Jordan Iacobucci is quite excited about Ironheart’s move away from using nanotechnology in its recent Marvel Comics Universe (MCU) television adaptation. From Iacobucci’s July 7, 2025 article for CBR (self-proclaimed World’s Top Destination for Comic, Movie & TV News), Note: Links have been removed,
After years of delays, Ironheart is finally streaming on Disney+. The six-episode series follows up on Dominique Thorne’s Riri Williams a few days after her adventures with Shuri and the Wakandans during the events of Black Panther: Wakanda Forever as she returns home to Chicago in hopes of building something “iconic.” Though she must navigate several trials and tribulations, Riri finally succeeds in her goal, completing a brand-new version of her Ironheart suit.
As Ironheart wraps up its run on Disney+, fans have plenty to break down, from its groundbreaking finale to its surprisingly great visuals. Many fans may find that the series is much better than they may have anticipated, especially after review-bombing tried to dismiss Ironheart before it even premiered. The series fixes several long-standing issues with the Marvel Cinematic Universe, including one particularly annoying trend that has plagued the franchise since Avengers: Infinity War
The MCU Uses Way Too Much Nanotechnology
Fans Aren’t Fond of the Nanotechnology Trend in the MCU
It all started in Avengers: Infinity War. During a confrontation with Ebony Maw and Cull Obsidian, Tony Stark debuted his new nanotechnology, which spread out across his body from a small compartment on his chest to form a new suit of armor.
Iron Man’s “Bleeding Edge” armor was only the beginning of the MCU’s love affair with nanotechnology, particularly when it comes to superhero suits. Infinity War also gives Spider-Man his own nanotech suit, the Iron Spider armor, which he wears for the remainder of the film and in his next several MCU appearances. Since then, almost every masked MCU hero has upgraded to similar costumes, from Black Panther to Ant-Man. As impressive as the technology may be, fans aren’t fond of the nanotech suits.
Nanotech suits make sense from a practical standpoint. If a hero can cause their suit to form around them with the press of a button, then they don’t have to worry about being caught off-guard by an emerging threat. Though these upgrades make sense, viewers lose something special as a result. The “Bleeding Edge” Iron Man armor and other nanotech suits lose the tangibility of previous MCU superhero costumes.
With nanotech, viewers are never made to feel as if the hero is really wearing a suit. This is largely because the actor isn’t wearing the suit on set. Often, nanotech is implemented as an excuse to use CGI to cover or uncover an actor’s face with their superhero mask at any given point in a scene. As a result, however, the suits themselves feel less real, looking more like images composited in a computer than something that someone would wear while fighting crime.
This issue gets worse when a particular film or series doesn’t allow its graphics team enough time to complete their animation processes. Films like Ant-Man and the Wasp: Quantumania are horrible examples of this trend, featuring suits that sometimes look as though they were cobbled together on a laptop an hour before the movie hit theaters. Fans have been vocal about their distaste for nanotech suits for years, but Marvel has only doubled down on this trend since Infinity War–until now.
The Ironheart armor feels real–much more real than any of the new nanotech suits introduced in recent MCU projects. In place of nanotechnology, Ironheart uses real technology to build her suit, and her series is so much better for it. It is much more visually appealing for viewers to see a tangible suit of armor on set with the actors.
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Iacobucci has a point in that, while nanotechnology is a real technology; the nanotechnology in Iron Man is not (at this time).
So, what about the science in science fiction?
Officially launched in 2008 by the US National Academy of Sciences (NAS), the Science and Entertainment Exchange (see its Wikipedia entry), is one of the programs that filmmakers and others can consult when producing a science fiction piece. This March 16, 2022 article by Marian Caballo for The Science Survey delves into the topic of the science in science fiction, Note: Links have been removed,
Science is the backbone of our world, which means that it inevitably underlies the plots of many popular films and television shows. As an avid cinephile and biology research student myself, I often catch myself trying to break down characters’ scientific name-drops, or pausing to examine the scribbles of equations on background blackboards.
For example: in Don’t Look Up, an original Netflix movie that depicts the danger of a comet hurtling towards Earth, scientists lay out a plan to warn the world of its impending doom. In The Amazing Spider-Man, Peter Parker accidentally helps to create villainous mutant lizards with his solution to the “The Decay Rate Algorithm,” a fictional derivation of the Gompertz–Makeham law of mortality. Avengers: Endgame features an elaborate time travel plan involving Deutsch propositions, eigenvalues and inverted Möbius strips. None were technically real scientific developments, of course, but how do they sound so real?
The answer: scientific consulting. This hidden field is dedicated to scientific advising in the entertainment industry, and it’s an exciting way for STEM [science, technology, engineering, and mathematics] professionals to become engaged in the world of fiction. These interactions connect Hollywood (writers, producers, directors), “with top STEM experts to create synergy between accurate science and engaging storytelling,” said Emilie Lorditch, founder of Real2Reel Science, a science consulting service for writers.
Media greatly impacts the public’s perception of science. According to The Pew Research Center, 81% of U.S. adults say they watch media involving criminal investigations, hospital/medical settings, or science fiction. The average American watches 84 movies a year. By placing STEM professionals on movie sets, scientists can not only assist in executing a narrative vision but also aid in sharing more engaging portrayals of STEM.
“The Hollywood, Health & Society program at USC [University of Southern California] has worked with multiple TV shows to develop storylines about organ donation, and has studied the impact of the plot on viewers’ knowledge, attitudes, and behavior,” said Lorditch, who believes science advising fosters mutual exchange. The USC Annenberg Norman Lear Center’s longitudinal impact studies focus on providing — then studying the impact of — information about health, safety and security in Hollywood projects.
While many science consultants work independently or through institutions like USC, the science advising wing of Hollywood primarily stems from The National Academy of Sciences’ Science & Entertainment Exchange. Founded in 2008, the Exchange aims to improve the science that appears in narrative mainstream media through a “soft-sell” approach. The Exchange has completed more than 2,300 consultations on projects such as A Wrinkle in Time, Watchmen, and various Marvel Studios films. The organization essentially serves as a direct hotline for filmmakers to reach researchers, medical professionals, and more — as befits the Exchange’s actual phone number, 1-844-NEED-SCI.
However, it isn’t a scientific consultant’s job to make sure films are 100% accurate. Science fiction is called science fiction for a reason, and scientists aren’t keen on incorporating factual science when it comes at the expense of compelling storytelling. “The story always comes first. Period,” said Jennifer Ouellette, founding director of The Science & Entertainment Exchange. She now covers science and culture as a senior writer at Ars Technica, and has published several science-related books.
Ouellette always made sure to advise scientists working on their first Hollywood films to not just shake their heads when presented with a script. “They should think about what needs to happen in that scene, and come up with an even better scientific explanation. That makes it a win-win,” said Ouellette, who cites The Expanse as some of the best science representation in film and TV.
Insisting that science/scientists should only be portrayed in a positive light is not a solution, either. “Scientists are flawed human beings just like everyone else, and those flaws are what make us interesting and complex characters,” she continued.
Ouellette’s husband — theoretical physicist Sean M. Caroll at the California Institute of Technology — has served as a science consultant himself, helping to devise Tony Stark’s famous time-warping plan in Avengers: Endgame. He also advised one of Ouellette’s favorite science TV moments: an episode of BONES, when a physicist represses his grief over his gymnast daughter’s death. Caroll spent days on set writing a series of physics equations on blackboards. But he wasn’t developing hard science for the sake of science.
By the end of the episode, the characters learn that “each equation represents a moment in his daughter’s life: learning to walk, then run; doing her first backflip; a vault; and so on, until the final equation, showing her finally at rest. The writers turned it into a poem written in equations, and it remains one of the most amazing moments I’ve seen on television in a long time,” said Ouellette.
On top of the fundamental fact that science must be in service of the story, the science doesn’t always have to be precise. “In the world of STEM, precision is crucial but for the majority of the public, not so much,” said Lorditch. Most viewers would agree. Spring Lin ’22 ignores “slightly questionable” scientific explanations, claiming they don’t interfere with the cinematic experience. “When there are no obvious wrongs in a movie, I usually don’t question it,” said Rita Chen ’22.
Science advisors also lurk on a surprisingly wide range of sets — whether it is on reality TV such as MTV’s Teen Mom, or behind the scenes of The Simpsons. …
It seems that physicists are having a moment in the pop culture scene and they are excited about two television series (Fallout and 3 Body Problem) televised earlier this year in US/Canada.
The world ends on Oct. 23, 2077, in a series of radioactive explosions—at least in the world of “Fallout,” a post-apocalyptic video game series that has now been adapted into a blockbuster TV show on Amazon’s Prime Video.
The literal fallout that ensues creates a post-apocalyptic United States that is full of mutated monstrosities, irradiated humans called ghouls and hard scrabble survivors who are caught in the middle of it all. It’s the material of classic Atomic Age sci-fi, the kind of pulp stories “Fallout” draws inspiration from for its retro-futuristic version of America.
But there is more science in this science fiction story than you might think, according to Pran Nath, Matthews distinguished university professor of physics at Northeastern University.
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“Fallout” depicts a post-apocalyptic world centuries after nuclear war ravaged the United States. Amazon MGM Studios Photo
In the opening moments of “Fallout,” which debuted on April 10 [2024], Los Angeles is hit with a series of nuclear bombs. Although it takes place in a clearly fictional version of La La Land –– the robots and glistening, futuristic skyscrapers in the distance are dead giveaways –– the nuclear explosions themselves are shockingly realistic.
Nath says that when a nuclear device is dropped there are three stages.
“When the nuclear blast occurs, because of the chain reaction, in a very short period of time, a lot of energy and radiation is emitted,” Nath says. “In the first instance, a huge flash occurs, which is the nuclear reaction producing gamma rays. If you are exposed to it, people, for example, in Hiroshima were essentially evaporated, leaving shadows.”
Depending on how far someone is from the blast, even those who are partially protected will have their body rapidly heat up to 50 degrees Celsius, or 122 degrees Fahrenheit, causing severe burns. The scalded skin of the ghouls in “Fallout” are not entirely unheard of (although their centuries-long lifespan stretches things a bit).
The second phase is a shockwave and heat blast –– what Nath calls a “fireball.” The shockwave in the first scene of “Fallout” quickly spreads from the blast, but Nath says it would probably happen even faster and less cinematically. It would travel around the speed of sound, around 760 miles per hour.
The shockwave also has a huge amount of pressure, “so huge … that it can collapse concrete buildings.” It’s followed by a “fireball” that would burn every building in the blast area with an intense heatwave.
“The blast area is defined as the area where the shockwaves and the fireball are the most intense,” Nath says. “For Hiroshima, that was between 1 and 2 miles. Basically, everything is destroyed in that blast area.”
The third phase of the nuclear blast is the fallout, which lasts for much longer and has even wider ranging impacts than the blast and shockwave. The nuclear blast creates a mushroom cloud, which can reach as high as 10 miles into the atmosphere. Carried by the wind, the cloud spreads radioactivity far outside the blast area.
“In a nuclear blast, up to 100 different radioactive elements are produced,” Nath says. “These radioactive elements have lifetimes which could be a few seconds, and they could be up to millions of years. … It causes pollution and damage to the body and injuries over a longer period, causing cancer and leukemia, things like this.”
A key part of the world of “Fallout” is the Vaults, massive underground bunkers the size of small towns that the luckiest of people get to retreat into when the world ends. The Vaults are several steps above most real-world fallout shelters, but Nath says that kind of protection would be necessary if you wanted to stay safe from the kind of radiation released by nuclear weapons, particularly gamma rays that can penetrate several feet of concrete.
“If you are further away and you keep inside and behind concrete, then you can avoid both the initial flash of the nuclear blast and also could probably withstand the shockwaves and the heatwave that follows, so the survivability becomes larger,” Nath says.
But what about all the radioactive mutants wandering around the post-apocalyptic wasteland?
It might seem like the colossal, monstrous mutant salamanders and giant cockroaches of “Fallout” are a science fiction fabrication. But there is a real-world basis for this, Nath says.
“There are various kinds of abnormalities that occur [with radiation,]” Nath says. “They can also be genetic. Radiation can create mutations, which are similar to spontaneous mutation, in animals and humans. In Chernobyl, for example, they are discovering animals which are mutated.”
In the Chernobyl Exclusion Zone, the genetics of wild dogs have been radically altered. Scientists hypothesize that thewolves near Chernobyl may have developed to be more resistant to radiation, which could make them “cancer resistant,” or at least less impacted by cancer. And frogs have adapted to have more melanin in their bodies, a form of protection against radiation, turning them black.
“Fallout” takes the horrifying reality of nuclear war and spins a darkly comic sci-fi yarn, but Nath says it’s important to remember how devastating these real-world forces are.
It’s estimated that as many as 146,000 people in Hiroshima and 80,000 people in Nagasaki were killed by the effects of the bombs dropped by the U.S. Today’s nuclear weapons are so much more powerful that there is very little understanding of the impact these weapons could have. Nath says the fallout could even exacerbate global warming.
“Thermonuclear war would be a global problem,” Nath says.
Although “Fallout” is a piece of science fiction, the reality of its world-ending scenario is terrifyingly real, says Pran Nath, Matthews distinguished university professor of physics at Northeastern University. Photo by Adam Glanzman/Northeastern University
Kudos to the photographer!
3 Body Problem (television series)
This one seems to have a lit a fire in the breasts of physicists everywhere. I have a number of written pieces and a video about this this show, which is based on a book by Liu Cixn. (You can find out more about Cixin and his work in his Wikipedia entry.)
“3 Body Problem,” Netflix’s new big-budget adaptation of Liu Cixin’s book series helmed by the creators behind “Game of Thrones,” puts the science in science fiction.
The series focuses on scientists as they attempt to solve a mystery that spans decades, continents and even galaxies. That means “3 Body Problem” throws some pretty complicated quantum mechanics and astrophysics concepts at the audience as it, sometimes literally, tries to bring these ideas down to earth.
However, at the core of the series is the three-body problem, a question that has stumped scientists for centuries.
What exactly is the three-body problem, and why is it still unsolvable? Jonathan Blazek, an assistant professor of physics at Northeastern University, explains that systems with two objects exerting gravitational force on one another, whether they’re particles or stars and planets, are predictable. Scientists have been able to solve this two-body problem and predict the orbits of objects since the days of Isaac Newton. But as soon as a third body enters the mix, the whole system gets thrown into chaos.
“The three-body problem is the statement that if you have three bodies gravitating toward each other under Newton’s law of gravitation, there is no general closed-form solution for that situation,” Blazek says. “Little differences get amplified and can lead to wildly unpredictable behavior in the future.”
In “3 Body Problem,” like in Cixin’s book, this is a reality for aliens that live in a solar system with three suns. Since all three stars are exerting gravitational forces on each other, they end up throwing the solar system into chaos as they fling each other back and forth. For the Trisolarans, the name for these aliens, it means that when a sun is jettisoned far away, their planet freezes, and when a sun is thrown extremely close to their planet, it gets torched. Worse, because of the three-body problem, these movements are completely unpredictable.
For centuries, scientists have pondered the question of how to determine a stable starting point for three gravitational bodies that would result in predictable orbits. There is still no generalizable solution that can be taken out of theory and modeled in reality, although recently scientists have started to find some potentially creative solutions, including with models based on the movements of drunk people.
“If you want to [predict] what the solar system’s going to do, we can put all the planets and as many asteroids as we know into a computer code and basically say we’re going to calculate the force between everything and move everything forward a little bit,” Blazek says. “This works, but to the extent that you’re making some approximations … all of these things will eventually break down and your prediction is going to become inaccurate.”
Blazek says the three-body problem has captivated scientific minds because it’s a seemingly simple problem. Most high school physics students learn Newton’s law of gravity and can reasonably calculate and predict the movement of two bodies.
Three-body systems, and more than three-body systems, also show up throughout the universe, so the question is incredibly relevant. Look no further than our solar system.
The relationship between the sun, Earth and our moon is a three-body system. But Blazek says since the sun exerts a stronger gravitational force on Earth and Earth does the same on the moon, it creates a pair of two-body systems with stable, predictable orbits –– for now.
Blazek says that although our solar system appears stable, there’s no guarantee that it will stay that way in the far future because there are still multi-body systems at play. Small changes like an asteroid hitting one of Jupiter’s moons and altering its orbit ever so slightly could eventually spiral into larger changes.
That doesn’t mean humanity will face a crisis like the one the Trisolarans face in “3 Body Problem.” These changes happen extremely slowly, but Blazek says it’s another reminder of why these concepts are interesting and important to think about in both science and science fiction.
“I don’t think anything is going to happen on the time scale of our week or even probably our species –– we have bigger problems than the instability of orbits in our solar system,” Blazek says. “But, that said, if you think about billions of years, during that period we don’t know that the orbits will stay as they currently are. There’s a good chance there will be some instability that changes how things look in the solar system.”
An April 12, 2024 news item on phys.org covers some of the same ground, Note: A link has been removed.
The science fiction television series 3 Body Problem, the latest from the creators of HBO’s Game of Thrones, has become the most watched show on Netflix since its debut last month. Based on the bestselling book trilogy Remembrance of Earth’s Past by Chinese computer engineer and author Cixin Liu, 3 Body Problem introduces viewers to advanced concepts in physics in service to a suspenseful story involving investigative police work, international intrigue, and the looming threat of an extraterrestrial invasion.
Yet how closely does the story of 3 Body Problem adhere to the science that it’s based on? The very name of the show comes from the three-body problem, a mathematical problem in physics long considered to be unsolvable.
Virginia Tech physicist Djordje Minic says, “The three-body problem is a very famous problem in classical and celestial mechanics, which goes back to Isaac Newton. It involves three celestial bodies interacting via the gravitational force—that is, Newton’s law of gravity. Unlike mathematical predictions of the motions of two-body systems, such as Earth-moon or Earth-sun, the three-body problem does not have an analytic solution.”
“At the end of the 19th century, the great French mathematician Henri Poincaré’s work on the three-body problem gave birth to what is known as chaos theory and the concept of the ‘butterfly effect.'”
Both the novels and the Netflix show contain a visualization of the three-body problem in action: a solar system made up of three suns in erratic orbit around one another. Virginia Tech aerospace engineer and mathematics expert Shane Ross discussed liberties the story takes with the science that informs it.
“There are no known configurations of three massive stars that could maintain an erratic orbit,” Ross said. “There was a big breakthrough about 20 years ago when a figure eight solution of the three-body problem was discovered, in which three equal-sized stars chase each other around on a figure eight-shaped course. In fact, Cixin Liu makes reference to this in his books. Building on that development, other mathematicians found other solutions, but in each case the movement is not chaotic.”
Ross elaborated, “It’s even more unlikely that a fourth body, a planet, would be in orbit around this system of three stars, however erratically — it would either collide with one or be ejected from the system. The situation in the book would therefore be a solution of the ‘four-body problem,’ which I guess didn’t have quite the right ring to use as a title.
“Furthermore, a stable climate is unlikely even on an Earth-like planet. At last count, there are at least a hundred independent factors that are required to create an Earth-like planet that supports life as we know it,” Ross said. “We have been fortunate to have had about 10,000 years of the most stable climate in Earth’s history, which makes us think climate stability is the norm, when in fact, it’s the exception. It’s likely no coincidence that this has corresponded with the rise of advanced human civilization.”
About Ross A professor of Aerospace and Ocean Engineering at Virginia Tech, Shane Ross directs the Ross Dynamics Lab, which specializes in mathematical modeling, simulation, visualization, and experiments involving oceanic and atmospheric patterns, aerodynamic gliding, orbital mechanics, and many other disciplines. He has made fundamental contributions toward finding chaotic solutions to the three-body problem. Read his bio …
About Minic Djordje Minic teaches physics at Virginia Tech. A specialist in string theory and quantum gravity, he has collaborated on award-winning research related to dark matter and dark energy. His most recent investigation involves the possibility that in the context of quantum gravity the geometry of quantum theory might be dynamical in analogy with the dynamical nature of spacetime geometry in Einstein’s theory of gravity. View his full bio …
For the last ‘3 Body Problem’ essay, there’s this April 5, 2023 article by Tara Bitran and Phillipe Thao for Netflix.com featuring comments from a physicist concerning a number of science questions,, Note: Links have been removed,
If you’ve raced through 3 Body Problem, the new series from Game of Thrones creators David Benioff and D.B. Weiss and True Blood writer Alexander Woo, chances are you want to know more about everything from Sophons and nanofibers to what actually constitutes a three-body problem. After all, even the show’s scientists are stumped when they witness their well-known theories unravel at the seams.
But for physicists like 3 Body Problem’s Jin (Jess Hong) and real-life astrophysicist Dr. Becky Smethurst (who researches how supermassive black holes grow at the University of Oxford and explains how scientific phenomena work in viral videos), answering the universe’s questions is a problem they’re delighted to solve. In fact, it’s part of the fun. “I feel like scientists look at the term ‘problem’ more excitedly than anybody else does,” Smethurst tells Tudum. “Every scientist’s dream is to be told that they got it wrong before and here’s some new data that you can now work on that shows you something different where you can learn something new.”
The eight-episode series, based on writer Cixin Liu’s internationally celebrated Remembrance of Earth’s Past trilogy, repeatedly defies human science standards and forces the characters to head back to the drawing board to figure out how to face humanity’s greatest threat. Taking us on a mind-boggling journey that spans continents and timelines, the story begins in ’60s China, when a young woman makes a fateful decision that reverberates across space and time into the present day. With humanity’s future in danger, a group of tight-knit scientists, dubbed the Oxford Five, must work against time to save the world from catastrophic consequences.
Dr. Matt Kenzie, associate professor of physics at University of Cambridge and 3 Body Problem’s science advisor, sits down with Tudum to dive into the science behind the series. So if you can’t stop thinking about stars blinking and chaotic eras, keep reading for all the answers to your burning scientific questions. Education time!
What is a Cherenkov tank?
In Episode 1, the Oxford Five’s former college professor, Dr. Vera Ye (Vedette Lim), walks out onto a platform at the top of a large tank and plunges to her death in a shallow pool of water below. If you were wondering what that huge tank was, it’s called a particle detector (sometimes also known as a Cherenkov tank). It’s used to observe, measure, and identify particles, including, in this case, neutrinos, a common particle that comes largely from the sun. “Part of the reason that they’re kind of interesting is that we don’t really understand much about them, and we suspect that they could be giving us clues to other types of physics in the universe that we don’t yet understand,” Dr. Kenzie told Netflix.
When a neutrino interacts with the water molecules stored inside the tank, it sets off a series of photomultiplier tubes — the little circles that line the tank Vera jumps into. Because Vera’s experiment is shut down and the water is reduced to a shallow level, the fall ends up killing her.
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What are nanofibers?
In the show, Auggie’s a trailblazer in nanofiber technology. She runs a company that designs self-assembling synthetic polymer nanofibers and hopes to use her latest innovation to solve world problems, like poverty and disease. But what are nanofibers and how do they work? Dr. Kenzie describes nanofiber technology as “any material with a width of nanometers” — in other words, one millionth of a millimeter in thickness. Nanofibers can be constructed out of graphene (a one-atom thick layer of carbon) and are often very strong. “They can be very flexible,” he adds. “They tend to be very good conductors of both heat and electricity.”
Is nanofiber technology real, and can it actually cut through human flesh?
Nanofiber technology does exist, although Dr. Kenzie says it’s curated and grown in labs under very specific conditions. “One of the difficulties is how you hold them in place — the scaffolding it’s called,” he adds. “You have to design molecules which hold these things whilst you’re trying to build them.”
After being tested on a synthetic diamond cube in Episode 2, we see the real horrors of nanofiber technology when it’s used to slice through human bodies in Episode 5. Although the nanofiber technology that exists today is not as mass produced as Auggie’s — due to the cost of producing and containing it — Dr. Kenzie says it’s still strong enough to slice through almost anything.
What can nanofiber technology be used for?
According to Dr. Kenzie, the nanofiber technology being developed today can be used in several ways within the manufacturing and construction industries. “If you wanted a machine that could do some precision cutting, then maybe [nanofiber] would be good,” he says. “I know they’re also tested in the safety of the munitions world. If you need to bulletproof a room or bulletproof a vest, they’re incredibly light and they’re incredibly strong.” He also adds that nanofiber technology is viewed as a material of the future, which can be used for water filtration — just as we see Auggie use it in the season finale.
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The Bitran and Thao piece includes another description of the 3 Body Problem but it’s the first I’ve seen that describes some of the other science.
Also mentioned in one of the excerpts in this posting is The Science and Entertainment Exchange (also known as The Science & Entertainment Exchange or Science & Entertainment Exchange) according to its Wikipedia entry, Note: Links have been removed,
The Science & Entertainment Exchange[1] is a program run and developed by the United States National Academy of Sciences (NAS) to increase public awareness, knowledge, and understanding of science and advanced science technology through its representation in television, film, and other media. It serves as a pro-science movement with the main goal of re-cultivating how science and scientists truly are in order to rid the public of false perceptions on these topics. The Exchange provides entertainment industry professionals with access to credible and knowledgeable scientists and engineers who help to encourage and create effective representations of science and scientists in the media, whether it be on television, in films, plays, etc. The Exchange also helps the science community understand the needs and requirements of the entertainment industry, while making sure science is conveyed in a correct and positive manner to the target audience.
Officially launched in November 2008, the Exchange can be thought of as a partnership between NAS and Hollywood, as it arranges direct consultations between scientists and entertainment professionals who develop science-themed content. This collaboration allows for industry professionals to accurately portray the science that they wish to capture and include in their media production. It also provides scientists and science organizations with the opportunity to communicate effectively with a large audience that may otherwise be hard to reach such as through innovative physics outreach. It also provides a variety of other services, including scheduling briefings, brainstorming sessions, screenings, and salons. The Exchange is based in Los Angeles, California.
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I hadn’t realized the exchange was physics specific. Given the success with physics, I’d expect the biology and chemistry communities would be eager to participate or start their own exchanges.
Back in 2019 Canada was having a problem with Malaysia and the Phillipines over the garbage (this is meant literally) that we were shipping over to those counties, which is why an article about Chinese science fiction writer, Chen Qiufan and his 2013 novel, The Waste Tide, caught my attention and I pubisihed this May 31, 2019 posting, “Chen Qiufan, garbage, and Chinese science fiction stories.” There’s a very brief mention of Liu Cxin in one of the excerpts.
After giving a basic explanation of the technology and some of the controversies in part 1 and offering more detail about the technology and about the possibility of designer babies in part 2; this part covers public discussion, a call for one and the suggestion that one is taking place in popular culture.
But a discussion does need to happen
In a move that is either an exquisite coincidence or has been carefully orchestrated (I vote for the latter), researchers from the University of Wisconsin-Madison have released a study about attitudes in the US to human genome editing. From an Aug. 11, 2017 University of Wisconsin-Madison news release (also on EurekAllert),
In early August 2017, an international team of scientists announced they had successfully edited the DNA of human embryos. As people process the political, moral and regulatory issues of the technology — which nudges us closer to nonfiction than science fiction — researchers at the University of Wisconsin-Madison and Temple University show the time is now to involve the American public in discussions about human genome editing.
In a study published Aug. 11 in the journal Science, the researchers assessed what people in the United States think about the uses of human genome editing and how their attitudes may drive public discussion. They found a public divided on its uses but united in the importance of moving conversations forward.
“There are several pathways we can go down with gene editing,” says UW-Madison’s Dietram Scheufele, lead author of the study and member of a National Academy of Sciences committee that compiled a report focused on human gene editing earlier this year. “Our study takes an exhaustive look at all of those possible pathways forward and asks where the public stands on each one of them.”
Compared to previous studies on public attitudes about the technology, the new study takes a more nuanced approach, examining public opinion about the use of gene editing for disease therapy versus for human enhancement, and about editing that becomes hereditary versus editing that does not.
The research team, which included Scheufele and Dominique Brossard — both professors of life sciences communication — along with Michael Xenos, professor of communication arts, first surveyed study participants about the use of editing to treat disease (therapy) versus for enhancement (creating so-called “designer babies”). While about two-thirds of respondents expressed at least some support for therapeutic editing, only one-third expressed support for using the technology for enhancement.
Diving even deeper, researchers looked into public attitudes about gene editing on specific cell types — somatic or germline — either for therapy or enhancement. Somatic cells are non-reproductive, so edits made in those cells do not affect future generations. Germline cells, however, are heritable, and changes made in these cells would be passed on to children.
Public support of therapeutic editing was high both in cells that would be inherited and those that would not, with 65 percent of respondents supporting therapy in germline cells and 64 percent supporting therapy in somatic cells. When considering enhancement editing, however, support depended more upon whether the changes would affect future generations. Only 26 percent of people surveyed supported enhancement editing in heritable germline cells and 39 percent supported enhancement of somatic cells that would not be passed on to children.
“A majority of people are saying that germline enhancement is where the technology crosses that invisible line and becomes unacceptable,” says Scheufele. “When it comes to therapy, the public is more open, and that may partly be reflective of how severe some of those genetically inherited diseases are. The potential treatments for those diseases are something the public at least is willing to consider.”
Beyond questions of support, researchers also wanted to understand what was driving public opinions. They found that two factors were related to respondents’ attitudes toward gene editing as well as their attitudes toward the public’s role in its emergence: the level of religious guidance in their lives, and factual knowledge about the technology.
Those with a high level of religious guidance in their daily lives had lower support for human genome editing than those with low religious guidance. Additionally, those with high knowledge of the technology were more supportive of it than those with less knowledge.
While respondents with high religious guidance and those with high knowledge differed on their support for the technology, both groups highly supported public engagement in its development and use. These results suggest broad agreement that the public should be involved in questions of political, regulatory and moral aspects of human genome editing.
“The public may be split along lines of religiosity or knowledge with regard to what they think about the technology and scientific community, but they are united in the idea that this is an issue that requires public involvement,” says Scheufele. “Our findings show very nicely that the public is ready for these discussions and that the time to have the discussions is now, before the science is fully ready and while we have time to carefully think through different options regarding how we want to move forward.”
Here’s a link to and a citation for the paper,
U.S. attitudes on human genome editing by Dietram A. Scheufele, Michael A. Xenos, Emily L. Howell, Kathleen M. Rose, Dominique Brossard1, and Bruce W. Hardy. Science 11 Aug 2017: Vol. 357, Issue 6351, pp. 553-554 DOI: 10.1126/science.aan3708
This paper is behind a paywall.
A couple of final comments
Briefly, I notice that there’s no mention of the ethics of patenting this technology in the news release about the study.
Moving on, it seems surprising that the first team to engage in germline editing in the US is in Oregon; I would have expected the work to come from Massachusetts, California, or Illinois where a lot of bleeding edge medical research is performed. However, given the dearth of financial support from federal funding institutions, it seems likely that only an outsider would dare to engage i the research. Given the timing, Mitalipov’s work was already well underway before the recent about-face from the US National Academy of Sciences (Note: Kaiser’s Feb. 14, 2017 article does note that for some the recent recommendations do not represent any change).
As for discussion on issues such as editing of the germline, I’ve often noted here that popular culture (including advertising with the science fiction and other dramas laid in various media) often provides an informal forum for discussion. Joelle Renstrom in an Aug. 13, 2017 article for slate.com writes that Orphan Black (a BBC America series featuring clones) opened up a series of questions about science and ethics in the guise of a thriller about clones. She offers a précis of the first four seasons (Note: A link has been removed),
If you stopped watching a few seasons back, here’s a brief synopsis of how the mysteries wrap up. Neolution, an organization that seeks to control human evolution through genetic modification, began Project Leda, the cloning program, for two primary reasons: to see whether they could and to experiment with mutations that might allow people (i.e., themselves) to live longer. Neolution partnered with biotech companies such as Dyad, using its big pharma reach and deep pockets to harvest people’s genetic information and to conduct individual and germline (that is, genetic alterations passed down through generations) experiments, including infertility treatments that result in horrifying birth defects and body modification, such as tail-growing.
She then provides the article’s thesis (Note: Links have been removed),
Orphan Black demonstrates Carl Sagan’s warning of a time when “awesome technological powers are in the hands of a very few.” Neolutionists do whatever they want, pausing only to consider whether they’re missing an opportunity to exploit. Their hubris is straight out of Victor Frankenstein’s playbook. Frankenstein wonders whether he ought to first reanimate something “of simpler organisation” than a human, but starting small means waiting for glory. Orphan Black’s evil scientists embody this belief: if they’re going to play God, then they’ll control not just their own destinies, but the clones’ and, ultimately, all of humanity’s. Any sacrifices along the way are for the greater good—reasoning that culminates in Westmoreland’s eugenics fantasy to genetically sterilize 99 percent of the population he doesn’t enhance.
Orphan Black uses sci-fi tropes to explore real-world plausibility. Neolution shares similarities with transhumanism, the belief that humans should use science and technology to take control of their own evolution. While some transhumanists dabble in body modifications, such as microchip implants or night-vision eye drops, others seek to end suffering by curing human illness and aging. But even these goals can be seen as selfish, as access to disease-eradicating or life-extending technologies would be limited to the wealthy. Westmoreland’s goal to “sell Neolution to the 1 percent” seems frighteningly plausible—transhumanists, who statistically tend to be white, well-educated, and male, and their associated organizations raise and spend massive sums of money to help fulfill their goals. …
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On Orphan Black, denial of choice is tantamount to imprisonment. That the clones have to earn autonomy underscores the need for ethics in science, especially when it comes to genetics. The show’s message here is timely given the rise of gene-editing techniques such as CRISPR. Recently, the National Academy of Sciences gave germline gene editing the green light, just one year after academy scientists from around the world argued it would be “irresponsible to proceed” without further exploring the implications. Scientists in the United Kingdom and China have already begun human genetic engineering and American scientists recently genetically engineered a human embryo for the first time. The possibility of Project Leda isn’t farfetched. Orphan Black warns us that money, power, and fear of death can corrupt both people and science. Once that happens, loss of humanity—of both the scientists and the subjects—is inevitable.
In Carl Sagan’s dark vision of the future, “people have lost the ability to set their own agendas or knowledgeably question those in authority.” This describes the plight of the clones at the outset of Orphan Black, but as the series continues, they challenge this paradigm by approaching science and scientists with skepticism, ingenuity, and grit. …
I hope there are discussions such as those Scheufele and Brossard are advocating but it might be worth considering that there is already some discussion underway, as informal as it is.
Having included an explanation of CRISPR-CAS9 technology along with the news about the first US team to edit the germline and bits and pieces about ethics and a patent fight (part 1), this part hones in on the details of the work and worries about ‘designer babies’.
The interest flurry
I found three articles addressing the research and all three concur that despite some of the early reporting, this is not the beginning of a ‘designer baby’ generation.
MIT Technology Review reported Thursday that a team of researchers from Portland, Oregon were the first team of U.S.-based scientists to successfully create a genetically modified human embryo. The researchers, led by Shoukhrat Mitalipov of Oregon Health and Science University, changed the DNA of—in MIT Technology Review’s words—“many tens” of genetically-diseased embryos by injecting the host egg with CRISPR, a DNA-based gene editing tool first discovered in bacteria, at the time of fertilization. CRISPR-Cas9, as the full editing system is called, allows scientists to change genes accurately and efficiently. As has happened with research elsewhere, the CRISPR-edited embryos weren’t implanted—they were kept sustained for only a couple of days.
In addition to being the first American team to complete this feat, the researchers also improved upon the work of the three Chinese research teams that beat them to editing embryos with CRISPR: Mitalipov’s team increased the proportion of embryonic cells that received the intended genetic changes, addressing an issue called “mosaicism,” which is when an embryo is comprised of cells with different genetic makeups. Increasing that proportion is essential to CRISPR work in eliminating inherited diseases, to ensure that the CRISPR therapy has the intended result. The Oregon team also reduced the number of genetic errors introduced by CRISPR, reducing the likelihood that a patient would develop cancer elsewhere in the body.
Separate from the scientific advancements, it’s a big deal that this work happened in a country with such intense politicization of embryo research. …
But there are a great number of obstacles between the current research and the future of genetically editing all children to be 12-foot-tall Einsteins.
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Ed Yong in an Aug. 2, 2017 article for The Atlantic offered a comprehensive overview of the research and its implications (unusually for Yong, there seems to be mildly condescending note but it’s worth ignoring for the wealth of information in the article; Note: Links have been removed),
… the full details of the experiment, which are released today, show that the study is scientifically important but much less of a social inflection point than has been suggested. “This has been widely reported as the dawn of the era of the designer baby, making it probably the fifth or sixth time people have reported that dawn,” says Alta Charo, an expert on law and bioethics at the University of Wisconsin-Madison. “And it’s not.”
Given the persistent confusion around CRISPR and its implications, I’ve laid out exactly what the team did, and what it means.
Who did the experiments?
Shoukhrat Mitalipov is a Kazakhstani-born cell biologist with a history of breakthroughs—and controversy—in the stem cell field. He was the scientist to clone monkeys. He was the first to create human embryos by cloning adult cells—a move that could provide patients with an easy supply of personalized stem cells. He also pioneered a technique for creating embryos with genetic material from three biological parents, as a way of preventing a group of debilitating inherited diseases.
Although MIT Tech Review name-checked Mitalipov alone, the paper splits credit for the research between five collaborating teams—four based in the United States, and one in South Korea.
What did they actually do?
The project effectively began with an elevator conversation between Mitalipov and his colleague Sanjiv Kaul. Mitalipov explained that he wanted to use CRISPR to correct a disease-causing gene in human embryos, and was trying to figure out which disease to focus on. Kaul, a cardiologist, told him about hypertrophic cardiomyopathy (HCM)—an inherited heart disease that’s commonly caused by mutations in a gene called MYBPC3. HCM is surprisingly common, affecting 1 in 500 adults. Many of them lead normal lives, but in some, the walls of their hearts can thicken and suddenly fail. For that reason, HCM is the commonest cause of sudden death in athletes. “There really is no treatment,” says Kaul. “A number of drugs are being evaluated but they are all experimental,” and they merely treat the symptoms. The team wanted to prevent HCM entirely by removing the underlying mutation.
They collected sperm from a man with HCM and used CRISPR to change his mutant gene into its normal healthy version, while simultaneously using the sperm to fertilize eggs that had been donated by female volunteers. In this way, they created embryos that were completely free of the mutation. The procedure was effective, and avoided some of the critical problems that have plagued past attempts to use CRISPR in human embryos.
Wait, other human embryos have been edited before?
There have been three attempts in China. The first two—in 2015 and 2016—used non-viable embryos that could never have resulted in a live birth. The third—announced this March—was the first to use viable embryos that could theoretically have been implanted in a womb. All of these studies showed that CRISPR gene-editing, for all its hype, is still in its infancy.
The editing was imprecise. CRISPR is heralded for its precision, allowing scientists to edit particular genes of choice. But in practice, some of the Chinese researchers found worrying levels of off-target mutations, where CRISPR mistakenly cut other parts of the genome.
The editing was inefficient. The first Chinese team only managed to successfully edit a disease gene in 4 out of 86 embryos, and the second team fared even worse.
The editing was incomplete. Even in the successful cases, each embryo had a mix of modified and unmodified cells. This pattern, known as mosaicism, poses serious safety problems if gene-editing were ever to be used in practice. Doctors could end up implanting women with embryos that they thought were free of a disease-causing mutation, but were only partially free. The resulting person would still have many tissues and organs that carry those mutations, and might go on to develop symptoms.
What did the American team do differently?
The Chinese teams all used CRISPR to edit embryos at early stages of their development. By contrast, the Oregon researchers delivered the CRISPR components at the earliest possible point—minutes before fertilization. That neatly avoids the problem of mosaicism by ensuring that an embryo is edited from the very moment it is created. The team did this with 54 embryos and successfully edited the mutant MYBPC3 gene in 72 percent of them. In the other 28 percent, the editing didn’t work—a high failure rate, but far lower than in previous attempts. Better still, the team found no evidence of off-target mutations.
This is a big deal. Many scientists assumed that they’d have to do something more convoluted to avoid mosaicism. They’d have to collect a patient’s cells, which they’d revert into stem cells, which they’d use to make sperm or eggs, which they’d edit using CRISPR. “That’s a lot of extra steps, with more risks,” says Alta Charo. “If it’s possible to edit the embryo itself, that’s a real advance.” Perhaps for that reason, this is the first study to edit human embryos that was published in a top-tier scientific journal—Nature, which rejected some of the earlier Chinese papers.
Is this kind of research even legal?
Yes. In Western Europe, 15 countries out of 22 ban any attempts to change the human germ line—a term referring to sperm, eggs, and other cells that can transmit genetic information to future generations. No such stance exists in the United States but Congress has banned the Food and Drug Administration from considering research applications that make such modifications. Separately, federal agencies like the National Institutes of Health are banned from funding research that ultimately destroys human embryos. But the Oregon team used non-federal money from their institutions, and donations from several small non-profits. No taxpayer money went into their work. [emphasis mine]
Why would you want to edit embryos at all?
Partly to learn more about ourselves. By using CRISPR to manipulate the genes of embryos, scientists can learn more about the earliest stages of human development, and about problems like infertility and miscarriages. That’s why biologist Kathy Niakan from the Crick Institute in London recently secured a license from a British regulator to use CRISPR on human embryos.
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Isn’t this a slippery slope toward making designer babies?
In terms of avoiding genetic diseases, it’s not conceptually different from PGD, which is already widely used. The bigger worry is that gene-editing could be used to make people stronger, smarter, or taller, paving the way for a new eugenics, and widening the already substantial gaps between the wealthy and poor. But many geneticists believe that such a future is fundamentally unlikely because complex traits like height and intelligence are the work of hundreds or thousands of genes, each of which have a tiny effect. The prospect of editing them all is implausible. And since genes are so thoroughly interconnected, it may be impossible to edit one particular trait without also affecting many others.
“There’s the worry that this could be used for enhancement, so society has to draw a line,” says Mitalipov. “But this is pretty complex technology and it wouldn’t be hard to regulate it.”
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Does this discovery have any social importance at all?
“It’s not so much about designer babies as it is about geographical location,” says Charo. “It’s happening in the United States, and everything here around embryo research has high sensitivity.” She and others worry that the early report about the study, before the actual details were available for scrutiny, could lead to unnecessary panic. “Panic reactions often lead to panic-driven policy … which is usually bad policy,” wrote Greely [bioethicist Hank Greely].
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As I understand it, despite the change in stance, there is no federal funding available for the research performed by Mitalipov and his team.
Finally, University College London (UCL) scientists Joyce Harper and Helen O’Neill wrote about CRISPR, the Oregon team’s work, and the possibilities in an Aug. 3, 2017 essay for The Conversation (Note: Links have been removed),
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The genome editing tool used, CRISPR-Cas9, has transformed the field of biology in the short time since its discovery in that it not only promises, but delivers. CRISPR has surpassed all previous efforts to engineer cells and alter genomes at a fraction of the time and cost.
The technology, which works like molecular scissors to cut and paste DNA, is a natural defence system that bacteria use to fend off harmful infections. This system has the ability to recognise invading virus DNA, cut it and integrate this cut sequence into its own genome – allowing the bacterium to render itself immune to future infections of viruses with similar DNA. It is this ability to recognise and cut DNA that has allowed scientists to use it to target and edit specific DNA regions.
When this technology is applied to “germ cells” – the sperm and eggs – or embryos, it changes the germline. That means that any alterations made would be permanent and passed down to future generations. This makes it more ethically complex, but there are strict regulations around human germline genome editing, which is predominantly illegal. The UK received a licence in 2016 to carry out CRISPR on human embryos for research into early development. But edited embryos are not allowed to be inserted into the uterus and develop into a fetus in any country.
Germline genome editing came into the global spotlight when Chinese scientists announced in 2015 that they had used CRISPR to edit non-viable human embryos – cells that could never result in a live birth. They did this to modify the gene responsible for the blood disorder β-thalassaemia. While it was met with some success, it received a lot of criticism because of the premature use of this technology in human embryos. The results showed a high number of potentially dangerous, off-target mutations created in the procedure.
Impressive results
The new study, published in Nature, is different because it deals with viable human embryos and shows that the genome editing can be carried out safely – without creating harmful mutations. The team used CRISPR to correct a mutation in the gene MYBPC3, which accounts for approximately 40% of the myocardial disease hypertrophic cardiomyopathy. This is a dominant disease, so an affected individual only needs one abnormal copy of the gene to be affected.
The researchers used sperm from a patient carrying one copy of the MYBPC3 mutation to create 54 embryos. They edited them using CRISPR-Cas9 to correct the mutation. Without genome editing, approximately 50% of the embryos would carry the patients’ normal gene and 50% would carry his abnormal gene.
After genome editing, the aim would be for 100% of embryos to be normal. In the first round of the experiments, they found that 66.7% of embryos – 36 out of 54 – were normal after being injected with CRIPSR. Of the remaining 18 embryos, five had remained unchanged, suggesting editing had not worked. In 13 embryos, only a portion of cells had been edited.
The level of efficiency is affected by the type of CRISPR machinery used and, critically, the timing in which it is put into the embryo. The researchers therefore also tried injecting the sperm and the CRISPR-Cas9 complex into the egg at the same time, which resulted in more promising results. This was done for 75 mature donated human eggs using a common IVF technique called intracytoplasmic sperm injection. This time, impressively, 72.4% of embryos were normal as a result. The approach also lowered the number of embryos containing a mixture of edited and unedited cells (these embryos are called mosaics).
Finally, the team injected a further 22 embryos which were grown into blastocyst – a later stage of embryo development. These were sequenced and the researchers found that the editing had indeed worked. Importantly, they could show that the level of off-target mutations was low.
A brave new world?
So does this mean we finally have a cure for debilitating, heritable diseases? It’s important to remember that the study did not achieve a 100% success rate. Even the researchers themselves stress that further research is needed in order to fully understand the potential and limitations of the technique.
In our view, it is unlikely that genome editing would be used to treat the majority of inherited conditions anytime soon. We still can’t be sure how a child with a genetically altered genome will develop over a lifetime, so it seems unlikely that couples carrying a genetic disease would embark on gene editing rather than undergoing already available tests – such as preimplantation genetic diagnosis or prenatal diagnosis – where the embryos or fetus are tested for genetic faults.
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As might be expected there is now a call for public discussion about the ethics about this kind of work. See Part 3.
For anyone who started in the middle of this series, here’s Part 1 featuring an introduction to the technology and some of the issues.
There’s been a minor flurry of interest in CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats; also known as CRISPR-CAS9), a gene-editing technique, since a team in Oregon announced a paper describing their work editing the germline. Since I’ve been following the CRISPR-CAS9 story for a while this seems like a good juncture for a more in-depth look at the topic. In this first part I’m including an introduction to CRISPR, some information about the latest US work, and some previous writing about ethics issues raised when Chinese scientists first announced their work editing germlines in 2015 and during the patent dispute between the University of California at Berkeley and Harvard University’s Broad Institute.
Introduction to CRISPR
I’ve been searching for a good description of CRISPR and this helped to clear up some questions for me (Thank you to MIT Review),
For anyone who’s been reading about science for a while, this upbeat approach to explaining how a particular technology will solve all sorts of problems will seem quite familiar. It’s not the most hyperbolic piece I’ve seen but it barely mentions any problems associated with research (for some of the problems see: ‘The interest flurry’ later in part 2).
Oregon team
Steve Connor’s July 26, 2017 article for the MIT (Massachusetts Institute of Technology) Technology Review breaks the news (Note: Links have been removed),
The first known attempt at creating genetically modified human embryos in the United States has been carried out by a team of researchers in Portland, Oregon, MIT Technology Review has learned.
The effort, led by Shoukhrat Mitalipov of Oregon Health and Science University, involved changing the DNA of a large number of one-cell embryos with the gene-editing technique CRISPR, according to people familiar with the scientific results.
Until now, American scientists have watched with a combination of awe, envy, and some alarm as scientists elsewhere were first to explore the controversial practice. To date, three previous reports of editing human embryos were all published by scientists in China.
Now Mitalipov is believed to have broken new ground both in the number of embryos experimented upon and by demonstrating that it is possible to safely and efficiently correct defective genes that cause inherited diseases.
Although none of the embryos were allowed to develop for more than a few days—and there was never any intention of implanting them into a womb—the experiments are a milestone on what may prove to be an inevitable journey toward the birth of the first genetically modified humans.
In altering the DNA code of human embryos, the objective of scientists is to show that they can eradicate or correct genes that cause inherited disease, like the blood condition beta-thalassemia. The process is termed “germline engineering” because any genetically modified child would then pass the changes on to subsequent generations via their own germ cells—the egg and sperm.
Some critics say germline experiments could open the floodgates to a brave new world of “designer babies” engineered with genetic enhancements—a prospect bitterly opposed by a range of religious organizations, civil society groups, and biotech companies.
The U.S. intelligence community last year called CRISPR a potential “weapon of mass destruction.”
Here’s a link to a citation for the groundbreaking paper,
Correction of a pathogenic gene mutation in human embryos by Hong Ma, Nuria Marti-Gutierrez, Sang-Wook Park, Jun Wu, Yeonmi Lee, Keiichiro Suzuki, Amy Koski, Dongmei Ji, Tomonari Hayama, Riffat Ahmed, Hayley Darby, Crystal Van Dyken, Ying Li, Eunju Kang, A.-Reum Park, Daesik Kim, Sang-Tae Kim, Jianhui Gong, Ying Gu, Xun Xu, David Battaglia, Sacha A. Krieg, David M. Lee, Diana H. Wu, Don P. Wolf, Stephen B. Heitner, Juan Carlos Izpisua Belmonte, Paula Amato, Jin-Soo Kim, Sanjiv Kaul, & Shoukhrat Mitalipov. Nature (2017) doi:10.1038/nature23305 Published online 02 August 2017
This paper appears to be open access.
CRISPR Issues: ethics and patents
In my May 14, 2015 posting I mentioned a ‘moratorium’ on germline research, the Chinese research paper, and the stance taken by the US National Institutes of Health (NIH),
The CRISPR technology has reignited a discussion about ethical and moral issues of human genetic engineering some of which is reviewed in an April 7, 2015 posting about a moratorium by Sheila Jasanoff, J. Benjamin Hurlbut and Krishanu Saha for the Guardian science blogs (Note: A link has been removed),
On April 3, 2015, a group of prominent biologists and ethicists writing in Science called for a moratorium on germline gene engineering; modifications to the human genome that will be passed on to future generations. The moratorium would apply to a technology called CRISPR/Cas9, which enables the removal of undesirable genes, insertion of desirable ones, and the broad recoding of nearly any DNA sequence.
Such modifications could affect every cell in an adult human being, including germ cells, and therefore be passed down through the generations. Many organisms across the range of biological complexity have already been edited in this way to generate designer bacteria, plants and primates. There is little reason to believe the same could not be done with human eggs, sperm and embryos. Now that the technology to engineer human germlines is here, the advocates for a moratorium declared, it is time to chart a prudent path forward. They recommend four actions: a hold on clinical applications; creation of expert forums; transparent research; and a globally representative group to recommend policy approaches.
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The authors go on to review precedents and reasons for the moratorium while suggesting we need better ways for citizens to engage with and debate these issues,
An effective moratorium must be grounded in the principle that the power to modify the human genome demands serious engagement not only from scientists and ethicists but from all citizens. We need a more complex architecture for public deliberation, built on the recognition that we, as citizens, have a duty to participate in shaping our biotechnological futures, just as governments have a duty to empower us to participate in that process. Decisions such as whether or not to edit human genes should not be left to elite and invisible experts, whether in universities, ad hoc commissions, or parliamentary advisory committees. Nor should public deliberation be temporally limited by the span of a moratorium or narrowed to topics that experts deem reasonable to debate.
I recommend reading the post in its entirety as there are nuances that are best appreciated in the entirety of the piece.
Shortly after this essay was published, Chinese scientists announced they had genetically modified (nonviable) human embryos. From an April 22, 2015 article by David Cyranoski and Sara Reardon in Nature where the research and some of the ethical issues discussed,
In a world first, Chinese scientists have reported editing the genomes of human embryos. The results are published1 in the online journal Protein & Cell and confirm widespread rumours that such experiments had been conducted — rumours that sparked a high-profile debate last month2, 3 about the ethical implications of such work.
In the paper, researchers led by Junjiu Huang, a gene-function researcher at Sun Yat-sen University in Guangzhou, tried to head off such concerns by using ‘non-viable’ embryos, which cannot result in a live birth, that were obtained from local fertility clinics. The team attempted to modify the gene responsible for β-thalassaemia, a potentially fatal blood disorder, using a gene-editing technique known as CRISPR/Cas9. The researchers say that their results reveal serious obstacles to using the method in medical applications.
“I believe this is the first report of CRISPR/Cas9 applied to human pre-implantation embryos and as such the study is a landmark, as well as a cautionary tale,” says George Daley, a stem-cell biologist at Harvard Medical School in Boston, Massachusetts. “Their study should be a stern warning to any practitioner who thinks the technology is ready for testing to eradicate disease genes.”
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Huang says that the paper was rejected by Nature and Science, in part because of ethical objections; both journals declined to comment on the claim. (Nature’s news team is editorially independent of its research editorial team.)
He adds that critics of the paper have noted that the low efficiencies and high number of off-target mutations could be specific to the abnormal embryos used in the study. Huang acknowledges the critique, but because there are no examples of gene editing in normal embryos he says that there is no way to know if the technique operates differently in them.
Still, he maintains that the embryos allow for a more meaningful model — and one closer to a normal human embryo — than an animal model or one using adult human cells. “We wanted to show our data to the world so people know what really happened with this model, rather than just talking about what would happen without data,” he says.
This, too, is a good and thoughtful read.
There was an official response in the US to the publication of this research, from an April 29, 2015 post by David Bruggeman on his Pasco Phronesis blog (Note: Links have been removed),
In light of Chinese researchers reporting their efforts to edit the genes of ‘non-viable’ human embryos, the National Institutes of Health (NIH) Director Francis Collins issued a statement (H/T Carl Zimmer).
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“NIH will not fund any use of gene-editing technologies in human embryos. The concept of altering the human germline in embryos for clinical purposes has been debated over many years from many different perspectives, and has been viewed almost universally as a line that should not be crossed. Advances in technology have given us an elegant new way of carrying out genome editing, but the strong arguments against engaging in this activity remain. These include the serious and unquantifiable safety issues, ethical issues presented by altering the germline in a way that affects the next generation without their consent, and a current lack of compelling medical applications justifying the use of CRISPR/Cas9 in embryos.” …
The US has modified its stance according to a February 14, 2017 article by Jocelyn Kaiser for Science Magazine (Note: Links have been removed),
Editing the DNA of a human embryo to prevent a disease in a baby could be ethically allowable one day—but only in rare circumstances and with safeguards in place, says a widely anticipated report released today.
The report from an international committee convened by the U.S. National Academy of Sciences (NAS) and the National Academy of Medicine in Washington, D.C., concludes that such a clinical trial “might be permitted, but only following much more research” on risks and benefits, and “only for compelling reasons and under strict oversight.” Those situations could be limited to couples who both have a serious genetic disease and for whom embryo editing is “really the last reasonable option” if they want to have a healthy biological child, says committee co-chair Alta Charo, a bioethicist at the University of Wisconsin in Madison.
Some researchers are pleased with the report, saying it is consistent with previous conclusions that safely altering the DNA of human eggs, sperm, or early embryos—known as germline editing—to create a baby could be possible eventually. “They have closed the door to the vast majority of germline applications and left it open for a very small, well-defined subset. That’s not unreasonable in my opinion,” says genome researcher Eric Lander of the Broad Institute in Cambridge, Massachusetts. Lander was among the organizers of an international summit at NAS in December 2015 who called for more discussion before proceeding with embryo editing.
But others see the report as lowering the bar for such experiments because it does not explicitly say they should be prohibited for now. “It changes the tone to an affirmative position in the absence of the broad public debate this report calls for,” says Edward Lanphier, chairman of the DNA editing company Sangamo Therapeutics in Richmond, California. Two years ago, he co-authored a Nature commentary calling for a moratorium on clinical embryo editing.
One advocacy group opposed to embryo editing goes further. “We’re very disappointed with the report. It’s really a pretty dramatic shift from the existing and widespread agreement globally that human germline editing should be prohibited,” says Marcy Darnovsky, executive director of the Center for Genetics and Society in Berkeley, California.
Interestingly, this change of stance occurred just prior to a CRISPR patent decision (from my March 15, 2017 posting),
I have written about the CRISPR patent tussle (Harvard & MIT’s [Massachusetts Institute of Technology] Broad Institute vs the University of California at Berkeley) previously in a Jan. 6, 2015 posting and in a more detailed May 14, 2015 posting. I also mentioned (in a Jan. 17, 2017 posting) CRISPR and its patent issues in the context of a posting about a Slate.com series on Frankenstein and the novel’s applicability to our own time. This patent fight is being bitterly fought as fortunes are at stake.
It seems a decision has been made regarding the CRISPR patent claims. From a Feb. 17, 2017 article by Charmaine Distor for The Science Times,
After an intense court battle, the US Patent and Trademark Office (USPTO) released its ruling on February 15 [2017]. The rights for the CRISPR-Cas9 gene editing technology was handed over to the Broad Institute of Harvard University and the Massachusetts Institute of Technology (MIT).
According to an article in Nature, the said court battle was between the Broad Institute and the University of California. The two institutions are fighting over the intellectual property right for the CRISPR patent. The case between the two started when the patent was first awarded to the Broad Institute despite having the University of California apply first for the CRISPR patent.
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Heidi Ledford’s Feb. 17, 2017 article for Nature provides more insight into the situation (Note: Links have been removed),
It [USPTO] ruled that the Broad Institute of Harvard and MIT in Cambridge could keep its patents on using CRISPR–Cas9 in eukaryotic cells. That was a blow to the University of California in Berkeley, which had filed its own patents and had hoped to have the Broad’s thrown out.
The fight goes back to 2012, when Jennifer Doudna at Berkeley, Emmanuelle Charpentier, then at the University of Vienna, and their colleagues outlined how CRISPR–Cas9 could be used to precisely cut isolated DNA1. In 2013, Feng Zhang at the Broad and his colleagues — and other teams — showed2 how it could be adapted to edit DNA in eukaryotic cells such as plants, livestock and humans.
Berkeley filed for a patent earlier, but the USPTO granted the Broad’s patents first — and this week upheld them. There are high stakes involved in the ruling. The holder of key patents could make millions of dollars from CRISPR–Cas9’s applications in industry: already, the technique has sped up genetic research, and scientists are using it to develop disease-resistant livestock and treatments for human diseases.
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I also noted this eyebrow-lifting statistic, “As for Ledford’s 3rd point, there are an estimated 763 patent families (groups of related patents) claiming CAS9 leading to the distinct possibility that the Broad Institute will be fighting many patent claims in the future.)
Part 3 is all about public discussion or, rather, the lack of and need for according to a couple of social scientists. Informally, there is some discussion via pop culture and Joelle Renstrom notes although she is focused on the larger issues touched on by the television series, Orphan Black and as I touch on in my final comments. CRISPR and editing the germline in the US (part 3 of 3): public discussions and pop culture
For almost a month I’ve been meaning to get to this Feb. 1, 2017 essay by Andrew Maynard (director of Risk Innovation Lab at Arizona State University) and Jack Stilgoe (science policy lecturer at University College London [UCL]) on the topic of artificial intelligence and principles (Note: Links have been removed). First, a walk down memory lane,
Today [Feb. 1, 2017] in Washington DC, leading US and UK scientists are meeting to share dispatches from the frontiers of machine learning – an area of research that is creating new breakthroughs in artificial intelligence (AI). Their meeting follows the publication of a set of principles for beneficial AI that emerged from a conference earlier this year at a place with an important history.
In February 1975, 140 people – mostly scientists, with a few assorted lawyers, journalists and others – gathered at a conference centre on the California coast. A magazine article from the time by Michael Rogers, one of the few journalists allowed in, reported that most of the four days’ discussion was about the scientific possibilities of genetic modification. Two years earlier, scientists had begun using recombinant DNA to genetically modify viruses. The Promethean nature of this new tool prompted scientists to impose a moratorium on such experiments until they had worked out the risks. By the time of the Asilomar conference, the pent-up excitement was ready to burst. It was only towards the end of the conference when a lawyer stood up to raise the possibility of a multimillion-dollar lawsuit that the scientists focussed on the task at hand – creating a set of principles to govern their experiments.
The 1975 Asilomar meeting is still held up as a beacon of scientific responsibility. However, the story told by Rogers, and subsequently by historians, is of scientists motivated by a desire to head-off top down regulation with a promise of self-governance. Geneticist Stanley Cohen said at the time, ‘If the collected wisdom of this group doesn’t result in recommendations, the recommendations may come from other groups less well qualified’. The mayor of Cambridge, Massachusetts was a prominent critic of the biotechnology experiments then taking place in his city. He said, ‘I don’t think these scientists are thinking about mankind at all. I think that they’re getting the thrills and the excitement and the passion to dig in and keep digging to see what the hell they can do’.
The concern in 1975 was with safety and containment in research, not with the futures that biotechnology might bring about. A year after Asilomar, Cohen’s colleague Herbert Boyer founded Genentech, one of the first biotechnology companies. Corporate interests barely figured in the conversations of the mainly university scientists.
Fast-forward 42 years and it is clear that machine learning, natural language processing and other technologies that come under the AI umbrella are becoming big business. The cast list of the 2017 Asilomar meeting included corporate wunderkinds from Google, Facebook and Tesla as well as researchers, philosophers, and other academics. The group was more intellectually diverse than their 1975 equivalents, but there were some notable absences – no public and their concerns, no journalists, and few experts in the responsible development of new technologies.
Maynard and Stilgoe offer a critique of the latest principles,
The principles that came out of the meeting are, at least at first glance, a comforting affirmation that AI should be ‘for the people’, and not to be developed in ways that could cause harm. They promote the idea of beneficial and secure AI, development for the common good, and the importance of upholding human values and shared prosperity.
This is good stuff. But it’s all rather Motherhood and Apple Pie: comforting and hard to argue against, but lacking substance. The principles are short on accountability, and there are notable absences, including the need to engage with a broader set of stakeholders and the public. At the early stages of developing new technologies, public concerns are often seen as an inconvenience. In a world in which populism appears to be trampling expertise into the dirt, it is easy to understand why scientists may be defensive.
I encourage you to read this thoughtful essay in its entirety although I do have one nit to pick: Why only US and UK scientists? I imagine the answer may lie in funding and logistics issues but I find it surprising that the critique makes no mention of the international community as a nod to inclusion.
For anyone interested in the Asolimar AI principles (2017), you can find them here. You can also find videos of the two-day workshop (Jan. 31 – Feb. 1, 2017 workshop titled The Frontiers of Machine Learning (a Raymond and Beverly Sackler USA-UK Scientific Forum [US National Academy of Sciences]) here (videos for each session are available on Youtube).
This ‘think’ piece is going to cover a fair bit of ground including science literacy in the general public and in the US Supreme Court, and what that might mean for science advice and UK Members of Parliament (MPs).
Science literacy generally and in the US Supreme Court
A science literacy report for the US National Academy of Sciences (NAS), due sometime from early to mid 2017, is being crafted with an eye to capturing a different perspective according to a March 24, 2016 University of Wisconsin-Madison news release by Terry Dewitt,
What does it mean to be science literate? How science literate is the American public? How do we stack up against other countries? What are the civic implications of a public with limited knowledge of science and how it works? How is science literacy measured?
These and other questions are under the microscope of a 12-member National Academy of Sciences (NAS) panel — including University of Wisconsin—Madison Life Sciences Communication Professor Dominique Brossard and School of Education Professor Noah Feinstein — charged with sorting through the existing data on American science and health literacy and exploring the association between knowledge of science and public perception of and support for science.
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The committee — composed of educators, scientists, physicians and social scientists — will take a hard look at the existing data on the state of U.S. science literacy, the questions asked, and the methods used to measure what Americans know and don’t know about science and how that knowledge has changed over time. Critically for science, the panel will explore whether a lack of science literacy is associated with decreased public support for science or research.
Historically, policymakers and leaders in the scientific community have fretted over a perceived lack of knowledge among Americans about science and how it works. A prevailing fear is that an American public unequipped to come to terms with modern science will ultimately have serious economic, security and civic consequences, especially when it comes to addressing complex and nuanced issues like climate change, antibiotic resistance, emerging diseases, environment and energy choices.
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While the prevailing wisdom, inspired by past studies, is that Americans don’t stack up well in terms of understanding science, Brossard is not so convinced. Much depends on what kinds of questions are asked, how they are asked, and how the data is analyzed.
It is very easy, she argues, to do bad social science and past studies may have measured the wrong things or otherwise created a perception about the state of U.S. science literacy that may or may not be true.
“How do you conceptualize scientific literacy? What do people need to know? Some argue that scientific literacy may be as simple as an understanding of how science works, the nature of science, [emphasis mine]” Brossard explains. “For others it may be a kind of ‘civic science literacy,’ where people have enough knowledge to be informed and make good decisions in a civics context.”
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Science literacy may not be just for the public, it would seem that US Supreme Court judges may not have a basic understanding of how science works. David Bruggeman’s March 24, 2016 posting (on his Pasco Phronesis blog) describes a then current case before the Supreme Court (Justice Antonin Scalia has since died), Note: Links have been removed,
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It’s a case concerning aspects of the University of Texas admissions process for undergraduates and the case is seen as a possible means of restricting race-based considerations for admission. While I think the arguments in the case will likely revolve around factors far removed from science and or technology, there were comments raised by two Justices that struck a nerve with many scientists and engineers.
Both Justice Antonin Scalia and Chief Justice John Roberts raised questions about the validity of having diversity where science and scientists are concerned [emphasis mine]. Justice Scalia seemed to imply that diversity wasn’t esential for the University of Texas as most African-American scientists didn’t come from schools at the level of the University of Texas (considered the best university in Texas). Chief Justice Roberts was a bit more plain about not understanding the benefits of diversity. He stated, “What unique perspective does a black student bring to a class in physics?”
To that end, Dr. S. James Gates, theoretical physicist at the University of Maryland, and member of the President’s Council of Advisers on Science and Technology (and commercial actor) has an editorial in the March 25 [2016] issue of Science explaining that the value of having diversity in science does not accrue *just* to those who are underrepresented.
Dr. Gates relates his personal experience as a researcher and teacher of how people’s background inform their practice of science, and that two different people may use the same scientific method, but think about the problem differently.
I’m guessing that both Scalia and Roberts and possibly others believe that science is the discovery and accumulation of facts. In this worldview science facts such as gravity are waiting for discovery and formulation into a ‘law’. They do not recognize that most science is a collection of beliefs and may be influenced by personal beliefs. For example, we believe we’ve proved the existence of the Higgs boson but no one associated with the research has ever stated unequivocally that it exists.
For judges who are under the impression that scientific facts are out there somewhere waiting to be discovered diversity must seem irrelevant. It is not. Who you are affects the questions you ask and how you approach science. The easiest example is to look at how women were viewed when they were subjects in medical research. The fact that women’s physiology is significantly different (and not just in child-bearing ways) was never considered relevant when reporting results. Today, researchers consider not only gender, but age (to some extent), ethnicity, and more when examining results. It’s still not a perfect but it was a step forward.
So when Brossard included “… an understanding of how science works, the nature of science …” as an aspect of science literacy, the judges seemed to present a good example of how not understanding science can have a major impact on how others live.
I’d almost forgotten this science literacy piece as I’d started the draft some months ago but then I spotted a news item about a science advice/MP ‘dating’ service in the UK.
MPs have expressed an overwhelming willingness to use a proposed new service to swiftly link them with academics in relevant areas to help ensure policy is based on the latest evidence.
A June 6, 2016 University of Exeter press release, which originated the news item, provides more detail about the proposed service and the research providing the supporting evidence (Note: A link has been removed),
The government is pursuing a drive towards evidence-based policy, yet policy makers still struggle to incorporate evidence into their decisions. One reason for this is limited easy access to the latest research findings or to academic experts who can respond to questions about evidence quickly.
Researchers at Cardiff University, the University of Exeter and University College London have today published results of the largest study to date reporting MPs’ attitudes to evidence in policy making and their reactions to a proposed Evidence Information Service (EIS) – a rapid match-making advisory service that would work alongside existing systems to put MPs in touch with relevant academic experts.
Dr Natalia Lawrence, of the University of Exeter, said: “It’s clear from our study that politicians want to ensure their decisions incorporate the most reliable evidence, but it can sometimes be very difficult for them to know how to access the latest research findings. This new matchmaking service could be a quick and easy way for them to seek advice from cutting-edge researchers and to check their understanding and facts. It could provide a useful complement to existing highly-valued information services.”
The research, published today in the journal Evidence and Policy, reports the findings of a national consultation exercise between politicians and the public. The researchers recruited members of the public to interview their local parliamentary representative. In total 86, politicians were contacted with 56 interviews completed. The MPs indicated an overwhelming willingness to use a service such as the EIS, with 85% supporting the idea, but noted a number of potential reservations related to the logistics of the EIS such as response time and familiarity with the service. Yet, the MPs indicated that their logistical reservations could be overcome by accessing the EIS via existing highly-valued parliamentary information services such as those provided by the House of Commons and Lords Libraries. Furthermore prior to rolling out the EIS on a nationwide basis it would first need to be piloted.
Developing the proposed EIS in line with feedback from this consultation of MPs would offer the potential to provide policy makers with rapid, reliable and confidential evidence from willing volunteers from the research community.
Professor Chris Chambers, of Cardiff University, said: “The government has given a robust steer that MPs need to link in more with academics to ensure decisions shaping the future of the country are evidence-based. It’s heartening to see that there is a will to adopt this system and we now need to move into a phase of developing a service that is both simple and effective to meet this need.”
The next steps for the project are parallel consultations of academics and members of the public and a pilot of the EIS, using funding from GW4 alliance of universities, made up of Bath, Bristol, Cardiff and Exeter.
What this study shows:
• The consultation shows that politicians recognise the importance of evidence-based policy making and agree on the need for an easier and more direct linkage between academic experts and policy makers.
• Politicians would welcome the creation of the EIS as a provider of rapid, reliable and confidential evidence.
What this study does not show:
• This study does not show how academics would provide evidence. This was a small-scale study which consulted politicians and has not attempted to give voice to the academic community.
• This study does not detail the mechanism of an operational EIS. Instead it indicates the need for a service such as the EIS and suggests ways in which the EIS can be operationalized.
This paper is behind a paywall open access. *Corrected June 17, 2016.*
It’s an interesting idea and I can understand the appeal. However, operationalizing this ‘dating’ or ‘matchmaking’ service could prove quite complex. I appreciate the logistics issues but I’m a little more concerned about the MPs’ science literacy. Are they going to be like the two US justices who believe that science is the pursuit of immutable facts? What happens if two MPs are matched up with a different scientist and those two scientists didn’t agree about what the evidence says. Or, what happens if one scientist is more cautious than the other. There are all kinds of pitfalls. I’m not arguing against the idea but it’s going to require a lot of careful consideration.
