" Meredith asked.  Everyone turned to look at her. "You say we are different, Mama.  Special.  So say we’re Protean.  And I believe you because I feel it."  She placed her palm over her chest. "I know it to be true now, all those dreams and feelings I've been having.  Wanting desperately to dive every day, despite the cold and exhaustion.  The buzzing and clicking in my head every time I'm near sea animals.  The pull of the cruiser.  It wasn't the cruiser calling me; it was the clutch.  I get it.  It makes sense.  It doesn't just make sense; I feel it to be true, deep in my bones." Meredith looked around at the other faces, nodding in quiet affirmation.   She looked back at Maya. "But, what can I possibly do to help?"  She pointed to the cluster of glowing orbs. "We have to move them, Mer," Maya answered calmly.  "There is an entire clutch buried underneath the cruiser.  And we believe our enemies have discovered the clutch as well.  That cybershark proves it.  It's only a matter of time before they attempt to destroy the clutch." "But what enemies, Maya?" asked Sam,  "Why would anyone want to destroy Proteans?" "It's a very long story," said Maya, "Longer than we have right now.  For now, I'll tell you that Proteans have been on this planet for much longer that humans, and there are those who view us as a threat to their plans." Sensing the next question coming from Hamish, Maya quickly added, "But I'm getting ahead of myself.  The point of showing this to you is so that you'll grasp the reality of the situation.”  She looked earnestly at each of the harvesters.   “You are Protean.  Your Rush is coming soon; you need to prepare yourself.  And we are all in danger.  So, other than your families, tell no one about any of this."   No one said a word as Maya’s words sank in. Slowly, almost hesitantly, Neha raised her hand. "Maya," she asked tentatively, "if everything you've told us is true, (and I believe it is) where did we all come from?" Maya looked at Neha and answered, "Years ago, Papa Gill and I harvested you from this very same clutch.  Ever since, we’ve been watching each of you for signs of your coming Rush.  Now it’s here.” The harvesters all looked at each other.  It made sense.  Everything made sense.  Except for one thing. With a look of realization and confusion, Meredith asked, "But Mama, what about my daddy?  Daddy was human.  How could I come from a, a pod?  Daddy was human." "Oh, my God," gasped Sam, "That's right.  I didn't even think of that." "It's true, Mer," answered Maya, "Your daddy was human.  And I'm sorry, Baby, but I have no idea what that means, or what's going to happen next for you.  You are truly different from everyone else: half human and half Protean.  All I know for sure is that I thought you were dead, drowned.   But your gills presented themselves and saved you.  And, they presented before you Rushed.  I've never seen that happen before." Maya looked at her daughter, wishing she had more answers. "Mer, whatever happens, you won't go through it alone.  I will be right there with you," Maya promised. “So will I,” assured Sam. Then Kaikane spoke up. "That means none of us, except for Meredith, actually have real parents.  The rest of us came from those pods, those stupid, disgusting pods."  He waved his hand like he was trying to knock the pods away. Maya looked at Kaikane with mild surprise. "No, Kai," said Neha, "Don't." "No!" snapped Kaikane.  "I want to know the truth!  I deserve to know!" He looked at Maya and asked, "My father isn't really my father, is he?" "You already know the answer, Kai," said Maya calmly.  "You've always known.  You may not have wanted to believe it, because the truth was too frightening.  But you knew." Kai looked at Maya.  Then he looked at Meredith, and the pods.  Maya was right.  He had always known.   He thought about that for a moment. "I hate you," he said flatly to Maya.  And he turned and walked out of the room. "Kai!" called Neha.  "Where are you going?" "Let him go, Neha," said Maya. "He needs to sort things out." "Mama," Meredith said, "Can I touch one?" Maya smiled, "Sure.  But let me warn you; your physical connection will create a link with all the daemons in the stasis pods.  You will have access to many shared memories.  So you may see things in your mind that won't make sense until you've had your own Rush.  But, I’ll be with you." Without completely understanding what Maya meant, and still a bit confused about what a "rush" was, Meredith nodded and approached the cluster of pods.  She knelt down and, taking hold of Maya’s hand, Meredith placed her marked hand on one of the pods.

She gasped as the familiar sensation in her head returned, this time like a wave.  Her head was filled with buzzing and clicking and voices. Clear voices, speaking.  It was a conversation, and it rushed forward with a stunning clarity.

"But you must cast the deciding vote, Caretta, it is your duty and responsibility as Sovereign!" "No, Superbia," replied Caretta calmly.  "My responsibility as Sovereign is to preserve the Republic of Proteus.  A vote either way will rend our unity down the middle.  I will not destroy what has taken a millennium to build.  The Council will continue to debate until a common resolution to the Human Issue can be found." The Room of Debate was empty, except for Superbia, who was anxiously pacing about, and Caretta, who was sitting calmly in her seat at the head of the large, oval-shaped table in the center of the room. "Caretta," Superbia turned and pleaded, "be reasonable.  You've seen the humans.  You know what they're like; they're savages.  They know nothing but war and rage.  We have only managed to maintain our borders through constant negotiation.  Humans don't respond to reason.  They are emotional and violent in their beliefs.  They must be controlled, not treated as equals." "Yes, there is truth in your words," said Caretta.  "Many humans are as you describe.  And it is precisely because of our constant efforts at negotiation and instruction, because we have taken the more difficult path of patience and understanding, that humans have not completely destroyed themselves.  You and I have both have met human leaders who would lead humanity to a better, more enlightened place, and we owe them the opportunity." "Owe them?" retorted Superbia.  "Owe? Them?  How do we owe those filthy savages anything?  They have no sense of reason or spirituality.  They show no respect or kinship to their own kind. If anything, they owe us! Certainly, some do speak of values, but then use them only to their advantage.  They murder and enslave each other!  How do we owe them any consideration at all?  Think, Caretta!  Imagine what will actually happen if we were to treat them as equals.  Imagine what would happen if we were to educate them and actually give them the gift of knowledge, of discernment, of science and technology.  What do you think they would do with that gift?  Do you actually believe they would respond in kind?  Do you believe they would grow intellectually?  Morally?  Spiritually?  No!  They would foolishly squander it." Caretta carefully placed her hands, palms down on the table, took a deep breath, and looked up at Superbia. "Be careful, Superbia, that you do not allow your argument to slip from logic to prejudice.  They are sentient beings.  Yes, they are immature as a race.  Yes, they lack the technology we possess.  They are a younger species.  At the moment, they are simple and naive, like adolescents.  So are the Ketos Megas, but we treat them with respect and freedom.  I am confident that Humanity will rise to its potential, if only given the opportunity." "Ketos Megas!" exclaimed Superbia, waving her hands out in exasperation.  "Ketos Megas don't wage war with one another.  And we are not talking of treating humans like we treat Ketos Megas.  We don't share our technology with Ketos Megas; we treat them like pets!  We are talking about sharing our technology, our culture, our wisdom; we are talking about elevating humans to the same level as Proteans.  And you are not so naive to not realize where that will lead.  We are talking, ultimately, of mingling Protean blood with that of a race that is barely beyond the Simia.  And that abomination simply cannot be allowed to happen!" Caretta sighed and looked down at her hands.  Once again, Superbia was becoming emotional about her position, and Caretta could see that nothing would be resolved at that moment.  She remained silent as she considered her options.

"You know I'm right," pleaded Superbia. "Why won't you vote with us, with the Realists?" Caretta looked at the Seal of Proteus in the center of the oval-shaped table, then up at Superbia and smiled warmly.  "My oldest and dearest friend, I do love and respect you.  But, I will not vote either way.  Both Altruists and Realists have become too fundamental and entrenched about a complex topic that demands more.  A vote in either direction right now would split the Republic, and we would descend into a civil schism.  They only way is to continue the debate until we can find a way that is agreeable to all." Superbia stood and looked down at Caretta and sadly understood what she must do next.  There was more than just the Republic at stake; it was their way of life that was in danger.  Caretta was being foolish and short-sighted.  Although she claimed no allegiance, she was the most altruistic of all of them, and foolishly so.  The Human Issue would soon become the Human Problem, and then the Human Threat.  It had to be dealt with now, preemptively, not to harm, but to control.  She wiped her emotions from her face, concealed her thoughts from being heard, and smiled warmly back at Caretta. "You are right, as usual, my Sovereign." Superbia bowed her head at Caretta and then smiled tersely.  "If I may be excused, I have pressing business in my district to which I must attend." Caretta's brow furrowed slightly at the formality in Superbia's tone.  She looked at her childhood friend, and felt both saddened and somewhat irritated   "There is another debate scheduled for tomorrow.  We can surely talk more then, Superbia." Superbia nodded graciously, bowed, and formally backed up three steps before turning her back to her Sovereign and walking out of the Room of Debate, leaving Caretta with her thoughts. As she walked through the long Navis that led from the Room of Debate to the covered Narthem of the Convene, a dark shape slid from behind one of the support pillars and slithered up to her side. "Well?  How did it go?" asked a low, gravelly voice. "She remains unmoved," whispered Superbia.   "Then we must move forward with our plans," rumbled the voice. "I am not quite as eager as you are, to simply supplant a millennia-old Republic.  Caretta is right about one thing; half of Proteus sides with the Altruists.  Anything we do must be done in a way that shifts their allegiance and belief to that of the Realists.  Otherwise, we will simply divide ourselves." "Then what do you suggest?" "We must make it clear to everyone that humans are dangerous, and not to be trusted.  It must happen in a way that proves they need to be controlled, and aligns all of Proteus to our cause.  But it cannot do any real damage, no loss of Protean life." "What about human life?" "I am against killing, any killing," said Superbia, looking away at the Seal of Proteus in the stained glass window overhead. Then she looked back at the figure and stated flatly, "We need physical proof." "Indeed," smiled the figure.  "Proof." Superbia lifted her left hand to her mouth, and spoke at the silver bracelet she was wearing, "Notify Avaritia and Socordia, to meet us at the Pillars in two days time."  The silver bracelet unfurled itself into a small, silver water dragon, opened its wings, and leapt into the air to deliver its master's message.  Superbia watched it fly out the open door to the Navis. Superbia then regarded dark figure, and said, "Gather Asmodeus, Gula and Ira.  Playing with the Kentron Generator is dangerous, and I want to be sure everyone is aligned and understands what we are proposing.  We only need two votes from the Altruists; Caritas and Humilitas are the most likely to turn.  But I want everyone to side with us.  Everyone.  All the Realists must agree to your plan before we move forward." "Excellent." rumbled the voice. "And, one more thing," Superbia turned and grabbed the dark figure's arm, "Do not forget yourself.  Although you may covet my seat on the Synod, it is mine.  Do not think for a moment that I am blind to your desires and ambition, your envy."  She drew out the last word slowly, like a long blade from its sheath.  "But you are not me.  As long as I sit, I will make the decisions for the Realists.  Are we clear on that point?" "Of course," the dark figure smiled broadly, and chuckled low and deep, and, smiling directly into Superbia's eyes, reached over and carefully plied her fingers from his arm.  Then, he bowed his head slightly. "MiDame." Superbia regarded the figure for a moment.  Then, without another word, she raised her chin, turned and strode out of the Convene and into the glare of the noonday sun. The dark figure watched her leave, and chuckling to himself, slowly walked out the side entrance.  

It was silent for a moment in the dark, cool hall.  Then, from an unlit corner of the Navis, a small, cloaked figured emerged from the shadows and rushed toward the Room of Debate.

"Meredith!" Meredith looked up in a fog.  Sam was standing over her, holding her shoulders. "Wha...?" Stammered Meredith,  "I saw.  I heard."  She pointed drunkenly at the orange, glowing eggs. "You were in some kind of weird trance, or something, girl," said Sam.  She furrowed her brow and looked at Maya for an explanation.  "What the fuck, Maya?" "Sam," said Maya, "Relax, okay?  It's alright.  She's fine.  She just connected to the daemons in the pods.  Give her some time to process what she saw, and she'll tell us later." Then Maya looked at the rest of the harvesters. "Papa Gill and I will mentor each of your through your Rushes.  There's nothing to worry about.  What we need to focus on is getting these pods out of here; the cruiser isn't a safe place anymore.  I need to know that you've heard what I've told you, and that you're up to the task" Maya looked around the room at each harvester and said, "Are you up to the task?"   As she looked around, each harvester nodded in agreement. Maya sighed heavily and said, "You make me proud." Then Sam broke in, "Maya, there's one question that no one has asked, and I know everyone is thinking." "What is it, Sam?" Sam paused and looked around the room.  Then, she focused her gaze on Meredith. "Where did that shark-thing come from, and why did it go after Meredith, and leave the rest of us alone?"  Sam looked directly at Maya, waiting for an answer that did not come.

[nancygduarteus]

Turning Piglets Into Personalized Avatars for Sick Kids

When Charles Konsitzke and Dhanu Shanmuganayagam first met, they were both just trying to get some peace and quiet. It was early 2014, and they were representing the University of Wisconsin-Madison at a fancy event to promote the university’s research to local politicians. After hours of talking to senators, Shanmuganayagam was fried, and went for a walk to clear his head. That’s when he bumped into Konsitzke, an administrator at the University of Wisconsin’s Biotechnology Center. They introduced themselves, and discussed their work. Shanmuganayagam said that he ran a facility that rears miniature pigs, which are genetically engineered to carry mutations found in human genetic disorders. Scientists can study the mini-pigs to better understand those diseases.

“And I said: I have a project for you,” Konsitzke recalls.

Konsitzke’s son Mason, now aged 7, was born with little brown birthmarks on his buttocks. Many kids have one or two of these café-au-lait spots and at first, Konsitzke thought they were cute. But after more appeared, he did some research and found that such spots are a common symptom of neurofibromatosis type 1 (NF-1)—an incurable inherited disease. Around Mason’s first birthday, a pediatrician confirmed the diagnosis.

Mason Konsitzke (Bryce Richter / University of Wisconsin-Madison)

NF-1 is an incredibly varied disease with many possible symptoms. The spots are the least of them. Some patients, Mason included, develop learning disabilities. Others develop bone and heart problems. Most commonly, patients get tumors on their skin and nerves; Mason already has one on the side of his face. These tumors are usually benign, but even so they can still disfigure. “It continues to grow, and if it runs out of space, it will deform his face outward,” says Konsitzke.

Konsitzke isn’t a scientist by training, but through his job he’s well connected to the scientific world. Once Mason’s diagnosis was in, he started asking around about NF-1 research. In particular, he wanted to know where the bottlenecks are. What was the single thing he could do that would most accelerate research into his son’s condition? And the answer that he kept hearing was: Find better animals to experiment on.

When studying diseases, scientists often turn to laboratory animals like mice and zebrafish. They can use these so-called model organisms to work out how mutations cause diseases, and to find and test possible treatments. But the usual lab animals aren’t a good fit for NF-1. They’re too small, and they don’t react in the same way to the mutations that cause the disease in humans. For example, studies in mice suggested that a drug called lovastatin might help to address the learning and attentional problems that accompany NF-1. But when the drug was tested on actual children, in a large clinical trial, it did nothing.

To better understand NF-1, Konsitzke learned, you need a species that’s closer in both size and biology to a person, and yet is still relatively easy to raise and study. That is, you need pigs. “Pigs closely represent humans,” says Neha Patel, who directs the UW neurofibromatosis clinic. “People with NF-1 have varied cognitive deficits, from severe learning issues to subtle problems. If you imagine studying those in a rat, you’d only get a crude picture of how that translates to humans. But pigs are intellectual animals.”

That’s why, in a quiet corner of the Wisconsin State Capitol, Konsitzke was so excited to meet Shanmuganayagam. Here was someone with experience in raising, engineering, and studying pigs. Here was just the guy he needed to give NF-1 research a boost.

Dhanu Shanmuganayagam (Bryce Richter / University of Wisconsin-Madison)

For his part, Shanmuganayagam was keen to take on a new challenge. “I know a lot of diseases,” he says, “but when Chuck told me [about NF-1], I thought, ‘I don’t know what this is.’ And I can’t believe I didn’t know because it’s not that rare.” Indeed, NF-1 affects at least one in every 2,500 babies, making it more common than other better-known genetic disorders like cystic fibrosis. And that figure is probably an underestimate, because many cases don’t present with obvious symptoms. “It’s under-recognized, and kids are not getting the best care,” says Patel. She’ll often see parents whose children clearly meet all the clinical criteria for the disease, and yet hadn’t been diagnosed for over a decade.

The disease has a low profile partly because its symptoms can be so disfiguring. Patients with NF-1 often “become closeted and sheltered,” says Konsitzke. “People don’t look at them or listen to them, so there’s no strong speaking voice for the disease.” The man whom Pope Francis embraced in 2013, whose face was covered in growths, had NF-1. Joseph Merrick, the so-called Elephant Man of 19th-century England, was once suspected of having had NF-1. “Our neuro-oncologist told us to take pictures of Mason now, and be prepared for his face to change,” says Konsitzke.

For different reasons, NF-1 has a low profile in the scientific community, too. It’s caused by mutations in a gene called neurofibromin 1 (confusingly also shortened to NF1), which is daunting to study because of its large size and unusual variability. “People fear it in the research realm,” says Konsitzke. There are more than 4,000 variants of the gene, each of which changes the symptoms of NF-1 in subtle ways.

Again, the pigs can help. Konsitzke and Shanmuganayagam aren’t just planning to develop pigs that can model the symptoms of NF-1. They want to use the revolutionary gene-editing technique known as CRISPR to create pigs that have the specific mutations of a particular individual. Each child with NF-1 would get their own personalized piglet, whose version of the NF1 gene matched their own. The piggy proxy could be monitored to see how the kid’s condition might progress, especially since they mature faster than humans do.

The pigs could also be used to test possible treatments. At the moment, people with NF-1 “are their own guinea pigs,” says Konsitze. “It takes years of tests and side effects to find something that works. My son is on a cocktail of four different meds.” Having an animal that mirrors the particulars of a person’s condition might make it quicker to narrow down the best treatments. And Konsitze argues that this should save enough money to compensate for the costs of creating a customized pig.

A pig undergoing surgery (Bryce Richter / University of Wisconsin-Madison)

Shanmuganayagam and his colleagues started actively trying to make the gene-edited pigs in 2014, with a shoestring budget of $50,000 from the Neurofibromatosis Network, which they bolstered through their own fund-raising efforts. (Two companies also developed pig models of NF-1 around the same time: Recombinetics, based in St. Paul, Minnesota; and Exemplar Genetics, in Sioux Center, Iowa.)

Jennifer Meudt, one of Shanmuganayagam’s colleagues, led the work. “Dhanu said: ‘We’re going to gene edit pigs,’” she says. “And I said: Okay, ha ha, how are we going to do this? My background is in botany.”

The easy way to do it would be to buy pig eggs from slaughterhouses, fertilize them in the lab, do any necessary gene editing, and inject them back into sows. But UW’s pig-rearing facility is kept free of disease-causing microbes, so the team can’t just implant their pigs with commercially sourced embryos. Instead, they have to artificially inseminate their own sows, collect the embryos, inject them with CRISPR ingredients, and put them back into other pigs.

The embryos themselves are hard to work with, because they’re not translucent like those of many other animals. “They look like little black balls, which makes it more difficult to inject when you don’t know where you’re poking,” says Meudt. There are logistical complications too. Meudt has to do the CRISPR injections in a building that’s 30 minutes from the pig facility, so the animals have to get shuttled back and forth. From start to finish, the process to make a single embryo starts at 4 in the morning, and ends at around 10 at night. “Those are well-traveled embryos,” Meudt says.

The team delivered their first edited animal in November 2016, which carried a set of NF-1 mutations that had been reported in an earlier published study. They have since engineered three more animals, each with a different cluster of mutations. All of these are essentially personalized—they represent someone’s case of NF-1, but those patients are anonymized.

The next step will be to create pigs that are openly personalized to specific people—and the team is in the midst of getting approval for that. “We slowed ourselves down for some ethical reasons,” says Shanmuganayagam. For example, if a personalized pig starts to show symptoms, and their child counterpart has not, how should the team communicate that information to a family? What happens if the pig dies early? Should a family even get to know which pig is “theirs”? “We’re trying to resolve that,” says Shanmuganayagam. “We might blind ourselves to whose pig is whose with the option of revealing at a later date. I’ve also had my group read Flowers for Algernon.”

from Health News And Updates https://www.theatlantic.com/science/archive/2017/12/turning-piglets-into-personalized-avatars-for-sick-kids/548204/?utm_source=feed

[ionecoffman]

Turning Piglets Into Personalized Avatars for Sick Kids

When Charles Konsitzke and Dhanu Shanmuganayagam first met, they were both just trying to get some peace and quiet. It was early 2014, and they were representing the University of Wisconsin-Madison at a fancy event to promote the university’s research to local politicians. After hours of talking to senators, Shanmuganayagam was fried, and went for a walk to clear his head. That’s when he bumped into Konsitzke, an administrator at the University of Wisconsin’s Biotechnology Center. They introduced themselves, and discussed their work. Shanmuganayagam said that he ran a facility that rears miniature pigs, which are genetically engineered to carry mutations found in human genetic disorders. Scientists can study the mini-pigs to better understand those diseases.

“And I said: I have a project for you,” Konsitzke recalls.

Konsitzke’s son Mason, now aged 7, was born with little brown birthmarks on his buttocks. Many kids have one or two of these café-au-lait spots and at first, Konsitzke thought they were cute. But after more appeared, he did some research and found that such spots are a common symptom of neurofibromatosis type 1 (NF-1)—an incurable inherited disease. Around Mason’s first birthday, a pediatrician confirmed the diagnosis.

Mason Konsitzke (Bryce Richter / University of Wisconsin-Madison)

NF-1 is an incredibly varied disease with many possible symptoms. The spots are the least of them. Some patients, Mason included, develop learning disabilities. Others develop bone and heart problems. Most commonly, patients get tumors on their skin and nerves; Mason already has one on the side of his face. These tumors are usually benign, but even so they can still disfigure. “It continues to grow, and if it runs out of space, it will deform his face outward,” says Konsitzke.

Konsitzke isn’t a scientist by training, but through his job he’s well connected to the scientific world. Once Mason’s diagnosis was in, he started asking around about NF-1 research. In particular, he wanted to know where the bottlenecks are. What was the single thing he could do that would most accelerate research into his son’s condition? And the answer that he kept hearing was: Find better animals to experiment on.

When studying diseases, scientists often turn to laboratory animals like mice and zebrafish. They can use these so-called model organisms to work out how mutations cause diseases, and to find and test possible treatments. But the usual lab animals aren’t a good fit for NF-1. They’re too small, and they don’t react in the same way to the mutations that cause the disease in humans. For example, studies in mice suggested that a drug called lovastatin might help to address the learning and attentional problems that accompany NF-1. But when the drug was tested on actual children, in a large clinical trial, it did nothing.

To better understand NF-1, Konsitzke learned, you need a species that’s closer in both size and biology to a person, and yet is still relatively easy to raise and study. That is, you need pigs. “Pigs closely represent humans,” says Neha Patel, who directs the UW neurofibromatosis clinic. “People with NF-1 have varied cognitive deficits, from severe learning issues to subtle problems. If you imagine studying those in a rat, you’d only get a crude picture of how that translates to humans. But pigs are intellectual animals.”

That’s why, in a quiet corner of the Wisconsin State Capitol, Konsitzke was so excited to meet Shanmuganayagam. Here was someone with experience in raising, engineering, and studying pigs. Here was just the guy he needed to give NF-1 research a boost.

Dhanu Shanmuganayagam (Bryce Richter / University of Wisconsin-Madison)

For his part, Shanmuganayagam was keen to take on a new challenge. “I know a lot of diseases,” he says, “but when Chuck told me [about NF-1], I thought, ‘I don’t know what this is.’ And I can’t believe I didn’t know because it’s not that rare.” Indeed, NF-1 affects at least one in every 2,500 babies, making it more common than other better-known genetic disorders like cystic fibrosis. And that figure is probably an underestimate, because many cases don’t present with obvious symptoms. “It’s under-recognized, and kids are not getting the best care,” says Patel. She’ll often see parents whose children clearly meet all the clinical criteria for the disease, and yet hadn’t been diagnosed for over a decade.

The disease has a low profile partly because its symptoms can be so disfiguring. Patients with NF-1 often “become closeted and sheltered,” says Konsitzke. “People don’t look at them or listen to them, so there’s no strong speaking voice for the disease.” The man whom Pope Francis embraced in 2013, whose face was covered in growths, had NF-1. Joseph Merrick, the so-called Elephant Man of 19th-century England, was once suspected of having had NF-1. “Our neuro-oncologist told us to take pictures of Mason now, and be prepared for his face to change,” says Konsitzke.

For different reasons, NF-1 has a low profile in the scientific community, too. It’s caused by mutations in a gene called neurofibromin 1 (confusingly also shortened to NF1), which is daunting to study because of its large size and unusual variability. “People fear it in the research realm,” says Konsitzke. There are more than 4,000 variants of the gene, each of which changes the symptoms of NF-1 in subtle ways.

Again, the pigs can help. Konsitzke and Shanmuganayagam aren’t just planning to develop pigs that can model the symptoms of NF-1. They want to use the revolutionary gene-editing technique known as CRISPR to create pigs that have the specific mutations of a particular individual. Each child with NF-1 would get their own personalized piglet, whose version of the NF1 gene matched their own. The piggy proxy could be monitored to see how the kid’s condition might progress, especially since they mature faster than humans do.

The pigs could also be used to test possible treatments. At the moment, people with NF-1 “are their own guinea pigs,” says Konsitze. “It takes years of tests and side effects to find something that works. My son is on a cocktail of four different meds.” Having an animal that mirrors the particulars of a person’s condition might make it quicker to narrow down the best treatments. And Konsitze argues that this should save enough money to compensate for the costs of creating a customized pig.

A pig undergoing surgery (Bryce Richter / University of Wisconsin-Madison)

Shanmuganayagam and his colleagues started actively trying to make the gene-edited pigs in 2014, with a shoestring budget of $50,000 from the Neurofibromatosis Network, which they bolstered through their own fund-raising efforts. (Two companies also developed pig models of NF-1 around the same time: Recombinetics, based in St. Paul, Minnesota; and Exemplar Genetics, in Sioux Center, Iowa.)

Jennifer Meudt, one of Shanmuganayagam’s colleagues, led the work. “Dhanu said: ‘We’re going to gene edit pigs,’” she says. “And I said: Okay, ha ha, how are we going to do this? My background is in botany.”

The easy way to do it would be to buy pig eggs from slaughterhouses, fertilize them in the lab, do any necessary gene editing, and inject them back into sows. But UW’s pig-rearing facility is kept free of disease-causing microbes, so the team can’t just implant their pigs with commercially sourced embryos. Instead, they have to artificially inseminate their own sows, collect the embryos, inject them with CRISPR ingredients, and put them back into other pigs.

The embryos themselves are hard to work with, because they’re not translucent like those of many other animals. “They look like little black balls, which makes it more difficult to inject when you don’t know where you’re poking,” says Meudt. There are logistical complications too. Meudt has to do the CRISPR injections in a building that’s 30 minutes from the pig facility, so the animals have to get shuttled back and forth. From start to finish, the process to make a single embryo starts at 4 in the morning, and ends at around 10 at night. “Those are well-traveled embryos,” Meudt says.

The team delivered their first edited animal in November 2016, which carried a set of NF-1 mutations that had been reported in an earlier published study. They have since engineered three more animals, each with a different cluster of mutations. All of these are essentially personalized—they represent someone’s case of NF-1, but those patients are anonymized.

The next step will be to create pigs that are openly personalized to specific people—and the team is in the midst of getting approval for that. “We slowed ourselves down for some ethical reasons,” says Shanmuganayagam. For example, if a personalized pig starts to show symptoms, and their child counterpart has not, how should the team communicate that information to a family? What happens if the pig dies early? Should a family even get to know which pig is “theirs”? “We’re trying to resolve that,” says Shanmuganayagam. “We might blind ourselves to whose pig is whose with the option of revealing at a later date. I’ve also had my group read Flowers for Algernon.”

Article source here:The Atlantic