Researchers Are Testing a New Stem Cell Therapy in the Hopes of Saving Millions from Blindness
Of all the infirmities of old age, failing sight is among the cruelest. It can mean the end not only of independence, but of a whole spectrum of joys—from gazing at a sunset or a grandchild's face to reading a novel or watching TV.
The Phase 1 trial will likely run through 2022, followed by a larger Phase 2 trial that could last another two or three years.
The leading cause of vision loss in people over 55 is age-related macular degeneration, or AMD, which afflicts an estimated 11 million Americans. As photoreceptors in the macula (the central part of the retina) die off, patients experience increasingly severe blurring, dimming, distortions, and blank spots in one or both eyes.
The disorder comes in two varieties, "wet" and "dry," both driven by a complex interaction of genetic, environmental, and lifestyle factors. It begins when deposits of cellular debris accumulate beneath the retinal pigment epithelium (RPE)—a layer of cells that nourish and remove waste products from the photoreceptors above them. In wet AMD, this process triggers the growth of abnormal, leaky blood vessels that damage the photoreceptors. In dry AMD, which accounts for 80 to 90 percent of cases, RPE cells atrophy, causing photoreceptors to wither away. Wet AMD can be controlled in about a quarter of patients, usually by injections of medication into the eye. For dry AMD, no effective remedy exists.
Stem Cells: Promise and Perils
Over the past decade, stem cell therapy has been widely touted as a potential treatment for AMD. The idea is to augment a patient's ailing RPE cells with healthy ones grown in the lab. A few small clinical trials have shown promising results. In a study published in 2018, for example, a University of Southern California team cultivated RPE tissue from embryonic stem cells on a plastic matrix and transplanted it into the retinas of four patients with advanced dry AMD. Because the trial was designed to test safety rather than efficacy, lead researcher Amir Kashani told a reporter, "we didn't expect that replacing RPE cells would return a significant amount of vision." Yet acuity improved substantially in one recipient, and the others regained their lost ability to focus on an object.
Therapies based on embryonic stem cells, however, have two serious drawbacks: Using fetal cell lines raises ethical issues, and such treatments require the patient to take immunosuppressant drugs (which can cause health problems of their own) to prevent rejection. That's why some experts favor a different approach—one based on induced pluripotent stem cells (iPSCs). Such cells, first produced in 2006, are made by returning adult cells to an undifferentiated state, and then using chemicals to reprogram them as desired. Treatments grown from a patient's own tissues could sidestep both hurdles associated with embryonic cells.
At least hypothetically. Today, the only stem cell therapies approved by the U.S. Food and Drug Administration (FDA) are umbilical cord-derived products for various blood and immune disorders. Although scientists are probing the use of embryonic stem cells or iPSCs for conditions ranging from diabetes to Parkinson's disease, such applications remain experimental—or fraudulent, as a growing number of patients treated at unlicensed "stem cell clinics" have painfully learned. (Some have gone blind after receiving bogus AMD therapies at those facilities.)
Last December, researchers at the National Eye Institute in Bethesda, Maryland, began enrolling patients with dry AMD in the country's first clinical trial using tissue grown from the patients' own stem cells. Led by biologist Kapil Bharti, the team intends to implant custom-made RPE cells in 12 recipients. If the effort pans out, it could someday save the sight of countless oldsters.
That, however, is what's technically referred to as a very big "if."
The First Steps
Bharti's trial is not the first in the world to use patient-derived iPSCs to treat age-related macular degeneration. In 2013, Japanese researchers implanted such cells into the eyes of a 77-year-old woman with wet AMD; after a year, her vision had stabilized, and she no longer needed injections to keep abnormal blood vessels from forming. A second patient was scheduled for surgery—but the procedure was canceled after the lab-grown RPE cells showed signs of worrisome mutations. That incident illustrates one potential problem with using stem cells: Under some circumstances, the cells or the tissue they form could turn cancerous.
"The knowledge and expertise we're gaining can be applied to many other iPSC-based therapies."
Bharti and his colleagues have gone to great lengths to avoid such outcomes. "Our process is significantly different," he told me in a phone interview. His team begins with patients' blood stem cells, which appear to be more genomically stable than the skin cells that the Japanese group used. After converting the blood cells to RPE stem cells, his team cultures them in a single layer on a biodegradable scaffold, which helps them grow in an orderly manner. "We think this material gives us a big advantage," Bharti says. The team uses a machine-learning algorithm to identify optimal cell structure and ensure quality control.
It takes about six months for a patch of iPSCs to become viable RPE cells. When they're ready, a surgeon uses a specially-designed tool to insert the tiny structure into the retina. Within days, the scaffold melts away, enabling the transplanted RPE cells to integrate fully into their new environment. Bharti's team initially tested their method on rats and pigs with eye damage mimicking AMD. The study, published in January 2019 in Science Translational Medicine, found that at ten weeks, the implanted RPE cells continued to function normally and protected neighboring photoreceptors from further deterioration. No trace of mutagenesis appeared.
Encouraged by these results, Bharti began recruiting human subjects. The Phase 1 trial will likely run through 2022, followed by a larger Phase 2 trial that could last another two or three years. FDA approval would require an even larger Phase 3 trial, with a decision expected sometime between 2025 and 2028—that is, if nothing untoward happens before then. One unknown (among many) is whether implanted cells can thrive indefinitely under the biochemically hostile conditions of an eye with AMD.
"Most people don't have a sense of just how long it takes to get something like this to work, and how many failures—even disasters—there are along the way," says Marco Zarbin, professor and chair of Ophthalmology and visual science at Rutgers New Jersey Medical School and co-editor of the book Cell-Based Therapy for Degenerative Retinal Diseases. "The first kidney transplant was done in 1933. But the first successful kidney transplant was in 1954. That gives you a sense of the time frame. We're really taking the very first steps in this direction."
Looking Ahead
Even if Bharti's method proves safe and effective, there's the question of its practicality. "My sense is that using induced pluripotent stem cells to treat the patient from whom they're derived is a very expensive undertaking," Zarbin observes. "So you'd have to have a very dramatic clinical benefit to justify that cost."
Bharti concedes that the price of iPSC therapy is likely to be high, given that each "dose" is formulated for a single individual, requires months to manufacture, and must be administered via microsurgery. Still, he expects economies of scale and production to emerge with time. "We're working on automating several steps of the process," he explains. "When that kicks in, a technician will be able to make products for 10 or 20 people at once, so the cost will drop proportionately."
Meanwhile, other researchers are pressing ahead with therapies for AMD using embryonic stem cells, which could be mass-produced to treat any patient who needs them. But should that approach eventually win FDA approval, Bharti believes there will still be room for a technique that requires neither fetal cell lines nor immunosuppression.
And not only for eye ailments. "The knowledge and expertise we're gaining can be applied to many other iPSC-based therapies," says the scientist, who is currently consulting with several companies that are developing such treatments. "I'm hopeful that we can leverage these approaches for a wide range of applications, whether it's for vision or across the body."
NEI launches iPS cell therapy trial for dry AMD
New elevators could lift up our access to space
Story by Big Think
When people first started exploring space in the 1960s, it cost upwards of $80,000 (adjusted for inflation) to put a single pound of payload into low-Earth orbit.
A major reason for this high cost was the need to build a new, expensive rocket for every launch. That really started to change when SpaceX began making cheap, reusable rockets, and today, the company is ferrying customer payloads to LEO at a price of just $1,300 per pound.
This is making space accessible to scientists, startups, and tourists who never could have afforded it previously, but the cheapest way to reach orbit might not be a rocket at all — it could be an elevator.
The space elevator
The seeds for a space elevator were first planted by Russian scientist Konstantin Tsiolkovsky in 1895, who, after visiting the 1,000-foot (305 m) Eiffel Tower, published a paper theorizing about the construction of a structure 22,000 miles (35,400 km) high.
This would provide access to geostationary orbit, an altitude where objects appear to remain fixed above Earth’s surface, but Tsiolkovsky conceded that no material could support the weight of such a tower.
We could then send electrically powered “climber” vehicles up and down the tether to deliver payloads to any Earth orbit.
In 1959, soon after Sputnik, Russian engineer Yuri N. Artsutanov proposed a way around this issue: instead of building a space elevator from the ground up, start at the top. More specifically, he suggested placing a satellite in geostationary orbit and dropping a tether from it down to Earth’s equator. As the tether descended, the satellite would ascend. Once attached to Earth’s surface, the tether would be kept taut, thanks to a combination of gravitational and centrifugal forces.
We could then send electrically powered “climber” vehicles up and down the tether to deliver payloads to any Earth orbit. According to physicist Bradley Edwards, who researched the concept for NASA about 20 years ago, it’d cost $10 billion and take 15 years to build a space elevator, but once operational, the cost of sending a payload to any Earth orbit could be as low as $100 per pound.
“Once you reduce the cost to almost a Fed-Ex kind of level, it opens the doors to lots of people, lots of countries, and lots of companies to get involved in space,” Edwards told Space.com in 2005.
In addition to the economic advantages, a space elevator would also be cleaner than using rockets — there’d be no burning of fuel, no harmful greenhouse emissions — and the new transport system wouldn’t contribute to the problem of space junk to the same degree that expendable rockets do.
So, why don’t we have one yet?
Tether troubles
Edwards wrote in his report for NASA that all of the technology needed to build a space elevator already existed except the material needed to build the tether, which needs to be light but also strong enough to withstand all the huge forces acting upon it.
The good news, according to the report, was that the perfect material — ultra-strong, ultra-tiny “nanotubes” of carbon — would be available in just two years.
“[S]teel is not strong enough, neither is Kevlar, carbon fiber, spider silk, or any other material other than carbon nanotubes,” wrote Edwards. “Fortunately for us, carbon nanotube research is extremely hot right now, and it is progressing quickly to commercial production.”Unfortunately, he misjudged how hard it would be to synthesize carbon nanotubes — to date, no one has been able to grow one longer than 21 inches (53 cm).
Further research into the material revealed that it tends to fray under extreme stress, too, meaning even if we could manufacture carbon nanotubes at the lengths needed, they’d be at risk of snapping, not only destroying the space elevator, but threatening lives on Earth.
Looking ahead
Carbon nanotubes might have been the early frontrunner as the tether material for space elevators, but there are other options, including graphene, an essentially two-dimensional form of carbon that is already easier to scale up than nanotubes (though still not easy).
Contrary to Edwards’ report, Johns Hopkins University researchers Sean Sun and Dan Popescu say Kevlar fibers could work — we would just need to constantly repair the tether, the same way the human body constantly repairs its tendons.
“Using sensors and artificially intelligent software, it would be possible to model the whole tether mathematically so as to predict when, where, and how the fibers would break,” the researchers wrote in Aeon in 2018.
“When they did, speedy robotic climbers patrolling up and down the tether would replace them, adjusting the rate of maintenance and repair as needed — mimicking the sensitivity of biological processes,” they continued.Astronomers from the University of Cambridge and Columbia University also think Kevlar could work for a space elevator — if we built it from the moon, rather than Earth.
They call their concept the Spaceline, and the idea is that a tether attached to the moon’s surface could extend toward Earth’s geostationary orbit, held taut by the pull of our planet’s gravity. We could then use rockets to deliver payloads — and potentially people — to solar-powered climber robots positioned at the end of this 200,000+ mile long tether. The bots could then travel up the line to the moon’s surface.
This wouldn’t eliminate the need for rockets to get into Earth’s orbit, but it would be a cheaper way to get to the moon. The forces acting on a lunar space elevator wouldn’t be as strong as one extending from Earth’s surface, either, according to the researchers, opening up more options for tether materials.
“[T]he necessary strength of the material is much lower than an Earth-based elevator — and thus it could be built from fibers that are already mass-produced … and relatively affordable,” they wrote in a paper shared on the preprint server arXiv.
After riding up the Earth-based space elevator, a capsule would fly to a space station attached to the tether of the moon-based one.
Electrically powered climber capsules could go up down the tether to deliver payloads to any Earth orbit.
Adobe Stock
Some Chinese researchers, meanwhile, aren’t giving up on the idea of using carbon nanotubes for a space elevator — in 2018, a team from Tsinghua University revealed that they’d developed nanotubes that they say are strong enough for a tether.
The researchers are still working on the issue of scaling up production, but in 2021, state-owned news outlet Xinhua released a video depicting an in-development concept, called “Sky Ladder,” that would consist of space elevators above Earth and the moon.
After riding up the Earth-based space elevator, a capsule would fly to a space station attached to the tether of the moon-based one. If the project could be pulled off — a huge if — China predicts Sky Ladder could cut the cost of sending people and goods to the moon by 96 percent.
The bottom line
In the 120 years since Tsiolkovsky looked at the Eiffel Tower and thought way bigger, tremendous progress has been made developing materials with the properties needed for a space elevator. At this point, it seems likely we could one day have a material that can be manufactured at the scale needed for a tether — but by the time that happens, the need for a space elevator may have evaporated.
Several aerospace companies are making progress with their own reusable rockets, and as those join the market with SpaceX, competition could cause launch prices to fall further.
California startup SpinLaunch, meanwhile, is developing a massive centrifuge to fling payloads into space, where much smaller rockets can propel them into orbit. If the company succeeds (another one of those big ifs), it says the system would slash the amount of fuel needed to reach orbit by 70 percent.
Even if SpinLaunch doesn’t get off the ground, several groups are developing environmentally friendly rocket fuels that produce far fewer (or no) harmful emissions. More work is needed to efficiently scale up their production, but overcoming that hurdle will likely be far easier than building a 22,000-mile (35,400-km) elevator to space.
New tech aims to make the ocean healthier for marine life
A defunct drydock basin arched by a rusting 19th century steel bridge seems an incongruous place to conduct state-of-the-art climate science. But this placid and protected sliver of water connecting Brooklyn’s Navy Yard to the East River was just right for Garrett Boudinot to float a small dock topped with water carbon-sensing gear. And while his system right now looks like a trio of plastic boxes wired up together, it aims to mediate the growing ocean acidification problem, caused by overabundance of dissolved carbon dioxide.
Boudinot, a biogeochemist and founder of a carbon-management startup called Vycarb, is honing his method for measuring CO2 levels in water, as well as (at least temporarily) correcting their negative effects. It’s a challenge that’s been occupying numerous climate scientists as the ocean heats up, and as states like New York recognize that reducing emissions won’t be enough to reach their climate goals; they’ll have to figure out how to remove carbon, too.
To date, though, methods for measuring CO2 in water at scale have been either intensely expensive, requiring fancy sensors that pump CO2 through membranes; or prohibitively complicated, involving a series of lab-based analyses. And that’s led to a bottleneck in efforts to remove carbon as well.
But recently, Boudinot cracked part of the code for measurement and mitigation, at least on a small scale. While the rest of the industry sorts out larger intricacies like getting ocean carbon markets up and running and driving carbon removal at billion-ton scale in centralized infrastructure, his decentralized method could have important, more immediate implications.
Specifically, for shellfish hatcheries, which grow seafood for human consumption and for coastal restoration projects. Some of these incubators for oysters and clams and scallops are already feeling the negative effects of excess carbon in water, and Vycarb’s tech could improve outcomes for the larval- and juvenile-stage mollusks they’re raising. “We’re learning from these folks about what their needs are, so that we’re developing our system as a solution that’s relevant,” Boudinot says.
Ocean acidification can wreak havoc on developing shellfish, inhibiting their shells from growing and leading to mass die-offs.
Ocean waters naturally absorb CO2 gas from the atmosphere. When CO2 accumulates faster than nature can dissipate it, it reacts with H2O molecules, forming carbonic acid, H2CO3, which makes the water column more acidic. On the West Coast, acidification occurs when deep, carbon dioxide-rich waters upwell onto the coast. This can wreak havoc on developing shellfish, inhibiting their shells from growing and leading to mass die-offs; this happened, disastrously, at Pacific Northwest oyster hatcheries in 2007.
This type of acidification will eventually come for the East Coast, too, says Ryan Wallace, assistant professor and graduate director of environmental studies and sciences at Long Island’s Adelphi University, who studies acidification. But at the moment, East Coast acidification has other sources: agricultural runoff, usually in the form of nitrogen, and human and animal waste entering coastal areas. These excess nutrient loads cause algae to grow, which isn’t a problem in and of itself, Wallace says; but when algae die, they’re consumed by bacteria, whose respiration in turn bumps up CO2 levels in water.
“Unfortunately, this is occurring at the bottom [of the water column], where shellfish organisms live and grow,” Wallace says. Acidification on the East Coast is minutely localized, occurring closest to where nutrients are being released, as well as seasonally; at least one local shellfish farm, on Fishers Island in the Long Island Sound, has contended with its effects.
The second Vycarb pilot, ready to be installed at the East Hampton shellfish hatchery.
Courtesy of Vycarb
Besides CO2, ocean water contains two other forms of dissolved carbon — carbonate (CO3-) and bicarbonate (HCO3) — at all times, at differing levels. At low pH (acidic), CO2 prevails; at medium pH, HCO3 is the dominant form; at higher pH, CO3 dominates. Boudinot’s invention is the first real-time measurement for all three, he says. From the dock at the Navy Yard, his pilot system uses carefully calibrated but low-cost sensors to gauge the water’s pH and its corresponding levels of CO2. When it detects elevated levels of the greenhouse gas, the system mitigates it on the spot. It does this by adding a bicarbonate powder that’s a byproduct of agricultural limestone mining in nearby Pennsylvania. Because the bicarbonate powder is alkaline, it increases the water pH and reduces the acidity. “We drive a chemical reaction to increase the pH to convert greenhouse gas- and acid-causing CO2 into bicarbonate, which is HCO3,” Boudinot says. “And HCO3 is what shellfish and fish and lots of marine life prefers over CO2.”
This de-acidifying “buffering” is something shellfish operations already do to water, usually by adding soda ash (NaHCO3), which is also alkaline. Some hatcheries add soda ash constantly, just in case; some wait till acidification causes significant problems. Generally, for an overly busy shellfish farmer to detect acidification takes time and effort. “We’re out there daily, taking a look at the pH and figuring out how much we need to dose it,” explains John “Barley” Dunne, director of the East Hampton Shellfish Hatchery on Long Island. “If this is an automatic system…that would be much less labor intensive — one less thing to monitor when we have so many other things we need to monitor.”
Across the Sound at the hatchery he runs, Dunne annually produces 30 million hard clams, 6 million oysters, and “if we’re lucky, some years we get a million bay scallops,” he says. These mollusks are destined for restoration projects around the town of East Hampton, where they’ll create habitat, filter water, and protect the coastline from sea level rise and storm surge. So far, Dunne’s hatchery has largely escaped the ill effects of acidification, although his bay scallops are having a finicky year and he’s checking to see if acidification might be part of the problem. But “I think it's important to have these solutions ready-at-hand for when the time comes,” he says. That’s why he’s hosting a second, 70-liter Vycarb pilot starting this summer on a dock adjacent to his East Hampton operation; it will amp up to a 50,000 liter-system in a few months.
If it can buffer water over a large area, absolutely this will benefit natural spawns. -- John “Barley” Dunne.
Boudinot hopes this new pilot will act as a proof of concept for hatcheries up and down the East Coast. The area from Maine to Nova Scotia is experiencing the worst of Atlantic acidification, due in part to increased Arctic meltwater combining with Gulf of St. Lawrence freshwater; that decreases saturation of calcium carbonate, making the water more acidic. Boudinot says his system should work to adjust low pH regardless of the cause or locale. The East Hampton system will eventually test and buffer-as-necessary the water that Dunne pumps from the Sound into 100-gallon land-based tanks where larvae grow for two weeks before being transferred to an in-Sound nursery to plump up.
Dunne says this could have positive effects — not only on his hatchery but on wild shellfish populations, too, reducing at least one stressor their larvae experience (others include increasing water temperatures and decreased oxygen levels). “If it can buffer water over a large area, absolutely this will [benefit] natural spawns,” he says.
No one believes the Vycarb model — even if it proves capable of functioning at much greater scale — is the sole solution to acidification in the ocean. Wallace says new water treatment plants in New York City, which reduce nitrogen released into coastal waters, are an important part of the equation. And “certainly, some green infrastructure would help,” says Boudinot, like restoring coastal and tidal wetlands to help filter nutrient runoff.
In the meantime, Boudinot continues to collect data in advance of amping up his own operations. Still unknown is the effect of releasing huge amounts of alkalinity into the ocean. Boudinot says a pH of 9 or higher can be too harsh for marine life, plus it can also trigger a release of CO2 from the water back into the atmosphere. For a third pilot, on Governor’s Island in New York Harbor, Vycarb will install yet another system from which Boudinot’s team will frequently sample to analyze some of those and other impacts. “Let's really make sure that we know what the results are,” he says. “Let's have data to show, because in this carbon world, things behave very differently out in the real world versus on paper.”