Larry David and the Game Theory of Anonymous Donations

By Brian Gallagher | June 20, 2018 3:51 pm
(Credit: s_bukley/Shutterstock)

(Credit: s_bukley/Shutterstock)

In a Curb Your Enthusiasm episode from 2007, Larry David and his wife Cheryl and their friends attend a ceremony to celebrate his public donation to the National Resources Defense Council, a non-profit environmental advocacy group. Little does he know that the actor Ted Danson, his arch-frenemy, also donated money, but anonymously. “Now it looks like I just did mine for the credit as opposed to Mr. Wonderful Anonymous,” David tells Cheryl. David feels upstaged, as if his public donation has been transformed from a generous gesture to an egotistical one. Cheryl says, about Danson, “Isn’t that great? He donated the whole wing. Didn’t want anybody to know.” “I didn’t need the world to know either!” David says. “Nobody told me I could be ‘anonymous’ and tell people!” He would have done it Danson’s way, he says, but, realizing the contradiction, he fumes, “You can’t have it halfway! You’re either anonymous, or you’re not.” What Danson did, David concludes, is “fake philanthropy and faux anonymity!” Read More

CATEGORIZED UNDER: Mind & Brain
MORE ABOUT: psychology

Organs Grown to Order

By Jeremy Rehm | June 19, 2018 3:04 pm
 Chimera: A genetically modified mouse embryo successfully grew a beating heart from rat stem cells. (Credit: Salk Institute)


Chimera: A genetically modified mouse embryo successfully grew a beating heart from rat stem cells. (Credit: Salk Institute)

More than 100,000 people in the United States need an organ transplant, but demand always outpaces supply. An average of 20 people in the nation died every day in 2016 because organs were unavailable, and that was despite record annual donations of more than 33,000.

Physicians have proposed many solutions to encourage organ donations, including payment. But scientists are looking elsewhere to ensure a better supply. Thanks to advances in genetic engineering, a new twist on using animals for transplants offers promise. Since the 1960s, a handful of patients have received an animal organ — xenotransplants of everything from a baboon liver to a whole chimpanzee heart. But many patients died because their immune system rejected the transplant.

Attempting to outwit evolution, Hiromitsu Nakauchi, a physician and geneticist at Stanford University, proposed a solution to this immunity problem: Instead of transplanting an animal’s organ, scientists could grow a customized human organ in an animal. By adding a patient’s own stem cells to an engineered animal embryo, Nakauchi and others hoped to grow a new, healthy organ ready for transplant.

Nakauchi was the first to demonstrate that the idea of growing one species’ organ in another species’ body was even possible, first between mice and rats in 2010. Another research group grew human cells in a pig in 2017, offering further proof of principle. Nakauchi recently reviewed his process in the Annual Review of Cell and Developmental Biology. We talked with him about this promising frontier as well as its many scientific, health and ethical challenges.

This conversation has been edited for length and clarity.

In your article, you talk about “mammalian chimeras.” What are those, and how do they relate to your research?

A chimera is an organism with cells from two genetically different individuals. The easiest chimera to understand is somebody with a heart transplant or bone marrow transplant: That patient has somebody else’s cells in their body. So they’re a chimera. My ultimate goal is to make human organs, and for that, we’re first trying to make animal chimeras.

Tell me a bit about that. How exactly does your idea work?

We’re basically mixing human stem cells with an animal embryo and some genetic engineering in between. The idea is that if we know how to control what genes code for, we should be able to generate organs from someone’s genetic blueprints.

About 25 years ago, I started working with hematopoietic stem cells, which are cells that can make all your blood cell types. At the time, they were the only stem cells we knew much about because they were used in bone marrow transplants. I still use them today. I thought if we studied and understood the mechanism of how those cells work, it may be possible to generate organs from a single cell using a patient’s own genetic blueprint.

In bone marrow transplants, the recipient must first have irradiation to remove his or her own hematopoietic stem cells. It’s called myeloablation, and without it, you really cannot ingraft stem cells. It’s like a hotel room: Unless the previous guests leave, and the room is empty, you can’t take any more guests.

So it cleans the slate to make room in the bone marrow for the new blood-forming cells?

Exactly. We still don’t know how it works, honestly, but without irradiation and emptying that so-called niche to create an open space, you really can’t ingraft donor stem cells. It’s quite amazing, and it’s a critical detail for my experiments.

If we just put stem cells into a normal animal embryo, our idea wouldn’t work because there’s no open niche in the embryo — it still has all the genes to make its own organ rather than the other individual’s. So the entire chimera would be a mix of cells from both individuals. But if we genetically modify the embryo so that it can’t make its own kidneys, for example, that will leave a space for the other individual’s genetic information to make the kidneys. That was the idea: Prepare a space for a certain organ in the animal embryo, combine the embryo with human stem cells to form a chimera, let it grow and you get an organ made of cells from the source you want — the patient.

Hiromitsu Nakauchi (Credit: Stanford University)

Hiromitsu Nakauchi (Credit: Stanford University)

In 2010, you implanted rat stem cells into a genetically engineered mouse embryo, and the mouse developed a rat’s pancreas. What did you learn from that experiment?

That was the initial experiment. The pancreas was functional, and those chimeric mice were happy, but the pancreas was mouse-sized; it was too small to transplant back to the rat. It showed organs can be generated in other species but couldn’t yet show they could be transplanted.

So we reversed the process in a later experiment. We injected mouse stem cells into rat embryos. This time we got a rat with a rat-sized mouse pancreas — a huge mouse pancreas. We couldn’t transplant the whole thing. But we could transplant islets, small clusters of cells that produce insulin in the pancreas. We do human-human islet transplants now to treat diabetes patients. We get those islets from people who’ve passed away, but again, the number of islets to transplant is very limited.

So that raises another question: Why can’t we just use organs from people who have died?

We don’t usually transplant from cadavers because the organ tends to be contaminated by bacteria immediately after death. You may know that if a patient is brain dead, heart transplant surgeons will take out the heart while it’s still beating. They don’t wait because the heart will start to deteriorate.

That’s a little shocking. So how do experiments with mice and rats lead to transplants for people?

Those early experiments provided evidence that a developing embryo can grow organs of other species. The organ was generated, useful and a perfect match. There’s no need for immunosuppression or fear of organ rejection because it’s the patient’s own organ. If this applies to humans and sheep or humans and pigs, we should be able to use a sheep embryo environment to grow human organs. Then cut it out and put it into the patient.

Isn’t that a long time to wait for an organ?

Pigs and sheep both grow very fast, so from our estimates, it would take about 10 months or less. It depends on the organ, though. For pancreas islets, it might require something like newborn piglets, whereas for something like a heart, you may have to wait longer.

What are the chances of a bacterial or viral infection?

Inside the animal body, it’s clean. Just like inside our abdomen, or in a uterus, or even in our bloodstream, it should be clean. Otherwise we’d get infected, right?

We do have specific pathogen-free pigs reared in a clean room that are regularly monitored for infections. So, that part is taken care of. Often brought up is the worry about pigs having an endogenous retrovirus, which some people say could activate and infect human cells. But that possibility has been almost denied. I’m not saying there’s no potential danger. There’s always a risk, and we’ll need a risk-benefit balance. But I consider a chance of getting some weird infection very small.

Editor’s note: Pig retroviruses called porcine endogenous retroviruses or PERVs are viruses that previously — maybe millions of years ago — infected pigs and left a bit of their viral DNA in all pigs. Studies have shown some of these viruses can reactivate in petri dish experiments using human cells, raising health concerns for xenotransplants. However, numerous studies looking at the threat of retroviruses infecting people have found no evidence of viral transmission.

What barriers or technical challenges still need to be solved?

A major barrier is doing these experiments in large animals — they’re not like mice and rats. They’re expensive, they can’t breed year-round, we can only use a limited number of them for experiments, and they’re evolutionarily distant from humans. But we now need to show we can generate organs in large animals. That’s the goal and the challenge, and we’ve still not succeeded. That’s my focus now. Once we’ve succeeded, then I’ll turn to the safety issues.

On a more technical side, gene editing technology has developed significantly over the past 10 years, which is great because otherwise using large animals would be impossible. We still need to optimize the culture conditions for human stem cells, though. When we use something like in vitro fertilization to make a sheep or pig embryo, we’d culture it for three or four days before embedding human stem cells. We still don’t know the best culture environment, however, and that’s causing reproducibility issues. We still need to develop that. Otherwise, this is pretty low-tech science.

Schematic shows how scientists might use animals to grow human organs.

If this sort of xenotransplant became practice, would we have animal farms meant specifically for transplants?

Probably not a farm, but we’d need a facility just like a farm. From the outside, it’s just a pig farm, but inside those pigs are human organs — your heart, your liver.

Aren’t there a lot of ethical issues with having farms meant just for harvesting organs? There’s something unsettling about that.

Yes, which is probably why the National Institutes of Health is not funding these studies, and Japanese companies follow government guidelines against making these chimeras. It’s an unpleasant feeling — an icky feeling. But we sacrifice maybe billions of pigs and sheep every year to eat, unless you’re vegetarian or vegan, which I’m sensitive to. If it’s OK to sacrifice animals for food, why not use a small part of those animals to save somebody’s life? I know many patients with a very low quality of life because of organ failures, diabetes, or complications from immunosuppressants after a transplant. Knowing these people as a medical doctor, I think this research is rational.

People have also talked about trying this in non-human primates. Is that really under consideration?

The idea is there, and I’m almost 100 percent certain we could make human organs in, say, a chimpanzee because we’re closely related. But it’s not easy because they’re not like mice and rats. They have very particular reproductive seasons and mate choices, it’s difficult to prepare a surrogate mother, and then it takes years for them to grow to a certain size.

And of course, there are the ethical questions. That’s an animal that looks somewhat human. That’s scary. I don’t like it. Unless it’s a kidney, which we could take one of, we’d have to sacrifice those chimps. But what are you going to do with a chimp with one kidney? We’d need to keep it, and that’s very expensive. So overall, it doesn’t really make sense. It’s not very practical.

How long until we might see this option for patients?

Five years ago, I thought we might be able to generate organs in pigs rather soon. But after doing some preliminary experiments, the genetic distance between these species and humans is too large. It’s not as simple as mice and rats, which diverged roughly 21 million years ago. But sheep and humans or pigs and humans separated about 94 million years ago. That makes it more challenging, and we don’t really know the factors hindering it; it could be a cell receptor, a ligand, cell adhesion molecules or something in the cell cycle. We don’t know.

How do people generally react to your work?

People initially have an icky feeling. But once I explain what we’re trying to do and the results we’re getting, they usually understand and become supportive, except for hardcore animal activists. I think people need to understand the benefits and potential risks of what we’re trying to do. Then people will understand better, and we’ll get more support, I hope.

Editor’s note: This story was updated March 25 to correct two points. The 2010 experiment by Hiromitsu Nakauchi involved induced pluripotent stem cells generated from rat skin cells, not pancreas cells, as the original story stated. Guidelines against developing chimeras in Japan were put in place by the government, not by companies.


This article originally appeared in Knowable Magazine, an independent journalistic endeavor from Annual Reviews. Sign up for the newsletter.

Knowable Magazine | Annual Reviews

CATEGORIZED UNDER: Health & Medicine

To Avoid Humans, More Wildlife Now Work the Night Shift

fox-london-night

An urban fox scavenges on the edge of a park. (Credit: Shutterstock)

For their first 100 million years on planet Earth, our mammal ancestors relied on the cover of darkness to escape their dinosaur predators and competitors. Only after the meteor-induced mass extinction of dinosaurs 66 million years ago could these nocturnal mammals explore the many wondrous opportunities available in the light of day.

Fast forward to the present, and the honeymoon in the sun may be over for mammals. They’re increasingly returning to the protection of night to avoid the Earth’s current terrifying super-predator: Homo sapiens. Read More

CATEGORIZED UNDER: Living World, Top Posts
MORE ABOUT: animals

How Can a Baby Have 3 Parents?

By Jennifer Barfield, Colorado State University | June 15, 2018 11:21 am
baby-3-parents

(Credit: Shutterstock)

It seems impossible, right? We have been taught from the time we were young that babies are made when a sperm and an egg come together, and the DNA from these two cells combine to make a unique individual with half the DNA from the mother and half from the father. So how can there be a third person involved in this process? Read More

When Does Hungry Become Hangry?

hangry-hungry-science

You’re ready to blow your top – but how much is due to your internal hunger and how much to external annoyances? (Credit: Shutterstock)

Have you ever been grumpy, only to realize that you’re hungry?

Many people feel more irritable, annoyed, or negative when hungry – an experience colloquially called being “hangry.” The idea that hunger affects our feelings and behaviors is widespread – from advertisements to memes and merchandise. But surprisingly little research investigates how feeling hungry transforms into feeling hangry. Read More

MORE ABOUT: psychology

When Did Humans First Learn to Count?

By Peter Schumer, Middlebury College | June 8, 2018 4:55 pm
Where did our written numbers come from? (Credit: Nikita Rogul/Shutterstock)

Where did our written numbers come from? (Credit: Nikita Rogul/Shutterstock)

The history of math is murky, predating any written records. When did humans first grasp the basic concept of a number? What about size and magnitude, or form and shape?

In my math history courses and my research travels in Guatemala, Egypt and Japan, I’ve been especially interested in the commonality and differences of mathematics from various cultures.

Although no one knows math’s exact origins, modern mathematicians like myself know that spoken language precedes written language by scores of millennia. Linguistic clues show how people around the world must have first developed mathematical thought.

Early Clues

Differences are easier to comprehend than similarities. The ability to distinguish more versus less, male versus female or short versus tall must be very ancient concepts. But the concept of different objects sharing a common attribute – such as being green or round or the idea that a single rabbit, a solitary bird and one moon all share the attribute of uniqueness – is far subtler.

In English, there are many different words for two, like “duo,” “pair” and “couple,” as well as very particular phrases such as “team of horses” or “brace of partridge.” This suggests that the mathematical concept of twoness developed well after humans had a highly developed and rich language.

By the way, the word “two” probably was once pronounced closer to the way it’s spelled, based on the modern pronunciation of twin, between, twain (two fathoms), twilight (where day meets night), twine (the twisting of two strands) and twig (where a tree branch splits in two).

Written language developed much later than spoken language. Unfortunately, much was recorded on perishable media, which have long since decayed. But some ancient artifacts that have survived do exhibit some mathematical sophistication.

For example, prehistoric tally sticks – notches incised on animal bones – are found in many locations around the world. Though these might not be proof of actual counting, they do suggest some sense of numerical record keeping. Certainly people were making one-to-one comparisons between the notches and external collections of objects – perhaps stones, fruits or animals.

A tally stick found in Scandinavia. (Credit: The British Museum, CC BY-NC-SA)

A tally stick found in Scandinavia. (Credit: The British Museum, CC BY-NC-SA)

Counting Objects

The study of modern “primitive” cultures offers another window into human mathematical development. By “primitive,” I mean cultures that lack a written language or the use of modern tools and technology. Many “primitive” societies have well-developed arts and a deep sense of ethics and morals, and they live within sophisticated societies with complex rules and expectations.

In these cultures, counting is often done silently by bending down fingers or pointing to specific parts of the body. A Papuan tribe of New Guinea can count from 1 to 22 by pointing to various fingers as well as to their elbows, shoulders, mouth and nose.

Most primitive cultures use object-specific counting, depending on what’s prevalent in their environment. For example, the Aztecs would count one stone, two stone, three stone and so on. Five fish would be “five stone fish.” Counting by a native tribe in Java begins with one grain. The Nicie tribe of the South Pacific counts by fruit.

English number words were probably object-specific as well, but their meanings have long been lost. The word “five” probably has something to do with “hand.” Eleven and 12 meant something akin to “one over” and “two over” – over a full count of 10 fingers.

The math Americans use today is a decimal, or base 10, system. We inherited it from the ancient Greeks. However, other cultures show a great deal of variety. Some ancient Chinese, as well as a tribe in South Africa, used a base 2 system. Base 3 is rare, but not unheard of among Native American tribes.

The ancient Babylonians used a sexagesimal, or base 60, system. Many vestiges of that system remain today. That’s why we have 60 minutes in an hour and 360 degrees in a circle.

Written Numbers

What about written numbers?

Plimpton 322: The world’s first trigonometric table. (Courtesy of the Rare Book and Manuscript Library, Columbia University. Historia Mathematica, CC BY-NC-ND)

Plimpton 322: The world’s first trigonometric table. (Courtesy of the Rare Book and Manuscript Library, Columbia University. Historia Mathematica, CC BY-NC-ND)

Ancient Mesopotamia had a very simple numerical system. It used just two symbols: a vertical wedge (v) to represent 1 and a horizontal wedge (<) to represent 10. So <<vvv could represent 23.

But the Mesopotamians had no concept of zero either as a number or as a place holder. By way of analogy, it would be as if a modern person were unable to distinguish between 5.03, 53 and 503. Context was essential.

The ancient Egyptians used different hieroglyphs for each power of 10. The number one was a vertical stroke, just as we currently use. But 10 was a heel bone, 100 a scroll or coiled rope, 1000 a lotus flower, 10,000 a pointed finger, 100,000 a tadpole and 1,000,000 the god Heh holding up the universe.

The numerals most of us know today developed over time in India, where computation and algebra were of utmost importance. It was also here that many modern rules for multiplication, division, square roots and the like were first born. These ideas were further developed and gradually transmitted to the Western world via Islamic scholars. That’s why we now refer to our numerals as the Hindu-Arabic numeral system.

The ConversationIt’s good for a young struggling math student to realize that it took thousands of years to progress from counting “one, two, many” to our modern mathematical world.

 

[This article was originally published on The Conversation. Read the original article.]

CATEGORIZED UNDER: Living World
MORE ABOUT: anthropology

In Russia’s Space Graveyard, Locals Scavenge Fallen Spacecraft for Profit

By Paul Cooper | June 7, 2018 10:45 am
Villagers collecting scrap from a crashed spacecraft, surrounded by thousands of white butterflies. Environmentalists fear for the region's future due to the toxic rocket fuel. (Credit: Jonas Bendiksen/Magnum)

Villagers collecting scrap from a crashed spacecraft, surrounded by thousands of white butterflies. Environmentalists fear for the region’s future due to the toxic rocket fuel. (Credit: Jonas Bendiksen/Magnum)

The Altai mountain region of Central Asia is a rugged and remote place. Right in the center of the continental landmass, it forms a crossroads between the Kazakh steppes, the snow forests of Siberia and the arid plains of Mongolia. It’s a landscape of granite, forced up by the inch-a-year collision of the Indian tectonic plate with Asia, then carved out over millions of years by streams of snowmelt. Siberian Ibex wander here along with musk deer feeding on the lichenous rocks and brown bears that follow the retreating snow fields in spring.

This might be one of the most remote places on earth, little accessible by road, but its peace is routinely broken in the most dramatic way. That’s because the Altai region sits right beneath the main flight path of the oldest, largest and busiest spaceport in the world: the Baikonur Cosmodrome. Debris from each rocket launch rains down on these remote hills, and the people of the region are forced to make a living among the falling scraps. Read More

From Mouth to Mind: How Language Governs Our Perceptions of Gender

By Cody Cottier | June 1, 2018 11:58 am
(Credit: pathdoc/Shutterstock)

(Credit: pathdoc/Shutterstock)

Take a second and try to talk about a person without mentioning gender.

If English is your native tongue, odds are you failed. But if you had been born in Indonesia, you might have succeeded.

Lera Boroditsky, who studies language and cognition at the University of California, San Diego, recalled a conversation with a colleague from the Southeast Asian country. He was asking her about someone she knew back in the states, and gender didn’t pop up until question 21.

“He didn’t seem to think it was that important,” she said.

In some cultures, maleness and femaleness aren’t the prominent traits they are in the U.S. In yet others, they’re even more salient.

How languages deal with gender can be divided into three classes: Some languages, like English, are natural gender languages. They are characterized by pronouns, and some nouns, denoting the gender of people and animals.

Others, like the Romance languages, are grammatically gendered. They place all nouns into gender categories, which don’t necessarily align with natural gender. Think “la casa” (feminine) and “el baño” (masculine). There is little consistency in the genders of words across languages, though. In some, including Spanish, the word for “manliness” is even feminine.

The third kind of language — which includes Indonesian, Finnish and Mandarin — is genderless. These still have words for man and woman, and for other words that designate gender, like “mother,” but they have no pronouns or linguistic signals for male and female, in living beings or objects.

Words Influence Thoughts

The way we perceive gender seems to depend on the way it’s presented to us as we’re learning. And our language is a big part of that. A growing body of research suggests that the language we speak, including its gender features, shapes the way we think and act.

In one study, Boroditsky asked speakers of German and Spanish to describe a bridge. The word is feminine in the former language, masculine in the latter. German speakers used adjectives like beautiful, elegant and fragile, while Spanish speakers viewed bridges as towering, dangerous and strong.

Other study participants, when asked to speak like different days of the week, chose masculine or feminine voices in accordance with the gender of the words for those days.

To Boroditsky and many scientists, these experiments and others like them provide solid evidence for a connection between the language and cognition. If a person grows up noting gender at every word, those habits of speech eventually bind them to a perception of the world as a realm with distinct male and female entities, with strong stereotypes for each.

“I think we tend to really believe the structures in our language,” Boroditsky said. “We believe they really reflect reality.”

(Credit: ricochet64/Shutterstock)

(Credit: ricochet64/Shutterstock)

Over the centuries, some philosophers even praised their mother (why not father?) tongues for capturing the “true” genders of objects. But there’s no evidence for that. Monolingual speakers are prone to accept their language as the truth, Boroditsky said, but people who have been exposed to another language “no longer have that illusion.”

No feature of a language is necessarily permanent. For example, Old English was grammatically gendered until partway through the middle ages, when changes in the way people spoke eventually eroded the vocal distinctions between male and female.

Boroditsky said Indo-European — which gave rise to English and scores of other languages in Europe, the Middle East and India — is thought to have developed gender because words associated with things that were biologically male or female tended to have endings that lined up with their respective gender, and other words with those endings got lumped in with them. Seen in this light, the gendering or de-gendering of language is not so much a deliberate process as it is a gradual evolution of sounds. Often, speakers don’t even notice the subtle shifts in the inflection of their speech over time, Boroditsky said.

But more recently, some countries are seeing efforts to intentionally alter language. Sweden did away with its formal pronouns decades ago to de-emphasize class distinctions, and some people in France are pushing for gender-neutral language. As it stands, many nouns for professions in French have only a masculine form. Proponents of inclusive writing believe this puts women at a disadvantage, and they hope to either introduce feminine versions of professional nouns, or create a neutral pronoun.

When Gendered Language Harms

Feminists have long argued that gendered language contributes to sexism, and some research supports this. One study found that speakers of Spanish and German, both gendered, expressed more sexist attitudes than English speakers.

Penelope Eckert, a professor of linguistics at Stanford University, said languages are largely a reflection of ideology.

For example, every time we use the masculine pronoun as all-encompassing (“if a person feels ill, he should call a doctor”), or mankind to mean all humans, it is a sign of our societal values and serves to reinforce them. Even phrases that include men and women (“good evening, ladies and gentlemen”) assume a binary gender system.

“You get those kinds of locutions all over the place,” Eckert said, “and they just sort of unconsciously affect the way we think about gender.”

Even the term “natural gender” in reference to languages like English is problematic, Eckert argues, because gender is a social construct rather than an inherent quality.

And the way we talk may affect more than our thoughts. Numerous studies have found higher gender inequality in countries with gendered languages, meaning our speech may indirectly impact the lives of women in just about every conceivable way.

That doesn’t mean that there aren’t benefits to sorting words by gender. It allows for more complexity in language, Boroditsky says, and more efficient mental processing. Because every noun fits into a category, and every verb and adjective that modifies it is marked accordingly, it’s easier to keep track of the relationships between words.

And though the practice of creating linguistic classifications is widespread, the idea that they must align with biological sex isn’t universal. Some languages divide their nouns into “animate” and “inanimate” categories, and others have more bizarre distinctions. One word group in the Australian Aboriginal language Dyirbal includes nouns for “women, fire and dangerous things.”

Distinguishing between genders in the way English does can also be helpful at certain points in a society’s development, Boroditsky said. If ideas of gender equality haven’t taken root, gendered language can keep women from becoming invisible.

“It brings people out of the shadows,” she said.

But as a culture develops, she added, gender is often an irrelevant detail that limits the scope of discussion. Whether a doctor is a man or a woman is not so important as whether they are a good doctor.

But the road to gender-neutral language is littered with obstacles. In languages like Spanish with gendered noun classes, the distinction is woven so deeply into the grammar that probably nothing but time could remove it. Even in the more modestly gendered English, grammarians have fought against modifications as slight as substituting “they” for “he” as the generic pronoun, even though the latter has been in popular use for hundreds of years.

The French Academy, the authority on language in France, has gone so far as to condemn gender-neutral language, calling it an “aberration.” The institution argues inclusive writing, and the confusion it would breed, poses a “deadly danger” to the language.

“People have to want to do it,” Boroditsky said. “In the end, language is a tool people change to fit their needs.”

Eckert agrees, saying: “it’s not going to happen magically overnight.” And no one thinks a pronoun shift would eradicate sexism altogether. But as we come to realize the impact of language on the mind, Boroditsky argues that eliminating the routine separation of genders in our speech could help to mute the differences we perceive in them.

“Maybe it’s time to be able to imagine a human without categorizing them by gender,” she said, “and see them as more of an individual.”

CATEGORIZED UNDER: Mind & Brain

A Bleary Unicorn: The Elusive Hangover Cure

By Troy Farah | May 30, 2018 3:00 pm
(Credit: Everett Collection/Shutterstock)

(Credit: Everett Collection/Shutterstock)

From freezing showers to ingesting prickly pear to smoking joints, everyone has a home remedy for alcohol’s notorious afterglow: the hangover. Mongolian men swear by pickled sheep eyes, ancient Egyptians wore necklaces of Alexandrian laurel, and one 17th century English physician even sold a hangover “cure” made with human skulls and dried vipers.

Hangovers are a problem that even predates writing. But today with the aid of modern medicine we can treat diarrhea or headaches with over-the-counter drugs — so why not hangovers too?

“Each year, many people die because they drink too much,” Yunfeng Lu, a chemical engineering professor at UCLA, said in a phone call. “And currently, we have no antidote.”

But that could change. New research from Lu and his colleagues published in the journal Advanced Materials demonstrates a “hangover pill” that can mitigate some of the damaging effects of alcohol. The antidote mimics the work of hepatocytes, or liver cells, and helps speed up the body’s alcohol metabolism. It’s basically supercharging your liver’s ability to clear alcohol from the bloodstream, resulting in far lower levels of intoxication.

To test their treatment, scientists got mice drunk by inserting tubes into their mouths and pumping ethanol directly to the stomach. Within a few minutes, the rodents became intoxicated and fell asleep. Then, the researchers injected nanocapsules of blood cells loaded with enzymes that help break down alcohol into less harmful byproducts. Afterwards, the mice were sacrificed and their livers were examined with fluorescent imaging to measure toxicity.

The blood alcohol content of the mice dropped by 45 percent within four hours and caused less organ damage than it would have normally. But this treatment probably isn’t coming to your local CVS anytime soon. Human trials are still a few years off, and so far, these nanocapsules are only being developed for emergency room settings, which saw a 61 percent jump in alcohol-related visits between 2006 and 2014.

And it’s not just problem drinkers that could use some relief. One survey of 2,000 people found that if you have only one hangover a month, it adds up to two years of total sick time over the course of a lifetime.

That’s why Lu and others are racing to find alternatives to help make alcohol’s aftermath suck less. But before we get to that, we need to understand what makes a hangover such a grating experience.

Getting Over The Hangover

Though nature may never have intended us to drink as much as we do today, the ability to digest ethanol, a tasteless liquid produced by fermented sugars, might have been crucial to our survival as a species 10 million years ago. Back then, the climate was rapidly changing, and fruit on the ground was more likely to ferment. The capacity to digest liquor would have been advantageous for our primate ancestors, who relied heavily on fruit for sustenance.

We largely owe our drinking abilities to ADH4, or alcohol dehydrogenase 4, an enzyme that lets us harvest the caloric traits of alcohol. But during the oxidation process that breaks alcohol down, ADH4 creates acetaldehyde, a known carcinogen that damages DNA. ALDH2 (aldehyde dehydrogenase), a liver enzyme that also protects the heart against heart attacks, breaks the acetaldehyde down into less toxic acetate, which later becomes carbon dioxide and water.

But the more you drink, the more acetaldehyde builds up, faster than the body can metabolize, creating noxious, even cancerous conditions. Long-term exposure can lead to health problems including high blood pressure, depression, and a leaky gut. In addition, the effects appear to be worse for women.

Yet, after all this time, the exact mechanisms of what causes a hangover still elude scientists. Acetaldehyde is a common culprit, but the most unpleasant hangover symptoms occur when acetaldehyde levels are low. Others blame dehydration, low blood sugar, or inflammatory proteins called cytokines, but the jury is still out.

So while Lu’s hangover antidote may be promising, it may not address all of the multiple pathways that can lead to alcohol toxicity. Other experimental chemicals have been found to have potential hangover-leavening effects, such as ampelopsin, also known as dihydromyricetin, a compound found in the Japanese raisin tree. It dampens the effects of alcohol withdrawal and can even reportedly sober you up faster by interacting with structures in the brain, called GABAA receptors, that alcohol normally interferes with.

Other drugs for mitigating alcohol withdrawal or excessive drinking are thought to act on these same GABAA receptors. They include naltrexone, acamprosate, benzodiazepines like Valium, and clomethiazole, which The Who’s drummer Keith Moon famously overdosed on. Yet, all of these drugs have limited success. Maybe it’s smarter to circumvent ethanol altogether by creating a drug that gives a buzz without the fuss.

Drinking Without the Drinks

The U.S. is currently in the grip of a drug overdose crisis, which killed 64,000 people in 2016, 42,000 from opioids alone. But alcohol-related deaths exceed 88,000 per year and have every year since at least 2006 — far outpacing the mortality of the opioid crisis.

Moderate drinking is probably fine. It even has some health benefits, if you ask the alcohol industry. Yet, if we have a drug epidemic, booze plays no small part. That’s why researchers believe using biochemistry to develop a safer alternative to alcohol is crucial. One idea: make a drug with no hepatotoxicity or comedown.

That’s the goal of Alcarelle, a U.K.-based startup that aims to develop a new drug to replace alcohol — one without side effects, including hangovers. Alcarelle was founded by neuropsychopharmacologist David Nutt, who was fired from his post as Britain’s chief drug czar, for saying alcohol is more dangerous than LSD. (He seems to be right, though, as some studies have demonstrated.)

“We are not aiming to replicate the action of alcohol, as this is very unpredictable and extremely harmful,” Emily Palmer, a researcher at Alcarelle, explained in an email. “Instead, we are aiming to create an alternative substance to alcohol, which would produce a tipsy-like feeling, replicating the enjoyment many people experiencing after drinking a few alcoholic beverages.”

(Credit: itakdalee/Shutterstock)

(Credit: itakdalee/Shutterstock)

But neuroscientist Lindsay Halladay isn’t so sure this can be done. “There is not going to be some magical chemical compound that is rewarding and has zero negative side effects,” she said in a call.

Halladay is an assistant psychology professor at Santa Clara University. The bulk of her research has focused on the underlying neural circuits involved in stress and addictive behavior — for example, what parts of the brain encourage us to keep drinking when we know we shouldn’t.

“There are a lot of compensatory mechanisms that the brain has,” she said. “If you take some drug that increases your dopamine levels, your brain is able to recognize, ‘Hey, this is too much dopamine, let me tweak some things,’ and lowers the endogenous level of dopamine. So there’s always this homeostasis.”

Halladay argued that a “safer” alcohol might encourage riskier drinking. Nutt has said in interviews his product won’t be able to get you drunk, even if you tried. But while the company says they’ve developed over 100 drug candidates, narrowing their choices down to a few contenders, the efficacy of their products has yet to be seen, but the company is confident their creation will deliver.

“I have an understanding of the science involved and an appreciation of the years of work and innovation which has got us to where we are now,” Palmer said. “I am confident that this quality and quantity of research will result an effective product.”

If Alcarelle can achieve its goal, it could save literally thousands of lives a year. But replacing alcohol in the hearts and minds of drinkers won’t be easy. The global liquor industry is expected to top $1.5 trillion globally by 2022, which means there’s a lot of competition, to say nothing of the regulatory hurdles Alcarelle faces from federal agencies.

Nonetheless, Alcarelle are optimistic we could see “alcosynths,” as they call them, on store shelves in about four years or so, if they can raise the estimated $20 million they need. And such products might find a warmer welcome than you might think. David Orren, managing director of Alcarelle, said in an email that their product has actually stirred some interest from alcohol companies eager to diversify.

“Drinks companies are already experiencing flat demand and senior executives are generally intrigued by the possibility of widening their product portfolios with an attractive ‘free from’ product that is appealing to health-conscious consumers,” Orren said.

Antabuse Before Liquor, Never Sicker

There may not yet be a drug that can reverse a hangover or subdue it altogether, but there is a medication that can cause one — a really painful, vomit-inducing one. It’s called disulfiram, or Antabuse, and it inhibits the alcohol-metabolizing enzymes that our bodies rely on to clear alcohol from our systems. Drinking even a small amount of hooch leads to a mass buildup of acetaldehyde, causing nausea, mental confusion, and even fainting. It’s enough to convince almost anyone to give up the sauce.

Disulfiram arose in 1881, used as a rubber manufacturing aid. In 1948, two Danish physicians decided to eat it, because that’s what you did back then, and discovered when drinking beers later that it didn’t make them feel so well. Now disulfiram is prescribed to treat chronic alcohol use, but its efficacy is debated.

“I’m always surprised that people take Antabuse because it is so horrible,” Halladay said. “You take it voluntarily, but it’s for individuals who have no other option. They’ve tried to quit drinking on their own. Addiction is obviously not a choice. People have tried everything else and eventually decide, ‘Let me take this drug that will make me incredibly sick if I give in.’”

But for most people, there’s nothing wrong with enjoying a drink now and again. Drugs like Antabuse are for extreme cases, and it’s likely that the majority of us will continue waking up with fuzzy heads and queasy stomachs after a night on the town for some time.

Even if you’re not quite down with the idea of an alcosynth, scientists are continuing to explore options for hangover relief. Some researchers are looking at extracts of the invasive vine kudzu to combat binge drinking and others are getting worms hungover to target new molecular pathways to alleviate alcohol withdrawal symptoms.

As for Lu, he’ll continue to test the safety of his enzyme-mimicking hangover antidote on animals — if it seems safe, human clinical trials could begin within a year. In the meantime, there is currently no panacea to avoid the pitfalls of hitting the bottle. So if you’re really tired of waking up with a headache, wishing you hadn’t chugged so many brewskis the night before, it might be best to quit drinking altogether.

CATEGORIZED UNDER: Health & Medicine
MORE ABOUT: medical technology

What Magnetic Fields Do to Your Brain and Body

By Erica Tennenhouse | May 25, 2018 11:39 am
(Credit: pippeeContributor/Shutterstock)

(Credit: pippeeContributor/Shutterstock)

There’s no escaping magnetic fields—they’re all around us. For starters, the Earth itself is like a giant magnet. A spinning ball of liquid iron in our planet’s core generates the vast magnetic field that moves our compass needles around and directs the internal compasses of migrating birds, bats, and other animals. On top of that, ever-industrious humans have produced artificial magnetic fields with power lines, transport systems, electrical appliances, and medical equipment.

We may not be able to see, hear, feel, or taste the magnetic fields that surround us, but some may wonder whether they can still exert effects on our bodies and brains. This question becomes more pertinent, and the answers more tantalizing, as the strength of the magnetic field in question gets cranked up.

Everyday Exposure

A magnetic field arises whenever a charged particle, like an electron or proton, moves around. Since the electric currents running through blenders, hairdryers, and wires in the walls of our homes consist of flowing electrons, they all generate magnetic fields. Through these sources, the average person is exposed to magnetic fields reaching 0.1 microtesla in strength on a daily basis. By comparison, the Earth’s magnetic field, which we are always exposed to (as long as we remain on the planet’s surface), is about 500 times stronger. That means the magnetic force penetrating your body as you lounge around your home or spend a day at the office is decidedly insignificant.

From time to time, a scientific study finds a link between living near high-voltage power lines and illness. Heightened risk of childhood leukemia is the most commonly cited potential health consequence, but whether or not the risk is real has been hard to pin down. One glaring issue is that scientists have yet to figure out the mechanism by which such weak magnetic fields—which are still in the microtesla range for homes next to power lines—could adversely affect the human body. In 2010, the International Commission on Non-Ionizing Radiation Protection concluded that the evidence that living near power lines increases the risk of the deadly blood cancer “is too weak to form the basis for exposure guidelines.”

(Credit: VILevi/Shutterstock)

An MRI machine. (Credit: VILevi/Shutterstock)

What’s the Threshold?

Meanwhile, a team of scientists at the Utilities Threshold Initiative Consortium (UTIC) has been busy working to figure out the threshold at which the human body shows a physiological response to a magnetic field. According to Alexandre Legros, a medical biophysicist at the Lawson Health Research Institute and Western University in London, Ontario and a UTIC scientist, the smallest magnetic field that has reliably been shown to trigger a response in humans is around 10,000 to 20,000 microtesla. But crucially, to produce the effect, the field cannot be static like Earth’s magnetic field; rather, it must change directions over time. When these strong, direction-shifting magnetic fields get directed at a human, small electrical currents begin to pulse through the body. Above that threshold, the currents can stimulate super-sensitive cells in the retina, known as graded potential neurons, giving the illusion of a white light flickering even when the affected person is in darkness; these visual manifestations are known as magnetophosphenes.

The 10,000-microtesla threshold is well above the strength of any magnetic field encountered in everyday life. So in what situations might magnetophosphenes occur?

Medical Magnets

“There’s only one circumstance in which you may perceive magnetophosphenes,” says Legros: “If you’re in an MRI [magnetic resonance imaging] machine and moving your head fast.” An MRI scanner is essentially a big magnet that produces a powerful magnetic field of around 3 tesla (or 3 million microtesla) — millions of times larger than the fields we’re normally exposed to. But because it’s a static magnetic field, MRI scanners don’t exert any noticeable effect on the body. That would change, however, if the patient inside the scanner were to rapidly move his or her head back and forth. “Moving quickly induces a time-varying field, so by doing that you are inducing currents in different structures of your brain,” says Legros. Those currents may lead to nausea, loss of balance, a metallic taste in your mouth, or in some cases, magnetophosphenes.

On par with the magnetic field of an MRI is the one produced by a medical procedure known as transcranial magnetic stimulation (TMS). But unlike MRI, which makes detailed pictures of the inside of the body, the purpose of TMS is to stimulate the brain. That task requires an electric current, which is why TMS relies on a magnetic pulse rather than a static magnetic field. When this pulse is delivered via an electromagnetic coil placed against the scalp, the resulting current jolts a particular part of the brain with the aim of treating neurological diseases like depression.

Out-of-this-World Magnetic Fields

The magnetic fields associated with MRI and TMS are the strongest that a human might realistically be exposed to. Still, they are “hilariously puny” compared to those found beyond our planet, says Paul Sutter, an astrophysicist at Ohio State University and chief scientist at the COSI Science Center in Columbus, Ohio. At the extreme lies the aptly-named magnetar, which is a rare type of neutron star with a magnetic field one thousand trillion times stronger than Earth’s.

An artist's impression of a magnetar. (Credit: ESO/L. Calçada/Wikipedia (CC BY 4.0))

An artist’s impression of a magnetar. (Credit: ESO/L. Calçada/Wikipedia (CC BY 4.0))

If any human ever got close to a magnetar, they would quickly find themselves in dire straits. “Strong magnetic fields can start to do surprising things,” says Sutter. At the atomic level, the strong magnetic field would move all of the positive charges in your body in one direction and the negative charges the other way, he explains; spherical atoms would stretch out into ellipses and soon they would start to resemble thin pencils. That drastic change in shape would interfere with basic chemistry, causing the normal forces and interactions between atoms and molecules in the body to break down. “The first thing you would notice is your entire nervous system, which is based on electrical charges moving throughout your body, is going to stop working,” says Sutter. “And then you basically dissolve.”

Sutter guarantees that our local neighborhood — which he defines as a radius of a few hundred light-years around Earth — has been surveyed and certified magnetar-free. None of these exotic objects are approaching us, and none of the massive stars nearby are likely to turn into magnetars when they die. The nearest magnetar is a safe distance of tens of thousands of light-years away. So, at least for the time being, we can rest easy and take comfort in our planet’s own meager magnetic field.

CATEGORIZED UNDER: Environment, Health & Medicine
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