Often called the window to the soul, the eyes are more sacred than other body parts, at least for some.
Eye transplants are desperately needed, but they're nowhere in sight. About 12.7 million people worldwide need a corneal transplant, which means that only one in 70 people who require them, get them. The gaps are international. Eye banks in the United Kingdom are around 20 percent below the level needed to supply hospitals, while Indian eye banks, which need at least 250,000 corneas per year, collect only around 45 to 50 thousand donor corneas (and of those 60 to 70 percent are successfully transplanted).
As for retinas, it's impossible currently to put one into the eye of another person. Artificial devices can be implanted to restore the sight of patients suffering from severe retinal diseases, but the number of people around the world with such “bionic eyes” is less than 600, while in America alone 11 million people have some type of retinal disease leading to severe vision loss. Add to this an increasingly aging population, commonly facing various vision impairments, and you have a recipe for heavy burdens on individuals, the economy and society. In the U.S. alone, the total annual economic impact of vision problems was $51.4 billion in 2017.
Even if you try growing tissues in the petri dish route into organoids mimicking the function of the human eye, you will not get the physiological complexity of the structure and metabolism of the real thing, according to Cosma. She is a member of a scientific consortium that includes researchers from major institutions from Spain, the U.K., Portugal, Italy and Israel. The consortium has received about $3.8 million from the European Union to pursue innovative eye research. Her team’s goal is to give hope to at least 2.2 billion people across the world afflicted with a vision impairment and 33 million who go through life with avoidable blindness.
Their method? Resuscitating cadaveric eyes for at least a month.
If we succeed, it will be the first intact human model of the eye capable of exploring and analyzing regenerative processes ex vivo. -- Maria Pia Cosma.
“We proposed to resuscitate eyes, that is to restore the global physiology and function of human explanted tissues,” Cosma said, referring to living tissues extracted from the eye and placed in a medium for culture. Their ECaBox is an ex vivo biological system, in which eyes taken from dead donors are placed in an artificial environment, designed to preserve the eye’s temperature and pH levels, deter blood clots, and remove the metabolic waste and toxins that would otherwise spell their demise.
Scientists work on resuscitating eyes in the lab of Maria Pia Cosma.
Courtesy of Maria Pia Cosma.
“One of the great challenges is the passage of the blood in the capillary branches of the eye, what we call long-term perfusion,” Cosma said. Capillaries are an intricate network of very thin blood vessels that transport blood, nutrients and oxygen to cells in the body’s organs and systems. To maintain the garland-shaped structure of this network, sufficient amounts of oxygen and nutrients must be provided through the eye circulation and microcirculation. “Our ambition is to combine perfusion of the vessels with artificial blood," along with using a synthetic form of vitreous, or the gel-like fluid that lets in light and supports the the eye's round shape, Cosma said.
The scientists use this novel setup with the eye submersed in its medium to keep the organ viable, so they can test retinal function. “If we succeed, we will ensure full functionality of a human organ ex vivo. It will be the first intact human model of the eye capable of exploring and analyzing regenerative processes ex vivo,” Cosma added.
A rapidly developing field of regenerative medicine aims to stimulate the body's natural healing processes and restore or replace damaged tissues and organs. But for people with retinal diseases, regenerative medicine progress has been painfully slow. “Experiments on rodents show progress, but the risks for humans are unacceptable,” Cosma said.
The ECaBox could boost progress with regenerative medicine for people with retinal diseases, which has been painfully slow because human experiments involving their eyes are too risky. “We will test emerging treatments while reducing animal research, and greatly accelerate the discovery and preclinical research phase of new possible treatments for vision loss at significantly reduced costs,” Cosma explained. Much less time and money would be wasted during the drug discovery process. Their work may even make it possible to transplant the entire eyeball for those who need it.
“It is a very exciting project,” said Sanjay Sharma, a professor of ophthalmology and epidemiology at Queen's University, in Kingston, Canada. “The ability to explore and monitor regenerative interventions will increasingly be of importance as we develop therapies that can regenerate ocular tissues, including the retina.”
Seemingly, there's no sacred religious text or a holy book prohibiting the practice of eye donation.
But is the world ready for eye transplants? “People are a bit weird or very emotional about donating their eyes as compared to other organs,” Cosma said. And much can be said about the problem of eye donor shortage. Concerns include disfigurement and healthcare professionals’ fear that the conversation about eye donation will upset the departed person’s relatives because of cultural or religious considerations. As just one example, Sharma noted the paucity of eye donations in his home country, Canada.
Yet, experts like Sharma stress the importance of these donations for both the recipients and their family members. “It allows them some psychological benefit in a very difficult time,” he said. So why are global eye banks suffering? Is it because the eyes are the windows to the soul?
Seemingly, there's no sacred religious text or a holy book prohibiting the practice of eye donation. In fact, most major religions of the world permit and support organ transplantation and donation, and by extension eye donation, because they unequivocally see it as an “act of neighborly love and charity.” In Hinduism, the concept of eye donation aligns with the Hindu principle of daan or selfless giving, where individuals donate their organs or body after death to benefit others and contribute to society. In Islam, eye donation is a form of sadaqah jariyah, a perpetual charity, as it can continue to benefit others even after the donor's death.
Meanwhile, Buddhist masters teach that donating an organ gives another person the chance to live longer and practice dharma, the universal law and order, more meaningfully; they also dismiss misunderstandings of the type “if you donate an eye, you’ll be born without an eye in the next birth.” And Christian teachings emphasize the values of love, compassion, and selflessness, all compatible with organ donation, eye donation notwithstanding; besides, those that will have a house in heaven, will get a whole new body without imperfections and limitations.
The explanation for people’s resistance may lie in what Deepak Sarma, a professor of Indian religions and philosophy at Case Western Reserve University in Cleveland, calls “street interpretation” of religious or spiritual dogmas. Consider the mechanism of karma, which is about the causal relation between previous and current actions. “Maybe some Hindus believe there is karma in the eyes and, if the eye gets transplanted into another person, they will have to have that karmic card from now on,” Sarma said. “Even if there is peculiar karma due to an untimely death–which might be interpreted by some as bad karma–then you have the karma of the recipient, which is tremendously good karma, because they have access to these body parts, a tremendous gift,” Sarma said. The overall accumulation is that of good karma: “It’s a beautiful kind of balance,” Sarma said.
For the Jews, Christians, and Muslims who believe in the physical resurrection of the body that will be made new in an afterlife, the already existing body is sacred since it will be the basis of a new refashioned body in an afterlife.---Omar Sultan Haque.
With that said, Sarma believes it is a fallacy to personify or anthropomorphize the eye, which doesn’t have a soul, and stresses that the karma attaches itself to the soul and not the body parts. But for scholars like Omar Sultan Haque—a psychiatrist and social scientist at Harvard Medical School, investigating questions across global health, anthropology, social psychology, and bioethics—the hierarchy of sacredness of body parts is entrenched in human psychology. You cannot equate the pinky toe with the face, he explained.
“The eyes are the window to the soul,” Haque said. “People have a hierarchy of body parts that are considered more sacred or essential to the self or soul, such as the eyes, face, and brain.” In his view, the techno-utopian transhumanist communities (especially those in Silicon Valley) have reduced the totality of a person to a mere material object, a “wet robot” that knows no sacredness or hierarchy of human body parts. “But for the Jews, Christians, and Muslims who believe in the physical resurrection of the body that will be made new in an afterlife, the [already existing] body is sacred since it will be the basis of a new refashioned body in an afterlife,” Haque said. “You cannot treat the body like any old material artifact, or old chair or ragged cloth, just because materialistic, secular ideologies want so,” he continued.
For Cosma and her peers, however, the very definition of what is alive or not is a bit semantic. “As soon as we die, the electrophysiological activity in the eye stops,” she said. “The goal of the project is to restore this activity as soon as possible before the highly complex tissue of the eye starts degrading.” Cosma’s group doesn’t yet know when they will be able to keep the eyes alive and well in the ECaBox, but the consensus is that the sooner the better. Hopefully, the taboos and fears around the eye donations will dissipate around the same time.
Doctors worry that fungal pathogens may cause the next pandemic.
Although C. auris typically doesn’t sicken healthy people, it afflicts immunocompromised hospital patients and may cause severe infections that can lead to sepsis, a life-threatening condition in which the overwhelmed immune system begins to attack the body’s own organs. Between 30 and 60 percent of patients who contract a C. auris infection die from it, according to the CDC. People who are undergoing stem cell transplants, have catheters or have taken antifungal or antibiotic medicines are at highest risk. “We’re coming to a perfect storm of increasing resistance rates, increasing numbers of immunosuppressed patients worldwide and a bug that is adapting to higher temperatures as the climate changes,” says Prabhavathi Fernandes, chair of the National BioDefense Science Board.
Most Candida species aren’t well-adapted to our body temperatures so they aren’t a threat. C. auris, however, thrives at human body temperatures.
Although medical professionals aren’t concerned at this point about C. auris evolving to affect healthy people, they worry that its presence in hospitals can turn routine surgeries into life-threatening calamities. “It’s coming,” says Fernandes. “It’s just a matter of time.”
An emerging global threat
“Fungi are found in the environment,” explains Fernandes, so Candida spores can easily wind up on people’s skin. In hospitals, they can be transferred from contact with healthcare workers or contaminated surfaces. Most Candida species aren’t well-adapted to our body temperatures so they aren’t a threat. C. auris, however, thrives at human body temperatures. It can enter the body during medical treatments that break the skin—and cause an infection. Overall, fungal infections cost some $48 billion in the U.S. each year. And infection rates are increasing because, in an ironic twist, advanced medical therapies are enabling severely ill patients to live longer and, therefore, be exposed to this pathogen.
The first-ever case of a C. auris infection was reported in Japan in 2009, although an analysis of Candida samples dated the earliest strain to a 1996 sample from South Korea. Since then, five separate varieties – called clades, which are similar to strains among bacteria – developed independently in different geographies: South Asia, East Asia, South Africa, South America and, recently, Iran. So far, C. auris infections have been reported in 35 countries.
In the U.S., the first infection was reported in 2016, and the CDC started tracking it nationally two years later. During that time, 5,654 cases have been reported to the CDC, which only tracks U.S. data.
What’s more notable than the number of cases is their rate of increase. In 2016, new cases increased by 175 percent and, on average, they have approximately doubled every year. From 2016 through 2022, the number of infections jumped from 63 to 2,377, a roughly 37-fold increase.
“This reminds me of what we saw with epidemics from 2013 through 2020… with Ebola, Zika and the COVID-19 pandemic,” says Robin Robinson, CEO of Spriovas and founding director of the Biomedical Advanced Research and Development Authority (BARDA), which is part of the U.S. Department of Health and Human Services. These epidemics started with a hockey stick trajectory, Robinson says—a gradual growth leading to a sharp spike, just like the shape of a hockey stick.
Another challenge is that right now medics don’t have rapid diagnostic tests for fungal infections. Currently, patients are often misdiagnosed because C. auris resembles several other easily treated fungi. Or they are diagnosed long after the infection begins and is harder to treat.
The problem is that existing diagnostics tests can only identify C. auris once it reaches the bloodstream. Yet, because this pathogen infects bodily tissues first, it should be possible to catch it much earlier before it becomes life-threatening. “We have to diagnose it before it reaches the bloodstream,” Walsh says.
The most alarming fact is that some Candida infections no longer respond to standard therapeutics.
“We need to focus on rapid diagnostic tests that do not rely on a positive blood culture,” says John Sperzel, president and CEO of T2 Biosystems, a company specializing in diagnostics solutions. Blood cultures typically take two to three days for the concentration of Candida to become large enough to detect. The company’s novel test detects about 90 percent of Candida species within three to five hours—thanks to its ability to spot minute quantities of the pathogen in blood samples instead of waiting for them to incubate and proliferate.
Unlike other Candida species C. auris thrives at human body temperatures
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Tackling the resistance challenge
The most alarming fact is that some Candida infections no longer respond to standard therapeutics. The number of cases that stopped responding to echinocandin, the first-line therapy for most Candida infections, tripled in 2020, according to a study by the CDC.
Now, each of the first four clades shows varying levels of resistance to all three commonly prescribed classes of antifungal medications, such as azoles, echinocandins, and polyenes. For example, 97 percent of infections from C. auris Clade I are resistant to fluconazole, 54 percent to voriconazole and 30 percent of amphotericin. Nearly half are resistant to multiple antifungal drugs. Even with Clade II fungi, which has the least resistance of all the clades, 11 to 14 percent have become resistant to fluconazole.
Anti-fungal therapies typically target specific chemical compounds present on fungi’s cell membranes, but not on human cells—otherwise the medicine would cause damage to our own tissues. Fluconazole and other azole antifungals target a compound called ergosterol, preventing the fungal cells from replicating. Over the years, however, C. auris evolved to resist it, so existing fungal medications don’t work as well anymore.
A newer class of drugs called echinocandins targets a different part of the fungal cell. “The echinocandins – like caspofungin – inhibit (a part of the fungi) involved in making glucan, which is an essential component of the fungal cell wall and is not found in human cells,” Fernandes says. New antifungal treatments are needed, she adds, but there are only a few magic bullets that will hit just the fungus and not the human cells.
Research to fight infections also has been challenged by a lack of government support. That is changing now that BARDA is requesting proposals to develop novel antifungals. “The scope includes C. auris, as well as antifungals following a radiological/nuclear emergency, says BARDA spokesperson Elleen Kane.
The remaining challenge is the number of patients available to participate in clinical trials. Large numbers are needed, but the available patients are quite sick and often die before trials can be completed. Consequently, few biopharmaceutical companies are developing new treatments for C. auris.
ClinicalTrials.gov reports only two drugs in development for invasive C. auris infections—those than can spread throughout the body rather than localize in one particular area, like throat or vaginal infections: ibrexafungerp by Scynexis, Inc., fosmanogepix, by Pfizer.
Scynexis’ ibrexafungerp appears active against C. auris and other emerging, drug-resistant pathogens. The FDA recently approved it as a therapy for vaginal yeast infections and it is undergoing Phase III clinical trials against invasive candidiasis in an attempt to keep the infection from spreading.
“Ibreafungerp is structurally different from other echinocandins,” Fernandes says, because it targets a different part of the fungus. “We’re lucky it has activity against C. auris.”
Pfizer’s fosmanogepix is in Phase II clinical trials for patients with invasive fungal infections caused by multiple Candida species. Results are showing significantly better survival rates for people taking fosmanogepix.
Although C. auris does pose a serious threat to healthcare worldwide, scientists try to stay optimistic—because they recognized the problem early enough, they might have solutions in place before the perfect storm hits. “There is a bit of hope,” says Robinson. “BARDA has finally been able to fund the development of new antifungal agents and, hopefully, this year we can get several new classes of antifungals into development.”
A space elevator would be cheaper and cleaner than using rockets
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.
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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.
This article originally appeared on Big Think, home of the brightest minds and biggest ideas of all time.
