Researchers say CRISPR edits to a human embryo worked. But critics still doubt it

When researchers announced last year that they had edited human embryos to repair a damaged gene that can lead to heart failure, critics called the report into question.

Now new evidence confirms that the gene editing was successful, reproductive and developmental biologist Shoukhrat Mitalipov and colleagues report August 8 in Nature. “All of our conclusions were basically right,” Mitalipov, of Oregon Health & Science University in Portland, said during a news conference on August 6.
But authors of two critiques published in the same issue of Nature say they still aren’t convinced.

At issue is the way that the gene was repaired. Mitalipov and colleagues used the molecular scissors CRISPR/Cas9 to cut a faulty version of a gene called MYBPC3 in sperm (SN: 9/2/17, p. 6). People who inherit this version of the gene often develop heart failure. Cutting the gene allows cells to fix the problem by replacing erroneous instructions in the gene with correct information.

Researchers supplied the correct information in the form of small foreign pieces of DNA, but the embryos ignored that repair template. Instead, Mitalipov and colleagues say, embryos used a healthy version of the gene on the mother’s chromosome to fix the error. That action is called gene conversion.

Gene conversion typically happens when reproductive, or germline, cells swap DNA before making eggs and sperm. So it was completely unexpected to find that type of repair happening in embryos, says geneticist Paul Thomas of the South Australian Health & Medical Research Institute in Acton.
If human embryos do ignore foreign bits of DNA that could be a problem for fixing genetic diseases that result when both parents pass on damaged versions of a gene. In that scenario, there would be no healthy version of the gene to copy and paste.

But Thomas and colleagues propose that Mitalipov’s group may not have detected gene conversion at all. Instead, large chunks may have been cut out of the chromosome containing the faulty version of the gene and not replaced. That wouldn’t fix the defective gene, but could make it look like gene conversion had happened, fooling researchers into thinking they’d made a repair.

Mitalipov’s group used a technique called polymerase chain reaction, or PCR, to confirm that they had repaired the faulty copy of the gene. PCR essentially photocopied stretches of the repaired gene for analysis. The team found that only the mother’s version of the gene was in the edited embryos. That result led the researchers to conclude that gene conversion had copied the maternal version of the gene onto the father’s chromosome.

But because the researchers weren’t able to take a closer look at the gene, they can’t be sure it was gene conversion, Thomas says. Cutting out a portion of the father’s gene would leave only the mother’s version to be copied during PCR. That might give the impression that the father’s gene was converted to the maternal form, when that piece of DNA is missing from the father’s gene.

Such large DNA deletions were common in experiments with mice, Thomas and colleagues say in one critique. About 45 to 57 percent of mouse embryos tested were missing big chunks of genetic material. But Mitalipov and colleagues didn’t report finding any evidence that portions of DNA were deleted from the human embryos.

“I find that surprising,” Thomas says. He is skeptical that the data presented in the new report completely settle the problem.

Rock solid evidence of gene correction was missing from Mitalipov’s original report, agrees Maria Jasin, a developmental biologist at Memorial Sloan Kettering Cancer Center in New York City. The new report presents more convincing data, “but I’m still left with this doubt,” says Jasin, a coauthor on the other critique. “I wouldn’t rule out that gene conversion can happen” in such cases, she says. But in mouse experiments, that type of repair happens infrequently, she says, and there’s no reason to suppose that human embryos do it more frequently.

While there is optimism that scientists will be able to repair broken genes in human embryos, researchers aren’t there yet, Jasin and Thomas say.

Given all the things that might go wrong with gene editing, such as accidentally making mutations, there’s no room for uncertainty about whether the technique works. “You have to be 100 percent confident,” Thomas says, “and we’re a long, long way from being in that position.”

New Horizons may have seen a glow at the solar system’s edge

The New Horizons spacecraft has spotted an ultraviolet glow that seems to emanate from near the edge of the solar system. That glow may come from a long-sought wall of hydrogen that represents where the sun’s influence wanes, the New Horizons team reports online August 7 in Geophysical Research Letters.

“We’re seeing the threshold between being in the solar neighborhood and being in the galaxy,” says team member Leslie Young of the Southwest Research Institute, based in Boulder, Colo.
Even before New Horizons flew past Pluto in 2015 (SN: 8/8/15, p. 6), the spacecraft was scanning the sky with its ultraviolet telescope to look for signs of the hydrogen wall. As the sun moves through the galaxy, it produces a constant stream of charged particles called the solar wind, which inflates a bubble around the solar system called the heliosphere. Just beyond the edge of that bubble, around 100 times farther from the sun than the Earth, uncharged hydrogen atoms in interstellar space should slow when they collide with solar wind particles. That buildup of hydrogen, or wall, should scatter ultraviolet light in a distinctive way.

The two Voyager spacecraft saw signs of such light scattering 30 years ago. One of those craft has since exited the heliosphere and punched into interstellar space (SN: 10/19/13, p. 19).

New Horizons is the first spacecraft in a position to double-check the Voyagers’ observations. It scanned the ultraviolet sky seven times from 2007 to 2017, space scientist Randy Gladstone of the Southwest Research Institute in San Antonio and colleagues report. As the spacecraft traveled, it saw the ultraviolet light change in a way that supports the decades-old observations. All three spacecraft saw more ultraviolet light farther from the sun than expected if there is no wall. But the team cautions that the light could also be from an unknown source farther away in the galaxy.

“It’s really exciting if these data are able to distinguish the hydrogen wall,” says space scientist David McComas of Princeton University, who was not involved in the new work. That could help figure out the shape and variability of the solar system’s boundary (SN: 5/27/17, p. 15).
After New Horizons flies past the outer solar system object Ultima Thule on New Year’s Day 2019 (SN Online: 3/14/18), the spacecraft will continue to look for the wall about twice each year until the mission’s end, hopefully 10 to 15 years from now, Gladstone says.

If the ultraviolet light drops off at some point, then New Horizons may have left the wall in its rear view mirror. But if the light never fades, then its source could be farther ahead — coming from somewhere deeper in space, says team member Wayne Pryor of Central Arizona College in Coolidge.

A galaxy 11.3 billion light-years away appears filled with dark matter

A distant galaxy appears filled with dark matter.

The outermost stars in the Cosmic Seagull, a galaxy 11.3 billion light-years away, race too fast to be propelled by the gravity of the galaxy’s gas and stars alone. Instead, they move as if urged on by an invisible force, indicating the hidden presence of dark matter, astrophysicist Verónica Motta of the University of Valparaíso in Chile and her colleagues report August 8 at arXiv.org.

“In our nearby universe, you see these halos of dark matter around galaxies like ours,” Motta says. “So we should expect that in the past, that halo was there, too.”
Motta and her colleagues used radio telescopes at the Atacama Large Millimeter/submillimeter Array (ALMA) to measure the speed of gas across the Cosmic Seagull’s disk, from the center out to about 9,800 light-years. They found that the galaxy’s stars speed up as they get farther from the galaxy’s center.

That’s a strange setup for most orbiting objects — when planets orbit a star, for instance, the most distant planets move slowest. But it can be explained if the galaxy’s far reaches are dominated by dark matter that speeds things along. Similar measurements of the Milky Way and neighboring galaxies provided one of the first signs that dark matter may exist, although physicists are still trying to detect the proposed particle directly (SN: 2/4/17, p. 15).

Her team’s finding contrasts with a recent claim that such distant galaxies are oddly lacking in dark matter. That idea comes from a 2017 study by astronomer Reinhard Genzel of the Max Planck Institute for Extraterrestrial Physics in Garching, Germany, and his colleagues, who found more than 100 distant galaxies keep their slower stars at the edges and faster stars closer in — little to no dark matter required (SN: 4/15/17, p. 10).
“In the astrophysical community, the [Genzel] result has been viewed with both excitement and skepticism,” says cosmologist Richard Ellis of University College London, who was not involved in either work. “It makes a lot of sense for others to examine galaxies at these [distances] in different ways.”

Motta and her colleagues were able to probe dark matter in the most distant galaxy yet, thanks to a massive galactic train wreck called the Bullet Cluster that acted as a huge cosmic telescope. The Cosmic Seagull lies behind the Bullet Cluster from Earth’s perspective, and the cluster’s mass distorts the Seagull’s light in a phenomenon called gravitational lensing.

That distortion earned the disk-shaped galaxy its name — the first images reminded Motta’s team of the seagull logo of a popular music festival in Viña del Mar, Chile. But it also made the galaxy appear magnified by a factor of 50 — a new record.

“Motta et al have exquisite data,” but their observations are limited, Ellis wrote in an e-mail. The team looked at only one galaxy, and that galaxy is much smaller and less massive than those that seem short on dark matter. Furthermore, the observations don’t cover the entire galactic disk, so the stars may be slower farther out than the team can see.

Motta agrees that a distant slowdown is possible, although her observations cover the same portion of the galaxy’s disk as the study of galaxies that seem light on dark matter.

“We are roughly at the place in which we should see the turning point” from fast to slow stars, if it exists, she says. “But we need to extend the study to get that.” Her team has been granted more time with ALMA next year to keep looking.

Cheese found in an Egyptian tomb is at least 3,200 years old

What may be the oldest known solid cheese has been found in an ancient Egyptian tomb.

Made from a mixture of cow milk and either sheep or goat milk, the cheese filled a broken clay jar unearthed from a 13th century B.C. tomb for Ptahmes, the mayor of the ancient city of Memphis, researchers report online July 25 in Analytical Chemistry.

Chemist Enrico Greco, who did the work while at the University of Catania in Italy, and colleagues used mass spectrometry to analyze the antique cheese — now a white, soapy lump weighing “several hundred grams.” Besides milk and whey proteins, the cheese contained remnants of bacteria that cause an infection called brucellosis, adding to evidence that ancient Egyptians may have grappled with the disease, Greco says.
Cheese making predates the new find by thousands of years, but preserved cheese is hard to come by (SN: 1/26/13, p. 16). Archaeologists found older curds draped around the necks of Bronze Age mummies in China, a different group of researchers reported in 2014 in the Journal of Archaeological Science. “There are other samples of dairy products in the literature, but not solid cheeses in the strict sense,” Greco says.

He says he did not sniff the cheese, but given its degraded state it is unlikely to have an odor, pleasant or not.

How salamanders can regrow nearly complete tails but lizards can’t

Salamanders and lizards can both regrow their tails, but not to equal perfection.

While a regenerated salamander tail closely mimics the original, bone and all, a lizard’s replacement is filled with cartilage and lacks nerve cells. That contrast is due to differences between stem cells in the animals’ spinal cords, researchers report online August 13 in Proceedings of the National Academy of Sciences.

When a salamander loses its tail, neural stem cells in the creature’s spinal cord can develop into any type of nervous system cell, including nerve cells, or neurons. But through evolution, lizard neural stem cells “have lost this ability,” says study coauthor Thomas Lozito, a biologist at the University of Pittsburgh. Lizards, while they can regrow cartilage and skin, cannot regenerate neurons, the researchers found.
Lozito and colleagues studied neural stem cells from the axolotl salamander (Ambystoma mexicanum) and from two lizard species — the green anole (Anolis carolinensis) and the mourning gecko (Lepidodactylus lugubris). The team also wondered if the lizard stem cells themselves weren’t capable of developing into neurons or if there was something about the environment of the lizard tail that prevented their regrowth. So the researchers implanted salamander neural stem cells into five gecko tail stumps. Some of the cells became neurons in the regrown tails, showing that the lizard stem cells were the problem.

The finding suggests that scientists would have to alter only the lizard stem cells instead of other parts of the tail to regrow a more complete appendage.

How lizards lost their ability to regenerate neurons and salamanders didn’t remains a mystery (SN: 11/28/15, p. 12). Scientists know that species’ places on the evolutionary tree have something to do with organisms’ ability to regrow body parts. “The more complex the species are, the less they can regenerate,” says developmental biologist Katharina Lust of the Research Institute of Molecular Pathology in Vienna, who was not involved in the study. Reptiles such as lizards are more complex organisms than amphibians like salamanders.
The researchers plan to use CRISPR/Cas9 gene editing to see if lizard neural stem cells can be modified to regenerate a perfect tail. Ultimately, the team hopes to one day coax stem cells in mammals to regenerate body parts.

“My goal is to make the first mouse that can regenerate its tail,” Lozito says. “We’re kind of using lizards as a stepping-stone.”

An elusive Higgs boson decay has finally been spotted

The Higgs boson has been spotted bottoming out — but that’s a good thing.

Physicists have detected the elementary particle decaying into two bottom quarks, exotic, short-lived particles that often appear in the aftermath of high-energy particle collisions. The elusive process was finally observed six years after the Higgs boson’s initial discovery, by physicists working at the Large Hadron Collider at CERN in Geneva. Researchers from two LHC experiments, ATLAS and CMS, reported their results simultaneously in a seminar held at CERN on August 28.
Scientists don’t detect the Higgs boson directly. Instead, they spot the debris produced when the Higgs disintegrates into less massive particles. The Higgs boson is expected to decay to two bottom quarks more than half of the time. But scientists hadn’t been able to tease out the process until now, because other mechanisms can produce bottom quarks and mimic the Higgs decay (SN: 9/3/16, p. 13). Scientists previously saw the Higgs break down into other types of particles, including particles of light called photons, a process which has fewer issues with Higgs impersonators.

With the Higgs boson’s unveiling in 2012, physicists filled in the last missing piece of the standard model, the theory of the fundamental constituents of matter (SN: 7/28/12, p. 5). But physicists still want to know more about the Higgs’ inner workings.

The standard model makes predictions of how often the Higgs should decay into different types of particles. Bottom quarks are one of six types of quarks in the standard model, each of which has different properties, such as mass and electric charge. While the lightest quarks make up commonplace particles like protons and neutrons, bottom quarks are relatively heavy and rare.

Physicists want to measure the various ways the Higgs boson decays to see if the rates match expectations. If not, that could mean something is wrong with the theory. But the new results upheld the standard model.

The United States and Brazil top the list of nations with the most gun deaths

Gun deaths occur worldwide, but a new survey reveals the hot spots for those that occur outside of war zones.

In 2016, firearm-related homicides, suicides and accidental deaths were highly concentrated. For example, just six countries — the United States, Brazil, Mexico, Colombia, Venezuela and Guatemala — accounted for about half of the estimated number of gun deaths unrelated to armed conflict, even though the nations together contributed less than 10 percent of the world’s population.
That’s just one takeaway from the first look at the global impact of interpersonal and self-inflicted gun violence on public health, published online August 28 in JAMA. Here’s the big picture:

Total global gun deaths rose from 1990 to 2016
Worldwide, an estimated 251,000 people died from guns due to homicide, suicide or unintentional injury in 2016. That’s up from an estimated 209,000 such firearm deaths in 1990, the team found by analyzing data from 195 countries and territories from 1990 to 2016.

In 2016, 64 percent of gun-related deaths were homicides, 27 percent were suicides and 9 percent were accidental deaths.
But the rate of gun deaths dipped a bit
The researchers looked at the global rate of firearm deaths, adjusted for differences in the distribution of ages in a population. The rate decreased slightly, from 4.2 deaths per 100,000 in 1990 to 3.4 deaths per 100,000 in 2016, because the global population grew.

Even so, “we can see the number of deaths due to gun violence — homicide, suicide, unintentional injury — is very high,” says study coauthor and global health researcher Mohsen Naghavi of the University of Washington in Seattle. “Gun violence is a public health problem.”
More gun deaths occur outside of war zones than inside
Globally, for every year studied save one, gun deaths due to homicide, suicide and unintentional injury exceeded those due to conflict and terrorism. The exception: 1994, the year of the Rwandan genocide. That year, the death toll from global conflict reached 551,000, compared with 232,000 deaths from gun homicides, suicides and unintentional injuries.

The United States and Brazil are hot spots of gun violence
These two countries accounted for 32 percent of the total number of estimated deaths in 2016. In Brazil and the other top four Latin America countries, most gun deaths were homicides. The high rate of gun homicide in these countries is associated with drug and weapon trafficking, research has found. One-fourth of all global gun-related homicides in 2016 took place in Brazil.
But in the United States, as in some other wealthy countries, such as France and Germany, suicide accounted for the majority of gun deaths in 2016. Thirty-five percent of all global firearm suicides that year occurred in the United States, the researchers estimate.

Suicide rates have risen across the United States since 1999 (SN: 7/7/18, p. 13). Previous research has shown that having guns in the house is linked to higher use of the weapons to commit suicide and to a larger number of unintentional gun-related deaths.

Rubidium atoms mimic the Eiffel Tower, a Möbius strip and other 3-D shapes

A new experiment gives rubidium atoms a certain je ne sais quoi.

Scientists arranged individual atoms of the element rubidium into a variety of 3-D shapes, including the Eiffel Tower. The team used a laser to trap atoms in the arrangements, performing a hologram-style technique to encode the complex positions. And moveable, laser-based “tweezers” (SN: 5/12/18, p. 24) shifted atoms that were in the wrong position, researchers from the Institut d’Optique Graduate School in Palaiseau, France, report in the Sept. 6 Nature.

In addition to the Parisian landmark, the researchers sculpted a cone, a doughnut and a Möbius strip — a twisted ring with the unusual property of having only one side (SN Online: 7/24/07). The technique may be helpful for creating atomic quantum computers, which could make calculations by manipulating the interactions between individual atoms (SN: 7/8/17, p. 28).

Jupiter’s magnetic field is surprisingly weird

If Earth’s magnetic field resembles that of a bar magnet, Jupiter’s field looks like someone took a bar magnet, bent it in half and splayed it at both ends.

The field emerges in a broad swath across Jupiter’s northern hemisphere and re-enters the planet both around the south pole and in a concentrated spot just south of the equator, researchers report in the Sept. 6 Nature.

“We were baffled” at the finding, says study coauthor Kimberly Moore, a graduate student at Harvard University.
The new look at Jupiter’s magnetic field comes courtesy of NASA’s Juno spacecraft, which has been orbiting the planet since July 2016 (SN: 6/25/16, p. 16). Relying on nearly 2,000 measurements of the field outside the planet, Moore and colleagues created maps detailing how the field emerges by calculating how it extends to roughly 10,000 kilometers below the cloud tops.
The results “complicate our picture of Jupiter’s interior,” Moore says. Planetary magnetism arises from electrically conductive fluids within a planet. Typical simulations for how these fluids generate magnetism can explain a field that resembles that of a bar magnet, such as Earth’s or Saturn’s, as well as those that are messy all over, like the ones at Uranus and Neptune. Jupiter’s split personality is harder to explain.

One possibility is that the extreme temperature and pressure near Jupiter’s core create a soup of rock and ice partly dissolved in liquid metallic hydrogen. Here, the interplay of turbulent layers might generate a convoluted magnetic field. Or perhaps squalls of helium rain closer to the clouds stir up conductive layers below, contorting the field before it emerges from the clouds.

These transparent fish turn rainbow with white light. Now, we know why

The ghost catfish transforms from glassy to glam when white light passes through its mostly transparent body. Now, scientists know why.

The fish’s iridescence comes from light bending as it travels through microscopic striped structures in the animal’s muscles, researchers report March 13 in the Proceedings of the National Academy of Sciences.

Many fishes with iridescent flair have tiny crystals in their skin or scales that reflect light (SN: 4/6/21). But the ghost catfish (Kryptopterus vitreolus) and other transparent aquatic species, like eel larvae and icefishes, lack such structures to explain their luster.

The ghost catfish’s see-through body caught the eye of physicist Qibin Zhao when he was in an aquarium store. The roughly 5-centimeter-long freshwater fish is a popular ornamental species. “I was standing in front of the tank and staring at the fish,” says Zhao, of Shanghai Jiao Tong University. “And then I saw the iridescence.”

To investigate the fish’s colorful properties, Zhao and colleagues first examined the fish under different lighting conditions. The researchers determined its iridescence arose from light passing through the fish rather than reflecting off it. By using a white light laser to illuminate the animal’s muscles and skin separately, the team found that the muscles generated the multicolored sheen.
The researchers then characterized the muscles’ properties by analyzing how X-rays scatter when traveling through the tissue and by looking at it with an electron microscope. The team identified sarcomeres — regularly spaced, banded structures, each roughly 2 micrometers long, that run along the length of muscle fibers — as the source of the iridescence.

The sarcomeres’ repeating bands, comprised of proteins that overlap by varying amounts, bend white light in a way that separates and enhances its different wavelengths. The collective diffraction of light produces an array of colors. When the fish contracts and relaxes its muscles to swim, the sarcomeres slightly change in length, causing a shifting rainbow effect.
The purpose of the ghost catfish’s iridescence is a little unclear, says Heok Hee Ng, an independent ichthyologist in Singapore who was not involved in the new study. Ghost catfish live in murky water and seldom rely on sight, he says. But the iridescence might help them visually coordinate movements when traveling in schools, or it could help them blend in with shimmering water to hide from land predators, like some birds, he adds.

Regardless of function, Ng is excited to see scientists exploring the ghost catfish’s unusual characteristics.

“Fishes actually have quite a number of these interesting structures that serve them in many ways,” he says. “And a lot of these structures are very poorly studied.”