Scientists Remove Disease-Causing Mutations from Human Embryos

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iStock

Researchers have successfully edited the genes of viable human embryos to repair mutations that cause a dangerous heart condition. The team published their controversial research in the journal Nature.

The versatile gene-editing technique known as CRISPR-Cas9 is no stranger to headlines. Scientists have already used it to breed tiny pigs, detect disease, and even embed GIFs in bacteria. As our understanding of the process grows more advanced and sophisticated, many researchers have wondered how it could be applied to human beings.

For the new study, an international team of researchers fertilized healthy human eggs with sperm from men with a disease called hypertrophic cardiomyopathy, a condition that can lead to sudden death in young people. The mutation responsible for the disease affects a gene called MYBPC3. It’s a dominant mutation, which means that an embryo only needs one bad copy of the gene to develop the disease.

Or, considered another way, this means that scientists could theoretically remove the disease by fixing that one bad copy.

Eighteen hours after fertilizing the eggs, the researchers went back in and used CRISPR-Cas9 to snip out mutated MYBPC3 genes in some of the embryos and replace them with healthy copies. Three days later, they checked back in to see how their subjects—which were, at this point, still microscopic balls of cells—had fared.

The treatment seemed successful. Compared to subjects in the control group, a significant number of edited embryos appeared mutation- and disease-free. The researchers also found no evidence that their intervention had led to any unwanted new mutations, although it is possible that the mutations were there and overlooked.

Our ability to edit human genes is improving by the day. But, many ethicists argue, just because we can do it doesn’t mean that we should. The United States currently prohibits germline editing of human embryos by government-funded researchers. But there’s no law against such experimentation in privately funded projects like this one.

The same day the new study was published, an international committee of genetics experts issued a consensus statement advising against editing any embryo intended for implantation (pregnancy and birth).

"While germline genome editing could theoretically be used to prevent a child being born with a genetic disease, its potential use also raises a multitude of scientific, ethical, and policy questions,” Derek T. Scholes of the American Society of Human Genetics said in a statement. “These questions cannot all be answered by scientists alone, but also need to be debated by society."

Ethicists and sociologists are concerned by the slippery slope of trying to build a better human. Many people with chronic illness and disability live happy, complete lives and report that they’re limited more by discrimination than by any medical issues.

Disability studies expert Lennard Davis of the University of Illinois says we can’t separate scientific decisions from our society’s history of violence against, and oppression of, disabled and sick people.

“A lot of this terrific science and technology has to take into account that the assumption of what life is like for people who are different is based on prejudice against disability,” he told Nature in 2016.

Rosemary Garland-Thomson is co-director of the Disability Studies Initiative at Emory University. Speaking to Nature, she said we are at a cultural and ethical precipice: “At our peril, we are right now trying to decide what ways of being in the world ought to be eliminated.”

8 Surprising Facts About Your Nose

iStock/AntonioGuillem
iStock/AntonioGuillem

Your nose is more than just a bump on your face—it’s an important part of the respiratory system and affects many other senses, including your taste and hearing. For being something that’s so central to our daily interactions with the world, there’s still a surprising amount to discover about the nose. Here's a bit of what we do know.

1. Your nose can detect billions of different odors.

Although the human nose is weak compared to canine sniffers, our noses can detect 1 trillion smells. Strangely, scientists still aren’t sure exactly how we smell. For decades, researchers thought the olfactory system worked through receptor binding, meaning molecules of different shapes and sizes bonded to specific parts of the nose like puzzle pieces, triggering smell recognition in the brain. But recently, biophysicist Luca Turin has proposed the nose detects smell through quantum vibrations. Turin suggests the frequency at which different molecules vibrate helps the nose identify them as different scents. The theory could explain why molecules of the same shape smell quite differently. Intriguing as it is, this new theory hasn’t been tested enough to be universally accepted.

2. Our big brains might have caused our noses to protrude.

As anyone who’s been to a zoo probably knows, great apes (the closest human ancestors) have flat nasal openings—and researchers found that type of nose is far more effective at inhaling air than the human version. So what’s up with ours? Scientists think the shape might be a by-product of our big brain. The growing cerebellum forced human faces to become smaller, which probably affected the nose as well.

3. Women's noses are more sensitive than men's.

In the battle of the sexes, women’s noses come out on top. When tested for odor detection and identification, women score consistently higher than men. This might have something to do with the size of their olfactory bulb, a structure in the brain that helps humans identify smells. One study found that women have, on average, 43 percent more cells in their olfactory bulb than men do—meaning they can smell more smells.

4. Holding your nose really does help you swallow something distasteful.

Think you like chocolate just because it tastes good? Think again. Smell is responsible for 75 to 95 percent of flavor, which explains why plugging your nose helps you swallow something unappetizing. More recently, chefs and neurologists have teamed up to create meals for cancer patients and others with a diminished sense of smell, such as the elderly. Cooking meals tailored to the smell-less could help stave off depression and improve the appetite without relying on sugar and salt.

5. Surgeons can regrow damaged noses.

When people have cancer or are in an accident, the nose can become infected or even be completely destroyed. But fear not. Plastic surgeons have a way to regrow your nose—on your forehead. Using cartilage from the ribs and tissue expanders that allow the skin to stretch and grow, a new nose can be formed to replace the old one. And while a nose growing out of your forehead looks odd, it's actually one of the best places for a new nose to grow. The forehead's blood vessels can be harnessed to help grow the tissue, and removing the new nose only leaves a small scar [PDF]. Doctors have performed the procedure in the U.S., China, and India.

6. Your nose can sense more than smells.

The nose doesn’t just translate odors in the nasal passage—the tip is also full of nerves that detect pain and temperature. This helps us “smell” non-odor smells. Even people who can no longer smell things with their olfactory system can detect substances like menthol, the minty compound that makes your skin tingle. (Unfortunately, they can’t detect pure scents like vanilla.)

7. About 20,000 liters of air pass through the nose every day.

The average adult breathes around 20,000 liters of air every day, which keeps the nose quite busy. As the first line of defense for the lungs, the nose filters out small particles like pollen and dust. It also adds moisture to the air and warms it so the lungs are saved from any irritation.

8. Anosmia is just one of several smell disorders affecting the nose.

There are plenty of things that can go wrong in your nose. Allergic rhinitis, sinus infections, and broken noses are just a few. But perhaps less well known are disorders that affect the nose’s ability to smell. Anosmia is the complete inability to detect odors and can be caused by illness, aging, radiation, chemical exposure, or even genetics. Equally bizarre are parosmia and phantosmia: The former changes your perception of smells, and the latter creates the perception of smells that don’t exist. Luckily, only 1 or 2 percent of North Americans suffer from any smell disorders.

The Overlooked Paleontologist Who May Have Inspired 'She Sells Sea Shells'

Wikimedia Commons // Public Domain
Wikimedia Commons // Public Domain

In the summer of 1844, King Frederick Augustus II of Saxony and his royal entourage were walking down Broad Street in the coastal town of Lyme Regis when they were drawn to the window of a cottage. Treasures lay on the other side of the glass: Coiled ammonite shells—long since turned to stone—were arranged in an appealing display, and in the center sat the petrified skull of a long-snouted sea reptile with pointed teeth and impossibly huge eyes.

A sign above the door read Anning's Fossil Depot. The King and his party stepped inside.

There were Jurassic-era fossils throughout the small, unassuming shop, and yet, the single most fascinating thing in the store may well have been its proprietor, Mary Anning. She'd spent a lifetime simultaneously providing for her family and unlocking the secrets of Lyme Regis's ancient past. Born into poverty in a society famed for its class consciousness, the 45-year-old businesswoman had defied the odds to become one of the world's most important scientific figures.

Though Anning didn't receive her due credit from the male naturalists who reaped the benefits of her labors, word of the fossil-hunter's many achievements still managed to spread far and wide during her lifetime. So it was with complete honesty that this daughter of a poor carpenter casually told the King's physician, "I am well known throughout the whole of Europe." And years after her death, her legacy would live on in the English language's most famous tongue twister: She sells seashells by the seashore.

A Dirty, Dangerous Job

The seashore where Anning's shop was located was on the English Channel in southwestern England, in a town called Lyme Regis. With its towering cliffs and tannish-white beaches, Lyme Regis has long been a prime vacation destination. In the late 18th and early 19th centuries, affluent Britons made it their seasonal home away from home. Meanwhile, the poorer citizens who lived in Lyme Regis year-round struggled to make ends meet.

Many supplemented their income by cashing in on the area's natural history. Around 200 million years ago, the Lyme Regis area lay at the bottom of a Jurassic sea. In Anning's time—and today—fossilized remains of marine animals from this period can be found protruding from the cliffs and scattered along the beaches that surround the coastal town. Realizing that rich tourists would pay a pretty penny to take home one of these natural curiosities, fossil hunters started selling their finds throughout Lyme Regis.

One of them was Mary's father, Richard Anning, a carpenter by trade. But even with two revenue streams, he struggled to provide for his family, and their life was marked by tragedy. Richard's wife, Molly, gave birth to their first child, Mary, in 1794, and a son, Joseph, in 1796. Mary died when she was just 4 after her dress caught on fire; Molly was pregnant with her third child at the time, and when she gave birth six months later, on May 21, 1799, she named the newborn girl Mary. A year later, the second Mary almost died as well when she, her nurse, and two female companions were struck by lightning while walking on the beach. All three women died, but Mary survived.

Of the Annings' 10 children, only Mary and Joseph reached adulthood. As they grew up, Richard taught them everything he knew about the fossil-collecting business, and he even made Mary a rock hammer so she could excavate small fossils for herself.

Fossil hunting was a perilous job, and over the years, the Annings had many close calls with rockslides and rapidly flooding shorelines. That's how Richard himself died in 1810. Out on an excursion that winter, he lost his footing and fell off a cliff. Months later, injuries sustained from the accident—coupled with a serious case of tuberculosis—claimed his life. He was 44 years old.

Following his death, Molly took charge of the family fossil shop, which basically consisted of a display table that the Annings would set up in front of their modest cottage near the River Lym. Keeping this business afloat was an economic necessity for Molly and her children—Richard had saddled them with a large debt.

"These Valuable Relics of a Former World"

Drawing of Ichthyosaurus from The American Museum Journal, circa 1900.
Drawing of Ichthyosaurus from The American Museum Journal, circa 1900.
American Museum of Natural History, Wikimedia Commons // No Restrictions

The family struggled for a year until, in 1811, Joseph—who was working as a part-time upholsterer's apprentice—discovered the 4-foot-long skull of an ancient marine reptile. Joseph and a hired team excavated the head, but Mary thought more bones might still be found. The following year, she returned to the site and proceeded to expose an entire spinal column, a set of ribs, and other bones.

Thrilled by her discovery, Mary recruited an excavation team of her own. As the creature's remains were slowly removed from the rock, the group realized that they had a genuine sea monster on their hands: When it was reunited with its skull, the specimen measured an amazing 17 feet long.

The remains belonged to a dolphin-like animal that would later be called Ichthyosaurus, which means "fish-lizard." Although the Annings did not discover the first known specimen of this genus (as some sources wrongly report), theirs was the most complete skeleton known at the time and therefore became the first to attract interest from Great Britain's scientists. The fossil was sold to Henry Hoste Henley, the Lord of Colway Manor, for £23. That's the equivalent of more than £1600 or $2000 in today's money—enough to purchase six months of food for the Anning family.

The Annings' ichthyosaur subsequently made its way to the British Museum, where, according to Hugh Torrens, a history of science professor at Keele University, "it aroused great interest as a denizen of the new world that the embryonic science of paleontology was beginning to reveal" [PDF]. When news of the sea dragon spread, the Annings—particularly Mary—became household names in Lyme Regis and beyond.

But fame has never guaranteed fortune. Even after the sale of Mary and Joseph's ichthyosaur, the family remained in dire economic straits for nearly a decade. Thankfully, an 1820 charity auction thrown in their honor by the wealthy fossil-collector Thomas Birch helped give the Annings some much-needed financial stability.

In 1824, Mary Anning met Lady Harriet Silvester, a rich London widow who was blown away by the self-taught beachcomber's paleontological expertise. "The extraordinary thing in this young woman," Silvester wrote in her diary, "is that she has made herself so thoroughly acquainted with the science that the moment she finds any bones she knows to what tribe they belong. She fixes the bones on a frame with cement and then makes drawings and has them engraved … It is certainly a wonderful instance of divine favour—that this poor, ignorant girl should be so blessed, for by reading and application she has arrived to that degree of knowledge as to be in the habit of writing and talking with professors and other clever men on the subject, and they all acknowledge that she understands more of the science than anyone else in this kingdom."

As the 1820s unfolded, Mary took over the reins of the shop from her mother—and running the shop was just one of her obligations. She was also primarily responsible for acquiring its new fossils. Molly had never been one for collecting, and Joseph's upholstery career was taking off. Combing the beaches, Mary came across many astonishing new specimens—including a few more Ichthyosaurus skeletons. As the Bristol Mirror reported in 1823, "This persevering female has for years gone daily in search of fossil remains of importance at every tide, for many miles under the hanging cliffs at Lyme, whose fallen masses are her immediate object, as they alone contain these valuable relics of a former world." The publication also noted that it was "to her exertions we owe nearly all of the fine specimens of Ichthyosauri of the great collections."

Pride, Prejudice, and a Plesiosaurus

An 1823 letter by Mary Anning describing her discovery of what would be identified as a Plesiosaurus.

An 1823 letter by Mary Anning describing her discovery of what would be identified as a Plesiosaurus.

Wikimedia Commons // Public Domain

On December 10, 1823, Mary made the discovery of a lifetime. While scouring the beach in the shadow of Black Ven cliff, she came upon a fossilized skull that was like nothing she'd seen before. The majority of the skulls she had found belonged to ichthyosaurs; they were long and narrow, a bit like the heads of dolphins or crocodiles. This skull, on the other hand, was small, beady-eyed, and had a mouthful of strange, needle-shaped teeth.

Working with some nearby villagers, Anning unearthed the rest of the mystery creature's body, which looked even stranger than the skull did. Attached to a stout torso and broad pelvis were four flippers and a diminutive tail. But the most peculiar thing about the animal was the long neck that accounted for nearly half of the 9-foot creature's length.

Anning contacted one of the only men in Europe who might fully appreciate her find: the paleontologist Reverend William Buckland. In conversations about the newborn science of paleontology, she could hold her own with anyone, experts like Buckland included. The 24-year-old devoured every scrap of fossil-related news published in the scientific journals of her time; this autodidact even taught herself French so that she could read articles published in that language. This is how Anning knew that some paleontologists—including Buckland and Reverend William Conybeare—believed that a few fossil bones previously attributed to Ichthyosaurus really belonged to an as-yet-unidentified kind of marine reptile. Conybeare had even come up with a name for this new beast: Plesiosaurus.

In her letter to Buckland, Anning provided a detailed sketch of her newest discovery. "I may venture to assure you that it is the only [Plesiosaurus skeleton] discovered in Europe," she told the scientist. This wasn't an empty boast: Anning had indeed found the first articulated Plesiosaurus remains known to science. Prior to that, nobody had any idea about what this mysterious animal looked like. Once he finished reading Anning's description, Buckland talked Richard Grenville, the first Duke of Buckingham, into buying the skeleton.

The animal's proportions were so bizarre that some scientists cried foul. Upon seeing a copy of Anning's sketch, the legendary French anatomist Baron Georges Cuvier was worried that the fossil was a hoax. In a letter to Conybeare, Cuvier suspiciously noted that "This discovery … surpasses all those that have been made so far [in Lyme Regis] and there is nothing more monstrous that one could expect to see" [PDF]. How could an animal with such an absurdly long neck possibly exist? The Baron felt that it didn't. Intensely skeptical of the find, Cuvier accused Anning of affixing a fossil snake's head and vertebrae to the body of an Ichthyosaurus. However, when it later became clear that her specimen had in no way been tampered with, the anatomist was forced to eat his words.

Famous, but Underappreciated

At an 1824 Geological Society of London meeting, Conybeare stole the show with a well-received presentation on the nearly complete Plesiosaurus from Lyme Regis. That same year, he published a paper on the specimen featuring detailed original illustrations. Neither his presentation nor his paper mentioned Anning by name.

Conybeare was just one of many scientists who furthered their own careers by writing papers about fossils that Anning had found. They rarely gave her credit, and to make matters worse, she couldn't publish her own findings in reputable journals because their editors didn't accept submissions from women. (One man who did give her credit when it was due was—perhaps surprisingly—Cuvier. "I see, however, that a skeleton discovered by Mademoiselle Marie Anning on the coast of the county of Dorset, although only five feet long, has not been allowed to be related to this species," he wrote in 1824.)

Nonetheless, institutionalized sexism didn't prevent Mary from continuing to make major discoveries. In 1824, she unearthed the first pterosaur skeleton that had ever been found outside of Germany. Anning was also probably the first person to identify fossilized poop, or a coprolite. (Sadly, Buckland—a frequent correspondent of hers—would subsequently take credit for this scatological breakthrough.) By 1826, she had earned enough money from fossil sales to relocate her family to a cottage on upper Broad Street. The main room on the ground level became the Annings' new store, complete with an attractive storefront window. It quickly emerged as a major tourist attraction, particularly for geology buffs. It hosted such celebrity visitors as Gideon Mantell, who, in 1825, had announced the discovery of Iguanodon, the first herbivorous dinosaur known to science.

But she was deprived of the formal recognition she longed for and deserved. Allegedly, when a young admirer penned a letter to Anning, she replied, "I beg your pardon for distrusting your friendship. The world has used me so unkindly, I fear it has made me suspicious of everyone" [PDF]. Anning would often confide in her good friend Maria Pinney, who once observed, "She says the world has used her ill and she does not care for it, according to her account these men of learning have sucked her brains, and made a great deal by publishing works of which she furnished the contents, while she derived none of the advantages."

Through it all, Anning never stopped fossil-hunting, even though it remained a perilous business. Once, in 1833, Anning was nearly killed by a sudden landslide that crushed her beloved black-and-white terrier, Tray, who liked to accompany her on the beaches."“[The] death of my old faithful dog has quite upset me," Anning told a friend. "The cliff that fell upon him and killed him in a moment before my eyes, and close to my feet … it was but a moment between me and the same fate."

By the mid-1830s, Anning's fortunes had begun to falter because of a bad investment. In 1835, Buckland, moved by her plight, talked the British Association for the Advancement of Science into granting Anning a £25 yearly annuity in honor of her outstanding contributions to paleontology. This kind gesture essentially amounted to the first significant acknowledgement by professional scientists of her achievements. Her bottom line in these lean years was bolstered by the occasional big purchase made by such fossil shop patrons.

The scientific community once again came to Anning's aid when she was diagnosed with breast cancer in 1846. As soon as the Geologic Society learned of her diagnosis, its members began raising money to cover her medical expenses. Anning died on March 9, 1847. Her funeral was paid for by the Geological Society, which also financed a stained-glass window dedicated to her memory that now sits at St. Michael's Parish Church in Lyme Regis.

Her amazing deeds were commemorated by Charles Dickens nearly two decades later. Though he probably never met Anning in person, the author of A Christmas Carol wrote a moving essay about her 18 years after she died. "Mary Anning, the Fossil Finder" ran in the February 1865 edition of his literary periodical All The Year Round. "Her history shows what humble people may do, if they have just purpose and courage enough, toward promoting the cause of science," Dickens wrote. "The carpenter's daughter has won a name for herself, and deserved to win it."

She Sells Seashells by the Seashore

You might not be familiar with Anning's name, but you've certainly heard of her, even if you didn't realize it. In 1908, songwriter Terry Sullivan—who penned a number of catchy ballads for British music halls—wrote a song widely believed to be about Anning's life whose lyrics have since been recited by just about every English-speaking person on Earth:

"She sells seashells on the seashore,
The shells she sells are seashells, I'm sure,
For if she sells seashells on the seashore,
Then I'm sure she sells sea shore shells."

And today, Anning—long overlooked by her contemporaries—is finally getting her due. The self-taught paleontologist is now a revered figure in paleontology circles. "More than anyone else at the time," Hugh Torrens said, "she showed what extraordinary things could turn up in the fossil record." The late evolutionary theorist Stephen Jay Gould shared this esteem for her. In his 1992 book Finders Keepers, Gould wrote that "Mary Anning [is] probably the most important unsung (or inadequately sung) collecting force in the history of paleontology."

This story was republished in 2019.

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