Scientists are working on eye transplants for vision loss. Who will sign up?
Awash in a fluid finely calibrated to keep it alive, a human eye rests inside a transparent cubic device. This ECaBox, or Eyes in a Care Box, is a one-of-a-kind system built by scientists at Barcelona’s Centre for Genomic Regulation (CRG). Their goal is to preserve human eyes for transplantation and related research.
In recent years, scientists have learned to transplant delicate organs such as the liver, lungs or pancreas, but eyes are another story. Even when preserved at the average transplant temperature of 4 Centigrade, they last for 48 hours max. That's one explanation for why transplanting the whole eye isn’t possible—only the cornea, the dome-shaped, outer layer of the eye, can withstand the procedure. The retina, the layer at the back of the eyeball that turns light into electrical signals, which the brain converts into images, is extremely difficult to transplant because it's packed with nerve tissue and blood vessels.
These challenges also make it tough to research transplantation. “This greatly limits their use for experiments, particularly when it comes to the effectiveness of new drugs and treatments,” said Maria Pia Cosma, a biologist at Barcelona’s Centre for Genomic Regulation (CRG), whose team is working on the ECaBox.
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.
With a deadly pandemic sweeping the planet, many are questioning the comfort and security we have taken for granted in the modern world.
A century ago, when an influenza pandemic struck, we barely knew what viruses were.
More than a century after the germ theory, we are still at the mercy of a microbe we can neither treat, nor control, nor immunize against. Even more discouraging is that technology has in some ways exacerbated the problem: cars and air travel allow a new disease to quickly encompass the globe.
Some say we have grown complacent, that we falsely assume the triumphs of the past ensure a happy and prosperous future, that we are oblivious to the possibility of unpredictable "black swan" events that could cause our destruction. Some have begun to lose confidence in progress itself, and despair of the future.
But the new coronavirus should not defeat our spirit—if anything, it should spur us to redouble our efforts, both in the science and technology of medicine, and more broadly in the advance of industry. Because the best way to protect ourselves against future disasters is more progress, faster.
Science and technology have overall made us much better able to deal with disease. In the developed world, we have already tamed most categories of infectious disease. Most bacterial infections, such as tuberculosis or bacterial pneumonia, are cured with antibiotics. Waterborne diseases such as cholera are eliminated through sanitation; insect-borne ones such as malaria through pest control. Those that are not contagious until symptoms appear, such as SARS, can be handled through case isolation and contact tracing. For the rest, such as smallpox, polio, and measles, we develop vaccines, given enough time. COVID-19 could start a pandemic only because it fits a narrow category: a new, viral disease that is highly contagious via pre-symptomatic droplet/aerosol transmission, and that has a high mortality rate compared to seasonal influenza.
A century ago, when an influenza pandemic struck, we barely knew what viruses were; no one had ever seen one. Today we know what COVID-19 is down to its exact genome; in fact, we have sequenced thousands of COVID-19 genomes, and can track its history and its spread through their mutations. We can create vaccines faster today, too: where we once developed them in live animals, we now use cell cultures; where we once had to weaken or inactivate the virus itself, we can now produce vaccines based on the virus's proteins. And even though we don't yet have a treatment, the last century-plus of pharmaceutical research has given us a vast catalog of candidate drugs, already proven safe. Even now, over 50 candidate vaccines and almost 100 candidate treatments are in the research pipeline.
It's not just our knowledge that has advanced, but our methods. When smallpox raged in the 1700s, even the idea of calculating a case-fatality rate was an innovation. When the polio vaccine was trialled in the 1950s, the use of placebo-controlled trials was still controversial. The crucial measure of contagiousness, "R0", was not developed in epidemiology until the 1980s. And today, all of these methods are made orders of magnitude faster and more powerful by statistical and data visualization software.
If you're seeking to avoid COVID-19, the hand sanitizer gel you carry in a pocket or purse did not exist until the 1960s. If you start to show symptoms, the pulse oximeter that tests your blood oxygenation was not developed until the 1970s. If your case worsens, the mechanical ventilator that keeps you alive was invented in the 1950s—in fact, no form of artificial respiration was widely available until the "iron lung" used to treat polio patients in the 1930s. Even the modern emergency medical system did not exist until recently: if during the 1918 flu pandemic you became seriously ill, there was no 911 hotline to call, and any ambulance that showed up would likely have been a modified van or hearse, with no equipment or trained staff.
As many of us "shelter in place", we are far more able to communicate and collaborate, to maintain some semblance of normal life, than we ever would have been. To compare again to 1918: long-distance telephone service barely existed at that time, and only about a third of homes in the US even had electricity; now we can videoconference over Zoom and Skype. And the enormous selection and availability provided by online retail and food delivery have kept us stocked and fed, even when we don't want to venture out to the store.
Let the virus push us to redouble our efforts to make scientific, technological, and industrial progress on all fronts.
"Black swan" calamities can strike without warning at any time. Indeed, humanity has always been subject to them—drought and frost, fire and flood, war and plague. But we are better equipped now to deal with them than ever before. And the more progress we make, the better prepared we'll be for the next one. The accumulation of knowledge, technology, industrial infrastructure, and surplus wealth is the best buffer against any shock—whether a viral pandemic, a nuclear war, or an asteroid impact. In fact, the more worried we are about future crises, the more energetically we should accelerate science, technology and industry.
In this sense, we have grown complacent. We take the modern world for granted, so much so that some question whether further progress is even still needed. The new virus proves how much we do need it, and how far we still have to go. Imagine how different things would be if we had broad-spectrum antiviral drugs, or a way to enhance the immune system to react faster to infection, or a way to detect infection even before symptoms appear. These technologies may seem to belong to a Star Trek future—but so, at one time, did cell phones.
The virus reminds us that nature is indifferent to us, leaving us to fend entirely for ourselves. As we go to war against it, let us not take the need for such a war as reason for despair. Instead, let it push us to redouble our efforts to make scientific, technological, and industrial progress on all fronts. No matter the odds, applied intelligence is our best weapon against disaster.
With millions of people left feeling helpless as COVID-19 sweeps across the U.S. and the rest of the planet, there is one way in which absolutely anyone can help fight the pandemic -- all you need is a computer and an Internet connection.
"The more donors that participate, the more science we're able to do."
The Folding@home project allows members of the public to contribute a portion of their computing power to a gigantic virtual network which has mushroomed over the past month to become the most powerful supercomputer on the planet.
As of April 6, more than one million people across the globe have donated some of their home computing resources to the project. Combined, this gives Folding@home processing powers that dwarf even NASA and IBM's most powerful devices. To join, all you have to do is go to this website and click 'Download Now' to load the Folding@home software on your computer. This runs in the background, and only adds your unused computing power to the project, so it will not drain resources from tasks you're trying to do.
"It's totally crazy," said Vincent Voelz, associate professor of chemistry at Temple University, Philadelphia, and one of the scientists leading the project. "A month ago, we had around 30,000 to 40,000 participants. And then last week, it rose up 400,000 and now we've hit a million. But the more donors that participate, the more science we're able to do."
Voelz and the other scientists behind Folding@home are using these vast resources to model the ever-changing shapes of the coronavirus's proteins, in the hopes of identifying vulnerabilities or 'pockets' in its structure that can be targeted with new drugs.
One of the reasons it's difficult to find treatments for viruses like COVID-19 and Ebola is because the proteins, the innate building blocks of the viral structure, have notoriously smooth surfaces, making it hard for drugs to bind to them.
But viral proteins don't stay still. They are constantly evolving and changing shape as the atoms within push and pull against each other. Having a supercomputer enables scientists to simulate all these different shapes, revealing potential weaknesses which were not immediately visible. And the more powerful the supercomputer, the faster these simulations can happen.
"Simulating these protein motions also enables us to answer basic questions such as what makes this new coronavirus strain different from previous strains," said Voelz. "Is there something about the dynamics of these proteins that makes it more virulent?"
Finding a genuinely novel drug for COVID-19 is particularly critical.
Once they have identified suitable pockets within the proteins of COVID-19, the Folding@home scientists can then take the many compounds being identified by chemists around the world as potential drugs, and try to predict which ones will stand the best chance of binding to those pockets and inhibiting the virus's ability to invade and take over human cells.
"We have so much bandwidth now with Folding@home that we really think we can make a dent with screening these, and prioritizing which compounds are then going to get experimentally tested," said Voeltz.
The team are particularly hopeful they can succeed, having already used the supercomputer to identify a new vulnerability in the Ebola virus, which could go on to yield a new treatment for the disease.
Finding a genuinely novel drug for COVID-19 is particularly critical. While researchers are also looking at repurposing existing medications, like the antimalarials Hydroxychloroquine and Chloroquine (which have just been approved by the FDA for emergency use in coronavirus patients), concerns remain about the safety of these treatments. Researchers at the Mayo Clinic recently warned that the use of these drugs could have the side effect of inducing heart problems and run the risk of sudden cardiac arrest.
But with the death toll increasing by the day, speed is of the essence. Voelz explains that the scientific community has been left playing catch-up, because a drug was never actually developed for the original SARS outbreak in the early 2000s. The enormous computational power of the Folding@home project has the potential to allow scientists to quickly answer some of the key questions needed to get a new treatment into the pipeline.
"We don't have a SARS drug for whatever reason," said Voelz. "So the missing ingredient really, is the basic science to reveal possible drug targets and then the pharma can take that information and do the engineering work and optimizing and clinically testing drugs. But we now have a lot of basic science going on in response to this pandemic."