#I should write more down about the physiology of EL's species

[eldritchships]

Olesborn's second set of teeth popping out at the slightest fright vs him helping smooth down EL-12's back spikes when they're pissed off

[amandajoyce118]

Captain Marvel Easter Eggs And References

My goal for Easter egg lists is always to get them up within a week of a movie’s opening, or the same night that a television episode airs, but I’ve had an injured wrist/thumb that has made writing difficult. So, Captain Marvel hasn’t been delayed because of a busy life, but because I’ve been trying to rest my hand. I’ve been wearing a brace and thumb stabilizer for most of my day for the last few weeks, so I should be getting back to normal soon.

As usual with my Easter egg lists, this list assumes you’ve seen the movie, and the rest of the Marvel Cinematic Universe  for that matter. There will be spoilers. You have been warned. I’m sticking mainly with comic and MCU references, so you won’t find a lot of pop culture ones here. If you want someone to give you the 90s rundown, I’m sure you can find it online.

The Stan Lee Tribute

Every MCU movie opens with the same sequence, highlighting the heroes that are part of the universe. This is the first Marvel movie to hit theaters since Stan Lee’s death, so they did something a little different. That sequence instead highlights him. The color scheme and the background text remains the same, but none of the actors are there, just shots of Stan Lee from different movies and red carpet events. I won’t lie. I’ve teared up a little every time I’ve seen it.

Hala

Both the name of the main planet and the capital city in the Kree Empire. MCU fans saw it before in Guardians of the Galaxy, though it was a bit darker and didn’t seem as tech-friendly. It makes me wonder just what happened in the years in between.

“There are tabs for that.”

Not an Easter egg, but a tiny bit of world building. Going into this movie, I think most people knew that Carol Danvers AKA Vers was really from Earth. But, I find it interesting that Yon-Rogg is so quick to offer Carol a Kree sleeping aid. It reinforces the idea we’ve seen on Agents of SHIELD that human and Kree physiology are relatively compatible.

Supreme Intelligence

Less of an Easter egg and more of a direct comic book adaptation, the Supreme Intelligence is also an A.I. in the comics. There, it’s made up of all of the minds of the smartest and most distinguished Kree after they day. That’s presumably what Yon-Rogg’s “join the collective” comment meant in the movie as well. The idea of it becoming the person you most admire is created for the movie.

Carol’s Inhibitor

The comics have tried many different inhibitors on characters with super powers over the years. The X-Men usually have collars. Alien species like their neural inhibitors though, which is what Carol appears to have when she trains with Yon-Rogg. Kudos to the MCU for keeping their tech consistent across movies and TV since it appears to be the same type as what Quake ends up with in the future on Agents of SHIELD. Interesting that Daisy’s is embedded in her brain tissue while Carol’s is on the surface of her skin. Something changed in the decades in between - probably the fact that Carol was able to disable hers. Then again, so was Daisy.

Starforce

This is considered a group of supervillains in the comics, so perhaps movie fans might have expected their turn if they knew that. A few of the members are different in the comics. For example, Yon-Rogg isn’t a member, but Ronan the Accuser is. ScreenRant did a good job at running down who’s who in the movie version since they’re all comic book characters. You can see that here.

Torfa

Torfa is a relatively new creation in the planets. It first popped up in 2014, which tells you the movie pulls from a lot of the new comic book continuity. Like the movie, Torfa was a planet where refugees lived. Also like the movie, not all of them survived the hostile atmosphere, though in the comics, it was chemicals, not Kree that were hostile. Carol also had it out with Starlord’s comic book dad there.

Talos

Talos is in the comics, but apparently he’s also a Star Trek reference. Not a Trekkie, though I do find the franchise interesting, so I’ll direct you to this article for a full explanation.

Carol’s Look

One of Carol’s most iconic looks in the comics is her mohawk. She gets it for the movie in the form of her helmet keeping her hair in place. Her uniform, with the green color scheme, is one all of Starforce uses, but it’s also a nod to the original Captain Marvel’s uniform in the comics. In fact, the color changing of her suit appears to be a nod to a few other costumes she had in the comics too. The red, yellow, and blue came later. I’m just glad we didn’t have her bathing-suit like uniform of her Ms. Marvel days.

Maria “Photon” Rambeau

Maria is created for the movie (her daughter is from the comics), and though we learn more about her much later, we see her callsign on her jet during Carol’s early flashbacks. Photon is actually one of the many superhero names Monica Rambeau uses in the comics. Nice touch.

Carol’s Family

Carol’s family flashbacks only ever show us her brother and her father. We don’t get much of an idea about her homelife other than her relatives not wanting her to be as rough as the boys. That’s very much a part of her comic book background. Her father favors her brother so much that, even though Carol has the better grades growing up, he only pays for her brother to get a university education. Carol joins the Air Force for the free tuition and to prove she’s as good as the boys to her father. (It’s also interesting that we never see her mother since a recent retcon in the comics has her mother as a Kree refuge and Carol’s birth name as Car-El as she’s half Kree.) It’s also interesting to note that a lot of Carol’s major stories in her classic comics involve her losing her memories and having to figure out who she is all over again.

Lieutenant Trouble

It’s a cute nickname for Monica with Carol’s military background. It’s also a nod to another little girl Carol new in the comics with the same nickname and Monica being a police officer in the comics when she’s introduced as an adult. She’s also from Louisiana, just like the Rambeaus are in the movie.

Dr. Lawson

We’ve got some genderbending going on for the new generation. In the comics, the original Captain Marvel is Mar-Vell, a Kree soldier sent to Earth to monitor the planet as it gets destroyed by Galactus. Mar-Vell comes to sympathize with humanity and turns on the Kree to help the humans. He also takes the guise of a scientist with NASA named Dr. Lawson while he’s undercover. Sounds familiar, except her Lawson and Mar-Vell are a woman and the race she sympathizes with are the Skrulls. The original story also had Mar-Vell and Carol ending up in an accident with a piece of Kree technology that left Carol with his powers. I love the twist on this origin story. There’s plenty of nods to the source material without Carol’s jealousy of Mar-Vell from the comics, and without her playing second fiddle to a heroic dude for a long time.

Project PEGASUS

In the comics, Project PEGASUS is a unit researching alternative energy sources. It also acts as a prison for those with superpowers. We’ve actually seen mention of it in the MCU before. For the MCU, it was created in the 1940s when Howard Stark found the Tesseract in the ocean while looking for Captain America. It was a joint venture between the Airforce, NASA, and what would become SHIELD to study it. It gets a mention in a few of the tie-in comics for the MCU movies, but specifically, Tony Stark mentions he wants files on it to JARVIS when he’s going through his dad’s stuff in Iron Man 2. A sign for it also appears on the wall in a SHIELD facility in Agents of SHIELD.

Blockbuster And Radio Shack

A+ choices for the businesses for Carol to run into. Two companies that are essentially extinct 20 years later, but were cutting edge at the time. (From what I understand the Blockbuster scenes were actually filmed at the last Blockbuster left in the US. It’s in Arizona. Go figure.)

True Lies

True Lies gets noticed in the video store because Carol shoots the standee, but the spy movie is known for a fighter jet sequence, and it was the first true “blockbuster” movie because it cost over $100 million to make - unheard of in 1994. The fighter jet prop used in it was also repurposed and used in The Avengers, so it’s like Easter egg inception here.

Universal Translator

So much is made about alien races speaking English in the MCU. In the comics, pretty much anyone traveling through space has a universal translator built into their ship or their helmets. This one off mention from Carol reminds us of that, though she’s likely speaking English anyway.

Coulson the Skrull

Phil Coulson appears as a rookie agent in the 90s. I’d wager this is one of his first big jobs since he’s still on evidence collection. You know him from the Iron Man and Avengers movies as well as, you know, Agents of SHIELD. I like that he’s the one a Skrull simulates instead of Fury because there were so many theories about who could be a Skrull when they were announced for this movie. It’s also a nice misdirect from Marvel that there’s concept art out there of Fury’s transformation from a Skrull, but not Coulson’s.

And, I mean, Nick Fury’s not an Easter egg, so I don’t need to remind you he basically started the MCU with Hulk and Iron Man, right? Though this movie does make me worry about his driving record in the MCU. He seems to end up in a lot of accidents.

Stan Lee And Mallrats

Stan Lee’s cameo is extra special because it’s also a nod to a real life cameo of his. How very meta. The script he’s holding on the train is for Kevin Smith’s Mallrats, where he really did say the line, “trust me, True Believers,” something he also said a lot in his editorials in the comics.

Kelly Sue Deconnick

When Carol gets off the train, she passes a woman with red hair and glasses in her walk. That’s Deconnick. She wrote the Captain Marvel comic book series a few years ago that this movie pulls a lot of its nods (and aesthetic) from. We can likely credit her with the surge in popularity Carol’s seen the last few years, and the reason she had a movie in development at all.

1989

In case there’s anything noteworthy for you in the year Carol ended up in Hala: Ron Perelman bought Marvel Entertainment Group, the massive X-Men Inferno story arc played out, the new Nick Fury: Agent of SHIELD comic launched, and Jubilee made her comic book debut.

1995

Likewise, for Carol’s return to Earth: the Age of Apocalypse comics launched, Thor made his 400th comic book appearance, comic books like The Fantastic Four and The Amazing Spider-Man had landmark issues as well, and a bunch of Punisher comics were cancelled, only for Marvel to turn around and launch a new Punisher comic later in the year. The Skrull Kill Crew mini series also launched.

SHIELD Logo

Thanks, Carol for calling out the fact that a covert group shouldn’t put their logo on everything. Fans have been saying that for years. Also, nice touch that it’s not the sleek and modern logo we see in Agents of SHIELD, but the older one seen on the Wall of Valor in the MCU before.

“Smile for me.”

I know that Brie Larson was asked about this moment in an interview and said it wasn’t an Easter egg. But the fact that she was criticized so much by male fans for not smiling in promotional materials made me add this to the list.

SHIELD Medical Examiner

Nelson Franklin played him. He also appeared in an episode of Agents of SHIELD. Maybe they’re just relatives.

A “Full Bird Colonel”

Carol calls Fury this during their chat at Pancho’s. His military history before joining SHIELD is right in line with the comics. Of course, he was from New York, not Alabama there. He also says he likes the B’s and spent time in Budapest. Not the same mission as Hawkeye and Black Widow though, right?

“Just Fury”

Nick Fury also points out that he only goes by Fury. Not Nicholas. Not Nick. Just Fury. I intend on going back and finding when in the MCU someone calls him Nick to his face. Maybe it’s like a distress signal for him.

“You look like someone’s disaffected niece.”

Fury says this to Carol when he points out her clothes not fitting in on a secret base. But it reminded me of the comments about her looking like Emily VanCamp, who plays Peggy Carter’s niece Sharon.

The Welcome Wagon

Carol’s not familiar with the term, though Fury is. Probably because that’s what they call the intake program for new “assets” with SHIELD. That’s what Coulson eventually wants Skye to do when he adds her to his team in Agents of SHIELD.

Ronan The Accuser

You probably recognize Lee Pace’s character from Guardians of the Galaxy. In that movie, he was after a little purple gem that turned out to be the Power Stone. He’s a Kree purist, out to conquer neighboring lands and make sure the Kree stay in power. He’s not all that different here. His mention of coming back for the weapon and the woman at the end is likely a nod to him pursuing other Infinity Stones, even if it’s not clear that he knows what they are here. By the time of Guardians, he’s got whole rituals he’s participating in, which includes painting his face in Blue Kree blood. It doesn’t look like he’s quite that fanatical here. He does, however, inspire loyalty in Korath, who eventually works for him directly, which does make me wonder what happened to Yon-Rog after this and how much Korath told Ronan about their encounter with Carol on Earth as well.

“That’s a flerken.”

Goose likely gets his name from Top Gun, but he gets his alien identity from the comics. In the comics from a few years ago, Carol has a companion on her spaceship - a cat named Chewie. As Rocket Raccoon points out to her, “that’s no cat. That’s a flerken.” Like Talos, Rocket was right. Chewie ends up having a whole litter of flerkens. Goose just eats things and people at convenient times.

Women Flying Combat

Maria notes that women weren’t allowed to fly combat in 1989. That’s true. They weren’t allowed to fly combat until 1993, a few years before the movie is set. The first woman to get to after the ban lifted? That would be Jeannie M. Leavitt. Now Brigadier General Leavitt, she actually trained Brie Larson for her role in the film and appears in the new Air Force ads.

ASIS

The name given to Lawson’s new aircraft, as mentioned briefly by Maria, is ASIS. It’s a nod to Marvel’s Ultimate universe where that version of Captain Marvel developed it. Carol was his head of security, and his girlfriend, in that universe.

A Kree Blood Transfusion

We find out that when Carol was brought to Hala, she needed a blood transfusion to stay alive. I like this nod to GH-325 on Agents of SHIELD, but it does make me wonder why Carol was saved from going mad. Is it because that particular Kree on the series had something in his blood that made everyone end up with it driven to find the ancient city? Is it because Carol was already brainwashed into thinking she was Kree? It’s interesting that Kree blood often comes with messing with memories though.

A Kree Imperial Cruiser

Mar-Vell much have had some military connections when she left Hala and came to Earth if she had a cruiser. We’ve seen them before in the MCU commanded by Ronan’s people. The design here is basically the same, but again, it looks like she’s got more tech, likely because the scientific nature of her work. It does make me wonder if she ever ran into the other smaller ships stationed near Earth that were monitoring the planet for Inhuman activity. (Remember the ones left in orbit to destroy the inhuman abominations in Agents of SHIELD?)

The Tesseract

The Space Stone certainly gets a lot of mileage in the MCU. Hydra wanted it, SHIELD experimented with it, Loki stole it, and now, we found out what else SHIELD was doing with it besides Fury’s secret weapons making team. Lawson, though we see her as part of the air force, is a SHIELD scientist. Like I said, PEGASUS is a joint effort by a few groups. She’s using the Tesseract for space travel though, like it should be.

Quadjet

Nice touch that Carol and Maria use a quadjet to rescue the Skrulls. Why? Because just a decade later SHIELD is using the later model - a quinjet.

Carol Stopping The Warheads

This imagery, like a lot of what comes with Carol glowing and flying, is straight out of the comics. She actually flies into Earth’s atmosphere and slows a sentinel from crashing to Earth in one comic. It looks nearly exactly like this sequence, except, you know, there are other Avengers with her in the comics.

Sizzling Power Lines

We hear the crackle of electricity and see power moving along the lines when Carol brings Yon-Rogg to Earth. This looks to be a nod to how her power works in the comics. She doesn’t just magically produce photo blasts. She absorbs ambient energy from her surroundings to fuel herself. That’s why she doesn’t technically need to eat, or even why she doesn’t need to breathe in the vacuum of space. Her power converts energy around her to sources to sustain her.

Mother Flerken

This has to be a nod to the fact that MCU movies don’t drop F-bombs, though Samuel L. Jackson loves them.

Mar-Vell. Two Words.

Fury mistakenly calls Mar-Vell Marvel. Carol corrects him. That’s kind of how the Captain Marvel term came to be in an alternate universe in the comics though. No one could pronounce Mahr-Vell in the Ultimate universe, so people called him Captain Marvel.

“We found her, and we weren’t even looking.”

I know that this is a nod to Fury’s eventual gathering of the Hulk, Iron Man, Thor, Captain America, Black Widow, and Hawkeye together. But this is also a reminder that for decades, SHIELD was seeking out people with powers. As Agents of SHIELD showed their audience, some of those people were then locked up and exploited by Hydra agents working undercover. SHIELD still likely has a lot of super powered skeletons in its closet.

Mid Credit Scene

What a surprise. Captain Marvel will show up after the pager is activated in Avengers: Endgame. We’re all surprised, right? (Sarcasm, I know.)

Special Thanks

During the credits, there are a slew of comic creators listed in the special thanks section. Among them are heavyweights like Brian Michael Bendis, Mark Waid, Ralph Macchio, Gene Conway, Jack Kirby, and Chris Claremont. I honestly missed that section the first time and didn’t read them fast enough to catch more. But they aren’t directly responsible for Captain Marvel, but instead had a huge effect on Marvel comics as a whole with massive runs for different properties.

Post Credit Scene

Goose coughing up that tesseract was necessary for Fury to later use to attempt to develop weapons, just like Hydra, in a secret SHIELD program that Captain America won’t like in The Avengers.

A few side notes:

Coulson’s Gut

To be perfectly honest, I feel like Coulson’s part was originally just a generic rookie SHIELD agent in the script. I think when they got the chance to add Clark Gregg to the cast, a few things changed, like this exchange between Fury and Carol about going with your gut instead of following orders. That has always been Coulson’s thing. And, even though Fury is always yelling at people to follow orders, it’s actually how he operates too. It’s why he’s always set up ways for himself, and his proteges, to work around the system. I like that it was touched on here since it’s such a big part of Agents of SHIELD.

Coulson’s Kree Knowledge

Does this create a plot hole? Coulson specifically remarks to Fury at the end of the movie that he heard a Kree took out his eye. But when Lady Sif made her appearance on Agents of SHIELD, Coulson had no visible reaction to her telling him that Kree were one of the blue skinned aliens she knows of. Also, does Coulson even know they were (mostly) blue? After all, he might not since his only face to face with a “Kree” was Carol. It makes me wonder if he suspected the alien that provided GH-325 was Kree all along. Obviously, this is just the kind of thing that happens when universes expand, and it can all be explained away with SHIELD’s use of their memory machine on him, but it still makes me wonder.

Fury And The Women Around Him

I love the theme in the MCU of Fury surrounding himself with powerful women. We’ve seen that Maria Hill is his right hand over and over - even when she was working for Stark. We also saw that he and Natasha Romanoff were close. He trusted her to do the dirty work Steve Rogers wouldn’t. We also know he trusted Sharon Carter and Melinda May to report to him directly during their spy work. Now, Carol Danvers inspires the Avengers Initiative and he invites Maria to work with him after spending one mission with her. I want to meet Fury’s mom. Because she must have been one hell of a woman.

That’s it. Anything I missed? Feel free to tell me because there’s no way I caught every Easter egg.

[anevolutionarymatter]

How Eliza Danvers Won a Nobel Prize

(Aka @thatsjustsupergirl​ is a bad influence. This spiraled out of control.)

Eliza was 13 when her mother was diagnosed with breast cancer. Memories from that age were always a bit hazy. She remembers sneaking into her parents room, and overhearing that her mom had felt a breast lump and was going to the doctor. She remembers skipping through the door after a long day in the 8th grade, and stuttering to a stop at the look on her mom’s face. She was 13, and she knew that cancer was a poisonous word.

Cancer — “the disease caused by an uncontrolled division of abnormal cells in a part of the body.” That’s the clinical definition. The problem with definitions is that they tend to fail to include what cancer means to a body, to a person, to a family. What do you do when your body is the one invading itself?

Cancer is what drove Eliza towards medicine. She remembers her mother through late nights at college, through stomach-churning study sessions in medical school, through every meticulously recorded failure in lab.

But then a little girl arrives to Earth in a pod. Five seconds after they meet, Eliza decides to push her cancer research to the backseat. She loves this little girl, and it drives her determination to understand alien physiology — to help Kara, Clark, and other aliens understand themselves.

And she loved her new work. There were so many unknowns — do aliens need vaccinations? (No, well… it depends.) What kind of nutrition does a growing alien need? What does a healthy heart sound like? Does blood even circulate the same way? What do aliens use for energy? Aliens deserved good health too.

Then, serendipitously, it was actually because of Eliza’s expertise in alien science that she was able to make a breakthrough in cancer research.

The Medusa virus was a truly terrifying creation, a devastatingly effective and desperately complex bioweapon, able to kill wide swaths of many species in one fell swoop. And unlike most viruses and bacteria, which were generally limited to infecting only a handful of species, Medusa could theoretically infect an infinite number of species. Eliza couldn’t understand how it was so efficiently lethal until she realized she had been looking at it all wrong. “Virus” was a misleading word. When Zor-El developed Medusa he created much more than a simple virus, he had developed something akin to a synthetic immune system.

Viruses have to have a “key” to gain access and cause infection, but an immune system doesn’t even need a key. It makes it simpler; it just recognizes what is “foreign” or “not self” and attacks that. So, Medusa didn’t have to recognize an infinite number of “aliens,” it only had to recognize what was “safe” and “self,” and not attack those, while attacking everything else.

(Not like me — attack.)

(Like me — no attack.)

It was brilliant. And once Eliza recognized the pattern, she realized that not only would she be able to save J’onn by reprogramming Medusa to attack any cells that were not his own, but perhaps there was a way to use Medusa to attack other cells that were “different.” To attack cancer cells.

It wasn’t as simple as she thought. It seemed easy, to just have Medusa target cancer cells like they had targeted White Martian cells in J’onn’s body. But no matter what she tried, Medusa would either attack every cell, cancerous or not, or attack no cells at all.

The problem was that cancer cells weren’t so clearly alien. Cancer was a wolf hidden in grandma’s clothes, and no one (should) want to potentially attack a grandma, so Medusa was stopped in its tracks. They would not kill without confirmation that this cancer wasn’t grandma. This was the reason why a human’s regular immune system couldn’t get rid of cancer.

But what was preventing Medusa from attacking these cells?

The realization came suddenly.

“It’s been incredibly frustrating,” Alex groused, “Winn and James keep insisting that they’re going to tell Kara about… you know, the shield… man… thing, but so far, nothing! Kara keeps wondering why they’re spending so much less time with her. I mean, Kara has been hanging out with Lena Luthor more now, which… is a whole other thing. But you know Kara, she needs constant stimulus. Between her and Maggie I feel like I barely have time to sit! Which, I’m not complaining about, because I obviously love them both very much, but sometimes…”

“Shields,” Eliza whispered, distractedly, “shields.”

Alex paused over the phone. “Oh, sorry, mom. Did you say something?”

Eliza blinked a few times, setting down her coffee mug on the countertop to reach over for a steno pad and hastily scribbling down, SHIELDS! “Sorry, honey, I was just distracted by my research for a second. Tell me more about how things are going with Maggie.”

“Are you sure? I know you’ve been struggling with Medusa, do you want to talk about it? Have you figured out how to prevent Medusa from attacking normal cells?”

Eliza smiled. “Oh sweetheart, I think you’ve already given me everything I need.”

Shielding — grandma’s clothes didn’t trick Medusa because it thought the wolf actually looked like Grandma. It was because grandma’s clothes were the signal, the shield that actually blocked Medusa. Take away the clothing, and the wolf would be exposed.

It was the breakthrough she needed. Eliza knew that this was it; this would revolutionize cancer treatment. So, Eliza and her team worked harder. And approximately thousands of coffee cups, hundreds of papers, and one potentially semi-permanent pipette shaped hand cramp later, they succeeded.

Eliza created a drug that blocked Medusa from recognizing grandma’s clothes, allowing it to attack the cancerous wolf. She saved countless lives.

Kara always knew that Eliza Danvers was a hero. Kara was the lucky girl who got to grow up with her kind smiles, warm hugs, and incredible intelligence. But today, everyone else would know that Eliza Danvers was a hero too.

Some would say it was a conflict of interest, but this was one piece she couldn’t let anyone else write. And anyway, how could anyone possibly be too biased about this?

THE NATIONAL CITY TRIBUNE: THE NOBEL PRIZE IN MEDICINE AWARDED TO ELIZA DANVERS. By: Kara Danvers

A/N: October is breast cancer awareness month and this was my attempt to pay homage to that while also highlighting some very cool science.

Besides Eliza Danvers being the best mom, this was inspired by the work of Dr. James Allison and Dr. Tasuku Honjo, who were both just awarded the Nobel Prize for their work in cancer research. Their work (the discovery of what prevented immune cells from attacking cancer cells) paved the way for immunotherapy.

In this story, the discovery of immunotherapy obviously occurs much later in Earth-38’s timeline (but also flying blonde aliens also aren’t around on this Earth, much to my chagrin). Grandma’s clothes are an analogy for the checkpoint between immune cells and self, while Medusa is used as a stand-in for CAR-T-cell therapy (a procedure where a person’s own immune cells are changed in a laboratory to specifically target cancer cells).

I’m always happy to talk science and Supergirl, so hit up the ask box if you feel so inclined.

(Read here on AO3)

[makingscipub]

From epigenetic landscapes to epigenetic pancakes

As somebody interested in metaphor, art and science, I was just starting to read Susan Merrill Squier’s book Epigenetic Landscapes: Drawings as metaphor (2017) (I am grateful to Cath Ennis for sending me this book), when Aleksandra Stelmach alerted me to a blog post entitled “Epigenetic Pancakes”. It was therefore inevitable that I should write a blog post on how we got from science to pseudoscience, from Waddington, famous for his epigenetic landscapes, to woo, and epigenetic pancakes.

I started to write this post as a little joke, but soon began hurtling down an Alice in Wonderland rabbit hole, past a portmonteau and ending up bumping into Humpty Dumpty! I leave it to serious historians of science to explore that rabbit hole in more detail, map its contours and point out some dangers.

Three epigenetic landscapes

Squier’s book takes inspiration from three drawings of so-called ‘epigenetic landscapes’ to study Conrad Hal Waddington’s (1905-1975) life, which straddled art and science (fascinating stuff), and the ways in which these images inspired later explorations in architecture, medicine, and feminism for example. Waddington was “a British developmental biologist, paleontologist, geneticist, embryologist and philosopher who laid the foundations for systems biology, epigenetics, and evolutionary developmental biology” (Wikipedia).

Epigenetics, as Squier points out, citing Alice in Wonderland, is a portmanteau word bringing together the two words epigenesis and genetics (p. 6). “The two meanings packed into this neologism fused the old Aristotelian expression for emergence, ‘epigenesis,’ with the rising field of genetics. Waddington formulated this new field in his Organisers and Genes (1940) […]. It was also in this work that Waddington presented the first version of his epigenetic landscape, a visual metaphor for the role played by stable pathways […] in the process of [embryological] development.” (Squier, p. 6)

This first epigenetic landscape was “a work of landscape art, commissioned by Waddington from his friend John Piper” (Squier, p. 11). It represented a paradoxical river flowing from and towards mountains and through it the central epigenetic concept of canalisation. In 1942, Waddington defined epigenetics as “the branch of biology which studies the causal interactions between genes and their products, which bring the phenotype into being” (Waddington, 1942).

In 1957 Waddington used the most iconic representation of the epigenetic landscape (the ‘ball on the hill’) in his book The strategy of the genes “to represent the process of cellular decision-making during development. At various points in this dynamic visual metaphor, the cell (represented by a ball) can take specific permitted trajectories, leading to different outcomes or cell fates.” (Goldberg et al., 2007)

The third image, also published in the 1957 book, represents the “underside of the landscape, wherein its surface topography is held in place by an apparatus of guy-wires and pulleys. Waddington meant for the guy-wires to represent the actions of genes, selected over the course of evolution to establish robust species-specific patterns of tissue differentiation. Such a landscape, with contours reinforced by strict genetic controls, would ensure that embryonic development proceeds in a robust and stereotyped fashion.” (Rajagopal and Stanger, 2016)

The second landscape become a ‘meme’, while the other two were largely forgotten. Waddington’s approach to epigenetics was side-lined by various developments in molecular biology and as early as “the 1950’s the term had become, in Lederberg’s view ‘a semantic morass’ (Lederberg, 2001)” (Tronick and Hunter, 2016). It still is a mess and a muddle. Some, like David Haig (2004), are a bit more charitable and show that epigenetics “had at least two semi-independent origins during the 20th century” and thus at least two independent meanings.

If you want to know more about how Waddington’s epigenetic landscapes were used over time, you should read not only Squier’s book, but also a 2013 article she quotes by Jan Baedke. He writes: “Until the late 1960s dozens of ‘landscape approaches’ emerged that applied the visual metaphor of the EL [epigenetic landscape] […] to highly diverse phenomena – in stem cell and evolutionary biology, but also in disciplines outside of biology such as topology, developmental psychology, science, technology, and society (STS) studies and cultural anthropology.” (p. 756)

Waddington and Chinese whispers

Once epigenetics emerged as part of molecular biology, rather than embryology and developmental genetics, Waddington’s metaphorical landscapes began to be transformed, almost through a process of Chinese whispers. John Greally has dissected one example of this, but there are many more. He looked at a 2017 article entitled “Genome-Wide Epigenetic Studies in Chicken: A Review” and then starts a twitter ‘thread’ by saying: “Let me show you how words get put into the mouth of Conrad Hal Waddington. A cautionary epigenetics tale”.

Greally quotes the following definitions of epigenetics from the 2017 article: “Waddington defined an epigenetic trait in the 1950s as ‘a trait with a stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence’. Nowadays, epigenetics is commonly defined as the molecular mechanisms involved in the regulation of gene expression that are reversible and heritable (by mitosis and potentially meiosis) without alteration of the DNA sequence.” The authors don’t reference Waddington, but only secondary sources!

However, as Greally stresses: “Repeat after me: Waddington’s #epigenetic landscape described how cell fates (epigenesis) could be affected by mutations (genetic). He fused the words epigenesis and genetics to create the word #epigenetic. He was not talking about heritability or memory at all.” And a later tweet in the thread says: Waddington’s #epigenetic landscape was a depiction of gene x *cell fate* (epigenesis), definitely not environment.”

Interestingly, environment and heritability have become the focus of interest in fields like ‘environmental epigenetics’, ‘Developmental Origins of Health and Disease’, and in STS. Some researchers are especially fascinated by transgenerational epigenetic inheritance. This is, as Kevin Mitchell explains, the rather misguided idea that “molecular memories of our ancestors’ experiences affect our own behaviour and physiology.” Transgenerational epigenetic inheritance has been demonstrated in some plants and animals, but never in humans. Despite this, there are many speculations about its potential impacts on policy and healthcare.

So, how were both heritability and environment gradually foregrounded in epigenetics? Here we have to look at research carried out by David L. Nanny and Robin Holliday.

As Greally points out: ”It was later that DL Nanney used the word #epigenetic (having been told by a Greek scholar that his preferred word paragenetic was not appropriate) to refer to cellular memory, the condition of persistent homeostasis after an exposure. We took the ball from Nanney and ran with it, even turning #epigenetics into transgenerational cellular memory, and eventually back-translated epi (above/upon) genetics (DNA sequence) to refer to all transcriptional regulation.” (For a more formal history of this transformation of ‘epigenetics’, see Lappalainen and Greally, 2017)

This back-translation of epigenetics almost gets us to the pancakes…but there is a bit more history to get through.

Holliday’s contribution to epigenetics is discussed in a paper (“What do you mean, ‘Epigenetic’?”) to which Greally links in the thread: “The addition of heritability to Waddington’s original definition by Holliday was a significant change. While Waddington’s definition does not preclude the inheritance of expression states [indeed Waddington (1942a) did briefly discuss heritability in his paper “The Epigenotype”], this aspect was not a fundamental part of his concept of epigenetics. Despite the more thorough discussion of heritable expression states by Nanney and others, this was the first definition to make heritability a necessary part of epigenetics.” Haig (2004) suspects that Hollidays 1987 article “The inheritance of epigenetic defects “was the critical paper that lit the fuse for the explosion in use of ‘epigenetic’ in the 1990s”.

Nowadays, epigenetics is everywhere, from molecular biology to STS, and with this appropriation of epigenetics come various interpretations and extrapolations. It has become the study of gene expression and gene regulation and its most popular metaphor is no longer the epigenetic landscape but the epigenetic switch. It is often defined in this way: “Epigenetics, as a simplified definition, is the study of biological mechanisms that will switch genes on and off.” Now we have almost come to the pancakes. One more step.

From epigenetic whispers to epigenetic wind

Over time, between the 1940s and now, epigenetics was linked ever more closely to the external environment and it also acquired an often transgenerational memory, so to speak. Many, especially social science commentators, saw this new type of inheritance and ‘memory’ as ‘deflating’ “the role of genes as causally privileged determinants of phenotypes” (Meloni and Testa, 2014: 434), as opening ways to overcoming old-fashioned reductionist, gene-centric and determinist genetics (Squier, 2017), and as freeing people from “the mainstream view of biology as an unchangeable form of secular destiny” (Meloni, 2014).

Using Squier’s book on Waddington’s landscapes as inspiration, Meloni speculates that “a hidden genetic potential can be reactivated by environmental exposures” (stressing however that this becomes increasingly difficult at ‘each bifurcation’ in the landscape) (Meloni, 2018).

In recent years, epigenetics has expanded to embrace the study of environmental, psychological, and even nutritional exposures. There is now a whole new field of ‘environmental epigenetics’ and another, rather niche one, of ‘nutritional epigenetics’. This new addition to the ever-expanding epigenetic family has been surveyed by one of the most prominent social scientists dealing with epigenetics, Hannah Landacker, in an article entitled “Food as exposure: Nutritional epigenetics and the new metabolism”.

Landecker reproduces an image of Waddington’s epigenetic landscape that has been slightly modified by the nutritional epigeneticist Roger Waterland. We see a human-faced cloud blowing at the ball at the top of the slope and the legend underneath the figure explains that this represents “nutrition as the wind that additionally influences cells during development, adding a contemporary variation to the classic [Waddington] diagram”.

Overall, epigenetics seemed to open doors to flexibility and plasticity. As Landecker points out: “the great hope of epigenetics is the essential plasticity of the body: if the body is open to environment, then it is open to environmental intervention”. Even advertisers of alternative health products and heath advice got in on the game and proclaimed “Genoplasticity: Maximise your Being”!.

And this is where the pancakes come in!

From epigenetic landscapes to epigenetic woo

Nutritional epigenetics is (probably) a respected scientific subfield of epigenetics. However, nutritional advice, especially by alternative healthcare providers, has also been infiltrated by epigenetics and not in a good way.

For example (and there are many more), in 2014 a book appeared with the title Epigenetics: The Death of the Genetic Theory of Disease Transmission. Here we read: “This nexus between nutrition and so-called genetic disease has been observed in both humans and primates, and it is the central theme of Epigenetics… Epigenetics is of vital importance to anyone who wants real knowledge about how the human body functions, and it provides a path for better health. Epigenetics dispels the dogma and misinformation propagated by medical institutions and doctors resistant to change. Epigenetics is the beginning of a new era of well-being on this planet.”

Just as some natural and many social scientists use epigenetics to challenge old genetic and genomic dogmas, so alternative health providers use epigenetics to challenge conventional medicine.

And so we finally come to the pancakes. The blog post entitled “Epigenetic pancakes” appeared on a blog maintained by a nutritionist and states: “This week on the blog we’re diving into a really awesomely inspiring topic: Epigenetics. What on earth does this have to do with pancakes? Well- the pancakes you choose to eat might just have an affect on how your genes choose to express themselves.”

Using a well-known metaphor she goes on to say: “What few of us realize is that we can change, or alter the genetic cards we’ve been dealt. We may have a certain set of cards in our hand, but we have the ability to re-regulate the DNA sequence to alter its expression. That is what epigenetic is about. Epigenetics is the ability to alter the expression of our genes by epi or outer influencing factors.” Epi is the magic word!

She has three lessons for us:

“1. The type of pancakes you eat could very well determine whether you get that hereditary disease as well as the health of your unborn children. 2. You can totally blame your parents for the gene card you’ve been dealt and the work you have to do to work against it, but you absolutely CAN NOT EVER shrug your shoulders as you eat your Big Mac and say “kidney stones, cancer, diabetes, arthritis, glaucoma, and heart attacks run in my family- it’s inevitable so I might as well enjoy this cow cocktail of a burger”. 3. We have absolutely every reason to do all we can to redefine our own genetic expression to help ensure the genetic switches responsible for diseases of degeneration and decay don’t get turned on and hopefully, don’t get passed on.”

This is the dream of gaining control over our genes through epigenetics – through life-style choices, nutrition, mediation, and so on. But, as many scientists and bloggers have pointed out: “All such claims are nonsense. All such claims are nonsense. All such claims are nonsense.”

From portmanteau to Humpty Dumpty

When epigenetic landscapes gradually turn into epigenetic pancakes, we are not only dealing with metaphorical transformation and creativity, but with Kafkaesque metamorphosis. How did we get there? I think this is partly due to not distinguishing metaphor from reality. Waddington’s metaphorical landscapes were supposed to make us think in new ways about biology, especially embryo development and genetics. They did that in spades. However, their creative potential became distorted over time, leading to a situation where epigenetics is not only what Alice in Wonderland called a portmanteau word, but also what she might have called a Humpty Dumpty word.

As Edith Heard, a renowned specialist working in the field of epigenetics, said recently, epigenetics has become “une discipline en plein boom depuis le début des années 2000 et qui fait couler beaucoup d’encre de par les espoirs, mais aussi les fantasmes, qu’elle suscite”.

Beware of paddlers of epigenetic fantasies!

    The post From epigenetic landscapes to epigenetic pancakes appeared first on Making Science Public.

via Making Science Public https://ift.tt/2TrwiYs