Embryonic Human DNA Has Just Been Successfully Repaired in the U.S.

U.S. scientists have successfully repaired DNA in a human embryo for the first time.

American researchers have announced the successful repair of a human embryo's genes. As reported in the journal Nature, they used CRISPR-cas9. On one hand, their success represents an exciting breakthrough and on the other, it's a stark reminder of all we don't yet understand about human genetics. That's because the repair of the gene occurred in a way that researchers didn't anticipate.


The gene they repaired is MYBPC3. A mutation in it causes hypertrophic cardiomyopathy (HCM). With HCM, which is estimated to occur in 700,000 to 725,000 U.S. citizens — 1 in 500's heart muscle becomes thickened. Many people lead normal lives with it, with or without treatment. HCM isn't restricted to any particular group or gender, either, but the disease is especially worrisome in young people, where its first symptom can be sudden death — in fact, it's the most common cause of death in young athletes.

Word of the repair first appeared in i News, followed a week later by the peer-reviewed study in Nature. An international team authored the study, with scientists from Oregon, California, China, and South Korea. They were led by senior author Shoukhrat Mitalipov, director of the Center for Embryonic Cell and Gene Therapy at Oregon Health and Science University (OHSU).

Mitalipov previously made a name for himself by introducing the first cloned stem cells from monkeys, the first “three-parent" monkeys, and making embryonic cells from human skin cells.


Shoukhrat Mitalipov (UYGHUR HUMAN RIGHTS PROJECT)

The new study involved embryos created with eggs from 12 healthy females injected with sperm from a male with the MYBPC3 mutation. The team tried twice, using a cas9 enzyme targeting the mutation they sought to snip out. The cas9 enzyme was accompanied by a synthetic DNA template modeled after a normal MYBPC3 gene, but chemically tagged so it could be identified by researchers later.

CRISPR After Fertilization

In the first experiments, the scientists fertilized 54 eggs with the sperm, and then injected the cas9 enzyme and template post-fertilization.

In 36 of the embryos (66.7%), the mutation was repaired. Of the remaining 18 (33.3%), 5 embryos were simply not repaired. The other 13 were more troubling: They contained a “mosaic" of repaired and unrepaired genes that may represent a potential time bomb for subsequent generations, one of the reasons many are encouraging caution when modifying embryos. Bioethicist L. Syd M Johnson tells Big Think, “It's one thing to use experimental gene therapies in patients, where the modifications will be isolated to that individual. It's something else entirely to make genomic changes that could potentially be passed on to future generations, which is what happens when you alter an embryo."

If you carry the MYBPC3 mutation, there's a 50% chance your children will develop HCM. It only takes one parent having the mutation for offspring to acquire the condition.

CRISPR During Fertilization — and a Surprise

In the second round, the scientists injected the sperm, cas9, and the DNA template together, and the the result was a pronounced increase in their success rate. In 42 of the 58 embryos, 72.4%, the mutation was successfully snipped out and replaced by cells without the MYBPC3 mutation. And — most encouragingly — no mosaic embryos were produced.

But here's the surprise, and the reminder of how much there still is to learn. The replaced DNA in all 41 of the repaired embryos was not from the injected DNA template — instead it was non-synthesized, or “wild," MYBPC3 material from the maternal egg. “We were so surprised that we just couldn't get this template that we made to be used," Mitalipov tells New York Times. “It was very new and unusual."

It also allows Mitalipov to hedge a bit as to just exactly what he and his team have done. “Everyone always talks about gene editing," he says. “I don't like the word 'editing.' We didn't edit or modify anything. All we did was unmodify a mutant gene using the existing wild-type maternal gene." In other words, we didn't implant synthetic DNA in anyone. This is why the title of his paper is “Correction of a Pathogenic Gene Mutation in Human Embryos." To be fair, “unmodifying" something should really mean to just leave it alone, and it may be more accurate to say that his team simply snipped out a mutation and the embryo unexpectedly did the rest.

Moral Concerns

The study notes the potential for repairing embryos with undesirable mutations before they're implanted during IVF, and others agree that reducing the number of defective embryos would be a positive thing. Not everyone's comfortable with the idea though. There is the issue of the potential for engineering “designer babies." Hank Greely, director of the Center for Law and the Biosciences at Stanford notes, “If you're in one camp, it's a horror to be avoided, and if you're in the other camp, it's desirable."

“There's an additional worry that this technology might be used for nefarious purposes," says Johnson, “to advance eugenicist policies, for example, to 'weed out' undesirable traits or people." She adds, “It's a small conceptual step to move from so-called undesirable traits to undesirable humans. Humans have an unfortunate history of taking that step."


(WINSLOW ANDERSON)

Going Forward

Mitalipov's next step is to see if he can similarly “unmodify" other mutations, including some that are trickier to target than MYBPC3s. The legal terrain in the U.S is not exactly welcoming of such efforts, with the Food and Drug Administration prohibited from permitting clinical trials of germline engineering, and the National Institutes of Health not funding research on gene-editing in humans. (Mitalipov's work was funded by OHSU, the Institute for Basic Science in South Korea, and some private foundations.) This may be starting to change, though — a committee of the National Academy of Sciences, Engineering and Medicine has recently endorsed the modification of human embryos for the purposes of repairing mutations that would otherwise lead to a serious condition if there's no other known remedy.

While the possibilities suggested by the study's success are obvious, the results weren't perfect, and there's more work to be done. As Gaétan Burgio told WIRED, “This is a remarkable paper that shows how much the field has progressed in just the last year or two. But I think for now everyone needs to chill down a bit."

Johnson notes, “We are talking about the future of the human species here. Before we rush headlong into a future where germline genetic modifications of humans might be possible, it's important to consider whether that's a future we really want, how the use of the technology will be controlled, who will have access to it, and how human individuals and the diversity of our species will be protected."

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A map of America’s most famous – and infamous

The 'People Map of the United States' zooms in on America's obsession with celebrity

Image: The Pudding
Strange Maps
  • Replace city names with those of their most famous residents
  • And you get a peculiar map of America's obsession with celebrity
  • If you seek fame, become an actor, musician or athlete rather than a politician, entrepreneur or scientist

Chicagoland is Obamaland

Image: The Pudding

Chicagoland's celebrity constellation: dominated by Barack, but with plenty of room for the Belushis, Brandos and Capones of this world.

Seen from among the satellites, this map of the United States is populated by a remarkably diverse bunch of athletes, entertainers, entrepreneurs and other persons of repute (and disrepute).

The multitalented Dwayne Johnson, boxing legend Muhammad Ali and Apple co-founder Steve Jobs dominate the West Coast. Right down the middle, we find actors Chris Pratt and Jason Momoa, singer Elvis Presley and basketball player Shaquille O'Neal. The East Coast crew include wrestler John Cena, whistle-blower Edward Snowden, mass murderer Ted Bundy… and Dwayne Johnson, again.

The Rock pops up in both Hayward, CA and Southwest Ranches, FL, but he's not the only one to appear twice on the map. Wild West legend Wyatt Earp makes an appearance in both Deadwood, SD and Dodge City, KS.

How is that? This 'People's Map of the United States' replaces the names of cities with those of "their most Wikipedia'ed resident: people born in, lived in, or connected to a place."

‘Cincinnati, Birthplace of Charles Manson'

Image: The Pudding

Keys to the city, or lock 'em up and throw away the key? A city's most famous sons and daughters of a city aren't always the most favoured ones.

That definition allows people to appear in more than one locality. Dwayne Johnson was born in Hayward, has one of his houses in Southwest Ranches, and is famous enough to be the 'most Wikipedia'ed resident' for both localities.

Wyatt Earp was born in Monmouth, IL, but his reputation is closely associated with both Deadwood and Dodge City – although he's most famous for the Gunfight at the O.K. Corral, which took place in Tombstone, AZ. And yes, if you zoom in on that town in southern Arizona, there's Mr Earp again.

The data for this map was collected via the Wikipedia API (application programming interface) from the English-language Wikipedia for the period from July 2015 to May 2019.

The thousands of 'Notable People' sections in Wikipedia entries for cities and other places in the U.S. were scrubbed for the person with the most pageviews. No distinction was made between places of birth, residence or death. As the developers note, "people can 'be from' multiple places".

Pageviews are an impartial indicator of interest – it doesn't matter whether your claim to fame is horrific or honorific. As a result, this map provides a non-judgmental overview of America's obsession with celebrity.

Royals and (other) mortals

Image: The Pudding

There's also a UK version of the People Map – filled with last names like Neeson, Sheeran, Darwin and Churchill – and a few first names of monarchs.

Celebrity, it is often argued, is our age's version of the Greek pantheon, populated by dozens of major gods and thousands of minor ones, each an example of behaviours to emulate or avoid. This constellation of stars, famous and infamous, is more than a map of names. It's a window into America's soul.

But don't let that put you off. Zooming in on the map is entertaining enough: celebrities floating around in the ether are suddenly tied down to a pedestrian level, and to real geography. And it's fun to see the famous and the infamous rub shoulders, as it were.

Barack Obama owns Chicago, but the suburbs to the west of the city are dotted with a panoply of personalities, ranging from the criminal (Al Capone, Cicero) and the musical (John Prine, Maywood) to figures literary (Jonathan Franzen, Western Springs) and painterly (Ivan Albright, Warrenville), actorial (Harrison Ford, Park Ridge) and political (Eugene V. Debs, Elmhurst).

Freaks and angels

Image: Dorothy

The People Map of the U.S. was inspired by the U.S.A. Song Map, substituting song titles for place names.

It would be interesting to compare 'the most Wikipedia'ed' sons and daughters of America's cities with the ones advertised at the city limits. When you're entering Aberdeen, WA, a sign invites you to 'come as you are', in homage to its most famous son, Kurt Cobain. It's a safe bet that Indian Hill, OH will make sure you know Neil Armstrong, first man on the moon, was one of theirs. But it's highly unlikely that Cincinnati, a bit further south, will make any noise about Charles Manson, local boy done bad.

Inevitably, the map also reveals some bitterly ironic neighbours, such as Ishi, the last of the Yahi tribe, captured near Oroville, CA. He died in 1916 as "the last wild Indian in North America". The most 'pageviewed' resident of nearby Colusa, CA is Byron de la Beckwith, Jr., the white supremacist convicted for the murder of Civil Rights activist Medgar Evers.

As a sampling of America's interests, this map teaches that those aiming for fame would do better to become actors, musicians or athletes rather than politicians, entrepreneurs or scientists. But also that celebrity is not limited to the big city lights of LA or New York. Even in deepest Dakota or flattest Kansas, the footlights of fame will find you. Whether that's good or bad? The pageviews don't judge...

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