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‘Embryo Models’ Challenge the Legal, Ethical, and Biological Concepts of an ‘Embryo’

‘Embryo Models’ Challenge the Legal, Ethical, and Biological Concepts of an ‘Embryo’

Meanwhile, Hanna’s team in Israel was growing mouse embryo models in a similar way, as they described in a paper in Cell that was published shortly before the paper from Zernicka-Goetz’s group. Hanna’s models too were made solely from embryonic stem cells, some of which had been genetically coaxed to become TSCs and XEN cells. “The entire synthetic organ-filled embryo, including extra-embryonic membranes, can all be generated by starting only with naive pluripotent stem cells,” Hanna said.

Hanna’s embryo models, like those made by Zernicka-Goetz, passed through all the expected early developmental stages. After 8.5 days, they had a crude body shape, with head, limb buds, a heart, and other organs. Their bodies were attached to a pseudo-placenta made of TSCs by a column of cells like an umbilical cord.

“These embryo models recapitulate natural embryogenesis very well,” Zernicka-Goetz said. The main differences may be consequences of the placenta forming improperly, since it cannot contact a uterus. Imperfect signals from the flawed placenta may impair the healthy growth of some embryonic tissue structures.

Without a better substitute for a placenta, “it remains to be seen how much further these structures will develop,” she said. That’s why she thinks the next big challenge will be to take embryo models through a stage of development that normally requires a placenta as an interface for the circulating blood systems of the mother and fetus. No one has yet found a way to do that in vitro, but she says her group is working on it.

Hanna acknowledged that he was surprised by how well the embryo models continued to grow beyond gastrulation. But he added that after working on this for 12 years, “you are excited and surprised at every milestone, but in one or two days you get used to it and take it for granted, and you focus on the next goal.”

Jun Wu, a stem cell biologist at the University of Texas Southwestern Medical Center in Dallas, was also surprised that embryo models made from embryonic stem cells alone can get so far. “The fact that they can form embryo-like structures with clear early organogenesis suggests we can obtain seemingly functional tissues ex utero, purely based on stem cells,” he said.

In a further wrinkle, it turns out that embryo models do not have to be grown from literal embryonic stem cells—that is, stem cells harvested from actual embryos. They can also be grown from mature cells taken from you or me and regressed to a stem cell-like state. The possibility of such a “rejuvenation” of mature cell types was the revolutionary discovery of the Japanese biologist Shinya Yamanaka, which won him a share of the 2012 Nobel Prize in Physiology or Medicine. Such reprogrammed cells are called induced pluripotent stem cells, and they are made by injecting mature cells (such as skin cells) with a few of the key genes active in embryonic stem cells.

So far, induced pluripotent stem cells seem able to do pretty much anything that real embryonic stem cells can do, including growing into embryo-like structures in vitro. And that success seems to sever the last essential connection between embryo models and real embryos: You don’t need an embryo to make them, which puts them largely outside existing regulations.

Growing Organs in the Lab

Even if embryo models have unprecedented similarity to real embryos, they still have many shortcomings. Nicolas Rivron, a stem cell biologist and embryologist at the Institute of Molecular Biotechnology in Vienna, acknowledges that “embryo models are rudimentary, imperfect, inefficient, and lack the capacity of giving rise to a living organism.”

The failure rate for growing embryo models is very high: Fewer than 1 percent of the initial cell clusters make it very far. Subtle abnormalities, mostly involving disproportionate organ sizes, often snuff them out, Hanna said. Wu believes more work is needed to understand both the similarities to normal embryos and the differences that may explain why mouse embryo models haven’t been able to grow beyond 8.5 days.

Pure Oxygen Speeds Up Learning. Can It Help Stroke Survivors Recover?

Pure Oxygen Speeds Up Learning. Can It Help Stroke Survivors Recover?

As a physical therapist in Shanghai, Zheng Wang worked with people recovering from strokes after their brains had been damaged by oxygen deprivation. They usually followed a predictable recovery pattern, making lots of progress over the first few visits, then hitting a wall. Patients asked when they’d finally feel normal, and Wang told them that they’d get better with time. “But actually,” he remembers, “I knew from the bottom of my heart that they wouldn’t improve much, no matter how hard we tried.”

Meanwhile, halfway across the world, Marc Dalecki, then an associate professor in the School of Kinesiology at Louisiana State University (LSU), couldn’t stop thinking about oxygen. Dalecki spent much of his early career studying scuba diving and remembers divers using nasal cannulas of O2 to help with everything from hypoxia to headaches. He always wondered whether this simple treatment could help neurological patients in rehab. “I promised myself that I would study it when I got my own research lab,” he says.

For its relatively small size, the brain consumes a ridiculous amount of power: 20 to 30 percent of the body’s energy at rest. To fuel all of its neurons, the brain depends on oxygen. When someone has a stroke or a head injury, the flow of oxygenated blood to the brain gets disrupted. Starved of oxygen, the brain tissue is damaged, leading to a host of problems with memory, speech, strength, and motor control.

Rehabilitation from brain trauma usually involves working with a physical therapist to relearn motor skills, building up the strength and coordination required for daily activities, like making coffee, writing, and brushing your teeth. Many physical therapists already use high-tech devices to help patients recover faster, from robots that move impaired limbs to virtual reality games that simulate aspects of day-to-day life that can’t be easily replicated in a hospital setting. But Wang and Dalecki both wondered whether oxygen could be the simple, cheap, accessible addition to neurological rehabilitation they’d been looking for. If they could give patients a little extra oxygen during early motor rehab sessions, they thought, it might help them relearn old skills faster.

The two of them joined forces in Dalecki’s lab at LSU, where Wang, frustrated as a clinician, decided to get a PhD in kinesiology. In a study published last week in Frontiers in Neuroscience, their team showed that sniffing pure oxygen while learning a challenging motor task helped healthy young people learn faster and perform better. They think this relatively low-cost, low-risk idea could be used to speed up stroke recovery.

For their study, they recruited 40 healthy young adults to each sit at a desk while wearing a nasal cannula. Their instructions were simple: Hold a stylus at the center of a tablet screen, then drag it to a target that pops up somewhere else, as quickly and efficiently as possible. But after a few trials, the relationship between the stylus and the screen shifted, creating a 60-degree difference between the line a participant thought they drew and the line that actually appeared on the screen. While the volunteers adjusted their line drawing to these new, more challenging circumstances, air started flowing through the cannula. Half of the participants got pure oxygen, while the other half got medical air (essentially an ultra-clean version of regular air). It was a quick blast, only during these few minutes of initial learning. Then the air flow shut off and the screen went back to normal.

Here Comes Euclid, the Telescope That Will Search for Dark Energy

Here Comes Euclid, the Telescope That Will Search for Dark Energy

After Euclid blasts off, it will travel to a spot called Lagrange point 2, about 1.5 million kilometers from Earth, where the telescope will have a clear view of deep space while being able to communicate with astronomers and enjoy continuous sunlight on its solar panels. The telescope is equipped with two instruments that will be used simultaneously: a visible-wavelength camera with 36 sensitive detectors called charge coupled devices, for measuring the shapes of billions of galaxies, and a near-infrared spectrometer and photometer, with 16 detectors that will provide a larger infrared field of view than any other space telescope. Euclid will begin its science mission later this year, after a few months of testing and calibrating those instruments.

It will share an L2 orbital parking spot near NASA’s James Webb Space Telescope, but “it’s kind of an anti-JWST. Instead of focusing on a very small piece of sky, the whole aim of Euclid is to widen out and look over a huge part of the sky,” says Mark McCaughrean, ESA’s senior adviser for science and exploration. Unlike the JWST and Hubble telescopes, Euclid won’t be zooming in on unique objects, but getting a panoramic view. “It’s a statistics mission. The aim is to drown yourself in so much data and so many galaxies, and then you can start teasing out the subtle signals,” McCaughrean says.

Astrophysicists on the Euclid team plan to make two kinds of critical measurements, both heavily involving statistics. The first will be a measurement of weak gravitational lensing, which happens when the gravity of massive objects—mostly dark matter—slightly bends the light coming from more distant galaxies, distorting their images. It can only be studied with catalogs containing lots and lots of galaxies.

That also goes for studying baryon acoustic oscillations. In the primordial universe, sound waves undulated through normal matter—a mix of particles and radiation. This created a measurable pattern in the density distribution of galaxies as they formed. Studying the patterns left behind by these oscillations at multiple snapshots in cosmic time will help Euclid scientists understand the expansion of the universe and the nature of dark energy.

To make headway on such statistics, Euclid’s instruments will collect troves of data, with image quality that’s similar to Hubble’s but spans 15,000 square degrees of the sky. That would take centuries to do using Hubble, says Luca Valenziano, a cosmologist at Italy’s National Institute for Astrophysics and member of the Euclid collaboration. “This is an incredible potential, and only Euclid can do that because it can explore the infrared sky, which is not accessible from the ground,” he says.

The use of infrared is a key way that Euclid will differ from surveying telescopes on the ground, like the Dark Energy Survey, the Dark Energy Spectroscopic Instrument, and the upcoming Vera Rubin Observatory. Earthbound telescopes can’t observe most infrared wavelengths, because the atmosphere blocks them. But space telescopes like Euclid and JWST can, provided they’re kept cool enough. (Infrared light is basically heat radiation.) Infrared instruments allow Euclid to penetrate dust clouds when examining galaxies, and enable a deeper probe into the universe’s past.

In recent years, astrophysicists like Mat Madhavacheril have used the Atacama Cosmology Telescope to study the biggest question related to the universe’s expansion: Why the measured expansion rate appears slightly different when using probes of the distant universe compared to when using nearby objects, like supernova explosions. Euclid could help finally resolve the puzzle, he says, because it will be their most powerful tool yet, able to systematically map a wide swath of the universe. “Euclid has a lot to offer. We’re excited about it, and when the Euclid data are public, we’ll jump on it,” he says.

Meet the Psychedelic Boom’s First Responders

Meet the Psychedelic Boom’s First Responders

That first year, Fireside trained more than 100 volunteers and conducted some 2,550 conversations with callers—including Greenberg. Within months of reaching Jasmine, he had walked away from his job (and psychedelically high salary) to focus on work “that adds value to the universe.” Eventually he got on the phone with Fireside again—this time not to ask for help but to offer it. By the time we spoke, he’d donated $100,000 and was poised to start as the organization’s CTO, working for free.

There’s a fairly obvious point I should make, maybe one that sometimes gets lost: While exceedingly rare, psychedelics can cause serious harm. A family history of mental illness can propel someone into a psychotic episode. And the symptoms of a trip can potentially obscure a simultaneous medical crisis. A 2022 lawsuit found MAPS partially responsible for the death of Baylee Gatlin, who received care from Zendo volunteers at a music festival in 2017 and later died from organ failure and heat stroke.

“What this movement is doing is absolutely helpful for many people,” says Charles Nemeroff, codirector of the Center for Psychedelic Research & Therapy at Dell Medical School at the University of Texas at Austin. But while the “vast number of case reports would suggest that these substances are relatively safe,” he adds, we’re still in the data-gathering phase.

For her part, O’Donnell calls the harm-reduction approach “incredibly valuable.” She also cautions that a single session with even a well-trained trip­sitter won’t necessarily be enough for someone whose past trauma is suddenly surfacing, or who is other­wise having a deeply disturbing experience.

The stakes, Nemeroff notes, are even higher than any one individual’s well-being. “What none of us want to have happen is that the unregulated use of psychedelics lead to tragedies, which then will result in a backlash,” he says. “It’s been so long since we’ve been able to actually study psychedelics.”

For now, there seems little danger of reversing our interest in psychedelics. Sara Gael, a harm reduction officer at MAPS, describes a societal inflection point behind the current psychedelic renaissance. As waves of dysfunction—economic despair, climate change, white supremacy—have surfaced in recent years, people have increasingly looked to these substances to turn the prism on their worlds.

All of this makes me wonder about the real essence of the psychedelic peer support movement. It is, of course, a movement specific to these substances, rooted in a specific context: a time when drug policy remains insistently retrograde and official support systems have crumbled. But maybe it’s also more than that.

Jail, Thorazine, Wavy Gravy, Zendo: As nodes on an arc, these represent a decades-long, mostly underground evolution in how we understand a very particular species of psychic distress, but also in how we help one another at a more general level.

Pires told me that the principles behind contemporary psychedelic peer support apply to regular life too—she uses some of those same skills with her kids. Slow down. Offer calm. Let feelings arise. Maybe good tripsitting isn’t all that different from being a good partner, a good friend, a good relative. And maybe one day we’ll look back and be struck by this era—not so much by our growing interest in these substances, but our shifting understanding of ourselves in their midst.

This article appears in the Jul/Aug 2023 issue. Subscribe now.

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The Kakhovka Dam Collapse Is an Ecological Disaster

The Kakhovka Dam Collapse Is an Ecological Disaster

While the world awaits evidence and further details about what exactly happened to the dam, there is no doubting the ecological harm the breach will cause. Around 600 square kilometers of the Kherson region are currently underwater along the southern part of the Dnipro River, says Veremiychyk. And above the dam, a vast quantity of water has now drained away, which will leave behind a desert full of polluted dust, he adds.

A video shared online by President Zelensky’s chief of staff, Andriy Yermak, shows what appears to be thousands of wriggling fish stranded on dry ground near the village of Maryanske, which is north of the Kakhovka Reservoir. According to Ukraine’s agricultural ministry, 95,000 metric tons of fish could be lost. The Ukrainian Ministry of Health posted a warning on Facebook advising people not to eat fish swept downstream by the flood waters. “There is a risk of botulism,” the post read, referring to a rare but serious condition caused by toxins released by several types of bacteria.

In the path of the flood waters lie homes, farms, wetlands, meadows, and national parks. Much of the wildlife living in these habitats will probably be wiped out, says Veremiychyk: “It will be big losses.”

NGOs and research groups in Ukraine have spelled out the possible ecological impacts. In a lengthy blog post, the Ukrainian Nature Conservation Group (UNCG) describes how dozens of fish species will likely be affected. Birds that rely on the waterways and wetlands, including the beautiful Eurasian spoonbill, reptiles such as the Caspian whipsnake, and vulnerable mammals like Nordmann’s mouse are also considered at risk. “These animals,” the authors of the blog post write, “have no means of survival in the turbulent flow.”

Turnbull says that nature-focused groups in Ukraine are already documenting the many ecological impacts of the war in order to gather hard evidence and establish the true extent of environmental destruction. We can expect to see reports detailing the consequences of the dam’s breaching in the coming months and years.

What is already obvious is the huge geographical reach of the disaster. Doug Weir, research and policy director at the Conflict and Environment Observatory, has been poring over satellite images of flooded areas downstream of the dam. “There are pretty significant oil slicks, or what appears to be oil, in the region of Kherson, which seem to be originating from some of the industrial buildings there,” he says. “That’s a risk we anticipated.”

He says that contaminants from septic tanks and wastewater treatment facilities could also be washed over the land. Kristina Hook, a specialist in Ukraine and Russia at Kennesaw State University, agrees that pollutants are a serious threat. “You’re looking at just a really dangerous and dirty type of water,” she says. And this is all happening right after many animals reproduced during the spring, she adds. This part of the world—the Eurasian Steppe, which stretches from Hungary to eastern China—is characterized by grasslands, plateaus, and, in many places, high levels of biodiversity.